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Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling

Chronic activation of stress hormones such as glucocorticoids leads to skeletal muscle wasting in mammals. However, the molecular events that mediate glucocorticoid-induced muscle wasting are not well understood. Here, we show that SIRT6, a chromatin-associated deacetylase indirectly regulates glucocorticoid-induced muscle wasting by modulating IGF/PI3K/AKT signaling. Our results show that SIRT6 levels are increased during glucocorticoid-induced reduction of myotube size and during skeletal muscle ...

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Sclerostin aggravates insulin signaling in skeletal muscle and hepatic steatosis via upregulation of ER stress by mTOR-mediated inhibition of autophagy under hyperlipidemic conditions

Recently, sclerostin (SCL), a circulating glycoprotein, was proposed to be a novel myokine involved in developing metabolic disorders. The association between SCL levels and insulin resistance in skeletal muscle, liver, and adipose tissue was studied in individuals with aggravated glucose tolerance. Thus, we hypothesized that elevated circulating SCL might affect skeletal muscle insulin signaling and hepatic lipid metabolism, and aimed to investigate the effects of SCL on skeletal muscle insulin ...

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Extracellular vesicles mediate the communication of adipose tissue with brain and promote cognitive impairment associated with insulin resistance

Type 2 diabetes with obesity-related insulin resistance as the main manifestation is associated with an increased risk of cognitive impairment. Adipose tissue plays an important role in this process. Here, we demonstrated that adipose tissue-derived extracellular vesicles (EVs) and their cargo microRNAs (miRNAs) mediate inter-organ communication between adipose tissue and the brain, which can be transferred into the brain in a membrane protein-dependent manner and enriched in neurons, especially ...

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Omega-3 polyunsaturated fatty acids play roles in skeletal muscle-adipose tissue crosstalk through myokines

Purpose: Skeletal muscle-adipose tissue crosstalk is important for maintaining metabolic homeostasis. Myokine plays an indispensable role in the skeletal muscle-adipose tissue crosstalk. This study was conducted to elucidate the association between Omega-3 polyunsaturated fatty acids (n-3 PUFAs) and myokine and figure out the role of n-3 PUFAs in the skeletal muscle-adipose tissue crosstalk. Methods: The mRNA expression of myokines, including IL-6, Irisin, IL-15, myostatin, FGF21, adiponectin, leptin ...

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Relationships between Uncoupling Protein Genes UCP1, UCP2 and UCP3 and Irisin Levels in Residents of the Coldest Region of Siberia

Currently, it is known that irisin can participate in the processes of thermoregulation and browning of adipose tissue, and, therefore, it is possible that it is involved in the microevolutionary mechanisms of adaptation to a cold. The aim of this study is to investigate the relationship between the uncoupling protein genes (UCP1, UCP2, UCP3) and the irisin levels in the residents of the coldest region of Siberia. The sample consisted of 279 Yakut people (185 females, 94 males, average age 19.8 ± ...

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Exercise effects on cardiovascular disease: from basic aspects to clinical evidence

Cardiovascular (CV) disease (CVD) remains the leading cause of major morbidity and CVD- and all-cause mortality in most of the world. It is now clear that regular physical activity (PA) and exercise training (ET) induces a wide range of direct and indirect physiologic adaptations and pleiotropic benefits for human general and CV health. Generally, higher levels of PA, ET, and cardiorespiratory fitness (CRF) are correlated with reduced risk of CVD, including myocardial infarction, CVD-related death, ...

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Irisin, an Effective Treatment for Cardiovascular Diseases?

Irisin, as one of the myokines induced by exercise, has attracted much attention due to its important physiological functions such as white fat browning, the improvement in metabolism, and the alleviation of inflammation. Despite the positive role that irisin has been proven to play in the prevention and treatment of cardiovascular diseases, whether it can become a biomarker and potential target for predicting and treating cardiovascular diseases remains controversial, given the unreliability of ...

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Exercise training-induced changes in immunometabolic markers in youth badminton athletes

The aim of this study was to investigate the metabolic and inflammatory fluctuations in two seasonal phases of badminton training, and the ability of youth badminton athletes to respond to an inflammatory challenge given by acute exercise on these markers. Thirteen youth badminton athletes who participated in national and international competitions were recruited. Metabolic and cytokine profile were measured at rest and in response to a maximal exercise intermittent test, in the pre- and final phases ...

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The influence of sexual activity on athletic performance: a systematic review and meta-analyses

Several anecdotal reports suggest that sex before competition can affect performance. Our objective was to perform a systematic review and meta-analysis to determine whether athletic performance or some physical fitness measure is affected by prior sexual activity. Web of Science (all databases) and Google Scholar were used to identify studies from which adult healthy subjects were included. As all studies were crossover trials, an inverse variance statistical method with random effects was used ...

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The evolving view of thermogenic fat and its implications in cancer and metabolic diseases

The incidence of metabolism-related diseases like obesity and type 2 diabetes mellitus has reached pandemic levels worldwide and increased gradually. Most of them are listed on the table of high-risk factors for malignancy, and metabolic disorders systematically or locally contribute to cancer progression and poor prognosis of patients. Importantly, adipose tissue is fundamental to the occurrence and development of these metabolic disorders. White adipose tissue stores excessive energy, while thermogenic ...

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Differences in spinal posture and mobility between children/adolescents with obesity and age-matched normal-weight individuals

The aim of this study was to cross-sectionally explore the association of obesity with spinal posture and mobility, commonly associated with musculoskeletal problems, by comparing the spinal parameters between 90 obese and 109 normal-weight children and adolescents. A non-invasive electromechanical device, the Idiag M360 (Idiag, Fehraltorf, Switzerland), was used to measure the spinal parameters. An age-and-sex-adjusted two-way analysis of variance (ANOVA) was used to determine postural and mobility ...

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Self-Perceived Physical Level and Fitness Performance in Children and Adolescents with Inflammatory Bowel Disease

ackground: Inflammatory bowel disease (IBD) patients show a higher risk of developing metabolic and cardiovascular diseases due to the presence of systemic low-grade chronic inflammation. Exercise can improve cardiovascular fitness and modulate the inflammatory processes. We evaluated the physical activity (PA) level and the fitness performance of children and adolescents with IBD. Patients and methods: We considered 54 pediatric patients with IBD (14.6 ± 2.2; 22 M), including CD (n = 27) ...

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Pomegranate Extract Augments Energy Expenditure Counteracting the Metabolic Stress Associated with High-Fat-Diet-Induced Obesity

Obesity is associated to a low grade of chronic inflammation leading to metabolic stress, insulin resistance, metabolic syndrome, dislipidemia, cardiovascular disease, and even cancer. A Mediterranean diet has been shown to reduce systemic inflammatory factors, insulin resistance, and metabolic syndrome. In this scenario, precision nutrition may provide complementary approaches to target the metabolic alterations associated to “unhealthy obesity”. In a previous work, we described a pomegranate ...

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Lactobacillus plantarum S9 alleviates lipid profile, insulin resistance, and inflammation in high-fat diet-induced metabolic syndrome rats

Probiotics are considered to play an crucial role in the treatment of high-fat diet (HFD)-induced lipid metabolic diseases, including metabolic syndrome (MS). This study aimed to investigate the effects of Lactobacillus plantarum S9 on MS in HFD-fed rats, and to explore the underlying role of probiotics in the treatment of MS. Sprague-Dawley rats were fed with HFD for 8 weeks, followed by the treatment of L. plantarum S9 for 6 weeks, and The body weight and blood glucose level of rats were detected ...

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Irisin is more strongly associated with leisure-time physical activity than resistin and high-density lipoprotein cholesterol are

Obectives: Irisin is a myokine with a potential role in cardiometabolic diseases, but previous studies have described inconsistencies between serum irisin and physical activity (PA). Our aim was to analyze the relationship between serum irisin and leisure-time PA (LTPA) in a large sample of the general adult population, and secondarily, to evaluate its relationship with two PA-related biomarkers (HDL cholesterol and resistin). Design: A cross-sectional study was nested in the “CDC of the Canary ...

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Irisin stimulates protective signaling pathways in rat hippocampal neurons

Physical exercise stimulates neuroprotective pathways, has pro-cognitive actions, and alleviates memory impairment in Alzheimer’s disease (AD). Irisin is an exercise-linked hormone produced by cleavage of fibronectin type III domain containing protein 5 (FNDC5) in skeletal muscle, brain and other tissues. Irisin was recently shown to mediate the brain benefits of exercise in AD mouse models. Here, we sought to obtain insight into the neuroprotective actions of irisin. We demonstrate that adenoviral-mediated ...

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Irisin Is Related to Non-Alcoholic Fatty Liver Disease (NAFLD)

Irisin is a cytokine involved in many metabolic pathways occurring, among others, in muscles, adipose tissue and liver. Thus, fluctuations in irisin levels are suggested to be related to metabolic diseases. Therefore, the purpose of our study was to evaluate whether irisin may be associated with non-alcoholic fatty liver disease (NAFLD). A total of 138 patients (70/68 male/female, mean age 65.61 ± 10.44 years) were enrolled in the study. The patients were assigned to the NAFLD group (n = 72, ...

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Stretching muscle cells induces transcriptional and splicing transitions and changes in SR proteins

Alternative splicing is an RNA processing mechanism involved in skeletal muscle development and pathology. Muscular diseases exhibit splicing alterations and changes in mechanobiology leading us to investigate the interconnection between mechanical forces and RNA processing. We performed deep RNA-sequencing after stretching muscle cells. First, we uncovered transcriptional changes in genes encoding proteins involved in muscle function and transcription. Second, we observed that numerous mechanosensitive ...

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Lumican, an Exerkine, Protects against Skeletal Muscle Loss

Exerkines are soluble factors secreted by exercised muscles, mimicking the effects of exercise in various organs, including the muscle itself. Lumican is reportedly secreted from muscles; however, its roles in skeletal muscle remain unknown. Herein, we found that lumican mRNA expression in the extensor digitorum longus was significantly higher in exercised mice than in unloading mice, and lumican stimulated myogenesis in vitro. Additionally, lumican knockdown significantly decreased muscle mass and ...

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The role of exercise-induced myokines in promoting angiogenesis

Ischemic diseases are a major cause of mortality or disability in the clinic. Surgical or medical treatment often has poor effect on patients with tissue and organ ischemia caused by diffuse stenoses. Promoting angiogenesis is undoubtedly an effective method to improve perfusion in ischemic tissues and organs. Although many animal or clinical studies tried to use stem cell transplantation, gene therapy, or cytokines to promote angiogenesis, these methods could not be widely applied in the clinic ...

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Immunoglobulin Superfamily Containing Leucine-Rich Repeat (Islr) Participates in IL-6-Mediated Crosstalk between Muscle and Brown Adipose Tissue to Regulate Energy Homeostasis

Brown adipose tissue (BAT) is functionally linked to skeletal muscle because both tissues originate from a common progenitor cell, but the precise mechanism controlling muscle-to-brown-fat communication is insufficiently understood. This report demonstrates that the immunoglobulin superfamily containing leucine-rich repeat (Islr), a marker of mesenchymal stromal/stem cells, is critical for the control of BAT mitochondrial function and whole-body energy homeostasis. The mice loss of Islr in BAT after ...

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Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases

Adipose tissues are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. Although white adipose tissue and brown adipose tissue are currently considered key endocrine organs, they differ functionally and morphologically. The existence of the beige or brite adipocytes, cells displaying intermediary characteristics between white and brown adipocytes, illustrates the plastic nature of the adipose tissue. These cells are generated through white adipose tissue browning, ...

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Implication of Irisin in Different Types of Cancer: A Systematic Review and Meta-Analysis

Cancer is a set of diseases characterized by several hallmark properties, such as increased angiogenesis, proliferation, invasion, and metastasis. The increased angiogenic activity constantly supplies the tumors with nutrients and a plethora of cytokines to ensure cell survival. Along these cytokines is a newly discovered protein, called irisin, which is released into the circulation after physical exercise. Irisin is the product of fibronectin type III domain-containing protein 5 (FNDC5) proteolytic ...

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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for ...

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Effects of three modes of physical activity on physical fitness and hematological parameters in older people with sarcopenic obesity: A systematic review and meta-analysis

Objective: This systematic review and meta-analysis assessed the effects of three modes of physical activity (PA) (aerobic training [AT], resistance training [RT], and aerobic combined with resistance training [MT]) on body composition (body weight [BW], body mass index [BMI] and percentage of body fat [BF%]), muscle mass (skeletal muscle mass [SM], appendicular skeletal muscle mass [ASM] and appendicular skeletal muscle mass index [ASMI]), muscle strength (handgrip strength [HG] and knee extension ...

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Exercise Induced-Cytokines Response in Marathon Runners: Role of ACE I/D and BDKRB2 +9/-9 Polymorphisms

Renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) have a different site of interaction and modulate vascular tone and inflammatory response as well on exercise adaptation, which is modulated by exercise-induced cytokines. The aim of the study was to evaluate the role of ACE I/D and BDKRB2 +9/−9 polymorphism on exercise-induced cytokine response. Seventy-four male marathon finishers, aged 30 to 55 years, participated in this study. Plasma levels of exercise-induced cytokines were ...

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Exercise training enhances muscle mitochondrial metabolism in diet-resistant obesity

Background: Current paradigms for predicting weight loss in response to energy restriction have general validity but a subset of individuals fail to respond adequately despite documented diet adherence. Patients in the bottom 20% for rate of weight loss following a hypocaloric diet (diet-resistant) have been found to have less type I muscle fibres and lower skeletal muscle mitochondrial function, leading to the hypothesis that physical exercise may be an effective treatment when diet alone is inadequate. ...

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Exercise training maintains cardiovascular health: signaling pathways involved and potential therapeutics

Exercise training has been widely recognized as a healthy lifestyle as well as an effective non-drug therapeutic strategy for cardiovascular diseases (CVD). Functional and mechanistic studies that employ animal exercise models as well as observational and interventional cohort studies with human participants, have contributed considerably in delineating the essential signaling pathways by which exercise promotes cardiovascular fitness and health. First, this review summarizes the beneficial impact ...

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Importance of frequency and intensity of strength training for work ability among physical therapists

The aim of the study was to evaluate the association between frequency and intensity of strength training participation and work ability among physical therapists (PTs). The Work Ability Index questionnaire (WAI) and a questionnaire about participation in strength training during leisure time were administered to a sample of Spanish PTs. In addition, participants provided information on gender, age, body mass index, education, substance use, working experience and working hours per week. The odds ...

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Association of Leisure Time Physical Activity Types and Risks of All-Cause, Cardiovascular, and Cancer Mortality Among Older Adults

Importance: Higher amounts of physical activity are associated with increased longevity. However, whether different leisure time physical activity types are differentially associated with mortality risk is not established. Objectives: To examine whether participation in equivalent amounts of physical activity (7.5 to <15 metabolic equivalent of task [MET] hours per week) through different activity types is associated with mortality risk and to investigate the shape of the dose-response association. Design, ...

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Signaling pathways in obesity: mechanisms and therapeutic interventions

Obesity is a complex, chronic disease and global public health challenge. Characterized by excessive fat accumulation in the body, obesity sharply increases the risk of several diseases, such as type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and is linked to lower life expectancy. Although lifestyle intervention (diet and exercise) has remarkable effects on weight management, achieving long-term success at weight loss is extremely challenging, and the prevalence of ...

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Adipocytes control food intake and weight regain via Vacuolar-type H+ ATPase

Energy metabolism becomes dysregulated in individuals with obesity and many of these changes persist after weight loss and likely play a role in weight regain. In these studies, we use a mouse model of diet-induced obesity and weight loss to study the transcriptional memory of obesity. We found that the ‘metabolic memory’ of obesity is predominantly localized in adipocytes. Utilizing a C. elegans-based food intake assay, we identify ‘metabolic memory’ genes that play a role ...

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Of mice and men: Considerations on adipose tissue physiology in animal models of obesity and human studies

The ever-increasing burden of obesity demands a better pathophysiological understanding, especially regarding adipose tissue pathophysiology. Animal models of obesity are of great importance in investigating potential mechanisms and implications of obesity. Many issues should be considered while interpreting the preclinical results as anatomical and pathophysiological differences exist among species. Importantly, the natural history of obesity development differs considerably. An important example ...

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A preliminary study on the role of Piezo1 channels in myokine release from cultured mouse myotubes

It has long been known that regular physical exercise induces short and long term benefits reducing the risk of cardiovascular disease, diabetes, osteoporosis, cancer and improves sleep quality, cognitive level, mobility, autonomy in enderly. More recent is the evidence on the endocrine role of the contracting skeletal muscle. Exercise triggers the release of miokines, which act in autocrine, paracrine and endocrine ways controlling the activity of muscles but also of other tissues and organs such ...

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RSPO3 is a novel contraction-inducible factor identified in an “in vitro exercise model” using primary human myotubes

The physiological significance of skeletal muscle as a secretory organ is now well known but we can only speculate as to the existence of as-yet-unidentified myokines, especially those upregulated in response to muscle contractile activity. We first attempted to establish an “insert-chamber based in vitro exercise model” allowing the miniature but high cell-density culture state enabling highly developed contractile human myotubes to be readily obtained by applying electric pulse stimulation ...

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Acute Neuromuscular, Physiological and Performance Responses After Strength Training in Runners: A Systematic Review and Meta-Analysis

Background: Strength training (ST) is commonly used to improve muscle strength, power, and neuromuscular adaptations and is recommended combined with runner training. It is possible that the acute effects of the strength training session lead to deleterious effects in the subsequent running. The aim of this systematic review and meta-analysis was to verify the acute effects of ST session on the neuromuscular, physiological and performance variables of runners. Methods: Studies evaluating running ...

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Clinical and Biological Adaptations in Obese Older Adults Following 12-Weeks of High-Intensity Interval Training or Moderate-Intensity Continuous Training

Sarcopenia and obesity are considered a double health burden. Therefore, the implementation of effective strategies is needed to improve the quality of life of older obese individuals. The aim of this study was to compare the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on functional capacities, muscle function, body composition and blood biomarkers in obese older adults. Adipose tissue gene expression and markers of muscle mitochondrial content ...

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Obesity impairs skeletal muscle repair through NID-1 mediated extracellular matrix remodeling by mesenchymal progenitors

Obesity triggers skeletal muscle physio-pathological alterations. However, the crosstalk between adipose tissue and myogenic cells remains poorly understood during obesity. We identified NID-1 among the adipose tissue secreted factors impairing myogenic potential of human myoblasts and murine muscle stem cells in vitro. Mice under High Fat Diet (HFD) displayed increased NID-1 expression in the skeletal muscle endomysium associated with intramuscular fat adipose tissue expansion and compromised muscle ...

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Meteorin-like protein (Metrnl): A metabolic syndrome biomarker and an exercise mediator

Metrnl is a secreted protein able to activate different intracellular signaling pathways in adipocytes, macrophages, myocytes and cardiomyocytes with physiological effects of the browning of white adipose tissue (BWT), insulin sensitivity, inflammation inhibition, skeletal muscle regeneration and heart protection. Shown to be regulated by obesity, diabetes, caloric restriction, weight loss and heart diseases, Metrnl is definitely involved in metabolic turbulences, and may play roles in metabolic ...

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Exercise hormone irisin prevents physical inactivity-induced cognitive decline in mice

We previously reported that physical inactivity (PI) induces cognitive decline and depressive states, which were ameliorated by regular exercise. However, the mechanism underlying the preventive effect of exercise remains unelucidated. Irisin has recently been identified as an exercise-inducible myokine that improves cognitive impairment. Plasma irisin levels increase during physical exercise; therefore, PI could lead to a decline in cognitive function by reducing plasma irisin. Therefore, this study ...

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Cinnamic Acid Attenuates Peripheral and Hypothalamic Inflammation in High-Fat Diet-Induced Obese Mice

Obesity is closely linked to chronic inflammation in peripheral organs and the hypothalamus. Chronic consumption of a high-fat diet (HFD) induces the differentiation of Ly6chigh monocytes into macrophages in adipose tissue, the liver, and the brain, as well as the secretion of pro-inflammatory cytokines. Although cinnamon improves obesity and related diseases, it is unclear which components of cinnamon can affect macrophages and inflammatory cytokines. We performed in silico analyses using ADME, ...

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Coronary flow velocity reserve is reduced in patients with an exaggerated blood pressure response to exercise

Coronary artery disease and cardiovascular mortality are increased in patients with an exaggerated blood pressure response to exercise. The exact cause of this increase remains unknown, but previous studies have indicated the presence of endothelial dysfunction in peripheral arteries and subclinical atherosclerosis in these patients. The present study aimed to clarify whether coronary microvascular dysfunction is also present in patients with exaggerated blood pressure response to exercise. A total ...

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Low muscle mass, low muscle function, and sarcopenia in the urban and rural elderly

Health outcomes of the elderly vary between rural and urban areas. Sarcopenia is diagnosed as loss of muscle strength or impaired physical performance, namely “low muscle function” and low muscle mass. Outcomes of low muscle mass and low muscle function are not equal. This study aimed to investigate the prevalence of low muscle mass, low muscle function, and sarcopenia in rural and urban populations and to determine whether regional differences were associated with each of these components. ...

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Effects of High-Intensity Interval Training on Selected Adipokines and Cardiometabolic Risk Markers in Normal-Weight and Overweight/Obese Young Males. A Pre-Post Test Trial

The study aimed to assess effects of high-intensity interval training (HIIT) on plasma adipokines and cardiometabolic markers in normal and excess weight youth. Eighteen healthy young males (18.2 ± 1.06 yrs.) were divided in normal-weight group (NWG; body mass index (BMI), 20.5 ± 1.51 kg/m2; n = 9) and excess-weight group (EWG; BMI, 30.8 ± 4.56 kg/m2; n = 9). Participants performed an eight-week HIIT program without caloric restriction. Body composition, plasma leptin, adiponectin, ...

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Lactate as a major myokine and exerkine

The roles of exerkines, factors released from tissues during exercise, in promoting health and longevity were recently addressed in the Review by Chow and colleagues (Chow, L. S. et al. Exerkines in health, resilience and disease. Nat. Rev. Endocrinol. 18, 273–289 (2022)1). However, their timely Review did not adequately describe the major and diverse roles of lactate in regulating metabolism and physiology. Here, we highlight important functions of lactate as an exerkine. https://doi.org/10.1038/s41574-022-00724-0  

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Exercise-induced signaling pathways to counteracting cardiac apoptotic processes

Cardiovascular diseases are the most common cause of death in the world. One of the major causes of cardiac death is excessive apoptosis. However, multiple pathways through moderate exercise can reduce myocardial apoptosis. After moderate exercise, the expression of anti-apoptotic proteins such as IGF-1, IGF-1R, p-PI3K, p-Akt, ERK-1/2, SIRT3, PGC-1α, and Bcl-2 increases in the heart. While apoptotic proteins such as PTEN, PHLPP-1, GSK-3, JNK, P38MAPK, and FOXO are reduced in the heart. Exercise-induced ...

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Effects of physical exercise on bone mineral density in older postmenopausal women: a systematic review and meta-analysis of randomized controlled trials

Summary: Osteoporosis or decreased bone mineral density (BMD) is the most important risk factor for fractures, especially in older postmenopausal women (PMW). However, the interactions between exercise training and bone mineral density are not completely understood. We evaluated the effects of physical exercise on BMD in women aged ≥ 60 years postmenopausal. Purpose: This systematic review and meta-analysis sets out to determine the effects of physical exercise on BMD in older postmenopausal ...

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Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging

Functional status is considered the main determinant of healthy aging. Impairment in skeletal muscle and the cardiovascular system, two interrelated systems, results in compromised functional status in aging. Increased oxidative stress and inflammation in older subjects constitute the background for skeletal muscle and cardiovascular system alterations. Aged skeletal muscle mass and strength impairment is related to anabolic resistance, mitochondrial dysfunction, increased oxidative stress and inflammation ...

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Seawater Hydration Modulates IL-6 and Apelin Production during Triathlon Events: A Crossover Randomized Study

A triathlon is an endurance event in which athletes need an efficient hydration strategy since hydration is restricted at different stages. However, it seems that seawater intake can be a suitable hydration alternative for this type of endurance event. Therefore, the aim of this study was to evaluate the efficacy of seawater hydration during a triathlon on cytokine production. Fifteen trained male triathletes (age = 38.8 ± 5.62 years old; BMI = 22.58 ± 2.51 kg/m2) randomly performed ...

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Mechanisms of skeletal muscle repair and regeneration in health and disease

Skeletal muscle is a structurally and functionally remarkable tissue composed of multinucleated post-mitotic muscle fibres. These fibres are filled with an exquisite, near crystalline array of assembled contractile proteins, capable of coupling ATP utilization to mechanical muscle contraction. Fully differentiated muscle has an incredible ability to protect and repair itself from significant muscle injuries. In fact, through activation of a resident population of stem cells known as satellite cells, ...

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Circulating Irisin Levels in Patients with Chronic Plaque Psoriasis

Irisin is an adipo-myokine, mainly synthetized in skeletal muscles and adipose tissues, that is involved in multiple processes. Only a few studies have evaluated serum irisin in psoriatic patients. This study aims to analyze serum irisin levels in patients with chronic plaque psoriasis, to compare them with values in controls, and to assess whether concentration of circulating irisin correlates with the severity of psoriasis, calculated by means of Psoriasis Area and Severity Index (PASI). We enrolled ...

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A newly identified myokine: irisin, and its relationship with chronic spontaneous urticaria and inflammation

Chronic spontaneous urticaria (CSU) is an important dermatological disease involving severe itchy urticaria lesions and/or angioedema. Urticaria and angioedema occur in the community at a rate of 25–30%. Many factors, such as inflammation, have been implicated in the etiology of CSU. Irisin is a newly identified adipocytokine shown by research to exhibit anti-inflammatory properties in addition to its many other effects. The aim of the study was to investigate, for the first time in the literature, ...

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T-bet+ B cells accumulate in adipose tissue and exacerbate metabolic disorder during obesity

Obesity is accompanied by inflammation in adipose tissue, impaired glucose tolerance, and changes in adipose leukocyte populations. These studies of adipose tissue from humans and mice revealed that increased frequencies of T-bet+ B cells in adipose tissue depend on invariant NKT cells and correlate with weight gain during obesity. Transfer of B cells enriched for T-bet+ cells exacerbates metabolic disorder in obesity, while ablation of Tbx21 specifically in B cells reduces serum IgG2c levels, inflammatory ...

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Hepatokine Fetuin B expression is regulated by leptin-STAT3 signalling and associated with leptin in obesity

Obesity is an expanding global public health problem and a leading cause of metabolic disorders. The hepatokine Fetuin B participates in regulating insulin resistance, glucose metabolism and liver steatosis. However, the mechanism underlying Fetuin B activation remains unclear. Our previous population-based study demonstrated a significant association between serum Fetuin B and body fat mass in an obese population, which indicates its potential in mediating obesity-related metabolic disorders. In ...

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EGFR-mediated activation of adipose tissue macrophages promotes obesity and insulin resistance

Obesity and obesity-related health complications are increasing in prevalence. Adipose tissue from obese subjects has low-grade, chronic inflammation, leading to insulin resistance. Adipose tissue macrophages (ATMs) are a source of proinflammatory cytokines that further aggravate adipocyte dysfunction. In response to a high fat diet (HFD), ATM numbers initially increase by proliferation of resident macrophages, but subsequent increases also result from infiltration in response to chemotactic signals ...

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Cinnamon extract improves abnormalities in glucose tolerance by decreasing Acyl-CoA synthetase long-chain family 1 expression in adipocytes

We previously demonstrated that cinnamon extract (CE) alleviates streptozotocin-induced type 1 diabetes in rats. The present study aimed to elucidate the detailed molecular target of cinnamon in cultured adipocytes and epididymal adipose tissue of type 2 diabetes model mice. Two-dimensional gel electrophoresis was employed to determine the molecular target of cinnamon in adipocytes. The function of Acyl-CoA synthetase long-chain family-1 (ACSL1), a molecular target of cinnamon that was identified ...

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The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

Obesity is a multifactorial and complex disease that often manifests in early childhood with a lifelong burden. Polygenic and monogenic obesity are driven by the interaction between genetic predisposition and environmental factors. Polygenic variants are frequent and confer small effect sizes. Rare monogenic obesity syndromes are caused by defined pathogenic variants in single genes with large effect sizes. Most of these genes are involved in the central nervous regulation of body weight; for example, ...

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Morning Exercise Reduces Abdominal Fat and Blood Pressure in Women; Evening Exercise Increases Muscular Performance in Women and Lowers Blood Pressure in Men

The ideal exercise time of day (ETOD) remains elusive regarding simultaneous effects on health and performance outcomes, especially in women. Purpose: Given known sex differences in response to exercise training, this study quantified health and performance outcomes in separate cohorts of women and men adhering to different ETOD. Methods: Thirty exercise-trained women (BMI = 24 ± 3 kg/m2; 42 ± 8 years) and twenty-six men (BMI = 25.5 ± 3 kg/m2; 45 ± 8 years) were randomized ...

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Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity

Under healthy conditions, the pancreas responds to a glucose challenge by releasing insulin. Insulin suppresses lipolysis in adipose tissue, thereby decreasing plasma glycerol concentration, and it regulates plasma glucose concentration through action in muscle and liver. Insulin resistance (IR) occurs when more insulin is required to achieve the same effects, and IR may be tissue-specific. IR emerges during puberty as a result of high concentrations of growth hormone and is worsened by youth-onset ...

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Insulin Resistance in Peripheral Tissues and the Brain: A Tale of Two Sites?

The concept of insulin resistance has been around since a few decades after the discovery of insulin itself. To allude to the classic Charles Dicken’s novel published 62 years before the discovery of insulin, in some ways, this is the best of times, as the concept of insulin resistance has expanded to include the brain, with the realization that insulin has a life beyond the regulation of glucose. In other ways, it is the worst of times as insulin resistance is implicated in devastating diseases, ...

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In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states

In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states Metabolic regulation in skeletal muscle is essential for blood glucose homeostasis. Obesity causes insulin resistance in skeletal muscle, leading to hyperglycemia and type 2 diabetes. In this study, we performed multiomic analysis of the skeletal muscle of wild-type (WT) and leptin-deficient obese (ob/ob) mice, and constructed regulatory transomic networks for ...

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Protocol and reference values for minimal detectable change of MyotonPRO and ultrasound imaging measurements of muscle and subcutaneous tissue

The assessment of muscle health is of paramount importance, as the loss of muscle mass and strength can affect performance. Two non-invasive tools that have been found to be useful in this are the MyotonPRO and rehabilitative ultrasound imaging, both have shown to be reliable in previous studies many of which conducted by the research team. This study aims to determine the reliability of previously unassessed local body structures and to determine their minimal detectable changes (MDC) to support ...

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Association between changes in handgrip strength and depression in Korean adults: a longitudinal panel study

Depression in older adults is a global socioeconomic burden. Identifying factors, such as physical activity or exercise that can help prevent depression is important. We aimed to investigate the relationship between changes in handgrip strength and the presence of depression using longitudinal, nationwide data of older Korean adults. Data from the Korean Longitudinal Study of Aging were used in this study. A total of 6783 participants who had undergone a handgrip strength test and completed the short-form ...

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Relationship between hyperhomocysteinemia and coexisting obesity with low skeletal muscle mass in asymptomatic adult population

The relationship between hyperhomocysteinemia (HHcy) and obesity with low skeletal muscle mass (LMM) has not been established. We aim to assess the association between HHcy and the coexistence of obesity and LMM in asymptomatic adult population. We conducted a population-based cross-sectional study among asymptomatic individuals who underwent measurements of plasma homocysteine and body composition analysis. HHcy was defined as > 15 umol/L, obesity as body mass index ≥ 25 ...

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Differences in trunk and lower extremity muscle activity during squatting exercise with and without hammer swing

Perturbation exercises enhance lower limb and trunk muscles, and adding swing perturbation while loading during exercise might improve muscle activation or strength. This study aimed to check variations in trunk and lower limb muscle activity during conventional isometric squats, and whether it will change with or without swing using the Hammerobics-synchronized squat method. Twelve healthy men participated in this study. Activities for the abductor hallucis, tibialis anterior, tibialis posterior, ...

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Judo training program improves brain and muscle function and elevates the peripheral BDNF concentration among the elderly

Programmed exercise interventions modulating both physical fitness and cognitive functions have become a promising tool to support healthy aging. The aim of this experiment was to determine the effect of a 12-week judo training (JEX) on cognitive processing and muscle function among the elderly. Forty participants were divided into two groups: the JEX group and the control group (CTL). Before and after 12-week of JEX, participants performed a battery of physiological and psychological tests. The ...

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R-spondin3 is a myokine that differentiates myoblasts to type I fibres

Muscle fibres are broadly categorised into types I and II; the fibre-type ratio determines the contractile and metabolic properties of skeletal muscle tissue. The maintenance of type I fibres is essential for the prevention of obesity and the treatment of muscle atrophy caused by type 2 diabetes or unloading. Some reports suggest that myokines are related to muscle fibre type determination. We thus explored whether a myokine determines whether satellite cells differentiate to type I fibres. By examining ...

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Mitochondrial proteostasis stress in muscle drives a long-range protective response to alleviate dietary obesity independently of ATF4

Mitochondrial quality in skeletal muscle is crucial for maintaining energy homeostasis during metabolic stresses. However, how muscle mitochondrial quality is controlled and its physiological impacts remain unclear. Here, we demonstrate that mitoprotease LONP1 is essential for preserving muscle mitochondrial proteostasis and systemic metabolic homeostasis. Skeletal muscle–specific deletion of Lon protease homolog, mitochondrial (LONP1) impaired mitochondrial protein turnover, leading to muscle ...

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Adipose and Skeletal Muscle Expression of Adiponectin and Liver Receptor Homolog-1 With Weight Loss and Aerobic Exercise

Context: Adiponectin is an adipokine mainly secreted by adipocytes that regulates the metabolism of lipids and glucose. Liver receptor homolog-1 (LRH-1), also named NR5A2, is a nuclear receptor that regulates lipid metabolism and homeostasis. Objective: The purpose of this study was to compare adiponectin and LRH-1 messenger RNA (mRNA) expression in adipose tissue and LRH-1 expression in skeletal muscle between men and women at baseline and to study the effects of aerobic exercise (AEX) training ...

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Exercise-induced FNDC5/irisin protects nucleus pulposus cells against senescence and apoptosis by activating autophagy

Intervertebral disc degeneration (IVDD) is a major cause of low back pain (LBP), and excessive senescence and apoptosis of nucleus pulposus (NP) cells are major pathological changes in IVDD. Physical exercise could effectively delay the process of intervertebral disc degeneration; however, its mechanism is still largely unknown. Irisin is an exercise-induced myokine released upon cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), and its levels ...

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Effects of different exercise intensities on prefrontal activity during a dual task

The effects of physical exercise on cognitive tasks have been investigated. However, it is unclear how different exercise intensities affect the neural activity. In this study, we investigated the neural activity in the prefrontal cortex (PFC) by varying the exercise intensity while participants performed a dual task (DT). Twenty healthy young adults performed serial subtraction while driving a cycle ergometer. Exercise intensity was set to one of three levels: low, moderate, or high intensity. We ...

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The crosstalk between endothelial cells and vascular smooth muscle cells aggravates high phosphorus-induced arterial calcification

Arterial calcification is highly prevalent, particularly in patients with end-stage renal disease (ESRD). The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is the critical process for the development of arterial calcification. However, the detailed mechanism of VSMCs calcification remains to be elucidated. Here, we investigated the role of exosomes (Exos) derived from endothelial cells (ECs) in arterial calcification and its potential mechanisms in ESRD. Accelerated VSMCs calcification ...

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The role of irisin in metabolic flexibility: Beyond adipose tissue browning

Metabolic flexibility is the ability to adapt to physiological and environmental changes in metabolic demand. Irisin was originally discovered as an exercise-induced myokine involved in fat browning. In this review, we summarize emerging evidence for the roles of irisin in regulating glucose metabolism and insulin sensitivity in skeletal muscle, neuroplasticity and satiety in central nervous system, β cell function and insulin secretion in the pancreas, bone remodeling, and adipose tissue function, ...

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Genetic variation of putative myokine signaling is dominated by biological sex and sex hormones

Skeletal muscle plays an integral role in coordinating physiological homeostasis, where signaling to other tissues via myokines allows for coordination of complex processes. Here, we aimed to leverage natural genetic correlation structure of gene expression both within and across tissues to understand how muscle interacts with metabolic tissues. Specifically, we performed a survey of genetic correlations focused on myokine gene regulation, muscle cell composition, cross-tissue signaling, and interactions ...

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Adipocyte lysoplasmalogenase TMEM86A regulates plasmalogen homeostasis and protein kinase A-dependent energy metabolism

Dysregulation of adipose tissue plasmalogen metabolism is associated with obesity-related metabolic diseases. We report that feeding mice a high-fat diet reduces adipose tissue lysoplasmalogen levels and increases transmembrane protein 86 A (TMEM86A), a putative lysoplasmalogenase. Untargeted lipidomic analysis demonstrates that adipocyte-specific TMEM86A-knockout (AKO) increases lysoplasmalogen content in adipose tissue, including plasmenyl lysophosphatidylethanolamine 18:0 (LPE P-18:0). ...

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Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life

Obesity is a pre-disposing condition for chronic obstructive pulmonary disease, asthma, and pulmonary arterial hypertension. Accumulating evidence suggests that metabolic influences during development can determine chronic lung diseases (CLD). We demonstrate that maternal obesity causes early metabolic disorder in the offspring. Here, interleukin-6 induced bronchial and microvascular smooth muscle cell (SMC) hyperproliferation and increased airway and pulmonary vascular resistance. The key anti-proliferative ...

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Ribonucleotide reductase M2B in the myofibers modulates stem cell fate in skeletal muscle

The balance among quiescence, differentiation, and self-renewal of skeletal muscle stem cells (MuSCs) is tightly regulated by their intrinsic and extrinsic properties from the niche. How the niche controls MuSC fate remains unclear. Ribonucleotide reductase M2B (Rrm2b) modulates MuSC quiescence/differentiation in muscle in response to injury. Rrm2b knockout in myofibers, but not in MuSCs, led to weakness of muscles, such as a loss of muscle mass and strength. After muscle injury, damaged myofibers ...

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Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity

Identifying genetic variants associated with lower waist-to-hip ratio can reveal new therapeutic targets for abdominal obesity. We use exome sequences from 362,679 individuals to identify genes associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI), a surrogate for abdominal fat that is causally linked to type 2 diabetes and coronary heart disease. Predicted loss of function (pLOF) variants in INHBE associate with lower WHRadjBMI and this association replicates in data from AMP-T2D-GENES. ...

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Adipose Tissue Myeloid-Lineage Neuroimmune Cells Express Genes Important for Neural Plasticity and Regulate Adipose Innervation

Peripheral nerves allow a bidirectional communication between brain and adipose tissues, and many studies have clearly demonstrated that a loss of the adipose nerve supply results in tissue dysfunction and metabolic dysregulation. Neuroimmune cells closely associate with nerves in many tissues, including subcutaneous white adipose tissue (scWAT). However, in scWAT, their functions beyond degrading norepinephrine in an obese state remain largely unexplored. We previously reported that a myeloid-lineage ...

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Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides

Muscle contraction depends on strictly controlled Ca2+ transients within myocytes. A major player maintaining these transients is the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase, SERCA. Activity of SERCA is regulated by binding of micropeptides and impaired expression or function of these peptides results in cardiomyopathy. To date, it is not known how homeostasis or turnover of the micropeptides is regulated. Herein, we find that the Drosophila endopeptidase Neprilysin 4 hydrolyzes SERCA-inhibitory ...

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Therapeutic exercise to improve motor function among children with Down Syndrome aged 0 to 3 years: a systematic literature review and meta‑analysis

The effects and the prescription parameters of therapeutic exercise are not clear. For this reason, is needed to determine the effect of therapeutic exercises on the motor function of children with Down Syndrome (DS) aged 0 to 3 years. The present study is systematic review and meta-analysis of effectiveness outcomes in this population: gait, balance, motor development, fine motor skills, and executive functions. The databases of PubMed, PEDro, EMBASE, SCIELO, Lilacs, Cochrane library were searched ...

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A single session of exercise reduces blood pressure reactivity to stress: a systematic review and meta-analysis

Stressful situations are common in everyday life and disturb homeostasis. So, an exercise session is a strategy to mitigate blood pressure (BP) peaks in response to stress (i.e., BP reactivity), decreasing the cardiovascular risk. This is a systematic review and meta-analysis that aims to verify the effects of a single session of physical exercises on BP reactivity to stress in adults. The searches were performed in digital databases (MEDLINE, LILACS, EMBASE, SPORTDiscus, and PsycInfo) and 29 studies ...

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Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity

Brown adipose tissue (BAT) has a role in maintaining systemic metabolic health in rodents and humans. Here, we show that metabolic stress induces BAT to produce coagulation factors, which then—together with molecules derived from the circulation—promote BAT dysfunction and systemic glucose intolerance. When mice were fed a high-fat diet (HFD), the levels of tissue factor, coagulation Factor VII (FVII), activated coagulation Factor X (FXa), and protease-activated receptor 1 (PAR1) expression ...

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Antidepressant Effect of Intermittent Long-Term Systemic Administration of Irisin in Mice

Depression is a psychiatric disorder increasingly diffused worldwide. Evidence suggests that irisin, a myokine secreted by contracting muscle, mediates beneficial effects on several targets, including the brain. Here, the potential antidepressant properties of long-term intermittent systemic irisin administration (100 µg/kg/weekly for 1 month) were evaluated in mice by the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT). Furthermore, to deepen the molecular pathways ...

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A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity

We investigated gluteal (GSAT) and abdominal subcutaneous adipose tissue (ASAT) DNA methylation of FKBP5 in response to a 12-week intervention in African women with obesity, as well as the effect of the rs1360780 single nucleotide polymorphism (SNP) on FKBP5 methylation, gene expression and post-exercise training adaptations in obesity and metabolic related parameters. Exercise (n = 19) participants underwent 12-weeks of supervised aerobic and resistance training while controls (n = 12) ...

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Adipose tissue thermogenesis by calcium futile cycling

Brown and beige adipocytes produce heat and control systemic energy via non-shivering thermogenesis (NST). Historically, thermogenesis in brown and beige adipocytes was thought to be exclusively through a mitochondria-localized protein, uncoupling protein 1 (UCP1). However, recent studies identified UCP1-independent thermogenic mechanisms in adipocytes. Importantly, UCP1-independent pathways significantly contribute to systemic energy and glucose homeostasis. The finding of UCP1-independent mechanisms ...

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Acute Beetroot Juice Supplementation Enhances Intermittent Running Performance but Does Not Reduce Oxygen Cost of Exercise among Recreational Adults

Nitrate (NO3−) supplementation has been reported to enhance intermittent exercise performance; however, its impact on oxygen (O2) cost during intermittent running exercise is unclear. The aim of this study was to assess if acute NO3− supplementation would elicit performance benefits in recreationally active individuals during the Yo–Yo intermittent recovery level 1 (Yo-Yo IR1) test, with its potential benefit on O2 consumption (VO2), in a double-blind, randomized, crossover study, ...

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Effects of Strength Training on Body Fat in Children and Adolescents with Overweight and Obesity: A Systematic Review with Meta-Analysis

Childhood overweight and obesity represent a growing public health problem worldwide. Since the 1980s, the global prevalence of overweight and obesity in childhood and adolescence has increased by 47%. The promotion of exercise is an important intervention to reduce the physical damage of obesity. The meta-analysis was conducted in accordance with the general guidelines for the reporting of systematic reviews and meta-analyses (PRISMA). The PubMed, SciELO, ScienceDirect and Google Scholar databases ...

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FKBP11 rewires UPR signaling to promote glucose homeostasis in type 2 diabetes and obesity

Chronic endoplasmic reticulum (ER) stress and sustained activation of unfolded protein response (UPR) signaling contribute to the development of type 2 diabetes in obesity. UPR signaling is a complex signaling pathway, which is still being explored in many different cellular processes. Here, we demonstrate that FK506-binding protein 11 (FKBP11), which is transcriptionally regulated by XBP1s, is severely reduced in the livers of obese mice. Restoring hepatic FKBP11 expression in obese mice initiates ...

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The different effects of intramuscularly-injected lactate on white and brown adipose tissue in vivo

Background: Lactate is an important product of glycolysis metabolism during exercise and has long been recognized as an important metabolic signaling molecule involved in inhibiting lipolysis and promoting lipogenesis, which consequently leads to regulated adipose tissue metabolism. However, recent studies have shown that lactate promotes the browning of white adipose tissue (WAT), which induces heat production and energy expenditure and ultimately causes weight loss. These studies assessing the ...

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Modulation of endoplasmic reticulum stress via sulforaphane-mediated AMPK upregulation against nonalcoholic fatty liver disease in rats

Nonalcoholic fatty liver disease (NAFLD) is a major health concern. Endoplasmic reticulum (ER) stress, inflammation, and metabolic dysfunctions may be targeted to prevent the progress of nonalcoholic fatty liver disease. Sulforaphane (SFN), a sulfur-containing compound that is abundant in broccoli florets, seeds, and sprouts, has been reported to have beneficial effects on attenuating metabolic diseases. In light of this, the present study was designed to elucidate the mechanisms by which SFN ameliorated ...

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Severe Hyperprolactinemia Promotes Brown Adipose Tissue Whitening and Aggravates High Fat Diet Induced Metabolic Imbalance

Background: The association of high serum prolactin and increased body weight is positive but controversial, therefore we hypothesized that additional factors such as diets and the impact of prolactin on brown adipose tissue may condition its metabolic effects. Methods: We used LacDrd2KO females with lifelong severe hyperprolactinemia due dopamine-D2 receptor deletion from lactotropes, and slow onset of metabolic disturbances, and compared them to their respective controls (Drd2 loxP/loxP). Food ...

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Association of the “Weekend Warrior” and Other Leisure-time Physical Activity Patterns With All-Cause and Cause-Specific Mortality: A Nationwide Cohort Study

Importance: It is unclear whether the weekly recommended amount of moderate to vigorous physical activity (MVPA) has the same benefits for mortality risk when activity sessions are spread throughout the week vs concentrated in fewer days. Objective: To examine the association of weekend warrior and other patterns of leisure-time physical activity with all-cause and cause-specific mortality. Design, Setting, and Participants: This large nationwide prospective cohort study included 350 978 adults ...

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Effects of Fatigue on Postural Sway and Electromyography Modulation in Young Expert Acrobatic Gymnasts and Healthy Non-trained Controls During Unipedal Stance

This study investigated whether expert acrobatic gymnasts respond differentially than their non-trained counterparts during a single-legged stance task performed before and after a protocol designed to induce fatigue in the ankle plantarflexor muscles in terms of (a) postural steadiness and (b) electromyography (EMG) activation. We hypothesized that neuromuscular adaptation due to training would lead to different behavior of center of pressure (COP) and EMG quantifiers after fatigue. Twenty eight ...

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Sit to stand muscle power reference values and their association with adverse events in Colombian older adults

Recently, a valid method to assess lower-body muscle power based on a sit-to-stand field test (STS) has been published. Our study aimed to describe lower-body muscle power in older individuals aged ≥ 60 years and examine the relationship of muscle weakness with adverse events according to gender- and age-specific muscle weakness cut-off points. A total of 3689 Colombian older adults (57.6% women, age 69.1 ± 6.9 years) from the 2015 Survey on Health, Well-Being, ...

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No effect of five days of bed rest or short-term resistance exercie prehabilitation on markers of skeletal muscle mitochondrial content and dynamics in older adults

Bed rest (BR) results in significant impairments in skeletal muscle metabolism. Mitochondrial metabolism is reportedly highly sensitive to disuse, with dysregulated fission-fusion events and impaired oxidative function previously reported. The effects of clinically relevant short-term BR (≤5 days) on mitochondrial protein expression are presently unclear, as are the effects of exercise prehabilitation as a potential counteractive intervention. The present study examined the effects of a 5-day ...

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Mitigating sarcoplasmic reticulum stress limits disuse-induced muscle loss in hindlimb unloaded mice

Muscle disuse in the hindlimb unloaded (HU) mice causes significant atrophy and weakness. However, the cellular and molecular mechanisms driving disuse-muscle atrophy remain elusive. We investigated the potential contribution of proteins dysregulation by sarcoplasmic reticulum (SR), a condition called SR stress, to muscle loss during HU. Male, c57BL/6j mice were assigned to ground-based controls or HU groups treated with vehicle or 4-phenylbutyrate (4-PBA), a potent inhibitor of SR stress, once a ...

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Irisin Attenuates Muscle Impairment during Bed Rest through Muscle-Adipose Tissue Crosstalk

The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy ...

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Molecular Basis of Irisin Regulating the Effects of Exercise on Insulin Resistance

Insulin resistance is recognized as one major feature of metabolic syndrome, and frequently emerges as a difficult problem encountered during long-term pharmacological treatment of diabetes. Insulin resistance often causes organs or tissues, such as skeletal muscle, adipose, and liver, to become less responsive or resistant to insulin. Exercise can promote the physiological function of those organs and tissues and benefits insulin action via increasing insulin receptor sensitivity, glucose uptake, ...

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Characterization of Redox Environment and Tryptophan Catabolism through Kynurenine Pathway in Military Divers’ and Swimmers’ Serum Samples

Endurance and resistance exercises, alone or in combination, induce metabolic changes that affect tryptophan (Trp) catabolism. The kynurenine pathway (KP) is the main route of Trp degradation, and it is modulated by the inflammatory and redox environments. Previous studies have shown that KP metabolites work as myokines that mediate the positive systemic effects related to exercise. However, it is poorly understood how different exercise modalities and intensities impact the KP. The aim of this study ...

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Impact of Exercise and Aging on Mitochondrial Homeostasis in Skeletal Muscle: Roles of ROS and Epigenetics

Aging causes degenerative changes such as epigenetic changes and mitochondrial dysfunction in skeletal muscle. Exercise can upregulate muscle mitochondrial homeostasis and enhance antioxidant capacity and represents an effective treatment to prevent muscle aging. Epigenetic changes such as DNA methylation, histone posttranslational modifications, and microRNA expression are involved in the regulation of exercise-induced adaptive changes in muscle mitochondria. Reactive oxygen species (ROS) play an ...

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The Potential Role of Myokines/Hepatokines in the Progression of Neuronal Damage in Streptozotocin and High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice

Background: Diabetes is highly prevalent, and the number of patients with diabetic sarcopenia and cognitive impairment has grown, leading to decreased quality of life. Although the exact mechanisms between sarcopenia and cognitive impairment have not been elucidated, it is speculated that muscle and liver-derived mediators might contribute to brain function. This study examined the molecular mechanisms associated with muscle-brain interaction accompanied by insulin resistance (IR) caused by aberrant ...

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Tryptophan recovery index as a new biomarker for fitness

The maximal oxygen uptake (VO2max) and maximal power output (Pmax) are commonly used parameters to evaluate the endurance fitness status. A connection between exercise and the kynurenine pathway (KP), which describes the metabolism of unused tryptophan, has already been reported. However, a potential association of the KP with endurance fitness levels remains unknown. In this study, adolescent competitive athletes performed an exhaustive incremental exercise test. Blood samples were taken before, ...

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Effects of tongue strengthening exercises on tongue muscle strength: a systematic review and meta-analysis of randomized controlled trials

Tongue strengthening exercise (TSE) has been proposed as an intervention to increase tongue strength and improve swallowing. However, clinical evidence of its effectiveness is lacking. In this review, seven databases were searched from inception to September 30, 2021 for randomized controlled trials that compared tongue strengths between the TSE intervention and control groups, obtained from maximal tongue elevation peak force in kilopascals (kPa). The Cochrane risk of bias tool was used for quality ...

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Comprehensive multi-cohort transcriptional meta-analysis of muscle diseases identifies a signature of disease severity

Muscle diseases share common pathological features suggesting common underlying mechanisms. We hypothesized there is a common set of genes dysregulated across muscle diseases compared to healthy muscle and that these genes correlate with severity of muscle disease. We performed meta-analysis of transcriptional profiles of muscle biopsies from human muscle diseases and healthy controls. Studies obtained from public microarray repositories fulfilling quality criteria were divided into six categories: ...

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Exercise-induced CITED4 expression is necessary for regional remodeling of cardiac microstructural tissue helicity

Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. However, the regional microstructural tissue effects of these molecular mechanisms in the heart have yet to be spatially linked and further elucidated. We show in exercised mice that the expression of CITED4, a transcriptional co-regulator necessary for cardioprotection, is regionally heterogenous in the heart with preferential significant increases in the lateral wall ...

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Effects of combined physical exercise on plasma lipid variables, paraoxonase 1 activity, and inflammation parameters in adults with obesity: a randomized clinical trial

Objective: We aimed to investigate whether combined physical exercise may affect plasma lipid variables, paraoxonase 1 (PON1) activity, and inflammation parameters in adults with obesity. Methods: Thirty-six participants were recruited to complete the study protocol. The mean age was 37 ± 1 years, and the baseline body mass index was 33.0 ± 0.4 kg/m2. Participants were allocated to the control group (CG) and the exercise group (EG). The EG performed three ...

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Effects of exercise training on brain metabolism and cognitive functioning in sleep apnea

Impaired glucose metabolism reflects neuronal/synaptic dysfunction and cognitive function decline in patients with obstructive sleep apnea (OSA). The study investigated the extent to which exercise training (ET) improves cerebral metabolic glucose rate (CMRgl) and cognitive function in patients with OSA. Patients with moderate to severe OSA were randomly assigned to ET (3 times/week, n = 23) or no intervention (control, n = 24). Echocardiography and apolipoprotein ε4 ...

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Circulating nitrate-nitrite reduces oxygen uptake for improving resistance exercise performance after rest time in well-trained CrossFit athletes

This study aimed to determine the effects of circulating nitrate plus nitrite (NOx) concentrations on resistance exercise performance, VO2 and biomarkers of muscle damage. Eleven well-trained male CrossFit athletes (29.2 ± 3.7 years, 78.9 ± 5.4 kg, 175.1 ± 6.3 cm) carried out a resistance exercise test after drinking 140 mL of beetroot juice (BJ) or placebo. The test consisted of repeating the same resistance exercise routine twice: wall ...

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Neurogenic effects of rotarod walking exercise in subventricular zone, subgranular zone, and substantia nigra in MPTP-induced Parkinson’s disease mice

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, and its incidence is predicted to increase worldwide. Striatal dopamine depletion caused by substantia nigra (SN) degeneration is a pathological hallmark of PD and is strongly associated with cardinal motor and non-motor symptoms. Previous studies have reported that exercise increases neuroplasticity and promotes neurorestoration by increasing neurotrophic factors and synaptic strength ...

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Age-dependent impact of two exercise training regimens on genomic and metabolic remodeling in skeletal muscle and liver of male mice

Skeletal muscle adapts to different exercise training modalities with age; however, the impact of both variables at the systemic and tissue levels is not fully understood. Here, adult and old C57BL/6 male mice were assigned to one of three groups: sedentary, daily high-intensity intermittent training (HIIT), or moderate intensity continuous training (MICT) for 4 weeks, compatible with the older group’s exercise capacity. Improvements in body composition, fasting blood glucose, and muscle ...

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Reduced and delayed myelination and volume of corpus callosum in an animal model of Fetal Alcohol Spectrum Disorders partially benefit from voluntary exercise

1 in 20 live births in the United States is affected by prenatal alcohol exposure annually, creating a major public health crisis. The teratogenic impact of alcohol on physical growth, neurodevelopment, and behavior is extensive, together resulting in clinical disorders which fall under the umbrella term of Fetal Alcohol Spectrum Disorders (FASD). FASD-related impairments to executive function and perceptual learning are prevalent among affected youth and are linked to disruptions to corpus callosum ...

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Effect of different types of exercise in adult subjects with fibromyalgia: a systematic review and meta-analysis of randomised clinical trials

Exercise has been recommended for fibromyalgia treatment. However, doubts related to exercise benefits remain unclear. The objective of this study was to summarise, through a systematic review with meta-analysis, the available evidence on the effects of aerobic, resistance and stretching exercise on pain, depression, and quality of life. Search was performed using electronic databases Pubmed and Cochrane Library. Studies with interventions based on aerobic exercise, resistance exercise and stretching ...

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Effect of modified Total Body Recumbent Stepper training on exercise capacity and thioredoxin in COPD: a randomized clinical trial

Exercise intolerance is one of the major symptoms of chronic obstructive pulmonary disease (COPD). Exercise training can benefit COPD patients, but the underlying mechanism remains unclear. The modified Total Body Recumbent Stepper (TBRS, Nustep-T4) can benefit patients with stroke, spinal cord injury and amyotrophic lateral sclerosis. Nevertheless, the effect of TBRS training alone on pulmonary rehabilitation (PR) in COPD patients remains largely unknown. We aimed to explore the effect of TBRS training ...

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Effects of different inspiratory muscle warm-up loads on mechanical, physiological and muscle oxygenation responses during high-intensity running and recovery

Inspiratory muscle warm-up (IMW) has been used as a resource to enhance exercises and sports performance. However, there is a lack of studies in the literature addressing the effects of different IMW loads (especially in combination with a shorter and applicable protocol) on high-intensity running and recovery phase. Thus, this study aimed to investigate the effects of three different IMW loads using a shorter protocol on mechanical, physiological and muscle oxygenation responses during and after ...

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Muscle function during single leg landing

Landing manoeuvres are an integral task for humans, especially in the context of sporting activities. Such tasks often involve landing on one leg which requires the coordination of multiple muscles in order to effectively dissipate kinetic energy. However, no prior studies have provided a detailed description of the strategy used by the major lower limb muscles to perform single-leg landing. The purpose of the present study was to understand how humans coordinate their lower limb muscles during a ...

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Differential Impact of Biological and Behavioral Traits on Post-exercise Energy Intake in Men and Women

Objectives: The energy intake response to exercise is highly variable and energy (over-) compensation via increased post-exercise energy intake occurs in some individuals but not others. In explorative analyses, we aimed to identify biological and behavioral predictors of post-exercise ad libitum energy intake and whether these predictors differ from ad libitum energy intake after rest. Methods: In a randomized crossover design, 57 healthy participants (21.7 ± 2.5 y; 23.7 ± 2.3 kg/m2, ...

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Loss of adipose TET proteins enhances β-adrenergic responses and protects against obesity by epigenetic regulation of β3-AR expression

β-adrenergic receptor (β-AR) signaling plays predominant roles in modulating energy expenditure by triggering lipolysis and thermogenesis in adipose tissue, thereby conferring obesity resistance. Obesity is associated with diminished β3-adrenergic receptor (β3-AR) expression and decreased β-adrenergic responses, but the molecular mechanism coupling nutrient overload to catecholamine resistance remains poorly defined. Ten-eleven translocation (TET) proteins are dioxygenases ...

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Angiotensin II Inhibits Insulin Receptor Signaling in Adipose Cells

Angiotensin II (Ang II) is a critical regulator of insulin signaling in the cardiovascular system and metabolic tissues. However, in adipose cells, the regulatory role of Ang II on insulin actions remains to be elucidated. The effect of Ang II on insulin-induced insulin receptor (IR) phosphorylation, Akt activation, and glucose uptake was examined in 3T3-L1 adipocytes. In these cells, Ang II specifically inhibited insulin-stimulated IR and insulin receptor substrate-1 (IRS-1) tyrosine-phosphorylation, ...

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Physical exercise and the functions of microRNAs

MicroRNAs (miRNAs) control RNA translation and are a class of small, tissue-specific, non-protein-coding RNAs that maintain cellular homeostasis through negative gene regulation. Maintenance of the physiological environment depends on the proper control of miRNA expression, as these molecules influence almost all genetic pathways, from the cell cycle checkpoint to cell proliferation and apoptosis, with a wide range of target genes. Dysregulation of the expression of miRNAs is correlated with several ...

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An exercise-inducible metabolite that suppresses feeding and obesity

Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2+ cells, including macrophages, monocytes ...

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Exercise protects intestinal epithelial barrier from high fat diet- induced permeabilization through SESN2/AMPKα1/HIF-1α signaling

Over-nutrition and a sedentary lifestyle are associated with increased intestinal permeability. This condition promotes obesity and associated metabolic disorders. Sestrin2 (SESN2) is a stress-inducible protein thought to promote the survival and recovery of epithelial cells and act as a positive regulator in exercise-induced improvements of glycolipid metabolism. Here we aimed to test the hypothesis that chronic exercise can protect intestinal barrier function against high-fat diet induced permeabilization ...

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Cerebrospinal fluid and plasma metabolomics of acute endurance exercise

Metabolomics has emerged as a powerful new tool in precision medicine. No studies have yet been published on the metabolomic changes in cerebrospinal fluid (CSF) produced by acute endurance exercise. CSF and plasma were collected from 19 young active adults (13 males and 6 females) before and 60 min after a 90-min monitored outdoor run. The median age, BMI, and VO2 max of subjects was 25 years (IQR 22–31), 23.2 kg/m2 (IQR 21.7–24.5), and 47 ml/kg/min (IQR 38–51), respectively. ...

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Stubborn Exercise Responders–Where to Next?

There is a wide variance in the magnitude of physiological adaptations after resistance or endurance training. The incidence of “non” or “poor” responders to training has been reported to represent as high as 40% of the project’s sample. However, the incidence of poor responders to training can be ameliorated with manipulation of either the training frequency, intensity, type and duration. Additionally, global non-response to cardio-respiratory fitness training is eliminated ...

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Effects of Exercise on Extracellular Vesicles in Patients with Metabolic Dysfunction: a Systematic Review

The aim of this study was to investigate the effect of exercise on extracellular vesicles (EVs) in patients with metabolic dysfunction. The literatures were searched until Apr 28, 2022, and 16 studies that met inclusion criteria were included in this review. The results showed that the concentrations of platelet-derived extracellular vesicles (PEVs) and endothelial cell-derived extracellular vesicles (EEVs) decreased after long-term exercise, especially for CD62E+ EEVs and CD105+ EEVs. Simultaneously, ...

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Effects of exercise intensity and duration at a predetermined exercise volume on executive function among Apolipoprotein E (APOE)-ɛ4 carriers

Emerging evidence indicates that acute exercise improves executive function, but its effects on higher-order executive functioning skills among people with a risk of Alzheimer’s disease are not well understood. This study addressed the effects of acute exercise on the planning dimension of executive function among late middle-age adults who carried Apolipoprotein (APOE)-ɛ4. Exercise volume was kept constant, but exercise intensity and duration were manipulated. Eighteen adults in the age range ...

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Downregulation of peripheral lipopolysaccharide binding protein impacts on perigonadal adipose tissue only in female mice

Background and aims: The sexual dimorphism in fat-mass distribution and circulating leptin and insulin levels is well known, influencing the progression of obesity-associated metabolic disease. Here, we aimed to investigate the possible role of lipopolysaccharide-binding protein (LBP) in this sexual dimorphism. Methods: The relationship between plasma LBP and fat mass was evaluated in 145 subjects. The effects of Lbp downregulation, using lipid encapsulated unlocked nucleomonomer agent containing ...

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Severe Muscle Deconditioning Triggers Early Extracellular Matrix Remodeling and Resident Stem Cell Differentiation into Adipocytes in Healthy Men

Besides the loss of muscle mass and strength, increased intermuscular adipose tissue (IMAT) is now a well-recognized consequence of muscle deconditioning as experienced in prolonged microgravity. IMAT content may alter the muscle stem cell microenvironment. We hypothesized that extracellular matrix structure alterations and microenvironment remodeling induced by fast and severe muscle disuse could modulate fibro-adipogenic progenitor fate and behavior. We used the dry immersion (DI) model that rapidly ...

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Factors that Moderate the Effect of Nitrate Ingestion On Exercise Performance in Adults: A Systematic Review With Meta-Analyses and Meta-Regressions

To identify how variables such as exercise condition, supplementation strategy, participant characteristics and demographics, and practices that control oral microbiota diversity could modify the effect of inorganic nitrate ingestion (as nitrate salt supplements, beetroot juice, and nitrate-rich vegetables) on exercise performance, we conducted a systematic review with meta-analysis. Studies were identified in PubMed, Embase, and Cochrane databases. Eligibility criteria included randomized controlled ...

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Duration of an acute moderate-intensity exercise session affects approach bias toward high-calorie food among individuals with obesity

Obesity is partly driven by unhealthy eating behaviors underpinned by an approach bias toward high-calorie food. Although exercise is a useful strategy for weight loss among individuals with obesity, whether exercise modulates this approach bias is unclear. This study assessed whether the duration of an acute moderate-intensity exercise altered the approach bias toward high-calorie food among individuals with obesity. In total, 24 individuals with obesity were included in this study with a randomized, ...

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Deletion of GPR30 Drives the Activation of Mitochondrial Uncoupling Respiration to Induce Adipose Thermogenesis in Female Mice

Thermogenic adipocytes possess a promising approach to combat obesity with its capability promoting energy metabolism. We previously discovered that deletion of GPR30 (GPRKO), a presumably membrane-associated estrogen receptor, protected female mice from developing obesity, glucose intolerance, and insulin resistance when challenged with a high-fat diet (HFD). In vivo, the metabolic phenotype of wild type (WT) and GPRKO female mice were measured weekly. Acute cold tolerance test was performed. Ex ...

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IL-1R-IRAKM-Slc25a1 signaling axis reprograms lipogenesis in adipocytes to promote diet-induced obesity in mice

Toll-like receptors/Interleukin-1 receptor signaling plays an important role in high-fat diet-induced adipose tissue dysfunction contributing to obesity-associated metabolic syndromes. Here, we show an unconventional IL-1R-IRAKM-Slc25a1 signaling axis in adipocytes that reprograms lipogenesis to promote diet-induced obesity. Adipocyte-specific deficiency of IRAKM reduces high-fat diet-induced body weight gain, increases whole body energy expenditure and improves insulin resistance, associated ...

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Influence of Nutritional Status and Physical Exercise on Immune Response in Metabolic Syndrome

Metabolic Syndrome (MetS) is a cluster of metabolic alterations mostly related to visceral adiposity, which in turn promotes glucose intolerance and a chronic systemic inflammatory state, characterized by immune cell infiltration. Such immune system activation increases the risk of severe disease subsequent to viral infections. Strong correlations between elevated body mass index (BMI), type-2-diabetes and increased risk of hospitalization after pandemic influenza H1N1 infection have been described. ...

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The Effects of Reconditioning Exercises Following Prolonged Bed Rest on Lumbopelvic Muscle Volume and Accumulation of Paraspinal Muscle Fat

Reduced muscle size and accumulation of paraspinal muscle fat content (PFC) have been reported in lumbopelvic muscles after spaceflights and head-down tilt (HDT) bed rest. While some information is available regarding reconditioning programs on muscle atrophy recovery, the effects on the accumulation of PFC are unknown. Recently, a device (the Functional Re-adaptive Exercise Device—FRED) has been developed which aims to specifically recruit lumbopelvic muscles. This study aimed to investigate ...

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Effects of Protein Supplementation Associated with Resistance Training on Body Composition and Muscle Strength in Older Adults: A Systematic Review of Systematic Reviews with Meta-analyses

Background: There are some controversial findings regarding the benefits of combining protein supplementation with resistance training in order to optimize adaptations to training in older adults. Objective: The aim of this review was to summarize the evidence from meta-analyses assessing the effects of protein supplementation combined with resistance training on body composition and muscle strength in the older population. Methods: We included systematic reviews with meta-analyses of randomized ...

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Lifetime body mass index and grip strength at age 46 years: the 1970 British Cohort Study

Background: Ongoing rises in obesity prevalence have prompted growing concerns about potential increases in the burden of age-related musculoskeletal conditions including sarcopenia and sarcopenic obesity. This is of particular concern for future generations of older adults who have lived more of their lives in an obesogenic environment than current generations of older adults. We aimed to study longitudinal associations between body mass index (BMI) and grip strength in midlife using data from a ...

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Exercise and Nutrition Strategies for Combating Sarcopenia and Type 2 Diabetes Mellitus in Older Adults

Medical and technology development have drastically the improved quality of life and, consequently, life expectancy. Nevertheless, the more people who enter the third-age, the more geriatric syndromes expand in the elderly. Sarcopenia and Type 2 diabetes mellitus (T2DM) are common diseases among the elderly and the literature has extensively studied these two diseases separately. Recent evidence, however, revealed that there is a bidirectional relationship between sarcopenia and T2DM. The aims of ...

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Determinants of Dropout from and Variation in Adherence to an Exercise Intervention: The STRRIDE Randomized Trials

Purpose: This study aimed to characterize the timing and self-reported determinants of exercise dropout among sedentary adults with overweight or obesity. We also sought to explore variations in adherence among individuals who completed a 6- to 8-month structured exercise intervention. Methods: A total of 947 adults with dyslipidemia (STRRIDE I, STRRIDE AT/RT) or prediabetes (STRRIDE-PD) were enrolled to either control or to 1 of 10 exercise interventions, ranging from doses of 8 to 23 kcal·kg−1·wk−1, ...

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Effects of Physical Exercise on Cardiometabolic Biomarkers and Inflammatory Markers in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: The prevalence of obesity among children as well as the beneficial effects of physical exercise (PE) on weight loss has been determined by modulating the secretory factors of adipose tissue. PE has also been shown to have beneficial effects on obesity. Objective: The objective of this systematic review and meta-analysis was to investigate the effects of physical exercise (PE) on adiponectin and other important health markers in children. Data sources: We searched 6 electronic databases ...

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Concurrent Training Promotes Greater Gains on Body Composition and Components of Physical Fitness Than Single-Mode Training (Endurance or Resistance) in Youth With Obesity

The prevalence of obesity in the pediatric population has become a major public health issue. Indeed, the dramatic increase of this epidemic causes multiple and harmful consequences, Physical activity, particularly physical exercise, remains to be the cornerstone of interventions against childhood obesity. Given the conflicting findings with reference to the relevant literature addressing the effects of exercise on adiposity and physical fitness outcomes in obese children and adolescents, the effect ...

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Circulating FGF21 vs. Stress Markers in Girls during Childhood and Adolescence, and in Their Caregivers: Intriguing Inter-Relations between Overweight/Obesity, Emotions, Behavior, and the Cared-Caregiver Relationship

Fibroblast growth factor-21 (FGF21) acts on several brain regions, including the hypothalamic paraventricular nucleus, which is involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study was to investigate the interrelations between FGF21 and stress indices in girls, as well as in their caregivers. 78 girls, aged between 5 and 15 years, were studied; 50 of them were overweight and obese (OB) and 28 in the control group (C). Serum FGF21 and hair and diurnal ...

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Sex differences in the relationships between body composition, fat distribution, and mitochondrial energy metabolism: a pilot study

Background: Adiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females. Methods: Thirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity ...

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Hypothalamic NPY-Y1R Interacts with Gonadal Hormones in Protecting Female Mice against Obesity and Neuroinflammation

We previously demonstrated that Npy1rrfb mice, which carry the conditional inactivation of the Npy1r gene in forebrain principal neurons, display a sexually dimorphic phenotype, with male mice showing metabolic, hormonal and behavioral effects and females being only marginally affected. Moreover, exposure of Npy1rrfb male mice to a high-fat diet (HFD) increased body weight growth, adipose tissue, blood glucose levels and caloric intake compared to Npy1r2lox male controls. We used conditional knockout ...

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Serotonin and dopamine modulate aging in response to food odor and availability

An organism’s ability to perceive and respond to changes in its environment is crucial for its health and survival. Here we reveal how the most well-studied longevity intervention, dietary restriction, acts in-part through a cell non-autonomous signaling pathway that is inhibited by the presence of attractive smells. Using an intestinal reporter for a key gene induced by dietary restriction but suppressed by attractive smells, we identify three compounds that block food odor effects in C. elegans, ...

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Dietary oleamide attenuates obesity induced by housing mice in small cages

Physical inactivity due to prolonged sedentary behavior induces obesity. Therefore, we investigated whether housing mice in small cages to mimic sedentary behavior induced obesity and whether dietary oleamide (cis-9,10-octadeceneamide) suppressed the induced obesity. A single oral administration of oleamide (50 mg/kg) to mice resulted in the accumulation of the exogenous oleamide in abdominal visceral fat. Next, mice were housed in small cages and oleamide (50 mg/kg/d) was orally administered for ...

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Evaluating anti-obesity potential, active components, and antioxidant mechanisms of Moringa peregrina seeds extract on high-fat diet-induced obesity

There are no medical drugs that provide an acceptable weight loss with minimal adverse effects. This study evaluated the Moringa peregrina (MP) seed extract's anti-obesity effect. Twenty-four (6/each group) male Sprague Dawley rats were divided into group Ι (control), group ΙΙ (high-fat diet [HFD]), group ΙΙΙ (HFD+ MP [250 mg/kg b.wt]), and group ΙV (HFD+ MP [500 mg/kg b.wt]). MP administration significantly ameliorated body weight gains and HFD induced ...

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The effects of brewers’ spent grain on high-fat diet-induced fatty liver

Obesity drives nonalcoholic fatty liver disease (NAFLD). This study investigated the effects of dietary brewers’ spent grain (BSG) supplementation on obesity-induced NAFLD. Mice fed a high-fat diet supplemented with 30% BSG (HFD30) had reduced body weight and decreased plasma total cholesterol (TC) concentrations compared with HFD-fed mice. Retroperitoneal white adipose tissue (RWAT) and liver weights were reduced. Consistent with reduced hepatic triacylglycerol, TC, and non-esterified fatty ...

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β-elemene regulates M1-M2 macrophage balance through the ERK/JNK/P38 MAPK signaling pathway

Macrophages are classified into classically activated M1 macrophages and alternatively activated M2 macrophages, and the two phenotypes of macrophages are present during the development of various chronic diseases, including obesity-induced inflammation. In the present study, β-elemene, which is contained in various plant substances, is predicted to treat high-fat diet (HFD)-induced macrophage dysfunction based on the Gene Expression Omnibus (GEO) database and experimental validation. β-elemene ...

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The effects of graded levels of calorie restriction XVIII: tissue specific changes in cell size and number in response to calorie restriction

Calorie restriction (CR) without malnutrition increases the health- and lifespan of diverse taxa. The mechanism(s) behind CR are debated but may be directly linked to body composition changes that maintain energy balance. During a deficit, energy is primarily obtained from white adipose tissue (WAT; utilized) whilst other tissues remain unchanged (protected) or grow (invested) relative to body mass. The changes in mass of 6 tissues from 48 male C57BL/6 mice following 3-months graded (10, 20, 30, ...

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Proteomic analysis reveals exercise training induced remodelling of hepatokine secretion and uncovers syndecan-4 as a regulator of hepatic lipid metabolism

Objective: Non-alcoholic fatty liver disease (NAFLD) is linked to impaired lipid metabolism and systemic insulin resistance, which is partly mediated by altered secretion of liver proteins known as hepatokines. Regular physical activity can resolve NAFLD and improve its metabolic comorbidities, however, the effects of exercise training on hepatokine secretion and the metabolic impact of exercise-regulated hepatokines in NAFLD remain unresolved. Herein, we examined the effect of endurance exercise ...

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Orosomucoid: a promising biomarker for the assessment of exercise-induced fatigue triggered by basic combat training

Background: Orosomucoid (ORM) is a positive acute phase protein verified to be upregulated in various forms of exercise-induced fatigued (EIF) rodents. However, its association with EIF among human beings remained unknown. This study aimed to explore the association between serum ORM and EIF triggered by military basic combat training (BCT). Methods: The degree of EIF were measured by Borg’s Rating of Perceived Exertion Scale (Borg-RPE-Scale®) as RPE score after BCT. Fifty-three male recruits ...

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Modeling human heterogeneity of obesity with diversity outbred mice reveals a fat mass-dependent therapeutic window for resolvin E1

Resolvin E1 (RvE1), a specialized pro-resolving mediator (SPM), improves glucose homeostasis in inbred mouse models of obesity. However, an impediment toward translation is that obesity is a highly heterogenous disease in which individuals will respond very differently to interventions such as RvE1. Thus, there is a need to study SPMs in the context of modeling the heterogeneity of obesity that is observed in humans. We investigated how RvE1 controls the concentration of key circulating metabolic ...

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Effects of Aerobic Training on Brain Plasticity in Patients with Mild Cognitive Impairment: A Systematic Review of Randomized Controlled Trials

The purpose of this study was to systematically review to find if aerobic exercise compared to no exercise or any other intervention affects brain plasticity among people with mild cognitive impairment (MCI). Searches were conducted in the Scopus, SciELO, PubMed, Web of Science, Science Direct, and Google Scholar databases. The included studies were randomized control trials (RCTs) written in English comprising individuals with MCI that evaluated the effects of aerobic training on brain-derived neurotrophic ...

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The effect of aerobic exercise on tumour blood delivery: a systematic review and meta-analysis

Purpose: Tumour blood vessels are structurally and functionally abnormal, resulting in areas of hypoxia and heterogeneous blood supply. Aerobic exercise may modulate tumour blood flow and normalise the tumour microenvironment to improve chemotherapy delivery. This systematic review and meta-analysis aimed to evaluate the effect of the aerobic exercise mode on tumour hypoxia, vascularisation and blood flow. Methods: Four online databases were searched. Preclinical and clinical randomised controlled ...

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Changes in adiponectin: leptin ratio among older adults with obesity following a 12-month exercise and diet intervention

Background: Excess adiposity is characterized by alterations in adipokine secretion such that circulating leptin concentrations are increased with reductions in adiponectin. An emerging biomarker for the assessment of this adipose tissue (AT) dysfunction is the adiponectin:leptin (AL) ratio. A low AL ratio may be suggestive of dysfunctional AT and, consequently, a heightened cardiometabolic disease risk. This ancillary study investigated the relationship between the AL ratio and cardiometabolic health ...

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Renal protection induced by physical exercise may be mediated by the irisin/AMPK axis in diabetic nephropathy

In patients with diabetes, it has been suggested that physical exercise may reduce albuminuria and the progression of renal disease. However, the molecular mechanism by which physical exercise protects the kidney in diabetes remains poorly understood. The aim of the present study was to determine the contribution of muscle irisin secretion induced by aerobic physical exercise with the subsequent activation of AMPK for kidney protection under diabetic conditions. Aerobic physical exercise in rats ...

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Sprint Interval Exercise Improves Cognitive Performance Unrelated to Postprandial Glucose Fluctuations at Different Levels of Normobaric Hypoxia

Objective: The aim of our study was to examine cognition response to sprint interval exercise (SIE) against different levels of hypoxia. Research design and methods: 26 recreational active males performed SIE (20 × 6 s of all-out cycling bouts, 15 s of passive recovery) under normoxia (FIO2: 0.209), moderate hypoxia (FIO2: 0.154), and severe hypoxia (FIO2: 0.112) in a single-blinded crossover design. Cognitive function and blood glucose were assessed before and after 0, 10, 30, and 60 min of ...

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Effects of Different Intensity Exercise on the Patients of Oxidative Stress Factors and Glycemic Control Type 2 Diabetes Mellitus

This study’s major purpose was to examine the impact of two various exercise intensities on glucagon-like peptide-1 and endoplasmic reticulum stress in teenagers with type 2 diabetes. Twenty teenagers with T2DM were recruited in the trial and randomly assigned to one of two groups: HIT (n = 10) or LIT (n = 10). At a heart rate of less than 45 percent, the low-intensity intense exercise group participated in aerobic activity training. Interval training with a heart ...

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Maternal secretin ameliorates obesity by promoting white adipose tissue browning in offspring

Our knowledge of the coordination of intergenerational inheritance and offspring metabolic reprogramming by gastrointestinal endocrine factors is largely unknown. Here, we showed that secretin (SCT), a brain-gut peptide, is downregulated by overnutrition in pregnant mice and women. More importantly, genetic loss of SCT in the maternal gut results in undesirable phenotypes developed in offspring including enhanced high-fat diet (HFD)-induced obesity and attenuated browning of inguinal white adipose ...

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Grandmaternal exercise improves metabolic health of second-generation offspring

Objective: A major factor in the growing world-wide epidemic of obesity and type 2 diabetes is the increased risk of transmission of metabolic disease from obese mothers to both first (F1) and second (F2) generation offspring. Fortunately, recent pre-clinical studies demonstrate that exercise before and during pregnancy improves F1 metabolic health, providing a potential means to disrupt this cycle of disease. Whether the beneficial effects of maternal exercise can also be transmitted to the F2 generation ...

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Associations of handgrip strength with morbidity and all-cause mortality of cardiometabolic multimorbidity

Background: Cardiometabolic multimorbidity (CM) is an increasing public health and clinical concern. However, predictors for the development and prognosis of CM are poorly understood. The aims of this study were to investigate the relation between handgrip strength (HGS) and the risk of CM and to examine the association of HGS with all-cause mortality risk among patients with CM. Methods: This prospective cohort study involved 493,774 participants from the UK Biobank. CM was defined as the simultaneous ...

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Functional yogurt fermented by two-probiotics regulates blood lipid and weight in a high-fat diet mouse model

We investigated the blood lipid regulation effects and mechanism of a functional Natto yogurt in a high-fat diet-induced hyperlipidemia mouse model. Natto yogurt was characteristically fermented by Bacillus natto and Lactobacillus plantarum with milk-soy dual protein as substrates. After 5 weeks of Natto yogurt consumption, the body weight, fat, and liver weight of mice were significantly improved, while serum levels of TG, TC, LDL, ALT, TBIL, and TBA were reduced. Natto yogurt significantly ...

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Omega-3 fatty acid epoxides produced by PAF-AH2 in mast cells regulate pulmonary vascular remodeling

Pulmonary hypertension is a fatal rare disease that causes right heart failure by elevated pulmonary arterial resistance. There is an unmet medical need for the development of therapeutics focusing on the pulmonary vascular remodeling. Bioactive lipids produced by perivascular inflammatory cells might modulate the vascular remodeling. Here, we show that ω-3 fatty acid-derived epoxides (ω-3 epoxides) released from mast cells by PAF-AH2, an oxidized phospholipid-selective phospholipase ...

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Changes in biceps brachii muscle hardness assessed by a push-in meter and strain elastography after eccentric versus concentric contractions

Changes in biceps brachii muscle hardness assessed by a push-in meter (PM) and strain elastography (SE) were compared between eccentric (ECC) and concentric contractions (CON) of the elbow flexors to test the hypothesis that muscle hardness would increase greater after ECC. Ten men performed 5 sets of 10 ECC with their non-dominant arms and 5 sets of 10 CON with their dominant arms using a dumbbell corresponding to 50% of maximum voluntary isometric contraction (MVIC) force at 90º elbow flexion. ...

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Skeletal muscle-specific overexpression of miR-486 limits mammary tumor-induced skeletal muscle functional limitations

miR-486 is a myogenic microRNA, and its reduced skeletal muscle expression is observed in muscular dystrophy. Transgenic overexpression of miR-486 using muscle creatine kinase promoter (MCK-miR-486) partially rescues muscular dystrophy phenotype. We had previously demonstrated reduced circulating and skeletal muscle miR-486 levels with accompanying skeletal muscle defects in mammary tumor models. To determine whether skeletal muscle miR-486 is functionally similar in dystrophies and cancer, we performed ...

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β-Aminoisobutyric acid, L-BAIBA, protects PC12 cells from hydrogen peroxide-induced oxidative stress and apoptosis via activation of the AMPK and PI3K/Akt pathway

β-Aminoisobutyric acid (BAIBA) is a myokine that is secreted from skeletal muscles by the exercise. Recently, increasing evidence has suggested the multifocal physiological activities of BAIBA. In this study, we investigated whether L-BAIBA has protective effects on rat pheochromocytoma (PC12) cells. Cultured PC12 cells were stimulated with L-BAIBA. Western blot analyses revealed that L-BAIBA stimulation significantly increased the phosphorylation of AMPK and Akt. In contrast, no effect was ...

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Tongue muscle mass is associated with total grey matter and hippocampal volumes in Dementia with Lewy Bodies

Background: Age-related neurodegeneration, sarcopenia, and ectopic fat accumulation are conditions with shared pathways that remain poorly understood. We have measured muscle volume and fat accumulation in masseter and tongue muscle, and aim to explore their association with the total grey matter volume using MRI in older adults recently diagnosed with Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB). Methods: In this cross-sectional study, people newly diagnosed with mild AD (n=33) ...

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Differing impact of phosphoglycerate mutase 1-deficiency on brown and white adipose tissue

Brown adipose tissue (BAT) is a metabolically active organ that contributes to the thermogenic response to cold exposure. In addition, other thermogenic cells termed beige adipocytes are generated in white adipose tissue (WAT) by cold exposure. Although activation of brown/beige adipose tissue is associated with mobilization of both glucose and lipids, few studies have focused on the role of glycolytic enzymes in regulating adipose tissue function. We generated mouse models with specific deletion ...

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Obesity Differentially Effects Visceral vs. Subcutaneous Adipose Arteries: Role of Shear Activated Kir2.1 and Alterations to the Glycocalyx in Mediating Endothelial Dysfunction

Obesity imposes well-established deficits to endothelial function; however, obesity-induced endothelial dysfunction is not observed in all vascular beds. Visceral adipose arteries (VAA), but not subcutaneous adipose arteries (SAA), exhibit endothelial dysfunction. Here we aimed to determine if differences in SAA vs. VAA endothelial function observed in obesity are attributed to differential impairment of Kir channels and alterations to the glycocalyx. We used a mouse model of diet-induced obesity ...

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Angiotensin-(1-7) Mas Receptors Localized to Proopiomelanocortin Neurons Tonically Regulate Insulin Sensitivity

Angiotensin (Ang)-(1-7), a protective hormone of the renin-angiotensin system, has emerged as a novel target to improve cardiovascular and metabolic functions in animal models. In addition to blood pressure lowering effects, recent studies from our laboratory and others have shown that Ang-(1-7) can promote insulin sensitization and weight loss in obese rodents. Our recent preliminary findings suggest these effects are centrally-mediated, with Ang-(1-7) mas receptors (MasR) widely distributed to ...

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Cyclooxygenase-2 in adipose tissue macrophages limits adipose tissue dysfunction in obese mice

Obesity-associated complications are causing increasing morbidity and mortality worldwide. Expansion of adipose tissue in obesity leads to a state of low-grade chronic inflammation and dysregulated metabolism, resulting in insulin resistance and metabolic syndrome. Adipose tissue macrophages (ATMs) accumulate in obesity and are a source of proinflammatory cytokines that further aggravate adipocyte dysfunction. Macrophages are rich sources of cyclooxygenase (COX), the rate limiting enzyme for prostaglandin ...

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Depletion of skeletal muscle satellite cells attenuates pathology in muscular dystrophy

Skeletal muscle can repair and regenerate due to resident stem cells known as satellite cells. The muscular dystrophies are progressive muscle wasting diseases underscored by chronic muscle damage that is continually repaired by satellite cell-driven regeneration. Here we generate a genetic strategy to mediate satellite cell ablation in dystrophic mouse models to investigate how satellite cells impact disease trajectory. Unexpectedly, we observe that depletion of satellite cells reduces dystrophic ...

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Unbiased proteomics, histochemistry, and mitochondrial DNA copy number reveal better mitochondrial health in muscle of high-functioning octogenarians

Background: Master athletes (MAs) prove that preserving a high level of physical function up to very late in life is possible, but the mechanisms responsible for their high function remain unclear. Methods: We performed muscle biopsies in 15 octogenarian world-class track and field MAs and 14 non-athlete age/sex-matched controls (NA) to provide insights into mechanisms for preserving function in advanced age. Muscle samples were assessed for respiratory compromised fibers, mitochondrial DNA (mtDNA) ...

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Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice

Within adipose tissue (AT), immune cells and parenchymal cells closely interact creating a complex microenvironment. In obesity, immune cell derived inflammation contributes to insulin resistance and glucose intolerance. Diet-induced weight loss improves glucose tolerance; however, weight regain further exacerbates the impairment in glucose homeostasis observed with obesity. To interrogate the immunometabolic adaptations that occur in AT during murine weight loss and weight regain, we utilized cellular ...

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A comprehensive dynamic model of the adipocyte

The adipose tissue contributes to energy homeostasis by storing excess energy as triglycerides when the energy status is high, and by releasing fatty acids when the energy status is low. In addition to the involvement in energy homeostasis, the adipose tissue also has a function of hormonal control exerted by the release of adipokines such as adiponectin. Dysregulations in the signaling pathways of these two functions are involved in the development of type 2 diabetes and related complications such ...

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The superior beneficial effects of exercise training versus hormone replacement therapy on skeletal muscle of ovariectomized rats

Previous studies have highlighted the positive effects of Estradiol (E2) replacement therapy and physical exercise on skeletal muscle during menopause. However, the comparison effects of exercise training (ET) and estradiol replacement therapy during menopause on skeletal muscle have not been investigated to date. This study aimed to compare the effects of endurance exercise training versus E2 replacement therapy on mitochondrial density, redox status, and inflammatory biomarkers in the skeletal ...

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Probiotics synergized with conventional regimen in managing Parkinson’s disease

Parkinson’s disease (PD) is mainly managed by pharmacological therapy (e.g., Benserazide and dopamine agonists). However, prolonged use of these drugs would gradually diminish their dopaminergic effect. Gut dysbiosis was observed in some patients with PD, suggesting close association between the gut microbiome and PD. Probiotics modulate the host’s gut microbiota beneficially. A 3-month randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the beneficial ...

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Influence of diet on acute endocannabinoidome mediator levels post exercise in active women, a crossover randomized study

The extended endocannabinoid system, also termed endocannabinoidome, participates in multiple metabolic functions in health and disease. Physical activity can both have an acute and chronic impact on endocannabinoid mediators, as does diet. In this crossover randomized controlled study, we investigated the influence of diet on the peripheral response to acute maximal aerobic exercise in a sample of active adult women (n = 7) with no underlying metabolic conditions. We compared the impact ...

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ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition—implications for COVID-19

Background: COVID-19 severity varies widely. Although some demographic and cardio-metabolic factors, including age and obesity, are associated with increasing risk of severe illness, the underlying mechanism(s) are uncertain. Subjects/methods: In a meta-analysis of three independent studies of 1471 participants in total, we investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 (ACE2), measured by RNA-Seq, which acts ...

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The relationships between physical activity, lumbar multifidus muscle morphology, and low back pain from childhood to early adulthood: a 12-year longitudinal study

We investigated the longitudinal associations between physical activity (PA), lumbar multifidus morphology, and impactful low back pain (LBP) in young people. Nine-year-old children were recruited from 25 primary schools and followed up at age 13, 16, and 21 years. We measured PA with accelerometers at age 9, 13, and 16; quantified patterns of lumbar multifidus intramuscular adipose tissue (IMAT) change from 13 to 16 years using magnetic resonance imaging; and recorded LBP and its impact with standardised ...

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The effect of low-intensity exercise on emotional and cognitive engagement in the classroom

This study examined whether engaging in physical exercise during a university class would have beneficial effect on students’ learning motivation. One hundred and forty-nine participants took part in a psychology class over nine weeks (one lesson per week); for each lesson, participants engaged in a three-minute physical activity (low-intensity aerobic exercise) or control activity (watching a video), about 20 min after the lesson started. Participants reported higher vigour and lower ...

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Dietary and lifestyle indices for hyperinsulinemia with the risk of obesity phenotypes: a prospective cohort study among Iranian adult population

Background: Previous studies have cited insulin-related disorders, including hyperinsulinemia, as one of the main causes of obesity risk and metabolic disorders. We aimed to investigate the association of the Empirical Dietary Index for Hyperinsulinemia (EDIH) and Empirical Lifestyle Index for Hyperinsulinemia (ELIH) with the risk of obesity phenotypes among Iranian adults. Methods: Present study was conducted on 2705 subjects, including 1604 metabolically healthy normal weights (MHNW) and 1101 ...

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All roads lead to Rome - a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer's disease

Age-related neurodegenerative disorders such as Alzheimer’s disease (AD) have become a critical public health issue due to the significantly extended human lifespan, leading to considerable economic and social burdens. Traditional therapies for AD such as medicine and surgery remain ineffective, impractical, and expensive. Many studies have shown that a variety of bioactive substances released by physical exercise (called “exerkines”) help to maintain and improve the normal functions ...

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Effects of obesity and acute resistance exercise on skeletal muscle angiogenic communication pathways

Introduction: Obesity (OB) impairs cell-to-cell communication signaling. Small extracellular vesicles (EVs), which includes exosomes, are released by skeletal muscle and participate in cell-to-cell communications including the regulation of angiogenesis. Resistance exercise (REx) increases muscle fiber size and capillarization. However, while obesity increases muscle fiber size, there is an inadequate increase in capillarization such that capillary density is reduced. It was hypothesized that REx ...

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Small Extracellular Vesicles From Brown Adipose Tissue Mediate Exercise Cardioprotection

Rationale: Long-term exercise provides reliable cardioprotection via mechanisms still incompletely understood. Although traditionally considered a thermogenic tissue, brown adipose tissue (BAT) communicates with remote organs (eg, the heart) through its endocrine function. BAT expands in response to exercise, but its involvement in exercise cardioprotection remains undefined. Objective: This study investigated whether small extracellular vesicles (sEVs) secreted by BAT and their contained microRNAs ...

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Exercise, healthy ageing, and the potential role of small extracellular vesicles

Extracellular vesicles (EVs) can be released from most cells in the body and act as intercellular messengers transferring information in their cargo to affect cellular function. A growing body of evidence suggests that a subset of EVs, referred to here as ‘small extracellular vesicles’ (sEVs), can accelerate or slow the processes of ageing and age-related diseases dependent on their molecular cargo and cellular origin. Continued exploration of the vast complexity of the sEV cargo aims ...

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Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults

We performed a systematic review, meta-analysis, and meta-regression to determine if increasing daily protein ingestion contributes to gaining lean body mass (LBM), muscle strength, and physical/functional test performance in healthy subjects. A protocol for the present study was registered (PROSPERO, CRD42020159001), and a systematic search of Medline, Embase, CINAHL, and Web of Sciences databases was undertaken. Only randomized controlled trials (RCT) where participants increased their daily protein ...

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Characterizing Extracellular Vesicles and Particles Derived from Skeletal Muscle Myoblasts and Myotubes and the Effect of Acute Contractile Activity

Extracellular vesicles (EVs), released from all cells, are essential to cellular communication and contain biomolecular cargo that can affect recipient cell function. Studies on the effects of contractile activity (exercise) on EVs usually rely on plasma/serum-based assessments, which contain EVs from many different cells. To specifically characterize skeletal muscle–derived vesicles and the effect of acute contractile activity, we used an in vitro model where C2C12 mouse myoblasts were differentiated ...

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The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance

Ischemic conditioning and exercise have been suggested for protecting against brain ischemia-reperfusion injury. However, the endogenous protective mechanisms stimulated by these interventions remain unclear. Here, in a comprehensive translational study, we investigated the protective role of extracellular vesicles (EVs) released after remote ischemic conditioning (RIC), blood flow restricted resistance exercise (BFRRE), or high-load resistance exercise (HLRE). Blood samples were collected from human ...

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Obesity and exercise training alter inflammatory pathway skeletal muscle small extracellular vesicle microRNAs

Obesity is associated with chronic inflammation characterized by increased levels of inflammatory cytokines, whereas exercise training reduces inflammation. Small extracellular vesicles (EVs; 30–150 nm) participate in cell-to-cell communication in part through microRNA (miRNA) post-transcriptional regulation of mRNA. We examined whether obesity and concurrent aerobic and resistance exercise training alter skeletal muscle EV miRNA content and inflammatory signalling. Vastus lateralis biopsies ...

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Myofibrillar protein synthesis rates are increased in chronically exercised skeletal muscle despite decreased anabolic signaling

The molecular responses to acute resistance exercise are well characterized. However, how cellular signals change over time to modulate chronic adaptations to more prolonged exercise training is less well understood. We investigated anabolic signaling and muscle protein synthesis rates at several time points after acute and chronic eccentric loading. Adult rat tibialis anterior muscle was stimulated for six sets of ten repetitions, and the muscle was collected at 0 h, 6 h, 18 h and 48 h. In the last ...

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The effect of fibroblast growth factor receptor inhibition on resistance exercise training-induced adaptation of bone and muscle quality in mice

Aging in mammals, including humans, is accompanied by loss of bone and muscular function and mass, characterized by osteoporosis and sarcopenia. Although resistance exercise training (RET) is considered an effective intervention, its effect is blunted in some elderly individuals. Fibroblast growth factor (FGF) and its receptor, FGFR, can modulate bone and muscle quality during aging and physical performance. To elucidate this possibility, the FGFR inhibitor NVP-BGJ398 was administrated to C57BL/6n ...

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Influence of caffeine on the maximal isometric and concentric force produced by skinned fibers

Caffeine is one of the most famous and widely used ergogenic drugs, especially by athletes to improve sports performance. Caffeine is known to enhance muscle contraction by facilitating Ca2+ release from the sarcoplasmic reticulum. While the effect of caffeine on the cross-bridge dynamics has also investigated, the results is controversial. Therefore, the purpose of this study was to examine the influence of caffeine on cross-bridge dynamics using skinned fiber preparations from rabbit soleus (N = 19 ...

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Novel brown adipose tissue candidate genes predicted by the human gene connectome

Brown adipose tissue (BAT) is a promising therapeutic target against obesity. Therefore, research on the genetic architecture of BAT could be key for the development of successful therapies against this complex phenotype. Hypothesis-driven candidate gene association studies are useful for studying genetic determinants of complex traits, but they are dependent upon the previous knowledge to select candidate genes. Here, we predicted 107 novel-BAT candidate genes in silico using the uncoupling protein ...

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Muscle contractions and pain sensation accompanying high-frequency electroporation pulses

To minimize neuromuscular electrical stimulation during electroporation-based treatments, the replacement of long monophasic pulses with bursts of biphasic high-frequency pulses in the range of microseconds was suggested in order to reduce muscle contraction and pain sensation due to pulse application. This treatment modality appeared under the term high-frequency electroporation (HF-EP), which can be potentially used for some clinical applications of electroporation such as electrochemotherapy, ...

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A randomized controlled trial for response of microbiome network to exercise and diet intervention in patients with nonalcoholic fatty liver disease

Exercise and diet are treatments for nonalcoholic fatty liver disease (NAFLD) and prediabetes, however, how exercise and diet interventions impact gut microbiota in patients is incompletely understood. We previously reported a 8.6-month, four-arm (Aerobic exercise, n = 29; Diet, n = 28; Aerobic exercise + Diet, n = 29; No intervention, n = 29) randomized, singe blinded (for researchers), and controlled intervention in patients with NAFLD and ...

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Enhancement of anaerobic glycolysis – a role of PGC-1α4 in resistance exercise

Resistance exercise training (RET) is an effective countermeasure to sarcopenia, related frailty and metabolic disorders. Here, we show that an RET-induced increase in PGC-1α4 (an isoform of the transcriptional co-activator PGC-1α) expression not only promotes muscle hypertrophy but also enhances glycolysis, providing a rapid supply of ATP for muscle contractions. In human skeletal muscle, PGC-1α4 binds to the nuclear receptor PPARβ following RET, resulting in downstream effects ...

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The myokine Fibcd1 is an endogenous determinant of myofiber size and mitigates cancer-induced myofiber atrophy

Decline in skeletal muscle cell size (myofiber atrophy) is a key feature of cancer-induced wasting (cachexia). In particular, atrophy of the diaphragm, the major muscle responsible for breathing, is an important determinant of cancer-associated mortality. However, therapeutic options are limited. Here, we have used Drosophila transgenic screening to identify muscle-secreted factors (myokines) that act as paracrine regulators of myofiber growth. Subsequent testing in mouse myotubes revealed that mouse ...

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Strength training alters the tissue fatty acids profile and slightly improves the thermogenic pathway in the adipose tissue of obese mice

Obesity is a disease characterized by the exacerbated increase of adipose tissue. A possible way to decrease the harmful effects of excessive adipose tissue is to increase the thermogenesis process, to the greater energy expenditure generated by the increase in heat in the body. In adipose tissue, the thermogenesis process is the result of an increase in mitochondrial work, having as substrate H+ ions, and which is related to the increased activity of UCP1. Evidence shows that stress is responsible ...

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Ketone body and FGF21 coordinately regulate fasting-induced oxidative stress response in the heart

Ketone body β-hydroxybutyrate (βOHB) and fibroblast growth factor-21 (FGF21) have been proposed to mediate systemic metabolic response to fasting. However, it remains elusive about the signaling elicited by ketone and FGF21 in the heart. Stimulation of neonatal rat cardiomyocytes with βOHB and FGF21 induced peroxisome proliferator-activated receptor α (PPARα) and PGC1α expression along with the phosphorylation of LKB1 and AMPK. βOHB and FGF21 induced transcription ...

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Many Ways to Rome: Exercise, Cold Exposure and Diet—Do They All Affect BAT Activation and WAT Browning in the Same Manner?

The discovery of functional brown adipose tissue (BAT) in adult humans and the possibility to recruit beige cells with high thermogenic potential within white adipose tissue (WAT) depots opened the field for new strategies to combat obesity and its associated comorbidities. Exercise training as well as cold exposure and dietary components are associated with the enhanced accumulation of metabolically-active beige adipocytes and BAT activation. Both activated beige and brown adipocytes increase their ...

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Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men

Preclinical studies have revealed that the elevation of nicotinamide adenine dinucleotide (NAD + ) upon the administration of nicotinamide mononucleotide (NMN), an NAD + precursor, can mitigate aging-related disorders; however, human data on this are limited. We investigated whether the chronic oral supplementation of NMN can elevate blood NAD + levels and alter physiological dysfunctions in healthy older participants. We administered 250 mg NMN per ...

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Alterations in intestinal microbiota in ultramarathon runners

To date, only one study has reported changes in the gut microbiome of an ultramarathon runner before and after competing in the race. Herein we aimed to investigate changes in intestinal microbiota in nine ultramarathon runners. Eight of the nine participants ran 96.102 km (up 8062 m, down 6983 km) and one ran 99.12 km (up 8448 m, down 7369 m) within 38–44 h. Intestinal microbiota alterations were examined at three timepoints: before (Pre), after (Post), and 10 days after (Recovery) the race. ...

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The relationship of muscular endurance and coordination and dexterity with behavioral and neuroelectric indices of attention in preschool children

This study investigated the associations of non-aerobic fitness (NAF) and motor competence (MC) with attention in 4–6 year-old preschoolers. The allocation of attentional resources and speed of stimulus categorization were examined using the amplitude and latency of P3 of event-related potentials respectively, while cortical activation related to general attention and task-specific discriminative processes were examined using event-related desynchronization (ERD) at lower (8–10 Hz) and ...

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Evaluation of skeletal muscle activity during foot training exercises using positron emission tomography

The foot exercises “rock-paper-scissors” and “towel gathering” are widely used in patients with lower limb disorders; however, there are no detailed reports on muscle activity during such training. We quantitatively evaluated the difference in skeletal muscle activity between the two exercises using positron emission tomography. Eight university student athletes were included. Four participants each were assigned to the foot rock-paper-scissors and towel gathering groups. ...

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Combined Effects of High-Intensity Aerobic Exercise Training and Ziziphus jujuba Extract on Tissue Nesfatin-1 in Rats

Nesfatin-1 is involved in metabolic/feeding regulation and prevention of cardiovascular disease. Previous studies have shown that exercise and herb supplementation can influence nesfatin-1 concentration. The present study investigated the effects of high-intensity training (HIT) and Ziziphus jujuba (ZJ) extract on tissue nesfatin-1 in rats. Twenty-eight female rats were randomly assigned to one of four groups i.e. 1) Saline-Control (SC), 2) Saline-High Intensity Training (ST), 3) Ziziphus jujuba-Control ...

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Effects of Functional Phenolics Dietary Supplementation on Athletes’ Performance and Recovery: A Review

In recent years, many efforts have been made to identify micronutrients or nutritional strategies capable of preventing, or at least, attenuating, exercise-induced muscle damage and oxidative stress, and improving athlete performance. The reason is that most exercises induce various changes in mitochondria and cellular cytosol that lead to the generation of reactive species and free radicals whose accumulation can be harmful to human health. Among them, supplementation with phenolic compounds seems ...

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Identification of Potential Muscle Biomarkers in McArdle Disease: Insights from Muscle Proteome Analysis

Glycogen storage disease type V (GSDV, McArdle disease) is a rare genetic myopathy caused by deficiency of the muscle isoform of glycogen phosphorylase (PYGM). This results in a block in the use of muscle glycogen as an energetic substrate, with subsequent exercise intolerance. The pathobiology of GSDV is still not fully understood, especially with regard to some features such as persistent muscle damage (i.e., even without prior exercise). We aimed at identifying potential muscle protein biomarkers ...

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Linoleic Acid Attenuates Denervation-Induced Skeletal Muscle Atrophy in Mice through Regulation of Reactive Oxygen Species-Dependent Signaling

Muscle atrophy is a major muscle disease, the symptoms of which include decreased muscle volume leading to insufficient muscular support during exercise. One cause of muscle atrophy is the induction of oxidative stress by reactive oxygen species (ROS). This study aimed to identify the antioxidant mechanism of linoleic acid (LA) in muscle atrophy caused by oxidative stress. H2O2 has been used to induce oxidative stress in myoblasts in vitro. C2C12 myoblasts treated with H2O2 exhibited decreased viability ...

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Effects of Low-Intensity and Long-Term Aerobic Exercise on the Psoas Muscle of mdx Mice: An Experimental Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a muscle disease characterized by the absence of the protein dystrophin, which causes a loss of sarcolemma integrity, determining recurrent muscle injuries, decrease in muscle function, and progressive degeneration. Currently, there is a need for therapeutic treatments to improve the quality of life of DMD patients. Here, we investigated the effects of a low-intensity aerobic training (37 sessions) on satellite cells, peroxisome proliferator-activated receptor-gamma ...

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Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent ...

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Harnessing the Power of Leptin: The Biochemical Link Connecting Obesity, Diabetes, and Cognitive Decline

In this review, the current understanding of leptin’s role in energy balance, glycemic regulation, and cognitive function is examined, and its involvement in maintaining the homeostatic “harmony” of these physiologies is explored. The effects of exercise on circulating leptin levels are summarized, and the results of clinical application of leptin to metabolic disease and neurologic dysfunction are reviewed. Finally, pre-clinical evidence is presented which suggests that synthetic ...

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Exerkines and long-term synaptic potentiation: Mechanisms of exercise-induced neuroplasticity

Physical exercise may improve cognitive function by modulating molecular and cellular mechanisms within the brain. We propose that the facilitation of long-term synaptic potentiation (LTP)-related pathways, by products induced by physical exercise (i.e., exerkines), is a crucial aspect of the exercise-effect on the brain. This review summarizes synaptic pathways that are activated by exerkines and may potentiate LTP. For a total of 16 exerkines, we indicated how blood and brain exerkine levels are ...

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Mechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance

The skeletal muscle is the largest organ in the body and secretes circulating factors, including myokines, which are involved in various cellular signaling processes. Skeletal muscle is vital for metabolism and physiology and plays a crucial role in insulin-mediated glucose disposal. Myokines have autocrine, paracrine, and endocrine functions, serving as critical regulators of myogenic differentiation, fiber-type switching, and maintaining muscle mass. Myokines have profound effects on energy metabolism ...

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Initial Muscle Quality Affects Individual Responsiveness of Interleukin-6 and Creatine Kinase following Acute Eccentric Exercise in Sedentary Obese Older Women

This study aimed to evaluate the time course and responsiveness of plasma interleukin-6 (IL-6) and creatine kinase (CK) levels following acute eccentric resistance exercise in sedentary obese older women with a different muscle quality index (MQI). Eighty-eight participants (69.4 ± 6.06 years) completed an acute eccentric resistance exercise (7 sets of 10 repetitions at 110% of 10-repetition maximum with 3 min rest interval). Participants were divided into two groups: high or low MQI according ...

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The Effects of Irisin Hormone and the FNDC5 Gene on Brain Functions and Exercise: A Systematic Review

Introduction: The aim of this systematic review was to regroup all systematic reviews, non-systematic reviews and all original articles between 2017 and 2021 (including June) into one convenient publication that would facilitate the theoretical and applied scientific investigations directed on the efficacy of exercise and brain function on irisin hormone and FNDC5 gene. Evidence Acquisition: The systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis ...

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Integrin αV Mediates the Effects of Irisin on Human Mature Adipocytes

Introdution and Aims: The myokine irisin is critical to modulating adipocytes thermogenesis and influence whole-body metabolism. However, whether there is difference in the effects of irisin on adipocytes derived from different depots remains unknown, and the receptor of irisin on adipocytes is still unclear. In this study, we determine the browning effect of irisin on adipocytes of subcutaneous and visceral human adipose tissue and explore the possibility that integrin αV was the receptor ...

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Acute/Chronic Responses of Combined Training on Serum Pro-thermogenic/Anti-inflammatory Inducers and Its Relation With Fed and Fasting State in Overweight Type 2 Diabetic Individuals

Concentrations of pro-thermogenic/anti-inflammatory inductors are influenced by fed/fasting, sedentary/trained states, and metabolic pattern. However, there is a lack of information on the interactions of these conditions, especially in humans. Thus, the present study aimed to evaluate the chronic and acute training responses as well as the fed/fasted states of serum pro-thermogenic/anti-inflammatory inducers in overweight type 2 diabetics individuals. Fifteen individuals with type 2 diabetes [body ...

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Biological Response of Irisin Induced by Different Types of Exercise in Obese Subjects: A Non-Inferiority Controlled Randomized Study

Background: Weight loss through physical exercise is warranted among obese individuals. Recently, a greater benefit in cardiorespiratory fitness was achievable with high-intensity interval training (HIIT) as compared with moderate intensity continuous training. The beneficial effect of training on CV health might be related to a specific modulation of circulating irisin, an adypo-myokine implicated in the regulation of energy expenditure. Methods: The present study investigates the circulating plasma ...

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Salutary effects of moderate but not high intensity aerobic exercise training on the frequency of peripheral T-cells associated with immunosenescence in older women at high risk of breast cancer: a randomized controlled trial

Background: Immunosenescence is described as age-associated changes within the immune system that are responsible for decreased immunity and increased cancer risk. Physically active individuals have fewer ‘senescent’ and more naïve T-cells compared to their sedentary counterparts, but it is not known if exercise training can rejuvenate ‘older looking’ T-cell profiles. We determined the effects of 12-weeks supervised exercise training on the frequency of T-cell subtypes ...

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AMP-activated protein kinase activation in skeletal muscle modulates exercise-induced uncoupled protein 1 expression in brown adipocyte in mouse model

Aerobic exercise is an effective intervention in preventing obesity and is also an important factor associated with thermogenesis. There is an increasing interest in the factors and mechanisms induced by aerobic exercise that can influence the metabolism and thermogenic activity in an individual. Recent studies suggest that exercise induced circulating factors (known as ‘exerkines’), which are able to modulate activation of brown adipose tissue (BAT) and browning of white adipose tissue. ...

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Nobiletin enhances plasma Interleukin-6 and C-X-C motif chemokine ligand 1 levels that are increased by treadmill running

Exercise increases the muscular secretion of Interleukin-6 (IL-6), which is partially regulated by β2-adrenergic receptor signaling. Nobiletin is a polymethoxyflavone (PMF) found in citrus fruits that induces the secretion of IL-6 from C2C12 myotubes, but it remains unclear whether nobiletin promotes IL-6 secretion during exercise. The aim of this study was to clarify the effects of nobiletin on IL-6 secretion during exercise. Nobiletin and epinephrine were found to synergistically increase ...

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Comprehensive Transcriptome Profiling of NAFLD- and NASH-Induced Skeletal Muscle Dysfunction

Nonalcoholic fatty liver disease (NAFLD), characterized by extensive triglyceride accumulation in hepatocytes, may progress to nonalcoholic steatohepatitis (NASH) with liver fibrosis and inflammation and increase the risk of cirrhosis, cancer, and death. It has been reported that physical exercise is effective in ameliorating NAFLD and NASH, while skeletal muscle dysfunctions, including lipid deposition and weakness, are accompanied with NAFLD and NASH. However, the molecular characteristics and ...

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The effects of whole-body vibration amplitude on glucose metabolism, inflammation, and skeletal muscle oxygenation

Whole-body vibration (WBV) is an exercise mimetic that elicits beneficial metabolic effects. This study aims to investigate the effects of WBV amplitude on metabolic, inflammatory, and muscle oxygenation responses. Forty women and men were assigned to a high (HI; n = 20, Age: 31 ± 6 y) or a low-amplitude group (LO; n = 20, Age: 33 ± 6 y). Participants engaged in 10 cycles of WBV [1 cycle =1 min of vibration followed by 30 s of rest], while gastrocnemius muscle oxygen consumption (mVO2) ...

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Too hard to die: Exercise training mediates specific and immediate SARS-CoV-2 protection

Several mechanisms may explain how exercise training mechanistically confers protection against coronavirus disease 2019 (COVID-19). Here we propose two new perspectives through which cardiorespiratory fitness may protect against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Physical exercise-activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling induces endothelial nitric oxide (NO) synthase (eNOS), increases NO bio-availability, and inhibits palmitoylation, ...

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Supraphysiological activation of TAK1 promotes skeletal muscle growth and mitigates neurogenic atrophy

Skeletal muscle mass is regulated through coordinated activation of multiple signaling pathways. TAK1 signalosome has been found to be activated in various conditions of muscle atrophy and hypertrophy. However, the role and mechanisms by which TAK1 regulates skeletal muscle mass remain less understood. Here, we demonstrate that supraphysiological activation of TAK1 in skeletal muscle of adult mice stimulates translational machinery, protein synthesis, and myofiber growth. TAK1 causes phosphorylation ...

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Inhibition of CXXC5 function reverses obesity-related metabolic diseases

Background: Metabolic diseases, including type 2 diabetes, have long been considered incurable, chronic conditions resulting from a variety of pathological conditions in obese patients. Growing evidence suggests the Wnt/β-catenin pathway is a major pathway in adipose tissue remodelling, pancreatic β-cell regeneration and energy expenditure through regulation of key metabolic target genes in various tissues. CXXC5-type zinc finger protein 5 (CXXC5) is identified negative feedback regulator ...

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Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

Preserving skeletal muscle function is essential to maintain life quality at high age. Calorie restriction (CR) potently extends health and lifespan, but is largely unachievable in humans, making “CR mimetics” of great interest. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, is considered a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow ...

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Relationship between different serum cartilage biomarkers in the acute response to running and jumping in healthy male individuals

The effect of physical activity on serum cartilage biomarkers is largely unknown. The purpose of the study was to systematically analyze the acute effect of two frequently used exercise interventions (running and jumping) on the correlation of seven serum biomarkers that reflect cartilage extracellular matrix metabolism. Fifteen healthy male volunteers (26 ± 4 years, 181 ± 4 cm, 77 ± 6 kg) participated in the repeated measurement study. ...

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IL-37 isoform D acts as an inhibitor of soluble ST2 to boost type 2 immune homeostasis in white adipose tissue

White adipose tissue (WAT) homeostasis substantiated by type 2 immunity is indispensable to counteract obesity and metabolic disorders. IL-33/suppression of tumorigenicity (ST) 2 signaling promotes type 2 response in WAT, while potential regulators remain to be discovered. We identified human IL-37 isoform D (IL-37D) as an effective trigger for ST2-mediated type 2 immune homeostasis in WAT. IL-37D transgene amplified ST2+ immune cells, promoted M2 macrophage polarization and type 2 cytokine secretion ...

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Cell Senescence and Central Regulators of Immune Response

Pathways regulating cell senescence and cell cycle underlie many processes associated with ageing and age-related pathologies, and they also mediate cellular responses to exposure to stressors. Meanwhile, there are central mechanisms of the regulation of stress responses that induce/enhance or weaken the response of the whole organism, such as hormones of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic and parasympathetic systems, thymic hormones, and the pineal hormone melatonin. ...

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Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool

The mechanisms by which exercise benefits patients with non-alcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, remain poorly understood. A non-targeted liquid chromatography-mass spectrometry (LC–MS)-based metabolomics analysis was used to identify metabolic changes associated with NAFLD in humans upon exercise intervention (without diet change) across four different sample types—adipose tissue (AT), plasma, urine, and stool. Altogether, 46 subjects with NAFLD ...

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Preventive aerobic training preserves sympathovagal function and improves DNA repair capacity of peripheral blood mononuclear cells in rats with cardiomyopathy

To evaluate the effect of preventive aerobic exercise training on sympathovagal function, cardiac function, and DNA repair capacity in a preclinical model of doxorubicin (DOX)-induced cardiomyopathy. Forty male Wistar-Kyoto rats were allocated into four groups (n = 10/group): D (DOX-treated) and C (controls) remained sedentary, and DT (DOX-trained) and CT (control-trained) performed aerobic training 4 days/week, during 4 weeks before exposure to DOX (4 mg/kg/week during 4 weeks) or ...

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Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice

Calorie restriction (CR) and fasting are common approaches to weight reduction, but the maintenance is difficult after resuming food consumption. Meanwhile, the gut microbiome associated with energy harvest alters dramatically in response to nutrient deprivation. Here, we reported that CR and high-fat diet (HFD) both remodeled the gut microbiota with similar microbial composition, Parabacteroides distasonis was most significantly decreased after CR or HFD. CR altered microbiota and reprogramed metabolism, ...

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Antioxidant, Anti-Obesity, Nutritional and Other Beneficial Effects of Different Chili Pepper: A Review

Fruits and vegetables are important components of a healthy diet. They are rich sources of vitamins and minerals, dietary fibre and a host of beneficial non-nutrient substances including plant sterols, flavonoids and other antioxidants. It has been reported that reduced intake of fruits and vegetables may increase the risk of non-communicable diseases (NCDs). Chili pepper, is a common and important spice used to enhance taste and nutrition. Over the years, reports have shown its potential as antioxidant ...

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Anti-Obesity and Anti-Hyperglycemic Effects of Meretrix lusoria Protamex Hydrolysate in ob/ob Mice

Meretrix lusoria (M. lusoria) is an economically important shellfish which is widely distributed in South Eastern Asia that contains bioactive peptides, proteins, and enzymes. In the present study, the extracted meat content of M. lusoria was enzymatic hydrolyzed using four different commercial proteases (neutrase, protamex, alcalase, and flavourzyme). Among the enzymatic hydrolysates, M. lusoria protamex hydrolysate (MLPH) fraction with MW ≤ 1 kDa exhibited the highest free radical scavenging ...

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Phenotypic differences between people varying in muscularity

Background: Body mass is the primary metabolic compartment related to a vast number of clinical indices and predictions. The extent to which skeletal muscle (SM), a major body mass component, varies between people of the same sex, weight, height, and age is largely unknown. The current study aimed to explore the magnitude of muscularity variation present in adults and to examine if variation in muscularity associates with other body composition and metabolic measures. Methods: Muscularity was defined ...

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Effects of reduced sedentary time on cardiometabolic health in adults with metabolic syndrome: A three-month randomized controlled trial

Objectives: The aim was to investigate if reducing sedentary behavior (SB) improves cardiometabolic biomarkers in adults with metabolic syndrome (MetS). Design: Randomized controlled trial. Methods: Sixty-four sedentary middle-aged adults with MetS were randomized into intervention (INT; n = 33) and control (CON; n = 31) groups. INT was guided to limit SB by 1 h/day through increased standing and light-intensity physical activity (LPA). CON was instructed to maintain usual habits. SB, ...

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Collaborative, Dyadic, and Individual Planning and Physical Activity: A Dyadic Randomized Controlled Trial

Objective: This study was designed to investigate the effects of collaborative, dyadic, and individual planning on moderate-to-vigorous physical activity (MVPA) in target person–partner dyads. Individual planning reflects an “I-for-me” planning of one person’s behavior. Collaborative planning refers to joint planning of both dyad members’ behavior (“We-for-us” planning), and dyadic planning refers to joint planning of only the target person’s behavior ...

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S-adenosyl-L-homocysteine extends lifespan through methionine restriction effects

Methionine restriction (MetR) can extend lifespan and delay the onset of aging-associated pathologies in most model organisms. Previously, we showed that supplementation with the metabolite S-adenosyl-L-homocysteine (SAH) extends lifespan and activates the energy sensor AMP-activated protein kinase (AMPK) in the budding yeast Saccharomyces cerevisiae. However, the mechanism involved and whether SAH can extend metazoan lifespan have remained unknown. Here, we show that SAH supplementation reduces ...

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The ergogenic effect of acute carnosine and anserine supplementation: dosing, timing, and underlying mechanism

Background: Recent studies suggest that acute-combined carnosine and anserine supplementation has the potential to improve the performance of certain cycling protocols. Yet, data on optimal dose, timing of ingestion, effective exercise range, and mode of action are lacking. Three studies were conducted to establish dosing and timing guidelines concerning carnosine and anserine intake and to unravel the mechanism underlying the ergogenic effects. Methods: First, a dose response study A was conducted ...

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Pre-sleep protein supplementation after an acute bout of evening resistance exercise does not improve next day performance or recovery in resistance trained men

Background: To evaluate the effect of pre-sleep protein supplementation after an acute bout of evening resistance training on next day performance and recovery the following day in physically active men. Methods: Eighteen resistance trained men performed a single bout of resistance exercise then received either a pre-sleep protein (PRO) supplement containing 40 g of casein protein (PRO; n = 10; mean ± SD; age = 24 ± 4 yrs; height = 1.81 ± 0.08 m; weight = 84.9 ± 9.5 kg) ...

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Effects of short-term betaine supplementation on muscle endurance and indices of endocrine function following acute high-intensity resistance exercise in young athletes

Objective: This study examined the effects of short-term betaine supplementation on muscle endurance, plasma lactate, testosterone and cortisol levels, and the testosterone to cortisol (T/C) ratio in response to acute resistance exercise (RE). Methods: Using a double-blind, crossover study design, 10 handball players (age ± SD = 16 ± 1 yrs) without prior-structured RE experience performed a high-intensity RE session (leg press followed by bench press; 5 sets to volitional fatigue using ...

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Role of Obesity, Physical Exercise, Adipose Tissue-Skeletal Muscle Crosstalk and Molecular Advances in Barrett’s Esophagus and Esophageal Adenocarcinoma

Both obesity and esophageal adenocarcinoma (EAC) rates have increased sharply in the United States and Western Europe in recent years. EAC is a classic example of obesity-related cancer where the risk of EAC increases with increasing body mass index. Pathologically altered visceral fat in obesity appears to play a key role in this process. Visceral obesity may promote EAC by directly affecting gastroesophageal reflux disease and Barrett’s esophagus (BE), as well as a less reflux-dependent effect, ...

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Exercised accelerated the production of muscle-derived kynurenic acid in skeletal muscle and alleviated the postmenopausal osteoporosis through the Gpr35/NFκB p65 pathway

Background: Reduced serum estrogen levels in postmenopausal patients not only aggravate bone loss but also impact myokine secretion. Emerging evidence has revealed the importance of myokines in bone metabolism, and exercise can interfere with the secretion of myokines. However, few studies have explored the impact of exercise on myokine secretion in the postmenopausal osteoporosis (PMOP) process. Methods: Ten-weeks-old C57B/L6 female mice were used for constructing the postmenopausal osteoporosis ...

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Physical Exercise Restrains Cancer Progression through Muscle-Derived Factors

A growing body of in vitro and in vivo studies suggests that physical activity offers important benefits against cancer, in terms of both prevention and treatment. However, the exact mechanisms implicated in the anticancer effects of exercise remain to be further elucidated. Muscle-secreted factors in response to contraction have been proposed to mediate the physical exercise-induced beneficial effects and be responsible for the inter-tissue communications. Specifically, myokines and microRNAs (miRNAs) ...

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Apelin Resistance Contributes to Muscle Loss during Cancer Cachexia in Mice

Cancer cachexia consists of dramatic body weight loss with rapid muscle depletion due to imbalanced protein homeostasis. We found that the mRNA levels of apelin decrease in muscles from cachectic hepatoma-bearing rats and three mouse models of cachexia. Furthermore, apelin expression inversely correlates with MuRF1 in muscle biopsies from cancer patients. To shed light on the possible role of apelin in cachexia in vivo, we generated apelin 13 carrying all the last 13 amino acids of apelin in D isomers, ...

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Modulating Tumour Hypoxia in Prostate Cancer Through Exercise: The Impact of Redox Signalling on Radiosensitivity

Prostate cancer is a complex disease affecting millions of men globally. Radiotherapy (RT) is a common treatment modality although treatment efficacy is dependent upon several features within the tumour microenvironment (TME), especially hypoxia. A hypoxic TME heightens radioresistance and thus disease recurrence and treatment failure continues to pose important challenges. However, the TME evolves under the influence of factors in systemic circulation and cellular crosstalk, underscoring its potential ...

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Gestational Exercise Increases Male Offspring’s Maximal Workload Capacity Early in Life

Mothers’ antenatal strategies to improve the intrauterine environment can positively decrease pregnancy-derived intercurrences. By challenging the mother–fetus unit, gestational exercise (GE) favorably modulates deleterious stimuli, such as high-fat, high-sucrose (HFHS) diet-induced adverse consequences for offspring. We aimed to analyze whether GE alters maternal HFHS-consumption effects on male offspring’s maximal workload performance (MWP) and in some skeletal muscle (the soleus—SOL ...

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Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs

Muscle wasting disease indications are among the most debilitating and often deadly noncommunicable disease states. As a comorbidity, muscle wasting is associated with different neuromuscular diseases and myopathies, cancer, heart failure, chronic pulmonary and renal diseases, peripheral neuropathies, inflammatory disorders, and, of course, musculoskeletal injuries. Current treatment strategies are relatively ineffective and can at best only limit the rate of muscle degeneration. This includes nutritional ...

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Irisin ameliorates neuroinflammation and neuronal apoptosis through integrin αVβ5/AMPK signaling pathway after intracerebral hemorrhage in mice

Background: Neuroinflammation is a crucial factor in the development of secondary brain injury after intracerebral hemorrhage (ICH). Irisin is a newly identified myokine that confers strong neuroprotective effects in experimental ischemic stroke. However, whether this myokine can exert neuroprotection effects after ICH remains unknown. This study aimed to investigate the impact of irisin treatment on neuroinflammation and neuronal apoptosis and the underlying mechanism involving integrin αVβ5/AMPK ...

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Identification of Coenzyme Q10 and Skeletal Muscle Protein Biomarkers as Potential Factors to Assist in the Diagnosis of Sarcopenia

The aim of this study was to explore the use of coenzyme Q10 and skeletal muscle protein biomarkers in the diagnosis of sarcopenia. Subjects with or without sarcopenia were recruited. The anthropometric, muscle strength and endurance measurements were assessed. Muscle proteins (albumin and creatine kinase), myokines (irisin and myostatin), and the coenzyme Q10 level were measured. Approximately half of the subjects suffered from a low coenzyme Q10 concentration (<0.5 μM). The levels of creatinine ...

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Ischemia during rest intervals between sets prevents decreases in fatigue during the explosive squat exercise: a randomized, crossover study

The study aimed to evaluate the impact of ischemia, used only before particular sets of a lower limb resistance exercise on power output. Ten healthy resistance-trained males (age = 26 ± 6 years; body mass = 90 ± 9 kg; training experience = 9 ± 7 years) performed two experimental sessions (with ischemia; control without ischemia) following a randomized crossover design. During the ischemic condition, ...

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EBI2 is a negative modulator of brown adipose tissue energy expenditure in mice and human brown adipocytes

Pharmacological activation of brown adipose tissue (BAT) is an attractive approach for increasing energy expenditure to counteract obesity. Given the side-effects of known activators of BAT, we studied inhibitors of BAT as a novel, alternative concept to regulate energy expenditure. We focused on G-protein-coupled receptors that are one of the major targets of clinically used drugs. Here, we identify GPR183, also known as EBI2, as the most highly expressed inhibitory G-protein-coupled receptor in ...

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Inflammatory cytokines and sarcopenia in Iranian adults-results from SARIR study

Some studies suggested the effects of inflammatory cytokines in reducing muscle mass and muscle strength and, performance. This study aimed to compare pro-inflammatory cytokines in sarcopenic and non-sarcopenic subjects. 120 men and women were selected out from the cross-sectional study ‘sarcopenia and its determinants among Iranian elders’ (SARIR). Sarcopenia was defined based on the first ‘European Working Group on sarcopenia in older people’ (EWGSOP1) guidelines. A fasting ...

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Adipocyte Gq signaling is a regulator of glucose and lipid homeostasis in mice

Obesity is the major driver of the global epidemic in type 2 diabetes (T2D). In individuals with obesity, impaired insulin action leads to increased lipolysis in adipocytes, resulting in elevated plasma free fatty acid (FFA) levels that promote peripheral insulin resistance, a hallmark of T2D. Here we show, by using a combined genetic/biochemical/pharmacologic approach, that increased adipocyte lipolysis can be prevented by selective activation of adipocyte Gq signaling in vitro and in vivo (in mice). ...

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Hypothesized pathways for the association of vitamin D status and insulin sensitivity with resting energy expenditure: a cross sectional mediation analysis in Australian adults of European ancestry

Background: The role of vitamin D in human energy expenditure requires confirmation. We explored whether insulin sensitivity (IS)/insulin resistance (IR) mediated the association of vitamin D status (25OHD) on resting energy expenditure (REE). Methods: REE, body composition (by DEXA) and clinical biochemistry of 155 Australian men and women were collated. A hypothesized mediation pathway through IS/IR on the direct association between 25OHD and REE was modeled, using three surrogate indices of IS/IR: ...

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The association between diabetes and hypertension with the number and extent of weight cycles determined from 6 million participants

The purpose of this study was to elucidate the association between weight cycling and clinical outcomes such as type 2 diabetes and hypertension with differential effects of baseline age and obesity. Nationwide data from 6,132,569 healthy adults who underwent five or more health screenings between 2002 and 2011 were analyzed and followed until December 2019 for type 2 diabetes and hypertension. Weight cycling was defined as a change in body weight followed by another change in the opposite direction. ...

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Irisin protects against vascular calcification by activating autophagy and inhibiting NLRP3-mediated vascular smooth muscle cell pyroptosis in chronic kidney disease

Irisin protects the cardiovascular system against vascular diseases. However, its role in chronic kidney disease (CKD) -associated vascular calcification (VC) and the underlying mechanisms remain unclear. In the present study, we investigated the potential link among Irisin, pyroptosis, and VC under CKD conditions. During mouse vascular smooth muscle cell (VSMC) calcification induced by β-glycerophosphate (β-GP), the pyroptosis level was increased, as evidenced by the upregulated expression ...

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Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle

The endoplasmic reticulum (ER) regulates cellular protein and lipid biosynthesis. ER dysfunction leads to protein misfolding and the unfolded protein response (UPR), which limits protein synthesis to prevent cytotoxicity. Chronic ER stress in skeletal muscle is a unifying mechanism linking lipotoxicity to metabolic disease. Unidentified signals from cells undergoing ER stress propagate paracrine and systemic UPR activation. Here, we induce ER stress and lipotoxicity in myotubes. We observe ER stress-inducing ...

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Exercise suppresses tumor growth independent of high fat food intake and associated immune dysfunction

Epidemiological data suggest that exercise training protects from cancer independent of BMI. Here, we aimed to elucidate mechanisms involved in voluntary wheel running-dependent control of tumor growth across chow and high-fat diets. Access to running wheels decreased tumor growth in B16F10 tumor-bearing on chow (− 50%) or high-fat diets (− 75%, p < 0.001), however, tumor growth was augmented in high-fat fed mice (+ 53%, p < 0.001). Tumor growth ...

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Aerobic exercise promotes the expression of ATGL and attenuates inflammation to improve hepatic steatosis via lncRNA SRA

The role of aerobic exercise in preventing and improving non-alcoholic fatty liver has been widely established. SRA is a long non-coding RNA, which has received increasing attention due to its important role in lipid metabolism. However, it is unclear whether aerobic exercise can prevent and treat hepatic lipid accumulation via SRA. The mice were randomly divided into four groups as follows, normal control group, normal aerobic exercise group, high-fat diet group (HFD), and high-fat diet plus aerobic ...

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Effect of different recovery modes during resistance training with blood flow restriction on hormonal levels and performance in young men: a randomized controlled trial

Background: Resistance training with blood flow restriction (BFR) results in hypertrophy, and its magnitude depends on various training variables. This study aimed to compare the long-term effect of passive recovery (PR) and active recovery (AR) during low-intensity resistance training with BFR on hormonal levels and performance in young men. Methods: In the randomized clinical trial, 20 men were randomly divided into PR and AR groups during resistance training with BFR. The intervention consisted ...

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The roles of catechins in regulation of systemic inflammation

Catechins are a phytochemical present in plants such as tea leaves, beans, black grapes, cherries, and cacao, and have various physiological activities. It is reported that catechins have a health improvement effect and ameliorating effect against various diseases. In addition, antioxidant activity, liver damage prevention, cholesterol lowering effect, and anti-obesity activity were confirmed through in vivo animal and clinical studies. Although most diseases are reported as ones mediating various ...

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The Effects of Carbohydrate versus Fat Restriction on Lipid Profiles in Highly Trained, Recreational Distance Runners: A Randomized, Cross-Over Trial

A growing number of endurance athletes have considered switching from a traditional high-carbohydrate/low-fat (HCLF) to a low-carbohydrate/high-fat (LCHF) eating pattern for health and performance reasons. However, few studies have examined how LCHF diets affect blood lipid profiles in highly-trained runners. In a randomized and counterbalanced, cross-over design, athletes (n = 7 men; VO2max: 61.9 ± 6.1 mL/kg/min) completed six weeks of two, ad libitum, LCHF (6/69/25% en carbohydrate/fat/protein) ...

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Myokines and Resistance Training: A Narrative Review

In the last few years, the muscular system has gained attention due to the discovery of the muscle-secretome and its high potency for retaining or regaining health. These cytokines, described as myokines, released by the working muscle, are involved in anti-inflammatory, metabolic and immunological processes. These are able to influence human health in a positive way and are a target of research in metabolic diseases, cancer, neurological diseases, and other non-communicable diseases. Therefore, ...

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Physiological Responses to Combat Sports in Metabolic Diseases: A Systematic Review

The aim of this systematic review was to investigate how individuals with metabolic diseases respond to combat sports and if they are feasible, safe, and applicable. A systematic literature search was conducted in PubMed, from inception until 22 January 2021. Studies were included if combat sport exercise sessions were clearly defined and participants had the following types of metabolic disease: type 1 or 2 diabetes mellitus, metabolic syndrome, overweight, and obesity. Eleven studies, involving ...

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The Impact of Exercise on Telomere Length, DNA Methylation and Metabolic Footprints

Aging as a major risk factor influences the probability of developing cancer, cardiovascular disease and diabetes, amongst others. The underlying mechanisms of disease are still not fully understood, but research suggests that delaying the aging process could ameliorate these pathologies. A key biological process in aging is cellular senescence which is associated with several stressors such as telomere shortening or enhanced DNA methylation. Telomere length as well as DNA methylation levels can ...

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Exerkines in health, resilience and disease

The health benefits of exercise are well-recognized and are observed across multiple organ systems. These beneficial effects enhance overall resilience, healthspan and longevity. The molecular mechanisms that underlie the beneficial effects of exercise, however, remain poorly understood. Since the discovery in 2000 that muscle contraction releases IL-6, the number of exercise-associated signalling molecules that have been identified has multiplied. Exerkines are defined as signalling moieties released ...

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Histone Deacetylases as Modulators of the Crosstalk Between Skeletal Muscle and Other Organs

Skeletal muscle plays a major role in controlling body mass and metabolism: it is the most abundant tissue of the body and a major source of humoral factors; in addition, it is primarily responsible for glucose uptake and storage, as well as for protein metabolism. Muscle acts as a metabolic hub, in a crosstalk with other organs and tissues, such as the liver, the brain, and fat tissue. Cytokines, adipokines, and myokines are pivotal mediators of such crosstalk. Many of these circulating factors ...

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Crosstalk between CYP2E1 and PPARα substrates and agonists modulate adipose browning and obesity

Although the functions of metabolic enzymes and nuclear receptors in controlling physiological homeostasis have been established, their crosstalk in modulating metabolic disease has not been explored. Genetic ablation of the xenobiotic-metabolizing cytochrome P450 enzyme CYP2E1 in mice markedly induced adipose browning and increased energy expenditure to improve obesity. CYP2E1 deficiency activated the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) target genes, ...

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Obesity and exercise training alter inflammatory pathway skeletal muscle small extracellular vesicle miRNAs

Obesity is associated with chronic inflammation characterized by increased levels of inflammatory cytokines, while exercise training reduces inflammation. Small EVs (30-150 nm) participate in cell-to-cell communication in part through miRNA post-transcriptional regulation of mRNA. Purpose: The current study examined if obesity and concurrent exercise training alter skeletal muscle: (1) EV miRNA content and (2) inflammatory signaling. Methods: Vastus lateralis biopsies were obtained from sedentary ...

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Effects of exercise intensity on white adipose tissue browning and its regulatory signals in mice

Adipose tissue has been classified into white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue the latter of which is produced as WAT changes into BAT due to exposure to cold temperature or exercise. In response to these stimulations, WAT produces heat by increasing mitochondrial contents and the expression of uncoupling protein 1 (UCP1), thus facilitating browning. Exercise is known to be one of the triggers for WAT browning, but the effects of exercise intensity on the ...

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N1-Methylnicotinamide: Is It Time to Consider as a Dietary Supplement for Athletes?

Exercise is considered to be a "medicine" due to its modulatory roles in metabolic disorders such as diabetes and obesity. The intensity and duration of exercise determine the mechanism of energy production by various tissues of the body, especially by muscles, in which the requirement for adenosine triphosphate (ATP) increases by as much as 100-fold. Naturally, athletes try to improve their exercise performance by dietary supplementation with, e.g., vitamins, metabolites, and amino acids. MNAM, ...

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Organokines and Exosomes: Integrators of Adipose Tissue Macrophage Polarization and Recruitment in Obesity

The prevalence of obesity is escalating and has become a worldwide health challenge coinciding with the development of metabolic diseases. Emerging evidence has shown that obesity is accompanied by the infiltration of macrophages into adipose tissue, contributing to a state of low-grade chronic inflammation and dysregulated metabolism. Moreover, in the state of obesity, the phenotype of adipose tissue macrophages switches from the M2 polarized state to the M1 state, thereby contributing to chronic ...

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Obesity: A Chronic Low-Grade Inflammation and Its Markers

As the prevalence of obesity continues to rise, the world is facing a major public health concern. Obesity is a complex disease associated with an increase in several inflammatory markers, leading to chronic low-grade inflammation. Of multifactorial etiology, it is often used as a measurement of morbidity and mortality. There remains much unknown regarding the association between obesity and inflammation. This review seeks to compile scientific literature on obesity and its associated inflammatory ...

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High-intensity interval training and moderate intensity training with exogenous adenosine counteract development of obesity in rats

Objectives: High-Intensity Interval Training (HIIT) and Moderate Intensity Training (MIT) can combat the obesity epidemic. However, studies comparing their effects on obesity show controversial findings regarding weight loss. Adenosine has emerged as a possible, novel therapeutic agent to treat obesity, but more preclinical studies on its efficacy are needed. Therefore, the objectives of this study were to compare the effects of HIIT and MIT on obesity, and further to determine the dose-dependent ...

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PET/MRI-evaluated brown adipose tissue activity may be related to dietary MUFA and omega-6 fatty acids intake

An investigation of new ways to activate brown adipose tissue (BAT) is highly valuable, as it is a possible tool for obesity prevention and treatment. The aim of our study was to evaluate the relationships between dietary intake and BAT activity. The study group comprised 28 healthy non-smoking males aged 21–42 years. All volunteers underwent a physical examination and 75-g OGTT and completed 3-day food intake diaries to evaluate macronutrients and fatty acid intake. Body composition measurements ...

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Patients with low muscle mass have characteristic microbiome with low potential for amino acid synthesis in chronic liver disease

Sarcopenia is thought to be related to the microbiome, but not enough reports in chronic liver disease (CLD) patients. In addition to the differences in microbiome, the role of the microbiome in the gut is also important to be clarified because it has recently been shown that the microbiome may produce branched-chain amino acids (BCAAs) in the body. In this single-center study, sixty-nine CLD patients were divided by skeletal muscle mass index (SMI) into low (L-SMI: n = 25) and normal ...

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Effects of Cardiorespiratory Fitness on Cerebral Oxygenation in Healthy Adults: A Systematic Review

Introduction: Exercise is known to improve cognitive functioning and the cardiorespiratory hypothesis suggests that this is due to the relationship between cardiorespiratory fitness (CRF) level and cerebral oxygenation. The purpose of this systematic review is to consolidate findings from functional near-infrared spectroscopy (fNIRS) studies that examined the effect of CRF level on cerebral oxygenation during exercise and cognitive tasks. Methods: Medline, Embase, SPORTDiscus, and Web of Science ...

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Why do humans undergo an adiposity rebound? Exploring links with the energetic costs of brain development in childhood using MRI-based 4D measures of total cerebral blood flow

Background: Individuals typically show a childhood nadir in adiposity termed the adiposity rebound (AR). The AR serves as an early predictor of obesity risk, with early rebounders often at increased risk; however, it is unclear why this phenomenon occurs, which could impede understandings of weight gain trajectories. The brain’s energy requirements account for a lifetime peak of 66% of the body’s resting metabolic expenditure during childhood, around the age of the AR, and relates inversely ...

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Oral administration of processed Cassia obtusifolia L. seed powder May reduce body weight and cholesterol in overweight patients with schizophrenia: A 36-week randomized, double-blind, controlled trial of high and low doses

Obesity in patients with schizophrenia is related to antipsychotic drug use, hypertension, diabetes, and dyslipidemia, which are critical risk factors for cardiovascular disease. Cassia seed is a traditional Chinese medicine that can be used to treat various eye disorders. Anthraquinone-containing Cassia seed were used to lower serum levels of fat and cholesterol. Aim of study: The effects of Cassia seed powder on body weight and lipids were investigated in overweight or obese patients with schizophrenia. Methods: ...

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Therapeutic routine with respiratory exercises improves posture, muscle activity, and respiratory pattern of patients with neck pain: a randomized controlled trial

Neck pain and forward head posture (FHP) are typical in prolonged smartphone users and need to be targeted for treatment. We aimed to compare the effect of a routine therapeutic program with and without respiratory exercises on smartphone users with FHP and non-specific chronic neck pain (NSCNP). Sixty patients (aged 24.7 ± 2.1 years) with FHP and NSCNP were randomly assigned to the routine therapeutic program (n = 20), combined respiratory exercises with a routine therapeutic ...

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The outstanding beneficial roles of irisin disorders

Depression is a widely observed psychiatric disorder that affects a quite large number of people all around the world. A major depressive disorder (MDD) is a multifactorial disease that IS associated with fluctuations in appetite, body weight, and energy situations in addition to serious mood problems. The aim of this review is to investigate a possible link between energy regulatory hormones of irisin and depressive disorders. Irisin is a hormone that plays a significant role in the regulation of ...

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Exercise for the Diabetic Gut—Potential Health Effects and Underlying Mechanisms

It can be assumed that changes in the gut microbiota play a crucial role in the development of type 2 diabetes mellitus (T2DM). It is generally accepted that regular physical activity is beneficial for the prevention and therapy of T2DM. Therefore, this review analyzes the effects of exercise training on the gut microbiota composition and the intestinal barrier function in T2DM. The current literature shows that regular exercise can influence the gut microbiota composition and the intestinal barrier ...

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Brain Mechanisms of Exercise-Induced Hypoalgesia: To Find a Way Out from “Fear-Avoidance Belief”

It is well known that exercise produces analgesic effects (exercise-induced hypoalgesia (EIH)) in animal models and chronic pain patients, but the brain mechanisms underlying these EIH effects, especially concerning the emotional aspects of pain, are not yet fully understood. In this review, we describe drastic changes in the mesocorticolimbic system of the brain which permit the induction of EIH effects. The amygdala (Amyg) is a critical node for the regulation of emotions, such as fear and anxiety, ...

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Interleukin 6 as an energy allocator in muscle tissue

Extensive research has shown that interleukin 6 (IL-6) is a multifunctional molecule that is both proinflammatory and anti-inflammatory, depending on the context. Here, we combine an evolutionary perspective with physiological data to propose that IL-6’s context-dependent effects on metabolism reflect its adaptive role for short-term energy allocation. This energy-allocation role is especially salient during physical activity, when skeletal muscle releases large amounts of IL-6. We predict ...

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Myokine Expression and Tumor-Suppressive Effect of Serum after 12 wk of Exercise in Prostate Cancer Patients on ADT

Purpose: Although several mechanisms have been proposed for the tumor-suppressive effect of exercise, little attention has been given to myokines, even though skeletal muscle is heavily recruited during exercise resulting in myokine surges. We measured resting serum myokine levels before and after an exercise-based intervention and the effect of this serum on prostate cancer cell growth. Methods: Ten prostate cancer patients undertaking androgen deprivation therapy (age, 73.3 ± 5.6 yr) undertook ...

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Exercise Therapy for People With Sarcopenic Obesity: Myokines and Adipokines as Effective Actors

Sarcopenic obesity is defined as a multifactorial disease in aging with decreased body muscle, decreased muscle strength, decreased independence, increased fat mass, due to decreased physical activity, changes in adipokines and myokines, and decreased satellite cells. People with sarcopenic obesity cause harmful changes in myokines and adipokines. These changes are due to a decrease interleukin-10 (IL-10), interleukin-15 (IL-15), insulin-like growth factor hormone (IGF-1), irisin, leukemia inhibitory ...

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Anabolic Factors and Myokines Improve Differentiation of Human Embryonic Stem Cell Derived Skeletal Muscle Cells

Skeletal muscle weakness is linked to many adverse health outcomes. Current research to identify new drugs has often been inconclusive due to lack of adequate cellular models. We previously developed a scalable monolayer system to differentiate human embryonic stem cells (hESCs) into mature skeletal muscle cells (SkMCs) within 26 days without cell sorting or genetic manipulation. Here, building on our previous work, we show that differentiation and fusion of myotubes can be further enhanced using ...

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The effect of exercise interventions on Irisin level a systematic review and meta-analysis of randomized controlled trials

Irisin is a hormone that is offered to be a hopeful remedial target in obesity and type 2 diabetes. It has received striking attention recently, whereas, the interactions between exercise training and irisin are still unclear. Therefore, this systematic review and meta-analysis investigated the impacts of exercise interventions on circulating irisin in adults. A systematic search was conducted in PubMed, CINAHL, MEDLINE, Cochrane, Google Scholar, and Scopus up to July 15, 2021. Twenty-four studies, ...

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FNDC5/Irisin: Physiology and Pathophysiology

A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular ...

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Adipose-tissue plasticity in health and disease

Adipose tissue, colloquially known as “fat,” is an extraordinarily flexible and heterogeneous organ. While historically viewed as a passive site for energy storage, we now appreciate that adipose tissue regulates many aspects of whole-body physiology, including food intake, maintenance of energy levels, insulin sensitivity, body temperature, and immune responses. A crucial property of adipose tissue is its high degree of plasticity. Physiologic stimuli induce dramatic alterations in adipose-tissue ...

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Disuse-associated loss of the protease LONP1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength

Mitochondrial proteolysis is an evolutionarily conseved quality-control mechanism to maintain proper mitochondrial integrity and function. However, the physiological relevance of stress-induced impaired mitochondrial protein quality remains unclear. Here, we demonstrate that LONP1, a major mitochondrial protease resides in the matrix, plays a role in controlling mitochondrial function as well as skeletal muscle mass and strength in response to muscle disuse. In humans and mice, disuse-related muscle ...

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Exercise in advanced prostate cancer elevates myokine levels and suppresses in-vitro cell growth

Background: Altering the systemic milieu through exercise has been proposed as a potential mechanism underlying exercise-driven tumour suppression. It is not yet known whether men with advanced prostate cancer can elicit such adaptations following a program of exercise. The purpose is to examine myokine levels of serum acquired from metastatic castrate-resistant prostate cancer (mCRPC) patients recruited to the INTERVAL-GAP4 trial before and after 6 months of exercise and its tumour-suppressive effect. Methods: ...

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Effect of Sleep Extension on Objectively Assessed Energy Intake Among Adults With Overweight in Real-life SettingsA Randomized Clinical Trial

Importance: Short sleep duration has been recognized as a risk factor for obesity. Whether extending sleep duration may mitigate this risk remains unknown. Objective: To determine the effects of a sleep extension intervention on objectively assessed energy intake, energy expenditure, and body weight in real-life settings among adults with overweight who habitually curtailed their sleep duration. Design, Setting, and Participants: This single-center, randomized clinical trial was conducted from ...

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Muscle protein synthesis and muscle/metabolic responses to resistance exercise training in South Asian and White European men

The aims of the current study, therefore, were to compare (1) free-living MPS and (2) muscle and metabolic adaptations to resistance exercise in South Asian and white European adults. Eighteen South Asian and 16 White European men were enrolled in the study. Free-living muscle protein synthesis was measured at baseline. Muscle strength, body composition, resting metabolic rate, VO2max and metabolic responses (insulin sensitivity) to a mixed meal were measured at baseline and following 12 weeks of ...

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Potential of micro-exercise to prevent long-term sickness absence in the general working population: prospective cohort study with register follow-up

This study assesses the potential of workplace-based micro-exercise (brief and simple exercise bouts) to prevent long-term sickness absence (LTSA) at the population level. In the Work Environment and Health in Denmark Study (2012–2018), we followed 70,130 workers from the general working population, without prior LTSA, for two years in the Danish Register for Evaluation of Marginalisation. We used Cox regression with model-assisted weights and controlled for various confounders. From 2012 to ...

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The energy balance model of obesity: beyond calories in, calories out

A recent Perspective article described the “carbohydrate-insulin model (CIM)” of obesity, asserting that it “better reflects knowledge on the biology of weight control” as compared to what was described as the “dominant energy balance model (EBM)” that fails to consider “biological mechanisms that promote weight gain”. Unfortunately, the Perspective conflated and confused the principle of energy balance, a law of physics which is agnostic as to obesity ...

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Home-based, supervised, and mixed exercise intervention on functional capacity and quality of life of colorectal cancer patients: a meta-analysis

This systematic review and meta-analysis of randomized controlled trials tested the effects of home-based, supervised, or mixed exercise interventions on the functional capacity (FC) and quality of life (QoL) in colorectal cancer patients. A literature search was performed using the PubMed, Embase, Cochrane, and Medline databases. Two reviewers screened the literature through March 10, 2021 for studies related to exercise and colorectal cancer. Of the 1161 screened studies in the initial search, ...

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Myokines in Appetite Control and Energy Balance

Efficacy of obesity treatments varies between individuals, highlighting the presence of responders and non-responders. Whilst exercise alone or exercise combined with diet leads to underwhelming weight loss for most, there exist super responders losing significant weight. Furthermore, in response to weight loss, the majority but not all patients tend to regain weight. Within the biopsychosocial model, biology as a determinant of response has been underappreciated. The understanding of the role that ...

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TAZ links exercise to mitochondrial biogenesis via mitochondrial transcription factor A

Mitochondria are energy-generating organelles and mitochondrial biogenesis is stimulated to meet energy requirements in response to extracellular stimuli, including exercise. However, the mechanisms underlying mitochondrial biogenesis remain unknown. Here, we demonstrate that transcriptional coactivator with PDZ-binding motif (TAZ) stimulates mitochondrial biogenesis in skeletal muscle. In muscle-specific TAZ-knockout (mKO) mice, mitochondrial biogenesis, respiratory metabolism, and exercise ability ...

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Single bout of exercise triggers the increase of vitamin D blood concentration in adolescent trained boys: a pilot study

Vitamin D is necessary for musculoskeletal health, however, the supplementation of vitamin D above the sufficiency level does not bring additional bone mass density (BMD), unlike physical exercise which enhances the bone formatting process. Regular physical activity has been shown to upregulate VDR expression in muscles and to increase circulating vitamin D. Here we investigate whether a single bout of exercise might change 25(OH)D3 blood concentration and how it affects metabolic response to exercise. ...

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Clusterin is involved in mediating the metabolic function of adipose SIRT1

SIRT1 is a metabolic sensor regulating energy homeostasis. The present study revealed that mice with selective overexpression of human SIRT1 in adipose tissue (Adipo-SIRT1) were protected from high-fat diet (HFD)-induced metabolic abnormalities. Adipose SIRT1 was enriched at mitochondria-ER contacts (MERCs) to trigger mitohormesis and unfolded protein response (UPRmt), in turn preventing ER stress. As a downstream target of UPRmt, clusterin was significantly upregulated and acted together with SIRT1 ...

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Effects of short sprint interval training on aerobic and anaerobic indices: A systematic review and meta-analysis

The effects of short sprint interval training (sSIT) with efforts of ≤10 seconds on maximal oxygen consumption (V̇O2max), aerobic and anaerobic performances remain unknown. To verify the effectiveness of sSIT in physically active adults and athletes, a systematic literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The databases PubMed/MEDLINE, ISI Web of Science, SPORTDiscus were systematically searched on the 9th of May ...

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Estimated Number of Deaths Prevented Through Increased Physical Activity Among US Adults

Previous studies suggest that a substantial number of deaths could be prevented annually by increasing population levels of physical activity. However, previous estimates have relied on convenience samples, used self-reported physical activity data, and assumed relatively large increases in activity levels (eg, more than 30 minutes per day). The potential public health benefit of changing daily physical activity by a manageable amount is not yet known. In this study, we used accelerometer measurements ...

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Renal failure suppresses muscle irisin expression, and irisin blunts cortical bone loss in mice

Background: Chronic renal failure induces bone mineral disorders and sarcopenia. Skeletal muscle affects other tissues, including bone, by releasing myokines. However, the effects of chronic renal failure on the interactions between muscle and bone remain unclear. Methods: We investigated the effects of renal failure on bone, muscle, and myokines linking muscle to bone using a mouse 5/6 nephrectomy (Nx) model. Muscle mass and bone mineral density (BMD) were analysed by quantitative computed tomography ...

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Dissociation of Bone Resorption and Formation in Spaceflight and Simulated Microgravity: Potential Role of Myokines and Osteokines?

The dissociation of bone formation and resorption is an important physiological process during spaceflight. It also occurs during local skeletal unloading or immobilization, such as in people with neuromuscular disorders or those who are on bed rest. Under these conditions, the physiological systems of the human body are perturbed down to the cellular level. Through the absence of mechanical stimuli, the musculoskeletal system and, predominantly, the postural skeletal muscles are largely affected. ...

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The high-intensity interval training introduced in physical education lessons decrease systole in high blood pressure adolescents

Increased resting blood pressure (BP) is a risk factor for many health complications. The prevalence of elevated BP is growing among adolescents. There is a need to investigate effective ways of decreasing excessive blood pressure in this age group. The study aim was to determine the effect of 10-weeks High-Intensive Interval Training (HIIT)—Tabata protocol—introduced in physical education (PE) lessons on resting blood pressure in adolescents. The sample included 52 boys aged 16.23 ± 0.33 ...

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Moderate Treadmill Exercise Modulates Gut Microbiota and Improves Intestinal Barrier in High-Fat-Diet-Induced Obese Mice via the AMPK/CDX2 Signaling Pathway

Objective: The aim of this study was to investigate the effects of moderate treadmill exercise on gut microbiota, expression of proteins associated with gut barrier and to elucidate the mechanisms underlying their role in high-fat-diet-induced obese mice. Methods: Six-week-old male C57BL/6 mice were randomly divided into standard chow diet control group (SD + Sed, n=6), chow diet exercise group (SD + Exe, n=6), high-fat diet control group (HFD + Sed, n=6) and high-fat diet exercise group (HFD + ...

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Acute effects of low-volume intermittent versus higher-volume continuous exercise on arterial stiffness in healthy young men

To compare the acute effects of low-volume intermittent and higher-volume continuous exercise on arterial stiffness, 20 healthy men (22.4 ± 0.4 years) were randomized to non-exercise control (CON), high-volume Continuous Exercise (CE), lower-volume Intermittent exercise of Long bouts with Long interval (ILL), of Long bouts with Short interval (ILS), and of Short bouts with Short interval trial (ISS). Exercise intensity was 35% heart rate reserve. Arterial stiffness in Cardio-ankle ...

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Metabolite Signature of Physical Activity and the Risk of Type 2 Diabetes in 7271 Men

Large population-based studies investigating the association of physical activity (PA) with the metabolite signature contribute significantly to the understanding of the effects of PA on metabolic pathways associated with the risk of type2 diabetes. Our study included 8749 Finnish men without diabetes at baseline recruited from the Metabolic Syndrome in Men (METSIM) cohort. We used a questionnaire to measure leisure-time PA. Metabolites were measured in 7271 men as a part of Metabolon’s untargeted ...

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The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments

Obesity is associated with hypothalamic–pituitary–testicular axis dysregulation in males. Here, we summarize recent evidence derived from clinical trials and studies in preclinical animal models regarding the role of androgen receptor (AR) signaling in the pathophysiology of males with obesity. We also discuss therapeutic strategies targeting the AR for the treatment of obesity and their limitations and provide insight into the future research necessary to advance this field. https://doi.org/10.1111/obr.13429

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Susceptibility to diet-induced obesity at thermoneutral conditions is independent of UCP1

Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high-caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity. However, studies investigating the role of UCP1 to protect against diet-induced obesity are controversial and rely on the ...

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Effect of Aerobic or Resistance Exercise, or Both, on Intermuscular and Visceral Fat and Physical and Metabolic Function in Older Adults With Obesity While Dieting

Background: Obesity exacerbates age-related effects on body composition and physical and metabolic function. Which exercise mode is most effective in mitigating these deleterious changes in dieting older adults with obesity is unknown. Methods: In a randomized controlled trial, we performed a head-to-head comparison of aerobic (AEX), resistance (REX), or combination (COMB) exercise during matched ~10% weight loss in 160 obese older adults. Prespecified analyses compared 6-month changes in intermuscular ...

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Exercise training modulates adipokines dysregulations in metabolic syndrome

Metabolic syndrome (MetS) is a cluster of risk factors for various metabolic diseases, and it is characterized by central obesity, dyslipidemia, hypertension, and insulin resistance. The core component for MetS is adipose tissue, which releases adipokines and influences physical health. Adipokines consist of pro and anti-inflammatory cytokines and contribute to various physiological functions. Generally, a sedentary lifestyle promotes fat accumulation and secretion of pro-inflammatory adipokines. ...

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Exercise Training Improves Memory Performance in Older Adults: A Narrative Review of Evidence and Possible Mechanisms

As human life expectancy increases, cognitive decline and memory impairment threaten independence and quality of life. Therefore, finding prevention and treatment strategies for memory impairment is an important health concern. Moreover, a better understanding of the mechanisms involved underlying memory preservation will enable the development of appropriate pharmaceuticals drugs for those who are activity limited. Exercise training as a non-pharmacological tool, has been known to increase the mean ...

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A new paradigm in sarcopenia: Cognitive impairment caused by imbalanced myokine secretion and vascular dysfunction

Sarcopenia characterized by reduced skeletal muscle mass and decreased muscle strength is increasing in prevalence globally. The pathophysiology of sarcopenia is related to various factors including hormonal imbalance, increased intracellular oxidative stress, reduction of food intake, advanced age, low body mass index, and low physical activity. Recently, sarcopenia has been reported to be associated with cognitive decline, and the common risk factors between sarcopenia and memory loss were observed ...

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Influence of adiponectin and inflammatory cytokines in fatty degenerative atrophic muscle

Tendon rupture and nerve injury cause fatty infiltration of the skeletal muscle, and the adipokines secreted from the infiltrated adipocytes are known to contribute to chronic inflammation. Therefore, in this study, we evaluated the effects of the adipokines on chronic inflammation using a rat sciatic nerve-crushed injury model. In vitro and in vivo experiments showed that the expression of adiponectin was decreased (0.3-fold) and the expression of Il6 (~ 3.8-fold) and Tnf (~ 6.2-fold) ...

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Adipocyte-specific Nos2 deletion improves insulin resistance and dyslipidemia through brown fat activation in diet-induced obese mice

Objective: Inducible nitric oxide (NO) synthase (NOS2) is a well-documented inflammatory mediator of insulin resistance in obesity. NOS2 expression is induced in both adipocytes and macrophages within adipose tissue during high-fat (HF)-induced obesity. Methods: Eight-week-old male mice with adipocyte selective deletion of the Nos2 gene (Nos2AD−KO) and their wildtype littermates (Nos2fl/fl) were subjected to chow or high-fat high-sucrose (HFHS) diet for 10 weeks followed by metabolic phenotyping ...

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Irisin: circulating levels in serum and its relation to gonadal axis

Irisin is an exercise-induced myokine/adipokine in mice and humans that plays an important role in ‘browning’ of white adipose tissue and has shown great potential as a treatment for some metabolic diseases, such as obesity, insulin resistance, and inflammation. The circulating irisin level is reported to be associated with exercise, obesity, diet, diseases, and exposure to different pharmacological agents. Several studies have attempted to characterize the role of irisin in PCOS and ...

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Irisin and Secondary Osteoporosis in Humans

Irisin is a peptide secreted by skeletal muscle following exercise that plays an important role in bone metabolism. Numerous experiments in vitro and in mouse models have shown that the administration of recombinant irisin promotes osteogenesis, protects osteocytes from dexamethasone-induced apoptosis, prevents disuse-induced loss of bone and muscle mass, and accelerates fracture healing. Although some aspects still need to be elucidated, such as the dose- and frequency-dependent effects of irisin ...

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The mediating roles of demand and satisfaction in formation process of physical exercise habits among college students

Considering the situation and disadvantages of being physically inactive as well as the nature and advantages of doing physical exercise regularly, there is a need to explore how physical exercise habits are cultivated and formed. The study was to examine the formation process of physical exercise habits. According to the Model of Physical Exercise and Habit, It was speculated that satisfaction, demand or chain from satisfaction to demand could mediate the relationship between physical exercise behavior ...

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The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: a systematic review and meta-analysis

The gut microbiome may be a mediator between obesity and health outcomes. However, it is unclear how intentional weight loss changes the gut microbiota and intestinal permeability. We aimed to systematically review and quantify this association. We searched Medline, Embase, CINAHL, Cochrane databases, and trial registries until June 2020 (PROSPERO: CRD42020205292). We included trials of weight loss interventions (energy-restricted diets, pharmacotherapy, bariatric surgery) reporting on the microbiome. ...

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Body mass index and cognitive decline among community-living older adults: the modifying effect of physical activity

Objective: To examine the associations between BMI categories and subsequent 3-year cognitive decline among older adults, and to test whether physical activity modifies the associations. Methods: Study sample included n = 1028 cognitively unimpaired older adults participating in the Étude sur la Santé des Aînés (ESA)-Services longitudinal study and followed 3 years later. Cognitive decline was defined as a decrease of > 3 points in MMSE scores ...

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The Impact of a High-Carbohydrate/Low Fat vs. Low-Carbohydrate Diet on Performance and Body Composition in Physically Active Adults: A Cross-Over Controlled Trial

Background: Recently, high-carbohydrate or low-carbohydrate (HC/LC) diets have gained substantial popularity, speculated to improve physical performance in athletes; however, the effects of short-term changes of the aforementioned nutritional interventions remain largely unclear. Methods: The present study investigated the impact of a three-week period of HC/low-fat (HC) diet followed by a three-week wash-out-phase and subsequent LC diet on the parameters of physical capacity assessed via cardiopulmonary ...

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Atlas of exercise metabolism reveals time-dependent signatures of metabolic homeostasis

Tissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is not fully defined. To understand how tissues independently and collectively respond to timed exercise, we applied a systems biology approach. We mapped and compared global metabolite responses of seven different mouse tissues and serum after an acute exercise bout performed at different times of the day. Comparative ...

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All roads lead to Rome — a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer's disease

Age-related neurodegenerative disorders such as Alzheimer’s disease (AD) have become a critical public health issue due to the significantly extended human lifespan, leading to considerable economic and social burdens. Traditional therapies for AD such as medicine and surgery remain ineffective, impractical, and expensive. Many studies have shown that a variety of bioactive substances released by physical exercise (called “exerkines”) help to maintain and improve the normal functions ...

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Impact of Physical Activity and Exercise on the Epigenome in Skeletal Muscle and Effects on Systemic Metabolism

Exercise and physical activity induces physiological responses in organisms, and adaptations in skeletal muscle, which is beneficial for maintaining health and preventing and/or treating most chronic diseases. These adaptations are mainly instigated by transcriptional responses that ensue in reaction to each individual exercise, either resistance or endurance. Consequently, changes in key metabolic, regulatory, and myogenic genes in skeletal muscle occur as both an early and late response to exercise, ...

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Enrichment of the exocytosis protein STX4 in skeletal muscle remediates peripheral insulin resistance and alters mitochondrial dynamics via Drp1

Mitochondrial dysfunction is implicated in skeletal muscle insulin resistance. Syntaxin 4 (STX4) levels are reduced in human diabetic skeletal muscle, and global transgenic enrichment of STX4 expression improves insulin sensitivity in mice. Here, we show that transgenic skeletal muscle-specific STX4 enrichment (skmSTX4tg) in mice reverses established insulin resistance and improves mitochondrial function in the context of diabetogenic stress. Specifically, skmSTX4tg reversed insulin resistance caused ...

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Priming cardiovascular exercise improves complex motor skill learning by affecting the trajectory of learning-related brain plasticity

In recent years, mounting evidence from animal models and studies in humans has accumulated for the role of cardiovascular exercise (CE) in improving motor performance and learning. Both CE and motor learning may induce highly dynamic structural and functional brain changes, but how both processes interact to boost learning is presently unclear. Here, we hypothesized that subjects receiving CE would show a different pattern of learning-related brain plasticity compared to non-CE controls, which in ...

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Abnormal whole-body energy metabolism in iron-deficient humans despite preserved skeletal muscle oxidative phosphorylation

Iron deficiency impairs skeletal muscle metabolism. The underlying mechanisms are incompletely characterised, but animal and human experiments suggest the involvement of signalling pathways co-dependent upon oxygen and iron availability, including the pathway associated with hypoxia-inducible factor (HIF). We performed a prospective, case–control, clinical physiology study to explore the effects of iron deficiency on human metabolism, using exercise as a stressor. Thirteen iron-deficient (ID) ...

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Behavioural and neuroplastic effects of a double-blind randomised controlled balance exercise trial in people with Parkinson’s disease

Balance dysfunction is a disabling symptom in people with Parkinson’s disease (PD). Evidence suggests that exercise can improve balance performance and induce neuroplastic effects. We hypothesised that a 10-week balance intervention (HiBalance) would improve balance, other motor and cognitive symptoms, and alter task-evoked brain activity in people with PD. We performed a double-blind randomised controlled trial (RCT) where 95 participants with PD were randomised to either HiBalance (n = 48) ...

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The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review

The physiological effects of physical exercise are ubiquitously reported as beneficial to the cardiovascular and musculoskeletal systems. Exercise is widely promoted by medical professionals to aid both physical and emotional wellbeing; however, mechanisms through which this is achieved are less well understood. Despite numerous beneficial attributes, certain types of exercise can inflict significant significant physiological stress. Several studies document a key relationship between exercise and ...

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Effect of eccentric and concentric contraction mode on myogenic regulatory factors expression in human vastus lateralis muscle

Skeletal muscle contractions are caused to release myokines by muscle fiber. This study investigated the myogenic regulatory factors, as MHC I, IIA, IIX, Myo-D, MRF4, Murf, Atrogin-1, Decorin, Myonection, and IL-15 mRNA expression in the response of eccentric vs concentric contraction. Eighteen healthy men were randomly divided into two eccentric and concentric groups, each of 9 persons. Isokinetic contraction protocols included maximal single-leg eccentric or concentric knee extension tasks at 60°/s ...

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Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice

Irisin is well-known to contribute to bone homeostasis due to its bidirectional regulation on osteogenesis and osteoclastogenesis. However, the mechanisms of irisin involved in mesenchymal stem/stromal cells (MSCs)-derived osteogenesis are still under investigated. Fibronectin type III domain-containing protein 5 (FNDC5) is the precursor protein of irisin, compare with wild type (WT) littermates, FNDC5-/- mice lost bone mass significantly, collectively evidenced by the decrease of bone mineral density ...

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Inter-organ Crosstalk in Pancreatic Islet Function and Pathology

Pancreatic β cells secrete insulin in response to glucose, a process that is regulated at multiple levels, including a network of input signals from other organ systems. Impaired islet function contributes the pathogenesis of type 2 diabetes mellitus (T2DM) and targeting inter-organ communications, such as GLP-1 signalling, to enhance β cell function has been proven to be a successful therapeutic strategy in the last decade. In this review, we will discuss recent advances in inter-organ ...

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Skeletal muscle derived Musclin protects the heart during pathological overload

Cachexia is associated with poor prognosis in chronic heart failure patients, but the underlying mechanisms of cachexia triggered disease progression remain poorly understood. Here, we investigate whether the dysregulation of myokine expression from wasting skeletal muscle exaggerates heart failure. RNA sequencing from wasting skeletal muscles of mice with heart failure reveals a reduced expression of Ostn, which encodes the secreted myokine Musclin, previously implicated in the enhancement of natriuretic ...

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Identification of a regulatory pathway inhibiting adipogenesis via RSPO2

Healthy adipose tissue remodeling depends on the balance between de novo adipogenesis from adipogenic progenitor cells and the hypertrophy of adipocytes. De novo adipogenesis has been shown to promote healthy adipose tissue expansion, which confers protection from obesity-associated insulin resistance. Here, we define the role and trajectory of different adipogenic precursor subpopulations and further delineate the mechanism and cellular trajectory of adipogenesis, using single-cell RNA-sequencing ...

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Protective effects of physical activity in colon cancer and underlying mechanisms: A review of epidemiological and biological evidence

Numerous epidemiological studies indicate that physical activity has a protective effect against colon cancer development and progression. Further, the relevant biological mechanisms where physical activity or exercise may improve survival have also been initially examined. In this review, we provide an overview of the epidemiological evidence to date which comprises 16 cohort studies of the effects of physical activity on colon cancer outcomes including cancer recurrence, cancer-specific and overall ...

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Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity

Beige and brown fat consume glucose and lipids to produce heat, using uncoupling protein 1 (UCP1). It is thought that full activation of brown adipose tissue (BAT) may increase total daily energy expenditure by 20%. Humans normally have more beige and potentially beige-able fat than brown fat. Strategies to increase beige fat differentiation and activation may be useful for the treatment of obesity and diabetes. Mice were fed chow or high-fat diet (HFD) with or without the iron chelator deferasirox. ...

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Effects of paternal overnutrition and interventions on future generations

In the last two decades, evidence from human and animal studies suggests that paternal obesity around the time of conception can have adverse effects on offspring health through developmental programming. This may make significant contributions to the current epidemic of obesity and related metabolic and reproductive complications like diabetes, cardiovascular disease, and subfertility/infertility. To date, changes in seminal fluid composition, sperm DNA methylation, histone composition, small non-coding ...

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Safety, efficacy and delivery of isometric resistance training as an adjunct therapy for blood pressure control: a modified Delphi study

Uncontrolled hypertension remains the major risk factor for cardiovascular disease. Isometric resistance training (IRT) has been shown to be a useful nonpharmacological therapy for reducing blood pressure (BP); however, some exercise physiologists and other health professionals are uncertain of the efficacy and safety of IRT. Experts’ consensus was sought in light of the current variability of IRT use as an adjunct treatment for hypertension. An expert consensus-building analysis (Delphi study) ...

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Quadriceps physiological response during the 1-min sit-to-stand test in people with severe COPD and healthy controls

We compared quadriceps oxygenation and surface electromyography (sEMG) responses during the 1-min sit-to-stand (1STS) in 14 people with severe COPD and 12 controls, in whom cardiorespiratory response, near-infrared spectroscopy signals (oxy [Hb-Mb], deoxy [Hb-Mb], total [Hb-Mb], and SmO2) and sEMG signals of the quadriceps were recorded. Time duration of each sit-to-stand cycle and the total work performed during the 1STS were measured. The quadriceps oxygenation parameters were normalized by reporting ...

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Association between the recognition of muscle mass and exercise habits or eating behaviors in female college students

This study aimed to examine the association between muscle mass and perception of body shape, desired body shape, physical strength, exercise habits, and eating behaviors. Height, weight, and body composition in 270 female university students were measured. The questionnaire on body shape perception, desired body shape, dieting experience, current, and past exercise habits, exercise preference, and eating behaviors were administered. The analysis of covariance with body fat mass as the covariate ...

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Multifactorial Mechanism of Sarcopenia and Sarcopenic Obesity. Role of Physical Exercise, Microbiota and Myokines

Obesity and ageing place a tremendous strain on the global healthcare system. Age-related sarcopenia is characterized by decreased muscular strength, decreased muscle quantity, quality, and decreased functional performance. Sarcopenic obesity (SO) is a condition that combines sarcopenia and obesity and has a substantial influence on the older adults’ health. Because of the complicated pathophysiology, there are disagreements and challenges in identifying and diagnosing SO. Recently, it has ...

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Factors Mediating Exercise-induced Organ Crosstalk

Exercise activates a plethora of metabolic and signalling pathways in skeletal muscle and other organs causing numerous systemic beneficial metabolic effects. Thus, regular exercise may ameliorate and prevent the development of several chronic metabolic diseases. Skeletal muscle is recognized as an important endocrine organ regulating systemic adaptations to exercise. Skeletal muscle may mediate crosstalk with other organs through the release of exercise-induced cytokines, peptides and proteins, ...

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Endothelial NOX5 Expression Modulates Thermogenesis and Lipolysis in Mice Fed with a High-Fat Diet and 3T3-L1 Adipocytes through an Interleukin-6 Dependent Mechanism

Obesity is a global health issue associated with the development of metabolic syndrome, which correlates with insulin resistance, altered lipid homeostasis, and other pathologies. One of the mechanisms involved in the development of these pathologies is the increased production of reactive oxygen species (ROS). One of the main producers of ROS is the family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, among which NOX5 is the most recently discovered member. The aim of the present ...

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Equal-Volume Strength Training With Different Training Frequencies Induces Similar Muscle Hypertrophy and Strength Improvement in Trained Participants

The main goal of the current study was to compare the effects of volume-equated training frequency on gains in muscle mass and strength. In addition, we aimed to investigate whether the effect of training frequency was affected by the complexity, concerning the degrees of freedom, of an exercise. Participants were randomized to a moderate training frequency group (two weekly sessions) or high training frequency group (four weekly sessions). Twenty-one participants (male: 11, female: 10, age: 25.9 ...

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Hepatic p38 Activation Modulates Systemic Metabolism Through FGF21-Mediated Interorgan Communication

The mechanisms underlying the pathogenesis of steatosis and insulin resistance in nonalcoholic fatty liver disease remain elusive. Increased phosphorylation of hepatic p38 has long been noticed in fatty liver; however, whether the activation of hepatic p38 is a cause or consequence of liver steatosis is unclear. Here, we demonstrate that hepatic p38 activation by MKK6 overexpression in the liver of mice induces severe liver steatosis, reduces fat mass, and elevates circulating fatty acid levels in ...

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Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter of hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% of patients with non-alcoholic fatty liver disease (NAFLD). Due to liver dysfunction and the numerous metabolic changes that commonly accompany the condition (obesity, insulin resistance, type 2 diabetes, and metabolic syndrome), the secretion of organokines is modified, which may contribute to the ...

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FGF1 and insulin control lipolysis by convergent pathways

Inexorable increases in insulin resistance, lipolysis, and hepatic glucose production (HGP) are hallmarks of type 2 diabetes. Previously, we showed that peripheral delivery of exogenous fibroblast growth factor 1 (FGF1) has robust anti-diabetic effects mediated by the adipose FGF receptor (FGFR) 1. However, its mechanism of action is not known. Here, we report that FGF1 acutely lowers HGP by suppressing adipose lipolysis. On a molecular level, FGF1 inhibits the cAMP-protein kinase A axis by activating ...

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Aging Leukocytes and the Inflammatory Microenvironment of the Adipose Tissue

Age-related immunosenescence, defined as an increase in inflammaging and the decline of the immune system, leads to tissue dysfunction and increased risk for metabolic disease. The elderly population is expanding, leading to a heightened need for therapeutics to improve health span. With age, many alterations of the immune system are observed, including shifts in the tissue-resident immune cells, increased expression of inflammatory factors, and the accumulation of senescent cells, all of which are ...

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Aerobic Exercise Combination Intervention to Improve Physical Performance Among the Elderly: A Systematic Review

The benefits of aerobic exercise for the elderly are well-known. They extend beyond cardiovascular changes and can reduce the inactivity-induced loss of strength, mobility, balance, and endurance that are vital for the safe performance of daily activities in older adults. However, the benefits of combined aerobic exercise with other exercises such as strength/resistance, multi-component and aerobic exercise remain unknown. The purpose of this study is to examine the effects of combined aerobic exercise ...

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May the Force and Mass Be With You – Evidence-Based Contribution of Mechano-Biological Descriptors of Resistance Exercise

Skeletal muscle is one of the most important tissues of the human body. It comprises up to 40% of the body mass and is crucial to survival. Hence, the maintenance of skeletal muscle mass and strength is pivotal. It is well-established that resistance exercise provides a potent anabolic stimulus to increase muscle mass and strength in men and women of all ages. Resistance exercise consists of mechano-biological descriptors, such as load, muscle action, number of repetitions, repetition duration, number ...

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The effect of toll-like receptor ligands on energy metabolism and myokine expression and secretion in cultured human skeletal muscle cells

Skeletal muscle plays an important role in glycaemic control and metabolic homeostasis, making it a tissue of interest with respect to type 2 diabetes mellitus. The aim of the present study was to determine if ligands of Toll-like receptors (TLRs) could have an impact on energy metabolism and myokine expression and secretion in cultured human skeletal muscle cells. The myotubes expressed mRNA for TLRs 1–6. TLR3, TLR4, TLR5 and TLR6 ligands (TLRLs) increased glucose metabolism. Furthermore, ...

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The short and long-term effects of aerobic, strength, or mixed exercise programs on schizophrenia symptomatology

The purpose of this study was to compare the effects of three different physical exercise programs on the symptomatology, body composition, physical activity, physical fitness, and quality of life of individuals with schizophrenia. A total of 432 patients were assessed for eligibility and 86 were randomized into the aerobic (n = 28), strength (n = 29) or mixed (n = 29) groups. Positive, negative, and general symptoms of psychosis, body mass index (BMI), physical ...

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Caffeine increases performance and leads to a cardioprotective effect during intense exercise in cyclists

The present study was designed to investigate the effects of different caffeine dietary strategies to compare the impact on athletic performance and cardiac autonomic response. The order of the supplementation was randomly assigned: placebo(4-day)-placebo(acute)/PP, placebo(4-day)-caffeine(acute)/PC and caffeine(4-day)-caffeine(acute)/CC. Fourteen male recreationally-trained cyclists ingested capsules containing either placebo or caffeine (6 mg kg−1) for 4 days. On day 5 (acute), capsules containing ...

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Regulation of aged skeletal muscle regeneration by circulating extracellular vesicles

Heterochronic blood exchange (HBE) has demonstrated that circulating factors restore youthful features to aged tissues. However, the systemic mediators of those rejuvenating effects remain poorly defined. We show here that the beneficial effect of young blood on aged muscle regeneration was diminished when serum was depleted of extracellular vesicles (EVs). Whereas EVs from young animals rejuvenate aged cell bioenergetics and skeletal muscle regeneration, aging shifts EV subpopulation heterogeneity ...

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Eccentric Exercise: Adaptations and Applications for Health and Performance

The goals of this narrative review are to provide a brief overview of the muscle and tendon adaptations to eccentric resistance exercise and address the applications of this form of training to aid rehabilitative interventions and enhance sports performance. This work is centered on the author contributions to the Special Issue entitled "Eccentric Exercise: Adaptations and Applications for Health and Performance". The major themes from the contributing authors include the need to place greater attention ...

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Muscle-to-fat ratio identifies functional impairments and cardiometabolic risk and predicts outcomes: biomarkers of sarcopenic obesity

Background: Sarcopenic obesity aims to capture the risk of functional decline and cardiometabolic diseases, but its operational definition and associated clinical outcomes remain unclear. Using data from the Longitudinal Aging Study of Taipei, this study explored the roles of the muscle-to-fat ratio (MFR) with different definitions and its associations with clinical characteristics, functional performance, cardiometabolic risk and outcomes. Methods: (1) Appendicular muscle mass divided by total ...

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Short and long-term effects of high-intensity interval training applied alone or with whole-body cryostimulation on glucose homeostasis and myokine levels in overweight to obese subjects

Background: COVID-19 pandemic has exacerbated the problem of physical inactivity and weight gain. Consequently, new strategies to counteract weight gain are being sought. Because of their accessibility, interval training and cold therapy are the most popular such strategies. We here aimed to examine the effect of 6 units of high-intensity interval training (HIIT), applied alone or in combination with 10 sessions of whole-body cryotherapy (WBC; 3 min at –110 ∘C per session) on incretins, ...

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The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes

Growing evidence supports the importance of the p53 tumor suppressor in metabolism but the mechanisms underlying p53-mediated control of metabolism remain poorly understood. Here, we identify the multifunctional E4F1 protein as a key regulator of p53 metabolic functions in adipocytes. While E4F1 expression is upregulated during obesity, E4f1 inactivation in mouse adipose tissue results in a lean phenotype associated with insulin resistance and protection against induced obesity. Adipocytes lacking ...

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β3-adrenergic receptor downregulation leads to adipocyte catecholamine resistance in obesity

The dysregulation of energy homeostasis in obesity involves multi-hormone resistance. Although leptin and insulin resistance have been well characterized, catecholamine resistance remains largely unexplored. Murine β3-adrenergic receptor expression in adipocytes is orders of magnitude higher compared to other isoforms. While resistant to classical desensitization pathways, its mRNA (Adrb3) and protein expression are dramatically downregulated after ligand exposure (homologous desensitization). ...

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Dietary supplements consumption and its association with socioeconomic factors, obesity and main non-communicable chronic diseases in the north of Iran: the PERSIAN Guilan Cohort Study (PGCS)

Background: Dietary supplements (DSs) use have become a growing trend worldwide, and it may be affected by demographic and sociocultural factors. Some people use supplements with the thought that they can improve their health, reduce symptoms and prevent disease. The aim of the present study was to define the frequency of DS use and its association with socioeconomic factors among participants with selected main non-communicable chronic diseases (NCDs) (diabetes, cardiovascular disease (CVD), hypertension ...

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Pathways in Skeletal Muscle: Protein Signaling and Insulin Sensitivity after Exercise Training and Weight Loss Interventions in Middle-Aged and Older Adults

Aging and obesity contribute to insulin resistance with skeletal muscle being critically important for maintaining whole-body glucose homeostasis. Both exercise and weight loss are lifestyle interventions that can affect glucose metabolism. The purpose of this study was to examine the effects of a six-month trial of aerobic exercise training or weight loss on signaling pathways in skeletal muscle in the basal condition and during hyperinsulinemia during a glucose clamp in middle-aged and older adults. ...

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Transcriptomic adaptation during skeletal muscle habituation to eccentric or concentric exercise training

Eccentric (ECC) and concentric (CON) contractions induce distinct muscle remodelling patterns that manifest early during exercise training, the causes of which remain unclear. We examined molecular signatures of early contraction mode-specific muscle adaptation via transcriptome-wide network and secretome analyses during 2 weeks of ECC- versus CON-specific (downhill versus uphill running) exercise training (exercise ‘habituation’). Despite habituation attenuating total numbers of exercise-induced ...

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Lack of Endothelial α1AMPK Reverses the Vascular Protective Effects of Exercise by Causing eNOS Uncoupling

Voluntary exercise training is an effective way to prevent cardiovascular disease, since it results in increased NO bioavailability and decreased reactive oxygen species (ROS) production. AMP-activated protein kinase (AMPK), especially its α1AMPK subunit, modulates ROS-dependent vascular homeostasis. Since endothelial cells play an important role in exercise-induced changes of vascular signaling, we examined the consequences of endothelial-specific α1AMPK deletion during voluntary exercise ...

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Comparing Acute, High Dietary Protein and Carbohydrate Intake on Transcriptional Biomarkers, Fuel Utilisation and Exercise Performance in Trained Male Runners

Manipulating dietary macronutrient intake may modulate adaptive responses to exercise, and improve endurance performance. However, there is controversy as to the impact of short-term dietary modification on athletic performance. In a parallel-groups, repeated measures study, 16 trained endurance runners (maximal oxygen uptake (V˙O2max): 64.2 ± 5.6 mL·kg−1·min−1) were randomly assigned to, and provided with, either a high-protein, reduced-carbohydrate (PRO) or a high-carbohydrate ...

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Paracrine FGFs target skeletal muscle to exert potent anti-hyperglycemic effects

Several members of the FGF family have been identified as potential regulators of glucose homeostasis. We previously reported that a low threshold of FGF-induced FGF receptor 1c (FGFR1c) dimerization and activity is sufficient to evoke a glucose lowering activity. We therefore reasoned that ligand identity may not matter, and that besides paracrine FGF1 and endocrine FGF21, other cognate paracrine FGFs of FGFR1c might possess such activity. Indeed, via a side-by-side testing of multiple cognate FGFs ...

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Balance of Autonomic Nervous Activity, Exercise, and Sleep Status in Older Adults: A Review of the Literature

While older people are frequently known to experience sleep disturbances, there are also many older people who have a good quality of sleep. However, little is known about the balance of autonomic nervous activity, exercise habits, and sleep status in healthy older adults. This study reviews the literature regarding balance of the autonomic nervous activity, exercise, and sleep in healthy older adults. Relevant articles were searched from electronic databases using the combination of the following ...

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The effect of exercise training interventions in adult kidney transplant recipients: a systematic review and meta-analysis of randomised control trials

Background: Kidney transplant recipients (KTRs) are characterised by adverse changes in physical fitness and body composition. Post-transplant management involves being physically active, although evidence for the effect of exercise is limited. Objective: To assess the effects of exercise training interventions in KTRs. Methods: NCBI PubMed (MEDLINE) and CENTRAL (EMBASE, WHO ICTRP) databases were searched up to March 2021 to identify eligible randomized controlled trials (RCTs) that studied exercise ...

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Effects of 5 Years Aerobic Exercise on Cognition in Older Adults: The Generation 100 Study: A Randomized Controlled Trial

Objective: The objective of this study was to investigate whether a 5-year exercise intervention and change in peak oxygen uptake (VO2peak) is associated with cognitive function in older adults. Methods: Nine hundred and forty-five participants (48% women, mean age at study end 78.2 ± 2.02 years) from the Generation 100 Study were randomized 2:1:1 to a control group, moderate-intensity continuous training or high-intensity interval training twice weekly for 5 years. Peak oxygen ...

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Exercise for counteracting post-acute COVID-19 syndrome in patients with cancer: an old but gold strategy?

Coronavirus disease (COVID-19) infection has caused morbidity and mortality at an unprecedented scale [1]. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel beta coronavirus responsible for new respiratory infections with mild-to-severe presentations in humans. At the beginning of the pandemic, major attention was directed to investigate the acute effect of COVID-19, as well as to identify potential therapeutic and preventive strategies to control the virus spread. More ...

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The role of physical exercise intensity to irisin levels on overweight and obese

Physical exercise is a non-pharmacological therapy that can secrete various types of myokines to treat obesity problems. One of the myokines that play a role is irisin. Irisin is a polypeptide hormone with 112 amino acid residues that are synthesized in skeletal muscle after the proteolytic precursor cleavage of fibronectin type III domain-containing protein 5 (FNDC5). The release of irisin in the blood circulation will stimulate the browning process in white fat tissue by inducing the expression ...

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Exercise rather than fluoxetine promotes oligodendrocyte differentiation and myelination in the hippocampus in a male mouse model of depression

Although selective serotonin reuptake inhibitor (SSRI) systems have been meaningfully linked to the clinical phenomena of mood disorders, 15–35% of patients do not respond to multiple SSRI interventions or even experience an exacerbation of their condition. As we previously showed, both running exercise and fluoxetine reversed depression-like behavior. However, whether exercise reverses depression-like behavior more quickly than fluoxetine treatment and whether this rapid effect is achieved ...

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Effects of exercise training on behavior and brain function after high dose isoproterenol-induced cardiac damage

Acute sympathetic stress can result in cardiac fibrosis, but may also lead to mental dysfunction. Exercise training after isoproterenol (ISO)-induced acute sympathetic stress was investigated regarding cardiac damage, neuroinflammation, brain function and behavior. Male Wistar rats (12 months) received ISO or saline. One week later, treadmill running or control handling (sedentary) started. After 4 weeks, cognitive- and exploratory behavior were evaluated, and heart and brain tissues were analyzed ...

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Exercise reduces systemic immune inflammation index (SII) in childhood cancer patients

While exercise and physical activity have been suggested to reduce mortality and symptoms in cancer, knowledge on these associations in patients with childhood cancer (CCPs) is sparse. Anti-inflammatory properties of exercise might mediate these beneficial effects. We investigated the influence of exercise on the inflammation markers neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic-immune-inflammation index (SII) and associations to patient-reported-outcomes in CCPs in a ...

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The importance of protein sources to support muscle anabolism in cancer: An expert group opinion

This opinion paper presents a short review of the potential impact of protein on muscle anabolism in cancer, which is associated with better patient outcomes. Protein source is a topic of interest for patients and clinicians, partly due to recent emphasis on the supposed non-beneficial effect of proteins; therefore, misconceptions involving animal-based (e.g., meat, fish, dairy) and plant-based (e.g., legumes) proteins in cancer are acknowledged and addressed. Although the optimal dietary amino acid ...

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Are people who use active modes of transportation more physically active? An overview of reviews across the life course

Regular physical activity prevents several non-communicable chronic conditions and premature mortality. The benefits of physical activity can be achieved through active transport, which refers to non-motorised/active means (e.g. walking, cycling, rollerblading) to move from one place to another. Active transport can be integrated into daily routines such as commuting to and from school and work. We undertook an overview of reviews to examine the association between active transport and physical activity ...

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Dose Response of Acute ATP Supplementation on Strength Training Performance

Background: Chronic oral ATP supplementation benefits cardiovascular health, muscular performance, body composition, and recovery while attenuating muscle breakdown and fatigue. A single 400 mg dose of oral ATP supplementation improved lower body resistance training performance and energy expenditure in recreational resistance trained males, however, the minimal effective dose is currently unknown. Materials and Methods: Twenty recreationally trained men (age 28.6 ± 1.0 years, body mass 81.2 ...

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Resistance training induces similar adaptations of upper and lower-body muscles between sexes

The purpose of the study was to compare sex adaptations in hypertrophy, strength and contractile properties of upper and lower-body muscles induced by resistance training (RT). Eighteen RT untrained male (MG) and female (FG) students (aged 24.1 ± 1.7 years, height: 1.75 ± 0.08 m, weight: 70.4 ± 12.3 kg) undervent 7 weeks of biceps curl and squat training (2 days/week, 60–70% repetition maximum, 3–4 sets, 120 s rest intervals, ...

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Myostatin and Sarcopenia in Elderly Among Haemodyalisis Patient

Background and Objective: Increased serum myostatin level might be one of the causes of impaired protein synthesis and protein degradation associated with decreased muscle mass accompanying older age, which is a component of sarcopenia in CKD patients undergoing hemodialysis. There are still very limited number of studies with varying and contradictory results. This study aims to analyze the relationship between serum myostatin and sarcopenia levels in elderly chronic kidney disease patients undergoing ...

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Metabolic responsiveness to training depends on insulin sensitivity and protein content of exosomes in insulin-resistant males

High-intensity interval training (HIIT) improves cardiorespiratory fitness (VO2max), but its impact on metabolism remains unclear. We hypothesized that 12-week HIIT increases insulin sensitivity in males with or without type 2 diabetes [T2D and NDM (nondiabetic humans)]. However, despite identically higher VO2max, mainly insulin-resistant (IR) persons (T2D and IR NDM) showed distinct alterations of circulating small extracellular vesicles (SEVs) along with lower inhibitory metabolic (protein kinase ...

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High-intensity training induces non-stoichiometric changes in the mitochondrial proteome of human skeletal muscle without reorganisation of respiratory chain content

Mitochondrial defects are implicated in multiple diseases and aging. Exercise training is an accessible, inexpensive therapeutic intervention that can improve mitochondrial bioenergetics and quality of life. By combining multiple omics techniques with biochemical and in silico normalisation, we removed the bias arising from the training-induced increase in mitochondrial content to unearth an intricate and previously undemonstrated network of differentially prioritised mitochondrial adaptations. We ...

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Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training

Despite good adherence to supervised endurance exercise training (EET), some individuals experience no or little improvement in peripheral insulin sensitivity. The genetic and molecular mechanisms underlying this phenomenon are currently not understood. By investigating genome-wide variants associated with baseline and exercise-induced changes (∆) in insulin sensitivity index (Si) in healthy volunteers, we have identified novel candidate genes whose mouse knockouts phenotypes were consistent with ...

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The ups and downs of caloric restriction and fasting: from molecular effects to clinical application

Age-associated diseases are rising to pandemic proportions, exposing the need for efficient and low-cost methods to tackle these maladies at symptomatic, behavioral, metabolic, and physiological levels. While nutrition and health are closely intertwined, our limited understanding of how diet precisely influences disease often precludes the medical use of specific dietary interventions. Caloric restriction (CR) has approached clinical application as a powerful, yet simple, dietary modulation that ...

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Effects of Exercise Type and Intensity on Visfatin and the Metabolic Syndrome in Obesity

Objective: Visfatin may regulate a variety of physiological functions and it has great potential to significantly enhance our knowledge of the treatment of metabolic syndrome. Metabolic syndrome (MS) refers to metabolic abnormalities, such as abdominal obesity, dyslipidemia, high low-density cholesterol, high blood pressure and diabetes, and physical activity is an important factor for the management of MS. Therefore, the purpose of this study is to investigate the effects of visfatin on MS and MS ...

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Ursolic acid does not change the cytokine levels following resistance training in healthy men: A pilot balanced, double-blind and placebo-controlled clinical trial

Ursolic acid (UA) is a natural compound that shows anti-inflammatory actions. However, no human studies have investigated the cytokine profile during the RT and UA consumption. The purpose of this study was to verify if UA is able to potentiate the anti-inflammatory activity after RT, reflecting in the reduction of blood inflammatory markers in healthy men. Twenty-seven participants were allocated to two groups: control (CON) (n = 13) and UA (n = 14). For 8 weeks, each group performed RT and consumed ...

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Mucin secretory action of capsaicin prevents high fat diet-induced gut barrier dysfunction in C57BL/6 mice colon

The gut barrier – including tight junction proteins (TJPs) and mucus layers, is the first line of defense against physical, chemical or pathogenic incursions. This barrier is compromised in various health disorders. Capsaicin, a dietary agonist of Transient receptor potential vanilloid 1 (TRPV1) channel, is reported to alleviate the complications of obesity. While it is well known to improve energy expenditure and metabolism, and prevent dysbiosis, the more local effects on the host gut – ...

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Egg and saturated fat containing breakfasts have no acute effect on acute glycemic control in healthy adults: a randomized partial crossover trial

Background/Objectives: High egg consumption is associated with poor glycemic control. Considering the widespread consumption of eggs, it is crucial to determine causality in this association. We tested if egg consumption acutely alters glucose disposal in the absence or presence of saturated fat, which is frequently consumed with eggs. Subjects/Methods: In a randomized partial crossover clinical trial, 48 subjects (consuming ≥ 1 egg/week) received two of four isocaloric, macronutrient-matched ...

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Is Obesity/Adiposity-Based Chronic Disease Curable: The Set Point Theory, the Environment, and Second Generation Medications

Adiposity-Based Chronic Disease (ABCD) is a chronic disease and requires life-long treatment and follow-up. Obesity protects obesity through altered regulation of caloric intake and set point mechanisms that maintains a high equilibrium body weight. Lifestyle interventions and obesity medications do not permanently alter the set point which often makes weight loss achieved by lifestyle short-lived and operates to drive weight regain once medications are discontinued. Bariatric surgery procedures ...

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Health Effects of Increasing Protein Intake Above the Current Population Reference Intake in Older Adults: A Systematic Review of the Health Council of the Netherlands

Whether older adults need more protein than younger adults is debated. The population reference intake for adults set by the European Food Safety Authority is 0.83 g/kg body weight (BW)/d based primarily on nitrogen balance studies, but the underlying data on health outcomes are outdated. An expert committee of the Health Council of the Netherlands conducted a systematic review (SR) of randomized controlled trials (RCTs) examining the effect of increased protein intake on health outcomes in older ...

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Acute exercise increases immune responses to SARS CoV-2 in a previously infected man

Evidence is emerging that exercise and physical activity provides protection against severe COVID-19 disease in patients infected with SARS-CoV-2, but it is not known how exercise affects immune responses to the virus. A healthy man completed a graded cycling ergometer test prior to and after SARS-CoV-2 infection, then again after receiving an adenovirus vector-based COVID-19 vaccine. Using whole blood SARS-CoV-2 peptide stimulation assays, IFN-γ ELISPOT assays, flow cytometry, ex vivo viral-specific ...

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Moderate exercise may prevent the development of severe forms of COVID-19, whereas high-intensity exercise may result in the opposite

Sedentary lifestyle increases the risk of hospitalization for COVID-19 independently of other factors. There is enough statistics to show that exercise prevents severe forms of COVID-19, but current recommendations do not set an upper limit for exercise intensity. The hypothesis presented in the paper states that intense exercise, through blood hypoxia, increases the expression of transmembrane angiotensin-converting enzyme 2 (tACE2) in the vascular endothelium, increasing the risk of developing ...

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Effectiveness of Multicomponent Exercise Interventions in Older Adults With Dementia: A Meta-Analysis

Background and Objectives: Multicomponent training (MT) combines aerobic, strength, postural, and balance exercises and may be a promising intervention strategy for dementia. This meta-analysis study aims to systematize evidence concerning the effectiveness of MT in physical fitness, cognition, and functionality on activities of daily living (ADL) in older adults with dementia and to identify moderation patterns regarding training variables. Research Design and Methods: 4 databases were systematically ...

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Calorie Restriction With Exercise Intervention Improves Inflammatory Response in Overweight and Obese Adults: A Systematic Review and Meta-Analysis

Background/Purpose: In this systematic review and meta-analysis, we assessed the effects of exercise (EX) combined with calorie restriction (CR) intervention on inflammatory biomarkers, and correlations between biomarkers and participants’ characteristics were calculated in overweight and obese adults. Methods: An article search was conducted through PubMed, Web of Science, EMBASE, the Cochrane database, Scopus, and Google Scholar to identify articles published up to April 2021. Studies that ...

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Acute Aerobic Exercise Induces Short-Term Reductions in Ambulatory Blood Pressure in Patients With Hypertension: A Systematic Review and Meta-Analysis

Chronic exercise reduces clinic and ambulatory blood pressure (BP), but the short-term effects of an acute exercise bout on ambulatory BP have not been studied widely. We reviewed the literature regarding the short-term effects of acute exercise on ambulatory BP in patients with hypertension and considered moderating factors (medication status and exercise modality/intensity) on ambulatory BP outcomes. A systematic search was conducted (PubMed, Cochrane Library, and Scopus; since inception to January ...

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Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat

Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 ...

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Psychological and biological resilience modulates the effects of stress on epigenetic aging

Our society is experiencing more stress than ever before, leading to both negative psychiatric and physical outcomes. Chronic stress is linked to negative long-term health consequences, raising the possibility that stress is related to accelerated aging. In this study, we examine whether resilience factors affect stress-associated biological age acceleration. Recently developed “epigenetic clocks” such as GrimAge have shown utility in predicting biological age and mortality. Here, we ...

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Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues

Brown and beige fat are specialized for energy expenditure by dissipating energy from glucose and fatty acid oxidation as heat. While glucose and fatty acid metabolism have been extensively studied in thermogenic adipose tissues, the involvement of amino acids in regulating adaptive thermogenesis remains little studied. Here, we report that asparagine supplementation in brown and beige adipocytes drastically upregulated the thermogenic transcriptional program and lipogenic gene expression, so that ...

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Lipolysis: cellular mechanisms for lipid mobilization from fat stores

The perception that intracellular lipolysis is a straightforward process that releases fatty acids from fat stores in adipose tissue to generate energy has experienced major revisions over the last two decades. The discovery of new lipolytic enzymes and coregulators, the demonstration that lipophagy and lysosomal lipolysis contribute to the degradation of cellular lipid stores and the characterization of numerous factors and signalling pathways that regulate lipid hydrolysis on transcriptional and ...

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The impact of muscle mass loss and deteriorating physical function on prognosis in patients receiving hemodialysis

Muscle mass loss and worsening physical function are crucial issues in patients receiving hemodialysis (HD). However, few studies have investigated the association between temporal changes in muscle mass and physical function in a large number of HD patients. We examined 286 patients receiving HD (males, 58%; age, 66.8 ± 13.0 years) at a single center, and calculated the percent changes in psoas muscle mass index (%PMI) using computed tomography over two screenings, once per ...

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Obesity risk is associated with altered cerebral glucose metabolism and decreased μ-opioid and CB1 receptor availability

Background: Obesity is a pressing public health concern worldwide. Novel pharmacological means are urgently needed to combat the increase of obesity and accompanying type 2 diabetes (T2D). Although fully established obesity is associated with neuromolecular alterations and insulin resistance in the brain, potential obesity-promoting mechanisms in the central nervous system have remained elusive. In this triple-tracer positron emission tomography study, we investigated whether brain insulin signaling, ...

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The manifold roles of protein S-nitrosylation in the life of insulin

Insulin, which is released by pancreatic islet β-cells in response to elevated levels of glucose in the blood, is a critical regulator of metabolism. Insulin triggers the uptake of glucose and fatty acids into the liver, adipose tissue and muscle, and promotes the storage of these nutrients in the form of glycogen and lipids. Dysregulation of insulin synthesis, secretion, transport, degradation or signal transduction all cause failure to take up and store nutrients, resulting in type 1 diabetes ...

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Brown adipose tissue prevents glucose intolerance and cardiac remodeling in high-fat-fed mice after a mild myocardial infarction

Background: Obesity increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes (T2D) after myocardial infarction (MI). Brown adipose tissue (BAT) is important to combat obesity and T2D, and increasing BAT mass by transplantation improves glucose metabolism and cardiac function. The objective of this study was to determine if BAT had a protective effect on glucose tolerance and cardiac function in high-fat diet (HFD) fed mice subjected to a mild MI. Methods: Male C57BL/6 ...

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Intramuscular fat in gluteus maximus for different levels of physical activity

We aimed to determine if gluteus maximus (GMAX) fat infiltration is associated with different levels of physical activity. Identifying and quantifying differences in the intramuscular fat content of GMAX in subjects with different levels of physical activity can provide a new tool to evaluate hip muscles health. This was a cross-sectional study involving seventy subjects that underwent Dixon MRI of the pelvis. The individuals were divided into four groups by levels of physical activity, from low ...

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Effects of yoga in men with prostate cancer on quality of life and immune response: a pilot randomized controlled trial

Background: Diagnosis and treatment of prostate cancer is associated with anxiety, fear, and depression in up to one-third of men. Yoga improves health-related quality of life (QoL) in patients with several types of cancer, but evidence of its efficacy in enhancing QoL is lacking in prostate cancer. Methods: In this randomized controlled study, 29 men newly diagnosed with localized prostate cancer were randomized to yoga for 6 weeks (n = 14) or standard-of-care (n = 15) ...

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Low-frequency exercise training improves cardiovascular fitness and strength during treatment for breast cancer: a single-arm intervention study

Aerobic and resistance exercise during and after cancer treatment are important for health-related outcomes, however treatment-specific barriers may inhibit adherence. We explored the effect of lower-frequency exercise training on fitness, body composition, and metabolic markers (i.e. glucose and lipids) in a group of recently diagnosed breast cancer patients. Fifty-two females ≥ 18 years with stage I–IIIB breast cancer were instructed to attend 2 cardiovascular and strength ...

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The Metabolic Signature of Cardiorespiratory Fitness: A Systematic Review

Background: Cardiorespiratory fitness (CRF) is a potent health marker, the improvement of which is associated with a reduced incidence of non-communicable diseases and all-cause mortality. Identifying metabolic signatures associated with CRF could reveal how CRF fosters human health and lead to the development of novel health-monitoring strategies. Objective: This article systematically reviewed reported associations between CRF and metabolites measured in human tissues and body fluids. Methods: ...

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Changes in white matter microstructure and MRI-derived cerebral blood flow after 1-week of exercise training

Exercise is beneficial for brain health, inducing neuroplasticity and vascular plasticity in the hippocampus, which is possibly mediated by brain-derived neurotrophic factor (BDNF) levels. Here we investigated the short-term effects of exercise, to determine if a 1-week intervention is sufficient to induce brain changes. Fifteen healthy young males completed five supervised exercise training sessions over seven days. This was preceded and followed by a multi-modal magnetic resonance imaging (MRI) ...

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The KRAB Domain-Containing Protein ZFP961 Represses Adipose Thermogenesis and Energy Expenditure through Interaction with PPARα

Adipose thermogenesis plays a pivotal role in whole-body metabolic homeostasis. Although transcriptional mechanisms that promote thermogenesis are extensively studied, the negative regulatory network is still poorly understood. Here, a Krüppel-associated box (KRAB) domain-containing zinc finger protein, ZFP961, as a potent repressor of the thermogenic program is identified. ZFP961 expression is induced by cold and β3-adrenergic agonist in adipose tissue. ZFP961 represses brown fat-selective ...

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Endurance exercise training-responsive miR-19b-3p improves skeletal muscle glucose metabolism

Skeletal muscle is a highly adaptable tissue and remodels in response to exercise training. Using short RNA sequencing, we determine the miRNA profile of skeletal muscle from healthy male volunteers before and after a 14-day aerobic exercise training regime. Among the exercise training-responsive miRNAs identified, miR-19b-3p was selected for further validation. Overexpression of miR-19b-3p in human skeletal muscle cells increases insulin signaling, glucose uptake, and maximal oxygen consumption, ...

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AMPK activator O304 improves metabolic and cardiac function, and exercise capacity in aged mice

Age is associated with progressively impaired, metabolic, cardiac and vascular function, as well as reduced work/exercise capacity, mobility, and hence quality of life. Exercise exhibit positive effects on age-related dysfunctions and diseases. However, for a variety of reasons many aged individuals are unable to engage in regular physical activity, making the development of pharmacological treatments that mimics the beneficial effects of exercise highly desirable. Here we show that the pan-AMPK ...

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Right heart exercise-training-adaptation and remodelling in endurance athletes

Long-term sports training leads to myocardial adaptations, with remodelling of the heart chambers. However, while myocardial adaptations of the left heart are well described, remodelling of the right heart and its impact on the development of arrhythmias is still debated. To conduct a systematic review on right ventricle (RV) and right atrium (RA) structural and functional changes in athletes who participate in long-term endurance training. Systematic review. A systematic literature search was conducted. ...

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Moderate-intensity exercise alleviates pyroptosis by promoting autophagy in osteoarthritis via the P2X7/AMPK/mTOR axis

Instability and excessive use of the knee joint can cause osteoarthritis (OA). Reasonable exercise can enhance the stability of the knee joint and prevent and relieve the occurrence and development of OA. As a key switch for inflammation, P2X purinoceptor 7 (P2X7) has attracted much attention in studies of OA. Exercise can regulate P2X7 expression and activation. However, the role of P2X7 in exercise-based prevention and treatment of OA is unknown. We previously showed that moderate-intensity exercise ...

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Exercise effects on muscle quality in older adults: a systematic review and meta-analysis

To systematically review and analyse the effects of exercise on morphological and neuromuscular muscle quality (MQ) outcomes in older adults and assess a range of possible moderators that may affect the impact of exercise on MQ outcomes. Using PRISMA guidelines, randomised controlled trials were searched in CINAHL, EMBASE, LILACS, PubMed, SciELO, Web of Science, MedNar, OpenGrey and OpenThesis databases. Eligible trials examined the effects of exercise interventions on morphological and neuromuscular ...

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Timing of objectively-collected physical activity in relation to body weight and metabolic health in sedentary older people: a cross-sectional and prospective analysis

Background: Little is known about the impact of timing as opposed to frequency and intensity of daily physical activity on metabolic health. Therefore, we assessed the association between accelerometery-based daily timing of physical activity and measures of metabolic health in sedentary older people. Methods: Hourly mean physical activity derived from wrist-worn accelerometers over a 6-day period was collected at baseline and after 3 months in sedentary participants from the Active and Healthy ...

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The combination of acute exercise and eye closure has a synergistic effect on alpha activity

Acute aerobic exercise increases the brain cortical activity in alpha frequency. Eye closure also increases alpha activity. However, whether the two have an additive or a synergistic effect on alpha activity has never been explored. This study observed electroencephalography (EEG) from fifteen participants seated on the cycle ergometer before, during, and after a cycling exercise with the eyes open and with them closed. Exercise intensity was set to a target heart rate (120–130 bpm), corresponding ...

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Home-Based HIIT and Traditional MICT Prescriptions Improve Cardiorespiratory Fitness to a Similar Extent Within an Exercise Referral Scheme for At-Risk Individuals

Exercise referral schemes (ERS) are used to promote physical activity within primary care. Traditionally, ERS are conducted in a gym or leisure-center setting, with exercise prescriptions based on moderate-intensity continuous training (MICT). Home-based high-intensity interval training (Home-HIIT) has the potential to reduce perceived barriers to exercise, including lack of time and access to facilities, compared to traditional MICT prescription used with ERS and improve health related outcomes. ...

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Impacts of essential amino acids on energy balance

Background: Obesity develops due to an imbalance in energy homeostasis, wherein energy intake exceeds energy expenditure. Increasing evidence shows that manipulations of dietary protein and their component amino acids affect the energy balance, resulting in changes in fat mass and body weight. Amino acids are not only the building blocks of proteins but also serve as signals regulating multiple biological pathways. Scope of review: We present the current available knowledge regarding the effects ...

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Effects of Exercise Training on Neurotrophic Factors and Subsequent Neuroprotection in Persons with Multiple Sclerosis - A Systematic Review and Meta-Analysis

Background: Evidence indicates that exercise holds the potential to counteract neurodegeneration experienced by persons with multiple sclerosis (pwMS), which is in part believed to be mediated through increases in neurotrophic factors. There is a need to summarize the existing evidence on exercise-induced effects on neurotrophic factors alongside neuroprotection in pwMS. Aim: To (1) systematically review the evidence on acute (one session) and/or chronic (several sessions) exercise-induced changes ...

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Physical Exercise Potentially Targets Epicardial Adipose Tissue to Reduce Cardiovascular Disease Risk in Patients with Metabolic Diseases: Oxidative Stress and Inflammation Emerge as Major Therapeutic Targets

Excess epicardial adiposity, within a state of obesity and metabolic syndrome, is emerging as an important risk factor for the development of cardiovascular diseases (CVDs). Accordingly, increased epicardial fat thickness (EFT) implicates the exacerbation of pathological mechanisms involving oxidative stress and inflammation within the heart, which may accelerate the development of CVDs. This explains increased interest in targeting EFT reduction to attenuate the detrimental effects of oxidative ...

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Effects of Vitamin D in Post-Exercise Muscle Recovery. A Systematic Review and Meta-Analysis

Vitamin D is a key micronutrient modulating function and health in skeletal muscle. Therefore, we sought to systematically review the role of vitamin D in muscle recovery. A search in different databases (PubMed/MEDLINE, WOS, Google Scholar, and Scopus) was carried out following PRISMA® and PICOS. The search period was from inception to April 2020. Changes in post-exercise muscle damage were quantified comparing experimental group vs. placebo in each study by using number of participants, standardized ...

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Irisin Is Correlated with Blood Pressure in Obstructive Sleep Apnea Patients

Background. Despite approximately 95% primary cases of hypertension, secondary hypertension seems to be common with resistant forms. Notably, obstructive sleep apnea (OSA) is known as a common cause of secondary hypertension and has a major characteristic of obesity. Irisin acts as a link between muscles and adipose tissues in obesity, playing an essential role in human blood pressure (BP) regulation. However, whether irisin is associated with secondary hypertension caused by OSA and how it takes ...

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Integrated genomic and proteomic analyses identify stimulus-dependent molecular changes associated with distinct modes of skeletal muscle atrophy

Skeletal muscle atrophy is a debilitating condition that occurs with aging and disease, but the underlying mechanisms are incompletely understood. Previous work determined that common transcriptional changes occur in muscle during atrophy induced by different stimuli. However, whether this holds true at the proteome level remains largely unexplored. Here, we find that, contrary to this earlier model, distinct atrophic stimuli (corticosteroids, cancer cachexia, and aging) induce largely different ...

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Pattern of Adiponectin, Osteocalcin, Irisin, FGF-21, and MCP-1 According to the Body Size Phenotype: Could They Be Markers of Metabolic Health in Mexican-Mestizo Middle-Aged Women?

Variations in levels of some adipokines, myokines, osteokines, hepatokines and inflammatory cytokines contribute to abnormal glucose and lipid metabolism. The aim of this study was to determine the pattern of adiponectin, osteocalcin (OCN), irisin, FGF-21, and MCP-1 according to the body size phenotype of middle-aged women, and their associations with BMI, visceral adipose tissue (VAT), and HOMA-IR. A cross-sectional study in 265 women aged from 40 to 65 years was performed. The biochemical characteristics ...

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The New Myokine Myonectin is Significantly Associated with Type 2 Diabetes in Elderly Patients

Introduction: The novel myokine myonectin is predominantly expressed in skeletal muscle and is involved in the regulation of metabolic homeostasis. A putative association between myonectin and type 2 diabetes mellitus (T2DM) has been discussed controversially in current literature. Hypothesis: We hypothesize that there is an association between myonectin and T2DM at different ages - this is addressed in the present study. Methods: We measured myonectin in 410 vascular risk patients with a mean ...

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Impact of Exercise on Gut Microbiota in Obesity

Physical activity, exercise, or physical fitness are being studied as helpful nonpharmacological therapies to reduce signaling pathways related to inflammation. Studies describing changes in intestinal microbiota have stated that physical activity could increase the microbial variance and enhance the ratio of Firmicutes/Bacteroidetes, and both actions could neutralize the obesity progression and diminish body weight. The aim of this review is to provide an overview of the literature describing the ...

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The Impact of Dysmetabolic Sarcopenia Among Insulin Sensitive Tissues: A Narrative Review

Sarcopenia is a common muscular affection among elderly individuals. More recently, it has been recognized as the skeletal muscle (SM) expression of the metabolic syndrome. The prevalence of sarcopenia is increasing along with visceral obesity, to which it is tightly associated. Nonetheless, it is a still underreported entity by clinicians, despite the worsening in disease burden and reduced patient quality of life. Recognition of sarcopenia is clinically challenging, and variability in study populations ...

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Effects of Low Doses of L-Carnitine Tartrate and Lipid Multi-Particulate Formulated Creatine Monohydrate on Muscle Protein Synthesis in Myoblasts and Bioavailability in Humans and Rodents

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM ...

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LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance

Dysregulation in adipokine biosynthesis and function contributes to obesity-induced metabolic diseases. However, the identities and functions of many of the obesity-induced secretory molecules remain unknown. Here, we report the identification of leucine-rich alpha-2-glycoprotein 1 (LRG1) as an obesity-associated adipokine that exacerbates high fat diet-induced hepatosteatosis and insulin resistance. Serum levels of LRG1 were markedly elevated in obese humans and mice compared to their respective ...

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Long-Term Evolution of Malnutrition and Loss of Muscle Strength after COVID-19: A Major and Neglected Component of Long COVID-19

Post-acute consequences of COVID-19, also termed long COVID, include signs and symptoms persisting for more than 12 weeks with prolonged multisystem involvement; most often, however, malnutrition is ignored. Method: The objective was to analyze persistent symptoms, nutritional status, the evolution of muscle strength and performance status (PS) at 6 months post-discharge in a cohort of COVID-19 survivors. Results: Of 549 consecutive patients hospitalized for COVID-19 between 1 March and 29 April ...

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Leptin receptor defect with diabetes causes skeletal muscle atrophy in female obese Zucker rats where peculiar depots networked with mitochondrial damages

Tibialis anterior muscles of 45-week-old female obese Zucker rats with defective leptin receptor and non-insulin dependent diabetes mellitus (NIDDM) showed a significative atrophy compared to lean muscles, based on histochemical-stained section’s measurements in the sequence: oxidative slow twitch (SO, type I) < oxidative fast twitch (FOG, type IIa) < fast glycolytic (FG, type IIb). Both oxidative fiber’s outskirts resembled ‘ragged’ fibers and, in these zones, ultrastructure ...

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The Response of Mitochondrial Respiration and Quantity in Skeletal Muscle and Adipose Tissue to Exercise in Humans with Prediabetes

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes, but its contribution to the early stages of dysglycemia remains poorly understood. By collecting a high-resolution stage-based spectrum of dysglycemia, our study fills this gap by evaluating derangement in both the function and quantity of mitochondria. We sampled mitochondria in skeletal muscle and subcutaneous adipose tissues of subjects with progressive advancement of dysglycemia under a three-month ...

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Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle

Skeletal muscles display sexually dimorphic features. Biochemically, glycolysis and fatty acid β-oxidation occur preferentially in the muscles of males and females, respectively. However, the mechanisms of the selective utilization of these fuels remains elusive. Here, we obtain transcriptomes from quadriceps type IIB fibers of untreated, gonadectomized, and sex steroid-treated mice of both sexes. Analyses of the transcriptomes unveil two genes, Pfkfb3 (phosphofructokinase-2) and Pdk4 (pyruvate ...

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Muscle Contractile Properties Measured at Submaximal Electrical Amplitudes and Not at Supramaximal Amplitudes Are Associated with Repeated Sprint Performance and Fatigue Markers

Background: The present study analyzes the associations between the muscle contractile properties (MCP) measured at different neuromuscular electrical stimulation amplitudes (NMESa) and the performance or transient fatigue after a bout of repeated sprints. Methods: Seventeen physically active male subjects performed six repeated sprints of 30 m with 30 s of passive recovery. Capillary blood creatine kinase (CK) concentration, knee extension or flexion isometric peak torque, tensiomyography, and repeated ...

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Effects of In Vitro Muscle Contraction on Thermogenic Protein Levels in Co‐Cultured Adipocytes

The crosstalk between the exercising muscle and the adipose tissue, mediated by myokines and metabolites, derived from both tissues during exercise has created a controversy between animal and human studies with respect to the impact of exercise on the browning process. The aim of this study was to investigate whether co-culturing of C2C12 myotubes and 3T3-L1 adipocytes under the stimuli of electrical pulse stimulation (EPS) mimicking muscle contraction can impact the expression of UCP1, PGC-1a, ...

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The Role of GDF15 as a Myomitokine

Growth differentiation factor 15 (GDF15) is a cytokine best known for affecting systemic energy metabolism through its anorectic action. GDF15 expression and secretion from various organs and tissues is induced in different physiological and pathophysiological states, often linked to mitochondrial stress, leading to highly variable circulating GDF15 levels. In skeletal muscle and the heart, the basal expression of GDF15 is very low compared to other organs, but GDF15 expression and secretion can ...

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Effects of Facial Isometric Exercise on Antioxidant Capacity

Background: Facial isometric exercise is a static contraction of facial muscles without any visible movement in the angle of the joints. To examine the effects of facial isometric exercise on subjective stress and oxidative stress/antioxidant capacity. Methods: In this study, we included 13 participants (6 males, 7 females; average age, 44.8 ± 19.6 years; age range: 20 - 74 years) who were exposed to constant temperature and humidity in a room. Fifteen minutes after entering the room, the ...

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Positive effect of combined exercise on adipokines levels and pubertal signs in overweight and obese girls with central precocious puberty

Background: The prevalence of precocious puberty is increasing. Obesity has been demonstrated to be associated with changes in the adipokine profile and incidence of early puberty in girls. This study assessed the pubertal signs, the levels of adiponectin, resistin, and tumor necrosis factor-alpha (TNF-α) after 12 weeks of combined exercise and 4 weeks of detraining in overweight and obese girls with precocious puberty. Methods: Thirty overweight and obese girls (aged 7–9) ...

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The acute effect of fasted exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release compared to fed exercise in healthy individuals: a systematic review and network meta-analysis

ObjectiveTo determine the acute effect of fasted and fed exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release. Methods: CENTRAL, Embase, MEDLINE, PsycInfo, PubMed, Scopus and Web of Science databases were searched to identify randomised, crossover studies in healthy individuals that compared the following interventions: (i) fasted exercise with a standardised post-exercise meal [FastEx + Meal], (ii) fasted exercise without a standardised ...

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Human Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues

Obesity-associated metabolic abnormalities comprise a cluster of conditions including dyslipidemia, insulin resistance, diabetes and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from the accumulation of white adipose tissues mainly due to the chronic imbalance of energy intake and energy expenditure. A variety of approaches to treat or prevent obesity, including lifestyle interventions, surgical weight loss procedures and pharmacological ...

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Could Irisin Levels be Affected by Physical Activity in Patients with Schizophrenia?

Objective: The aim of this study was to explore the effect of physical activity and metabolic parameters on irisin levels in patients with schizophrenia and healthy controls. Methods: Ninety-six patients with schizophrenia and 63 healthy controls comprised the study population. The participants were separated into three groups: inactive, low activity, and sufficiently active according to International Physical Activity Questionnaire short form (IPAQ-SF). We measured irisin levels using Enzyme linked ...

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Metabolic and inflammatory health in SARS-CoV-2 and the potential role for habitual exercise in reducing disease severity

Introduction: The rapid emergence and spread of SARS-CoV-2 in late 2019 has infected millions of people worldwide with significant morbidity and mortality with various responses from health authorities to limit the spread of the virus. Although population-wide inoculation is preferred, currently, there is large variation and disparity in the acquisition, development, and deployment of vaccination programs in many countries. Even with availability of a vaccine, achieving herd immunity does not guarantee ...

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Exercise Intervention for Academic Achievement Among Children: A Randomized Controlled Trial

OBJECTIVES: Physical inactivity is an important health concern worldwide. In this study, we examined the effects of an exercise intervention on children’s academic achievement, cognitive function, physical fitness, and other health-related outcomes. METHODS: We conducted a population-based cluster randomized controlled trial among 2301 fourth-grade students from 10 of 11 public primary schools in 1 district of Ulaanbaatar between February and December 2018. Schools were allocated to an intervention ...

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Translation and validation of the Persian version of Godin Leisure-Time Exercise Questionnaire in patients with multiple sclerosis

Objective: The purpose of this study is to translate, culturally adapt and evaluate the validity and reliability of the Persian (Farsi) version of GLTEQ in patients with multiple sclerosis. Methods: This study had three phases, including translation of the questionnaire into Persian and making cultural adaptation, evaluation of pre-final version of questionnaire’s comprehensibility in a pilot study, and investigation of reliability and validity of the final version of the translated questionnaire. ...

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Exercise improves vascular health: Role of mitochondria

Vascular mitochondria constantly integrate signals from environment and respond accordingly to match vascular function to metabolic requirements of the organ tissues, while mitochondrial dysfunction contributes to vascular aging and pathologies such as atherosclerosis, stenosis, and hypertension. As an effective lifestyle intervention, exercise induces extensive mitochondrial adaptations through vascular mechanical stress and the increased production and release of reactive oxygen species and nitric ...

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Prehabilitative Resistance Exercise Reduces Neuroinflammation and Improves Mitochondrial Health in Aged Mice with Perioperative Neurocognitive Disorders

Background: Perioperative neurocognitive dysfunction remains a significant problem in vulnerable groups such as the elderly. While experimental data regarding its possible pathogenic mechanisms accumulates, therapeutic options for this disorder are limited. In this study, we evaluated the neuroprotective effect of a period of preconditioning resistant training on aged mice following abdominal surgery. Further, we examined the underlying mechanism from the perspective of neuroinflammatory state and ...

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Exercise Ameliorates Diabetic Kidney Disease in Type 2 Diabetic Fatty Rats

Lifestyle improvement, including through exercise, has been recognized as an important mode of therapy for the suppression of diabetic kidney disease (DKD). However, the detailed molecular mechanisms by which exercise exerts beneficial effects in the suppression of DKD have not yet been fully elucidated. In this study, we investigate the effects of treadmill exercise training (TET) for 8 weeks (13 m/min, 30 min/day, 5 days/week) on kidney injuries of type 2 diabetic male rats with obesity (Wistar ...

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Effects of exercise on AKT/PGC1-α/FOXO3a pathway and muscle atrophy in cisplatin-administered rat skeletal muscle

Cisplatin has been reported to cause side effects such as muscle wasting in humans and rodents. The physiological mechanisms involved in preventing muscle wasting, such as the regulation of AKT, PGC1-α, and autophagy-related factor FOXO3a by MuRF 1 and Atrogin-1, remain unclear following different types of exercise and in various skeletal muscle types. Eight-week-old male Wistar rats (n = 34) were assigned to one of four groups: control (CON, n = 6), cisplatin injection (1 mg/kg) without exercise ...

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Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype

Skeletal muscle regeneration is a complex process involving crosstalk between immune cells and myogenic precursor cells, i.e., satellite cells. In this scenario, macrophage recruitment in damaged muscles is a mandatory step for tissue repair since pro-inflammatory M1 macrophages promote the activation of satellite cells, stimulating their proliferation and then, after switching into anti-inflammatory M2 macrophages, they prompt satellite cells’ differentiation into myotubes and resolve inflammation. ...

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Exercise training and probiotic supplementation effects on skeletal muscle apoptosis prevention in type-Ι diabetic rats

Aims: Hyperglycemia occurring in the diabetic condition can cause apoptosis via the mitochondrial pathway with higher pro-apoptotic protein expression. Probiotics are viable microorganisms that have anti-diabetic and antioxidant effects. Also, exercise may affect the signaling pathways of skeletal muscle apoptosis. This study examined the aerobic exercise training and probiotic supplementation effects on some apoptotic indices of the soleus muscle in diabetic rats-induced by streptozotocin. Main ...

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The Effects of Exercise on White and Brown Adipose Tissue Cellularity, Metabolic Activity and Remodeling

Emerging evidence suggests a significant functional role of adipose tissue in maintaining whole-body metabolic health. It is well established that obesity leads to compositional and morphological changes in adipose tissue that can contribute to the development of cardiometabolic disorders. Thus, the function and size of adipocytes as well as perfusion and inflammation can significantly impact health outcomes independent of body mass index. Lifestyle interventions such as exercise can improve metabolic ...

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Exercise Training: The Holistic Approach in Cardiovascular Prevention

Nowadays, there are robust clinical and pathophysiological evidence supporting the beneficial effects of physical activity on cardiovascular (CV) system. Thus, the physical activity is considered a key strategy for CV prevention. In fact, exercise training exerts favourable effects on all risk factors for CV diseases (i.e. essential hypertension, type 2 diabetes mellitus, hypercholesterolemia, obesity, metabolic syndrome, etc…). In addition, all training modalities such as the aerobic (continuous ...

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Profiling of ob/ob mice skeletal muscle exosome-like vesicles demonstrates combined action of miRNAs, proteins and lipids to modulate lipid homeostasis in recipient cells

We have determined the lipid, protein and miRNA composition of skeletal muscle (SkM)-released extracellular vesicles (ELVs) from Ob/ob (OB) vs wild-type (WT) mice. The results showed that atrophic insulin-resistant OB-SkM released less ELVs than WT-SkM, highlighted by a RAB35 decrease and an increase in intramuscular cholesterol content. Proteomic analyses of OB-ELVs revealed a group of 37 proteins functionally connected, involved in lipid oxidation and with catalytic activities. OB-ELVs had modified ...

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Mitochondrial-nuclear cross-talk in the human brain is modulated by cell type and perturbed in neurodegenerative disease

Mitochondrial dysfunction contributes to the pathogenesis of many neurodegenerative diseases. The mitochondrial genome encodes core respiratory chain proteins, but the vast majority of mitochondrial proteins are nuclear-encoded, making interactions between the two genomes vital for cell function. Here, we examine these relationships by comparing mitochondrial and nuclear gene expression across different regions of the human brain in healthy and disease cohorts. We find strong regional patterns that ...

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Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

Neural tissue is one of the main oxygen consumers in the mammalian body, and a plentitude of metabolic as well as signaling processes within the brain is accompanied by the generation of reactive oxygen (ROS) and nitrogen (RNS) species. Besides the important signaling roles, both ROS and RNS can damage/modify the self-derived cellular components thus promoting neuroinflammation and oxidative stress. While previously, the latter processes were thought to progress linearly with age, newer data point ...

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Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition

Cancer incidence increases with age and is a leading cause of death. Caloric restriction (CR) confers benefits on health and survival and delays cancer. However, due to CR’s stringency, dietary alternatives offering the same cancer protection have become increasingly attractive. Short cycles of a plant-based diet designed to mimic fasting (FMD) are protective against tumorigenesis without the chronic restriction of calories. Yet, it is unclear whether the fasting time, level of dietary restriction, ...

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Comparative Characteristics of Sensorimotor Reactions of Highly Qualified Athletes with Different Types of Heart Rate Regulation

The purpose of the study was a comparative analysis of sensorimotor reactions in highly trained athletes with different types of heart rate regulation. Materials and methods. 202 highly trained male athletes aged 22.6±2.8 years, who are engaged in acyclic sports – martial arts (karate, taekwondo, kickboxing, boxing, freestyle wrestling, Greco-Roman wrestling, judo, sambo) and games (water polo, soccer) were examined. The experience in sports was 10.3±3.1 years. All studies were ...

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Interpreting "anti-inflammatory" cytokine responses to exercise: Focus on interleukin-10

Circulating concentrations of canonically pro- and anti-inflammatory cytokines are commonly measured when evaluating the anti-inflammatory effects of exercise. An important caveat to interpreting systemic cytokine concentrations as evidence for the anti-inflammatory effects of exercise is the observed dissociation between circulating cytokine concentrations and cytokine function at the tissue/cellular level. The dichotomization of cytokines as pro- or anti-inflammatory also overlooks the context-dependence ...

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Enhanced pro-BDNF-p75NTR pathway activity in denervated skeletal muscle

Aims: Brain derived neurotrophic factor (BDNF) and the related receptors TrkB and p75NTR are expressed in skeletal muscle, yet their functions remain to be fully understood. Skeletal muscle denervation, which occurs in spinal injury, peripheral neuropathies, and aging, negatively affects muscle mass and function. In this study, we wanted to understand the role of BDNF, TrkB, and p75NTR in denervation-induced adverse effects on skeletal muscle. Main methods: Mice with unilateral sciatic denervation ...

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Skeletal muscle energy metabolism in obesity

Comparing energy metabolism in human skeletal muscle and primary skeletal muscle cells in obesity, while focusing on glucose and fatty acid metabolism, shows many common changes. Insulin-mediated glucose uptake in skeletal muscle and primary myotubes is decreased by obesity, whereas differences in basal glucose metabolism are inconsistent among studies. With respect to fatty acid metabolism, there is an increased uptake and storage of fatty acids and a reduced complete lipolysis, suggesting alterations ...

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Myokine Expression and Tumor-suppressive Effect of Serum following 12 Weeks of Exercise in Prostate Cancer Patients on ADT

Purpose: Although several mechanisms have been proposed for the tumor-suppressive effect of exercise, little attention has been given to myokines even though skeletal muscle is heavily recruited during exercise resulting in myokine surges. We measured resting serum myokine levels before and after an exercise-based intervention and the effect of this serum on prostate cancer cell growth. Methods: Ten prostate cancer patients undertaking androgen deprivation therapy (ADT) (age 73.3 ± 5.6 yrs) ...

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Effects of the exercise-inducible myokine irisin on proliferation and malignant properties of ovarian cancer cells through the HIF-1 α signaling pathway

Background Exercise has been shown to be associated with reduced risk and improving outcomes of several types of cancers. Irisin −a novel exercise-related myokine- has been proposed to exert beneficial effects in metabolic disorders including cancer. No previous studies have investigated whether irisin may regulate malignant characteristics of ovarian cell lines. Methods In the present study, we aimed to explore the effect of irisin on viability and proliferation of ovarian cancer cells which ...

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Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health

Objectives: Regular physical exercise improves health by reducing the risk of a plethora of chronic disorders. We hypothesized that endurance exercise training remodels the activity of gene enhancers in skeletal muscle and that this remodeling contributes to the beneficial effects of exercise on human health. Methods and results: By studying changes in histone modifications, we mapped the genome-wide positions and activities of enhancers in skeletal muscle biopsies collected from young sedentary ...

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Effects of Algorithmic Music on the Cardiovascular Neural Control

Music influences many physiological parameters, including some cardiovascular (CV) control indices. The complexity and heterogeneity of musical stimuli, the integrated response within the brain and the limited availability of quantitative methods for non-invasive assessment of the autonomic function are the main reasons for the scarcity of studies about the impact of music on CV control. This study aims to investigate the effects of listening to algorithmic music on the CV regulation of healthy subjects ...

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Vitamin D and Muscle Health: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials

The objective of this study was to investigate the effects of vitamin D supplementation versus placebo on muscle health. For this systematic review and trial-level meta-analysis of placebo-controlled trials, a systematic search of randomized controlled trials published until October 2020 was performed in Medline, Embase, and Google Scholar. We included studies in humans (except athletes) on supplementation with vitamin D2 or D3 versus placebo, regardless of administration form (daily, bolus, and ...

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Ulk1, Not Ulk2, Is Required for Exercise Training-Induced Improvement of Insulin Response in Skeletal Muscle

Unc51 like autophagy activating kinase 1 (Ulk1), the primary autophagy regulator, has been linked to metabolic adaptation in skeletal muscle to exercise training. Here we compared the roles of Ulk1 and homologous Ulk2 in skeletal muscle insulin action following exercise training to gain more mechanistic insights. Inducible, skeletal muscle-specific Ulk1 knock-out (Ulk1-iMKO) mice and global Ulk2 knock-out (Ulk2-/-) mice were subjected to voluntary wheel running for 6 weeks followed by assessment ...

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SESN2 protects against denervated muscle atrophy through unfolded protein response and mitophagy

Denervation of skeletal muscles results in a rapid and programmed loss of muscle size and performance, termed muscle atrophy, which leads to a poor prognosis of clinical nerve repair. Previous researches considered this process a result of multiple factors, such as protein homeostasis disorder, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis, while their intrinsic association remains to be explored. In this study, Sestrin2 (SESN2), a stress-inducible protein, was shown ...

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Stimulation of Non-canonical NF-κB Through Lymphotoxin-β-Receptor Impairs Myogenic Differentiation and Regeneration of Skeletal Muscle

Myogenic differentiation, muscle stem cell functionality, and regeneration of skeletal muscle are cellular processes under tight control of various signaling pathways. Here, we investigated the role of non-canonical NF-κB signaling in myogenic differentiation, muscle stem cell functionality, and regeneration of skeletal muscle. We stimulated non-canonical NF-κB signaling with an agonistically acting antibody of the lymphotoxin beta receptor (LTβR). Interestingly, we found that stimulation ...

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Muscle-derived exophers promote reproductive fitness

Organismal functionality and reproduction depend on metabolic rewiring and balanced energy resources. However, the crosstalk between organismal homeostasis and fecundity and the associated paracrine signaling mechanisms are still poorly understood. Using Caenorhabditis elegans, we discovered that large extracellular vesicles (known as exophers) previously found to remove damaged subcellular elements in neurons and cardiomyocytes are released by body wall muscles (BWM) to support embryonic growth. ...

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‘Fat but powerful’ paradox: association of muscle power and adiposity markers with all-cause mortality in older adults from the EXERNET multicentre study

Objectives: To assess the influence of muscle power and adiposity on all-cause mortality risk and to evaluate the ‘fat but powerful’ (F+P) (or ‘fat but fit’) paradox in older adults. Methods: A total of 2563 older adults (65‒91 years old) from the EXERNET multicentre study were included. Adiposity (body mass index (BMI), waist circumference, body fat percentage (BF%) and fat index), allometric and relative power (sit-to-stand muscle power test) and various covariates (age, ...

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Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice

Objective: To investigate the abundance and the prevalence of Dysosmobacter welbionis J115T, a novel butyrate-producing bacterium isolated from the human gut both in the general population and in subjects with metabolic syndrome. To study the impact of this bacterium on host metabolism using diet-induced obese and diabetic mice. Design We analysed the presence and abundance of the bacterium in 11 984 subjects using four human cohorts (ie, Human Microbiome Project, American Gut Project, Flemish ...

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Energetic cost of walking and Brain Atrophy in Mid-to-Late Life

Background: Higher energetic costs for mobility are associated with declining gait speed and slow gait is linked to cognitive decline and Alzheimer’s disease. However, the physiological underpinnings of gait and brain health have not been well explored. We examined the associations of the energetic cost of walking with brain volume in cognitively unimpaired adults from the Baltimore Longitudinal Study of Aging. Methods: We used brain MRI data from 850 participants (mean baseline age 66.3±14.5 ...

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A single bout of exercise improves vascular insulin sensitivity in adults with obesity

Objective: This crossover study explored the impact of a single bout of exercise on insulin-stimulated responses in conduit arteries and capillaries. Methods: Twelve sedentary adults (49.5 [7.8] years; maximal oxygen consumption [VO2max]: 23.7 [5.4] mL/kg/min) with obesity (BMI 34.5 [4.3] kg/m2) completed a control and exercise bout (70% VO2max to expend 400 kcal). Sixteen hours later, participants underwent a 2-hour euglycemic-hyperinsulinemic clamp (90 mg/dL; 40 mU/m2/min) to determine vascular ...

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Arcuate Nucleus-Dependent Regulation of Metabolism—Pathways to Obesity and Diabetes Mellitus

The central nervous system (CNS) receives information from afferent neurons, circulating hormones, and absorbed nutrients and integrates this information to orchestrate the actions of the neuroendocrine and autonomic nervous systems in maintaining systemic metabolic homeostasis. Particularly the arcuate nucleus of the hypothalamus (ARC) is of pivotal importance for primary sensing of adiposity signals, such as leptin and insulin, and circulating nutrients, such as glucose. Importantly, energy state–sensing ...

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Upregulation of Thioesterase Superfamily Member 2 in Skeletal Muscle Promotes Hepatic Steatosis and Insulin Resistance

Background: Thioesterase superfamily member 2 (Them2) is highly expressed in liver and oxidative tissues, where it hydrolyzes long chain fatty acyl-CoA esters to free fatty acids and CoA. Although mice globally lacking Them2 (Them2-/-) are protected against diet-induced obesity, hepatic steatosis and insulin resistance, liver-specific Them2-/- mice remain susceptible. The aim of this study was to test whether Them2 activity in extrahepatic oxidative tissues is a primary determinant of hepatic steatosis ...

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AgRP neurons: Regulators of feeding, energy expenditure, and behavior

Neurons in the hypothalamic arcuate nucleus (ARC) that express agouti-related peptide (AgRP) govern a critical aspect of survival: the drive to eat. Equally important to survival is the timing at which food is consumed—seeking or eating food to alleviate hunger in the face of a more pressing threat, like the risk of predation, is clearly maladaptive. To ensure optimal prioritization of behaviors within a given environment, therefore, AgRP neurons must integrate signals of internal need states ...

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Multiple Leptin Signalling Pathways in the Control of Metabolism and Fertility: A Means to Different Ends?

The adipocyte-derived ‘satiety promoting’ hormone, leptin, has been identified as a key central regulator of body weight and fertility, such that its absence leads to obesity and infertility. Plasma leptin levels reflect body adiposity, and therefore act as an ‘adipostat’, whereby low leptin levels reflect a state of low body adiposity (under-nutrition/starvation) and elevated leptin levels reflect a state of high body adiposity (over-nutrition/obesity). While genetic leptin ...

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Oxytocin and Food Intake Control: Neural, Behavioral, and Signaling Mechanisms

The neuropeptide oxytocin is produced in the paraventricular hypothalamic nucleus and the supraoptic nucleus of the hypothalamus. In addition to its extensively studied influence on social behavior and reproductive function, central oxytocin signaling potently reduces food intake in both humans and animal models and has potential therapeutic use for obesity treatment. In this review, we highlight rodent model research that illuminates various neural, behavioral, and signaling mechanisms through which ...

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Energy deficiency impairs resistance training gains in lean mass but not strength: A meta-analysis and meta-regression

Short-term energy deficits impair anabolic hormones and muscle protein synthesis. However, the effects of prolonged energy deficits on resistance training (RT) outcomes remain unexplored. Thus, we conducted a systematic review of PubMed and SportDiscus for randomized controlled trials performing RT in an energy deficit (RT+ED) for ≥3 weeks. We first divided the literature into studies with a parallel control group without an energy deficit (RT+CON; Analysis A) and studies without RT+CON (Analysis ...

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Acute Effects of High Doses of Caffeine on Bar Velocity during the Bench Press Throw in Athletes Habituated to Caffeine: A Randomized, Double-Blind and Crossover Study

Chronic intake of caffeine may produce a reduction in the potential performance benefits obtained with the acute intake of this substance. For this reason, athletes habituated to caffeine often use high doses of caffeine (≥9 mg/kg) to overcome tolerance to caffeine ergogenicity due to chronic intake. The main objective of the current investigation was to evaluate the effects of high caffeine doses on bar velocity during an explosive bench press throw in athletes habituated to caffeine. Twelve ...

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Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis

Background: Previous narrative reviews have concluded that dietary nitrate (NO3−) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO3− on various aspects of exercise performance (i.e., endurance vs. strength vs. ...

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New Recommendations for T2D Management: Beneficial Impact of Exerkines on Pancreatic β-Cells Function and Glucose Homeostasis in Skeletal Muscle

Exercise is considered as one of the main therapeutic strategies to improve glycemic regulation in diabetic patients. Current recommendation for diabetes management is a 3 to 5 times a week 150 min of moderate-to-moderate intensive physical activity.However, these could be refined thanks to recent studies. Furthermore, favorable effect generated by exerkines from the better understanding of mechanism involved in the exercise-associated, would allow the identification of future innovative molecules ...

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Crosstalk between Metabolic Disorders and Immune Cells

Metabolic syndrome results from multiple risk factors that arise from insulin resistance induced by abnormal fat deposition. Chronic inflammation owing to obesity primarily results from the recruitment of pro-inflammatory M1 macrophages into the adipose tissue stroma, as the adipocytes within become hypertrophied. During obesity-induced inflammation in adipose tissue, pro-inflammatory cytokines are produced by macrophages and recruit further pro-inflammatory immune cells into the adipose tissue to ...

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Exercise tolls the bell for key mediators of low-grade inflammation in dysmetabolic conditions

Metabolic conditions share a common low-grade inflammatory milieu, which represents a key-factor for their ignition and maintenance. Exercise is instrumental for warranting systemic cardio-metabolic balance, owing to its regulatory effect on inflammation. This review explores the effect of physical activity in the modulation of sub-inflammatory framework characterizing dysmetabolic conditions. Regular exercise suppresses plasma levels of TNFα, IL-1β, FFAs and MCP-1, in dysmetabolic subjects. ...

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Clock proteins and training modify exercise capacity in a daytime-dependent manner

Exercise and circadian biology are closely intertwined with physiology and metabolism, yet the functional interaction between circadian clocks and exercise capacity is only partially characterized. Here, we tested different clock mutant mouse models to examine the effect of the circadian clock and clock proteins, namely PERIODs and BMAL1, on exercise capacity. We found that daytime variance in endurance exercise capacity is circadian clock controlled. Unlike wild-type mice, which outperform in the ...

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Muscle-Bone Crosstalk in Chronic Obstructive Pulmonary Disease

Sarcopenia and osteoporosis are common musculoskeletal comorbidities of chronic obstructive pulmonary disease (COPD) that seriously affect the quality of life and prognosis of the patient. In addition to spatially mechanical interactions, muscle and bone can also serve as endocrine organs by producing myokines and osteokines to regulate muscle and bone functions, respectively. As positive and negative regulators of skeletal muscles, the myokines irisin and myostatin not only promote/inhibit the differentiation ...

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Fetuin-B, a potential link of liver-adipose tissue cross talk during diet-induced weight loss–weight maintenance

Background/objectives: Numerous hepatokines are involved in inter-organ cross talk regulating tissue-specific insulin sensitivity. Adipose tissue lipolysis represents a crucial element of adipose insulin sensitivity and is substantially involved in long-term body weight regulation after dietary weight loss. Thus, we aimed to analyze the impact of the hepatokine Fetuin-B in the context of weight loss induced short- and long-term modulation of adipose insulin sensitivity. Subjects/methods: 143 subjects ...

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Insulin Resistance in Skeletal Muscle Selectively Protects the Heart in Response to Metabolic Stress

Obesity and type 2 diabetes mellitus (T2DM) are the leading causes of cardiovascular morbidity and mortality. Although insulin resistance is believed to underlie these disorders, anecdotal evidence contradicts this common belief. Accordingly, obese patients with cardiovascular disease have better prognoses relative to leaner patients with the same diagnoses, whereas treatment of T2DM patients with thiazolidinedione, one of the popular insulin-sensitizer drugs, significantly increases the risk of ...

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Hepatic Steatosis Contributes to the Development of Muscle Atrophy via Inter-Organ Crosstalk

Individuals with hepatic steatosis often display several metabolic abnormalities including insulin resistance and muscle atrophy. Previously, we found that hepatic steatosis results in an altered hepatokine secretion profile, thereby inducing skeletal muscle insulin resistance via inter-organ crosstalk. In this study, we aimed to investigate whether the altered secretion profile in the state of hepatic steatosis also induces skeletal muscle atrophy via effects on muscle protein turnover. To investigate ...

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Prenatal exercise in fetal development: a placental perspective

Maternal obesity (MO) and gestational diabetes mellitus (GDM) are common in western societies, which impair fetal development and predispose offspring to metabolic dysfunction. Placenta is the organ linking the mother to her fetus, and MO suppresses the development of vascular system and expression of nutrient transporters in placenta, thereby affecting fetal development. For maintaining its proper physiological function, placenta is energy demanding, which is met through extensive oxidative phosphorylation. ...

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Muscle-secreted neurturin couples myofiber oxidative metabolism and slow motor neuron identity

Endurance exercise promotes skeletal muscle vascularization, oxidative metabolism, fiber-type switching, and neuromuscular junction integrity. Importantly, the metabolic and contractile properties of the muscle fiber must be coupled to the identity of the innervating motor neuron (MN). Here, we show that muscle-derived neurturin (NRTN) acts on muscle fibers and MNs to couple their characteristics. Using a muscle-specific NRTN transgenic mouse (HSA-NRTN) and RNA sequencing of MN somas, we observed ...

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Complexity of skeletal muscle degeneration: Multi-systems pathophysiology and organ crosstalk in dystrophinopathy

Duchenne muscular dystrophy is a highly progressive muscle wasting disorder due to primary abnormalities in one of the largest genes in the human genome, the DMD gene, which encodes various tissue-specific isoforms of the protein dystrophin. Although dystrophinopathies are classified as primary neuromuscular disorders, the body-wide abnormalities that are associated with this disorder and the occurrence of organ crosstalk suggest that a multi-systems pathophysiological view should be taken for a ...

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Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities

Skeletal muscle adaptations to resistance and endurance training include increased ribosome and mitochondrial biogenesis, respectively. Such adaptations are believed to contribute to the notable increases in hypertrophy and aerobic capacity observed with each exercise mode. Data from multiple studies suggest the existence of a competition between ribosome and mitochondrial biogenesis, in which the first adaptation is prioritized with resistance training while the latter is prioritized with endurance ...

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Mechanisms of inter-organ crosstalk mediated by tryptophan metabolism

Physical exercise and nutrition balance the “energy in-energy out” equilibrium that keeps the system at a dynamic homeostasis, energetically speaking. However, this is a simplistic vision of a dynamic system that is in a constant fine-tuning of all of its parts. Physical exercise benefits for metabolic health go beyond its “energy out” role: it modulates whole body metabolism, insulin sensitivity and induces favorable remodeling in other tissues through secreted factors. Old ...

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Mitochondria-cytokine crosstalk following skeletal muscle injury and disuse: a mini-review

Skeletal muscle mitochondria are highly adaptable, highly dynamic organelles that maintain the functional integrity of the muscle fiber by providing ATP for contraction and cellular homeostasis (e.g., Na+/K+ ATPase). Emerging as early modulators of inflammation, mitochondria sense and respond to cellular stress. Mitochondria communicate with the environment, in part, by release of physical signals called mitochondrial-derived damage-associated molecular patterns (mito-DAMPs) and deviation from ...

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Identification of Sclerostin as a Putative New Myokine Involved in the Muscle-to-Bone Crosstalk

Bone and muscle have been recognized as endocrine organs since they produce and secrete “hormone-like factors” that can mutually influence each other and other tissues, giving rise to a “bone–muscle crosstalk”. In our study, we made use of myogenic (C2C12 cells) and osteogenic (2T3 cells) cell lines to investigate the effects of muscle cell-produced factors on the maturation process of osteoblasts. We found that the myogenic medium has inhibitory effects on bone cell ...

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2,6-Dimethoxy-1,4-benzoquinone increases skeletal muscle mass and performance by regulating AKT/mTOR signaling and mitochondrial function

Background: 2,6-Dimethoxy-1,4-benzoquinone (DMBQ), a natural phytochemical present in fermented wheat germ, has been reported to exert anti-cancer, anti-inflammatory, and anti-adipogenic effects. However, the effect of DMBQ on muscle hypertrophy and myoblast differentiation has not been elucidated. Purpose: We investigated the effect of DMBQ on skeletal muscle mass and muscle function and then determined the possible mechanism of DMBQ. Methods: To examine myogenic differentiation and hypertrophy, ...

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Circulating small extracellular vesicles increase after an acute bout of moderate-intensity exercise in pregnant compared to non-pregnant women

The physiological and molecular mechanisms linking prenatal physical activity and improvements in maternal–fetal health are unknown. It is hypothesized that small extracellular vesicles (EVs, ~ 10–120 nm) are involved in tissue cross-talk during exercise. We aimed to characterize the circulating small EV profile of pregnant versus non-pregnant women after an acute bout of moderate-intensity exercise. Pregnant (N = 10) and non-pregnant control (N = 9) ...

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Endurance training alleviates MCP-1 and TERRA accumulation at old age in human skeletal muscle

Both oxidative stress and telomere transcription are up-regulated by acute endurance exercise in human skeletal muscle. Whether and how life-long exercise training influences the antioxidant system response at transcriptional level and TERRA expression is unknown, especially during aging. Response to acute endurance exercise was investigated in muscle biopsies of 3 male subjects after 45 min of cycling. MCP-1 and SOD1 mRNA levels increased up to, 15-fold and 63%, respectively, after the cycling session ...

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Functional significance of gain-of-function H19 lncRNA in skeletal muscle differentiation and anti-obesity effects

Background: Exercise training is well established as the most effective way to enhance muscle performance and muscle building. The composition of skeletal muscle fiber type affects systemic energy expenditures, and perturbations in metabolic homeostasis contribute to the onset of obesity and other metabolic dysfunctions. Long noncoding RNAs (lncRNAs) have been demonstrated to play critical roles in diverse cellular processes and diseases, including human cancers; however, the functional importance ...

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How does the skeletal muscle communicate with the brain in health and disease?

Endocrine mechanisms have been largely associated with metabolic control and tissue cross talk in mammals. Classically, myokines comprise a class of signaling proteins released in the bloodstream by the skeletal muscle, which mediate physiological and metabolic responses in several tissues, including the brain. Recent exciting evidence suggests that myokines (e.g. cathepsin B, FNDC5/irisin, interleukin-6) act to control brain functions, including learning, memory, and mood, and may mediate the beneficial ...

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Mitophagy Directs Muscle-Adipose Crosstalk to Alleviate Dietary Obesity

The quality of mitochondria in skeletal muscle is essential for maintaining metabolic homeostasis during adaptive stress responses. However, the precise control mechanism of muscle mitochondrial quality and its physiological impacts remain unclear. Here, we demonstrate that FUNDC1, a mediator of mitophagy, plays a critical role in controlling muscle mitochondrial quality as well as metabolic homeostasis. Skeletal-muscle-specific ablation of FUNDC1 in mice resulted in LC3-mediated ...

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Physical Exercise Protects Against Endothelial Dysfunction in Cardiovascular and Metabolic Diseases

Increasing evidence shows that endothelial cells play critical roles in maintaining vascular homeostasis, regulating vascular tone, inhibiting inflammatory response, suppressing lipid leakage, and preventing thrombosis. The damage or injury of endothelial cells induced by physical, chemical, and biological risk factors is a leading contributor to the development of mortal cardiovascular and cerebrovascular diseases. However, the underlying mechanism of endothelial injury remains to be elucidated. ...

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Acute Impacts of Different Types of Exercise on Circulating α-Klotho Protein Levels

Introduction: Elevated plasma α-klotho (αKl) protects against several ageing phenotypes and has been proposed as a biomarker of a good prognosis for different diseases. The beneficial health effects of elevated plasma levels of soluble αKl (SαKl) have been likened to the positive effects of exercise on ageing and chronic disease progression. It has also been established that molecular responses and adaptations differ according to exercise dose. The aim of this study is to ...

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Postnatal exercise protects offspring from high-fat diet-induced reductions in subcutaneous adipocyte beiging in C57Bl6/J Mice

Maternal low-protein and postnatal high-fat (HF) diets program offspring obesity and type 2 diabetes mellitus (T2DM) risk by epigenetically reducing beige adipocytes (BA) via increased G9a protein expression (Histone3 Lysine9 dimethyl transferase), an inhibitor of the BA marker fibroblast growth factor 21 (FGF21). Conversely, offspring exercise reduces fat mass and white adipocytes, but the mechanisms are not yet understood. This work investigated whether exercise reduces offspring obesity and T2DM ...

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Roles of Skeletal Muscle-Derived Exosomes in Organ Metabolic and Immunological Communication

Skeletal muscles secrete various factors, such as proteins/peptides, nucleotides, and metabolites, which are referred to as myokines. Many of these factors are transported into extracellular bodily fluids in a free or protein-bound form. Furthermore, several secretory factors have been shown to be wrapped up by small vesicles, particularly exosomes, secreted into circulation, and subsequently regulate recipient cells. Thus, exosome contents can be recognized as myokines. In recipient cells, proteins, ...

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Potential Improvement in Rehabilitation Quality of 2019 Novel Coronavirus by Isometric Training System; Is There “Muscle-Lung Cross-Talk”?

  The novel Coronavirus Disease 2019 (COVID-19) crisis is now present in more than 200 countries. It started in December 2019 and has, so far, led to more than 149, 470,968 cases, 3,152,121 deaths, and 127,133,013 survivors recovered by 28 April 2021. COVID-19 has a high morbidity, and mortality of 2%, on average, whereas most people are treated after a period of time. Some people who recover from COVID-19 are left with 20 to 30% decreased lung function. In this context, exercise focused on ...

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Inter-organ cross-talk in metabolic syndrome

Maintenance of systemic homeostasis and the response to nutritional and environmental challenges require the coordination of multiple organs and tissues. To respond to various metabolic demands, higher organisms have developed a system of inter-organ communication through which one tissue can affect metabolic pathways in a distant tissue. Dysregulation of these lines of communication contributes to human pathologies, including obesity, diabetes, liver disease and atherosclerosis. In recent ...

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The wonder exerkines—novel insights: a critical state-of-the-art review

Several benefits can be acquired through physical exercise. Different classes of biomolecules are responsible for the cross-talk between distant organs. The secretome of skeletal muscles, and more widely the field of organokines, is ever-expanding. “Exerkine” has emerged as the umbrella term covering any humoral factors secreted into circulation by tissues in response to exercise. This review aims at describing the most interesting exerkines discovered in the last 3 years, which are paving ...

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Muscle-tendon cross talk during muscle wasting

In organisms from flies to mammals, the initial formation of a functional tendon is completely dependent on chemical signals from muscles (myokines). However, how myokines affect the maturation, maintenance, and regeneration of tendons as a function of age is completely unstudied. Here we discuss the role of four myokines—fibroblast growth factors (FGF), myostatin, the secreted protein acidic and rich in cysteine (SPARC) miR-29—in tendon development and hypothesize a role for these factors ...

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Complexity of skeletal muscle degeneration: multi-systems pathophysiology and organ crosstalk in dystrophinopathy

Duchenne muscular dystrophy is a highly progressive muscle wasting disorder due to primary abnormalities in one of the largest genes in the human genome, the DMD gene, which encodes various tissue-specific isoforms of the protein dystrophin. Although dystrophinopathies are classified as primary neuromuscular disorders, the body-wide abnormalities that are associated with this disorder and the occurrence of organ crosstalk suggest that a multi-systems pathophysiological view should be taken for a ...

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Fusion and beyond: Satellite cell contributions to loading-induced skeletal muscle adaptation

Satellite cells support adult skeletal muscle fiber adaptations to loading in numerous ways. The fusion of satellite cells, driven by cell-autonomous and/or extrinsic factors, contributes new myonuclei to muscle fibers, associates with load-induced hypertrophy, and may support focal membrane damage repair and long-term myonuclear transcriptional output. Recent studies have also revealed that satellite cells communicate within their niche to mediate muscle remodeling in response to resistance exercise, ...

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Cilia, Centrosomes and Skeletal Muscle

Primary cilia are non-motile, cell cycle-associated organelles that can be found on most vertebrate cell types. Comprised of microtubule bundles organised into an axoneme and anchored by a mature centriole or basal body, primary cilia are dynamic signalling platforms that are intimately involved in cellular responses to their extracellular milieu. Defects in ciliogenesis or dysfunction in cilia signalling underlie a host of developmental disorders collectively referred to as ciliopathies, reinforcing ...

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Management of Oxidative Stress: Crosstalk Between Brown/Beige Adipose Tissues and Skeletal Muscles

Exercise plays an important role in the physiology, often depending on its intensity, duration, and frequency. It increases the production of reactive oxygen species (ROS). Meanwhile, it also increases antioxidant enzymes involved in the oxidative damage defense. Prolonged, acute, or strenuous exercise often leads to an increased radical production and a subsequent oxidative stress in the skeletal muscles, while chronic regular or moderate exercise results in a decrease in oxidative stress. Notably, ...

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Altitude, Exercise, and Skeletal Muscle Angio-Adaptive Responses to Hypoxia: A Complex Story

Hypoxia, defined as a reduced oxygen availability, can be observed in many tissues in response to various physiological and pathological conditions. As a hallmark of the altitude environment, ambient hypoxia results from a drop in the oxygen pressure in the atmosphere with elevation. A hypoxic stress can also occur at the cellular level when the oxygen supply through the local microcirculation cannot match the cells’ metabolic needs. This has been suggested in contracting skeletal myofibers ...

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Discovery of Thymosin Beta-4 as a Human Exerkine and Growth Factor

Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in inter-organ crosstalk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin beta-4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X ...

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Exosomes as mediators of intercellular crosstalk in metabolism

Exosomes are nanoparticles secreted by all cell types and are a large component of the broader class of nanoparticles termed extracellular vesicles (EVs). Once secreted, exosomes gain access to the interstitial space and ultimately the circulation, where they exert local paracrine or distal systemic effects. Because of this, exosomes are important components of an intercellular and intraorgan communication system capable of carrying biologic signals from one cell type or tissue to another. The exosomal ...

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Metabolic Remodeling in Skeletal Muscle Atrophy as a Therapeutic Target

Skeletal muscle is a highly responsive tissue, able to remodel its size and metabolism in response to external demand. Muscle fibers can vary from fast glycolytic to slow oxidative, and their frequency in a specific muscle is tightly regulated by fiber maturation, innervation, or external causes. Atrophic conditions, including aging, amyotrophic lateral sclerosis, and cancer-induced cachexia, differ in the causative factors and molecular signaling leading to muscle wasting; nevertheless, all of these ...

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Characterization of the Skeletal Muscle Secretome Reveals a Role for Extracellular Vesicles and IL1α/IL1β in Restricting Fibro/Adipogenic Progenitor Adipogenesis

Repeated mechanical stress causes injuries in the adult skeletal muscle that need to be repaired. Although muscle regeneration is a highly efficient process, it fails in some pathological conditions, compromising tissue functionality. This may be caused by aberrant cell–cell communication, resulting in the deposition of fibrotic and adipose infiltrates. Here, we investigate in vivo changes in the profile of skeletal muscle secretome during the regeneration process to suggest new targetable ...

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New Peptides as Potential Players in the Crosstalk Between the Brain and Obesity, Metabolic and Cardiovascular Diseases

According to the World Health Organization report published in 2016, 650 million people worldwide suffer from obesity, almost three times more than in 1975. Obesity is defined as excessive fat accumulation which may impair health with non-communicable diseases such as diabetes, cardiovascular diseases (hypertension, coronary artery disease, stroke), and some cancers. Despite medical advances, cardiovascular complications are still the leading causes of death arising from obesity. Excessive fat accumulation ...

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Associations Between Plasma Growth and Differentiation Factor-15 with Aging Phenotypes in Muscle, Adipose Tissue, and Bone

Growth and differentiation factor 15 (GDF-15) is associated with muscle, fat, and bone metabolism; however, this association has not been well characterized. Plasma GDF-15, appendicular skeletal muscle mass (ASM), fat mass (FM), and bone mineral density (BMD) were measured in 146 postmenopausal women. GDF-15 levels were higher in subjects with low Body Mass Index (BMI)-adjusted ASM than in those without (median [interquartile range] 831.3 [635.4-1011.4] vs. 583.8 [455.8-771.1] pg/mL, p = 0.018). ...

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FGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis

Aged skeletal muscle is markedly affected by fatty muscle infiltration, and strategies to reduce the occurrence of intramuscular adipocytes are urgently needed. Here, we show that fibroblast growth factor-2 (FGF-2) not only stimulates muscle growth but also promotes intramuscular adipogenesis. Using multiple screening assays upstream and downstream of microRNA (miR)-29a signaling, we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between ...

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Function and regulation of muscle stem cells in skeletal muscle development and regeneration: a narrative review

Skeletal muscle plays an essential role in generating the mechanical force necessary to support the movement of our body and daily exercise. Compared with cardiac and smooth muscle, in mammals, skeletal muscle exhibits remarkable regenerative capacity in response to damage. Muscle stem cells, also known as satellite cells, directly contribute to regeneration. Here, we review primary and secondary myogenesis processes with a focus on muscle stem cells, as well as the function and regulation of muscle ...

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Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease

Dysregulation of brain iron metabolism is one of the pathological features of aging and Alzheimer’s disease (AD), a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. While physical inactivity is one of the risk factors for AD and regular exercise improves cognitive function and reduces pathology associated with AD, the underlying mechanisms remain unclear. The purpose of the study is to explore the effect of regular physical exercise on modulation ...

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The Role of the Skeletal Muscle Secretome in Mediating Endurance and Resistance Training Adaptations

Exercise, in the form of endurance or resistance training, leads to specific molecular and cellular adaptions not only in skeletal muscles, but also in many other organs such as the brain, liver, fat or bone. In addition to direct effects of exercise on these organs, the production and release of a plethora of different signaling molecules from skeletal muscle are a centerpiece of systemic plasticity. Most studies have so far focused on the regulation and function of such myokines in acute exercise ...

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Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging

In the last decade, clear evidence has emerged that the cellular components of skeletal muscle are important sites for the release of proteins and peptides called “myokines”, suggesting that skeletal muscle plays the role of a secretory organ. After their secretion by muscles, these factors serve many biological functions, including the exertion of complex autocrine, paracrine and/or endocrine effects. In sum, myokines affect complex multi-organ processes, such as skeletal muscle trophism, ...

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Does a Vegetarian Diet Affect the Levels of Myokine and Adipokine in Prepubertal Children?

Myokines are cytokines secreted by muscle and exert autocrine, paracrine, or endocrine effects. Myokines mediate communication between muscle and other organs, including adipose tissue. The aim of the study was to assess serum myokines and their relationships with adipokines and anthropometric and nutritional parameters in children following vegetarian and omnivorous diets. One hundred and five prepubertal children were examined. Among them there were 55 children on a vegetarian diet and 50 children ...

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New Functions of Vav Family Proteins in Cardiovascular Biology, Skeletal Muscle, and the Nervous System

Vav proteins act as tyrosine phosphorylation-regulated guanosine nucleotide exchange factors for Rho GTPases and as molecular scaffolds. In mammals, this family of signaling proteins is composed of three members (Vav1, Vav2, Vav3) that work downstream of protein tyrosine kinases in a wide variety of cellular processes. Recent work with genetically modified mouse models has revealed that these proteins play key signaling roles in vascular smooth and skeletal muscle cells, specific neuronal subtypes, ...

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Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models

Skeletal muscle is essential to maintain vital functions such as movement, breathing, and thermogenesis, and it is now recognized as an endocrine organ. Muscles release factors named myokines, which can regulate several physiological processes. Moreover, skeletal muscle is particularly important in maintaining body homeostasis, since it is responsible for more than 75% of all insulin-mediated glucose disposal. Alterations of skeletal muscle differentiation and function, with subsequent dysfunctional ...

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The Sleep-Immune Crosstalk in Health and Disease

Sleep and immunity are bidirectionally linked. Immune system activation alters sleep, and sleep in turn affects the innate and adaptive arm of our body’s defense system. Stimulation of the immune system by microbial challenges triggers an inflammatory response, which, depending on its magnitude and time course, can induce an increase in sleep duration and intensity, but also a disruption of sleep. Enhancement of sleep during an infection is assumed to feedback to the immune system to promote ...

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Astrocyte Crosstalk in CNS Inflammation

Astrocytes control multiple processes in the nervous system in health and disease. It is now clear that specific astrocyte subsets or activation states are associated with specific genomic programs and functions. The advent of novel genomic technologies has enabled rapid progress in the characterization of astrocyte heterogeneity and its control by astrocyte interactions with other cells in the central nervous system (CNS). In this review, we provide an overview of the multifaceted roles of ...

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Role of Irisin in Myocardial Infarction, Heart Failure, and Cardiac Hypertrophy

Irisin is a myokine derived from the cleavage of fibronectin type III domain-containing 5. Irisin regulates mitochondrial energy, glucose metabolism, fatty acid oxidation, and fat browning. Skeletal muscle and cardiomyocytes produce irisin and affect various cardiovascular functions. In the early phase of acute myocardial infarction, an increasing irisin level can reduce endothelial damage by inhibiting inflammation and oxidative stress. By contrast, higher levels of irisin in the later phase of ...

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Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery ...

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Exercise-induced myokines and their effect on prostate cancer

Exercise is recognized by clinicians in the field of clinical oncology for its potential role in reducing the risk of certain cancers and in reducing the risk of disease recurrence and progression; yet, the underlying mechanisms behind this reduction in risk are not fully understood. Studies applying post-exercise blood serum directly to various types of cancer cell lines provide insight that exercise might have a role in inhibiting cancer growth via altered soluble and cell-free blood contents. ...

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Muscle multiorgan crosstalk with MG53 as a myokine for tissue repair and regeneration

Through stress and injury to tissues, the cell membrane is damaged and can lead to cell death and a cascade of inflammatory events. Soluble factors that mitigate and repair membrane injury are important to normal homeostasis and are a potential therapeutic intervention for regenerative medicine. A myokine is a type of naturally occurring factors that come from muscle and have impact on remote organs. MG53, a tripartite motif-containing family protein, is such a myokine which has protective effects ...

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Roles of physical exercise in neurodegeneration: reversal of epigenetic clock

The epigenetic clock is defined by the DNA methylation (DNAm) level and has been extensively applied to distinguish biological age from chronological age. Aging-related neurodegeneration is associated with epigenetic alteration, which determines the status of diseases. In recent years, extensive research has shown that physical exercise (PE) can affect the DNAm level, implying a reversal of the epigenetic clock in neurodegeneration. PE also regulates brain plasticity, neuroinflammation, and molecular ...

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Sclerostin and bone remodeling biomarkers responses to whole-body cryotherapy (− 110 °C) in healthy young men with different physical fitness levels

We investigated the effects of single and repeated exposures to whole-body cryotherapy on biomarkers of bone remodeling and osteo-immune crosstalk: sclerostin, osteocalcin (OC), C-terminal cross-linked telopeptide of type I collagen (CTx-I), osteoprotegerin (OPG) and free soluble receptor activator for nuclear factor κ B ligand (sRANKL). The study included 22 healthy males, grouped in high physical fitness level (HPhL) and low physical fitness level (LPhL), all undergone 10 consecutive sessions ...

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Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk

Background: Non-alcoholic steatohepatitis (NASH) has become one of the most common liver diseases and is still without approved pharmacotherapy. Lifestyle interventions using exercise and diet change remain the current treatment of choice and even a small weight loss (5–7%) can already have a beneficial effect on NASH. However, the underlying molecular mechanisms of exercise and diet interventions remain largely elusive, and it is unclear whether they exert their health effects via similar ...

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Crosstalk between mitochondrial dysfunction, oxidative stress, and age related neurodegenerative disease: Etiologies and therapeutic strategies

Mitochondrial function is vital for normal cellular processes. Mitochondrial damage and oxidative stress have been greatly implicated in the progression of aging, along with the pathogenesis of age-related neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Although antioxidant therapy has been proposed for the prevention and treatment of age-related NDs, unraveling ...

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Muscle, Bone, and Fat Crosstalk: the Biological Role of Myokines, Osteokines, and Adipokines

Skeletal muscle and bone are connected anatomically and physiologically, and play a crucial role in human locomotion and metabolism. Historically, the coupling between muscle and bone has been viewed in light of mechanotransduction, which dictates that the mechanical forces applied to muscle are transmitted to the skeleton to initiate bone formation. However, these organs also communicate through the endocrine system, orchestrated by a family of cytokines namely myokines (derived from myocytes) and ...

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Myokines mediate the cross talk between skeletal muscle and other organs

Myokines are muscle-derived cytokines and chemokines that act extensively on organs and exert beneficial metabolic functions in the whole-body through specific signal networks. Myokines as mediators provide the conceptual basis for a whole new paradigm useful for understanding how skeletal muscle communicates with other organs. In this review, we summarize and discuss classes of myokines and their physiological functions in mediating the regulatory roles of skeletal muscle on other organs and ...

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COVID-19 and Crosstalk With the Hallmarks of Aging

Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older ...

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Metabolic communication during exercise

The coordination of nutrient sensing, delivery, uptake and utilization is essential for maintaining cellular, tissue and whole-body homeostasis. Such synchronization can be achieved only if metabolic information is communicated between the cells and tissues of the entire organism. During intense exercise, the metabolic demand of the body can increase approximately 100-fold. Thus, exercise is a physiological state in which intertissue communication is of paramount importance. In this Review, ...

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TLR9 and beclin 1 crosstalk regulates muscle AMPK activation in exercise

The activation of adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle coordinates systemic metabolic responses to exercise1. Autophagy—a lysosomal degradation pathway that maintains cellular homeostasis2—is upregulated during exercise, and a core autophagy protein, beclin 1, is required for AMPK activation in skeletal muscle3. Here we describe a role for the innate immune-sensing molecule Toll-like receptor 9 (TLR9)4, and its interaction with beclin 1, ...

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Organ Crosstalk and the Modulation of Insulin Signaling

A highly complex network of organ communication plays a key role in regulating metabolic homeostasis, specifically due to the modulation of the insulin signaling machinery. As a paradigm, the role of adipose tissue in organ crosstalk has been extensively investigated, but tissues such as muscles and the liver are equally important players in this scenario. Perturbation of organ crosstalk is a hallmark of insulin resistance, emphasizing the importance of crosstalk molecules in the modulation of insulin ...

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Multi-Organ Involvement in COVID-19: Beyond Pulmonary Manifestations

Coronavirus Disease 19 (COVID-19), due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become an on-going global health emergency affecting over 94 million cases with more than 2 million deaths globally. Primarily identified as atypical pneumonia, it has developed into severe acute respiratory distress syndrome (ARDS), a multi-organ dysfunction with associated fatality. Ever since its emergence, COVID-19 with its plethora of clinical presentations has signalled its dynamic nature ...

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Muscle-Organ Crosstalk: Focus on Immunometabolism

Skeletal muscle secretes several hundred myokines that facilitate communication from muscle to other organs, such as, adipose tissue, pancreas, liver, gut, and brain. The biological roles of myokines include effects on e.g., memory and learning, as well as glucose and lipid metabolism. The present minireview focuses on recent developments showing that exercise-induced myokines are involved in immunometabolism of importance for the control of e.g., tumor growth and chronic inflammation. In this ...

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Skeletal Muscle-Adipose Tissue-Tumor Axis: Molecular Mechanisms Linking Exercise Training in Prostate Cancer

Increased visceral adiposity may influence the development of prostate cancer (PCa) aggressive tumors and cancer mortality. White adipose tissue (WAT), usually referred to as periprostatic adipose tissue (PPAT), surrounds the prostatic gland and has emerged as a potential mediator of the tumor microenvironment. Exercise training (ET) induces several adaptations in both skeletal muscle and WAT. Some of these effects are mediated by ET-induced synthesis and secretion of several proteins, known as myo- ...

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BDNF Impact on Biological Markers of Depression – Role of Physical Exercise and Training

Depression is the most common and devastating psychiatric disorder in the world. Its symptoms, especially during the pandemic, are observed in all age groups. Exercise training (ET) is well known as a non-pharmacological strategy to alleviate clinical depression. The brain-derived neurotrophic factor (BDNF) is one of the biological factors whose expression and secretion are intensified in response to ET. BDNF is also secreted by contracted skeletal muscle that likely exerts para-, auto- and endocrine ...

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Impact of Intrinsic Muscle Weakness on Muscle-Bone Crosstalk in Osteogenesis Imperfecta

Bone and muscle are highly synergistic tissues that communicate extensively via mechanotransduction and biochemical signaling. Osteogenesis imperfecta (OI) is a heritable connective tissue disorder of severe bone fragility and recently recognized skeletal muscle weakness. The presence of impaired bone and muscle in OI leads to a continuous cycle of altered muscle–bone crosstalk with weak muscles further compromising bone and vice versa. Currently, there is no cure for OI and understanding the ...

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Role of Physical Activity in Bone-Muscle Crosstalk: Biological Aspects and Clinical Implications

Bone and muscle tissues influence each other through the integration of mechanical and biochemical signals, giving rise to bone-muscle crosstalk. They are also known to secrete osteokines, myokines, and cytokines into the circulation, influencing the biological and pathological activities in local and distant organs and cells. In this regard, even osteoporosis and sarcopenia, which were initially thought to be two independent diseases, have recently been defined under the term "osteosarcopenia", ...

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A simple model of immune and muscle cell crosstalk during muscle regeneration

Muscle injury during aging predisposes skeletal muscles to increased damage due to reduced regenerative capacity. Some of the common causes of muscle injury are strains, while other causes are more complex muscle myopathies and other illnesses, and even excessive exercise can lead to muscle damage. We develop a new mathematical model based on ordinary differential equations of muscle regeneration. It includes the interactions between the immune system, healthy and damaged myonuclei as well as satellite ...

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Are Sarcopenia and Cognitive Dysfunction Comorbid after Stroke in the Context of Brain–Muscle Crosstalk?

Stroke is a leading cause of death and disability and is responsible for a significant economic burden. Sarcopenia and cognitive dysfunction are common consequences of stroke, but there is less awareness of the concurrency of these conditions. In addition, few reviews are available to guide clinicians and researchers on how to approach sarcopenia and cognitive dysfunction as comorbidities after stroke, including how to assess and manage them and implement interventions to improve health outcomes. ...

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Neuroplastic Effect of Exercise Through Astrocytes Activation and Cellular Crosstalk

Physical exercise is an effective therapy for neurorehabilitation. Exercise has been shown to induce remodeling and proliferation of astrocyte. Astrocytes potentially affect the recruitment and function of neurons; they could intensify responses of neurons and bring more neurons for the process of neuroplasticity. Interactions between astrocytes, microglia and neurons modulate neuroplasticity and, subsequently, neural circuit function. These cellular interactions promote the number and function of ...

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A Review of the Role of Endo/Sarcoplasmic Reticulum-Mitochondria Ca2+ Transport in Diseases and Skeletal Muscle Function

The physical contact site between a mitochondrion and endoplasmic reticulum (ER), named the mitochondria-associated membrane (MAM), has emerged as a fundamental platform for regulating the functions of the two organelles and several cellular processes. This includes Ca2+ transport from the ER to mitochondria, mitochondrial dynamics, autophagy, apoptosis signalling, ER stress signalling, redox reaction, and membrane structure maintenance. Consequently, the MAM is suggested to be involved in, and as ...

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Extracellular Vesicles and Exosomes: Insights From Exercise Science.

The benefits of exercise on health and longevity are well-established, and evidence suggests that these effects are partially driven by a spectrum of bioactive molecules released into circulation during exercise (e.g., exercise factors or ‘exerkines’). Recently, extracellular vesicles (EVs), including microvesicles (MVs) and exosomes or exosome-like vesicles (ELVs), were shown to be secreted concomitantly with exerkines. These EVs have therefore been proposed to act as cargo carriers ...

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Morphological Evidence of Telocytes in Skeletal Muscle Interstitium of Exercised and Sedentary Rodents

Skeletal muscle atrophy, resulting from states of hypokinesis or immobilization, leads to morphological, metabolic, and functional changes within the muscle tissue, a large variety of which are supported by the stromal cells populating the interstitium. Telocytes represent a recently discovered population of stromal cells, which has been increasingly identified in several human organs and appears to participate in sustaining cross-talk, promoting regenerative mechanisms and supporting differentiation ...

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The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection

Regular exercise is associated with pronounced health benefits. The molecular processes involved in physiological adaptations to exercise are best understood in skeletal muscle. Enhanced mitochondrial functions in muscle are central to exercise-induced adaptations. However, regular exercise also benefits the brain and is a major protective factor against neurodegenerative diseases, such as the most common age-related form of dementia, Alzheimer's disease, or the most common neurodegenerative motor ...

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Exploring the relationship between gut microbiota and exercise: short-chain fatty acids and their role in metabolism.

The human body is host to a multitude of bacteria, fungi, viruses and other species in the intestine, collectively known as the microbiota. Dietary carbohydrates which bypass digestion and absorption are broken down and fermented by the microbiota to produce short-chain fatty acids (SCFAs). Previous research has established the role of SCFAs in the control of human metabolic pathways. In this review, we evaluate SCFAs as a metabolic regulator and how they might improve endurance performance in athletes. ...

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Hypothalamus-skeletal muscle crosstalk during exercise and its role in metabolism modulation

Physical inactivity is a major public health problem that contributes to the development of several pathologies such as obesity, type 2 diabetes and cardiovascular diseases. Regular exercise mitigates the progression of these metabolic problems and contributes positively to memory and behavior. Therefore, public health agencies have incorporated exercise in the treatment of widespread disorders. The hypothalamus, specifically the ventromedial and the arcuate nuclei, responds to exercise activity ...

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Crosstalk between Mast Cells and Lung Fibroblasts

Mast cells play an important role in asthma, however, the interactions between mast cells, fibroblasts and epithelial cells in idiopathic pulmonary fibrosis (IPF) are less known. The objectives were to investigate the effect of mast cells on fibroblast activity and migration of epithelial cells. Lung fibroblasts from IPF patients and healthy individuals were co-cultured with LAD2 mast cells or stimulated with the proteases tryptase and chymase. Human lung fibroblasts and mast cells were cultured ...

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