Journal of Exercise & Organ Cross Talk

Abstract Dear Editor-in-Chief
The global epidemic of childhood obesity continues to challenge healthcare systems, with recent epidemiological data confirming a tenfold increase in prevalence over four decades. While the complications of pediatric obesity are well documented, the field of predictive medicine urgently requires reliable biomarkers that identify at-risk children before irreversible metabolic dysfunction develops. The Journal of Exercise & Organ Cross Talk has consistently highlighted the importance of inter-organ communication in metabolic health. Herein, we propose that the brain-muscle-adipose tissue triad represents a pivotal axis for developing predictive strategies in childhood obesity.
Recent evidence has substantially advanced our understanding of adipose tissue signaling in pediatric populations. A study of 104 children aged 7-18 years demonstrated that circulating spexin and adiponectin are significantly associated with insulin resistance in pediatric obesity. Notably, spexin exhibited a biphasic pattern characterized by an initial compensatory increase followed by a decompensated decrease, suggesting its potential as an early warning signal for metabolic deterioration. Adiponectin emerged as an independent determinant of HOMA-IR (β = −0.577, p = 0.005), reinforcing the central role of adipose-derived signals in systemic insulin sensitivity (Lian et al., 2026). These findings position adipokines as accessible biomarkers for stratifying risk in children with obesity.
Expanding beyond adipose tissue, large-scale proteomic analyses have revealed multi-organ signatures of cardiometabolic risk. In a cross-sectional study of 4,024 children and adolescents, Stinson and colleagues identified protein signatures linking obesity to dyslipidemia, insulin resistance, and hypertension. Using machine learning approaches, a three-protein panel (CDCP1, FGF21, HAOX1) combined with liver enzymes improved prediction of steatotic liver disease compared to enzymes alone (ROC-AUC = 0.83 vs. 0.77, p < 0.05). Importantly, reductions in adiposity during a one-year intervention were associated with decreased inflammatory cytokines, demonstrating the modifiable nature of these biomarkers (Stinson et al., 2026). This work underscores that circulating proteomic signatures reflect integrated signals from multiple organs, including liver, adipose tissue, and potentially skeletal muscle.
The central nervous system's role in this crosstalk cannot be overlooked. A comprehensive Mendelian randomization study investigating the fat-brain axis revealed bidirectional causal relationships between body fat measures and brain phenotypes. Body fat composition showed negative genetic correlations with intelligence and cognitive performance, while positive correlations emerged with attention-deficit/hyperactivity disorder, stroke, and depression. These genetic insights suggest that the brain is not merely a passive recipient of peripheral metabolic signals but actively participates in a bidirectional dialogue with adipose tissue. For predictive medicine, this implies that neurobehavioral assessments could complement biochemical markers in identifying children at greatest metabolic risk (Baranova et al., 2025).
The convergence of these findings carries translational implications. First, the identification of early biomarkers such as spexin and adiponectin enables risk stratification before frank insulin resistance develops. Second, proteomic signatures incorporating multiple organ-derived proteins offer enhanced predictive accuracy for specific outcomes like steatotic liver disease. Third, genetic evidence linking brain phenotypes to body fat measures suggests that predictive models should incorporate both biochemical and neurobehavioral parameters.
For JEOCT readers, these advances highlight opportunities for exercise-based interventions targeting inter-organ communication Physical activity potently modulates the secretome of skeletal muscle, adipose tissue, and potentially the brain. Understanding how exercise-induced signals influence the brain-muscle-adipose triad could inform personalized exercise prescriptions for children with obesity. Future research should prioritize longitudinal studies mapping the temporal dynamics of these biomarkers during childhood development and in response to lifestyle interventions.
In conclusion, the brain-muscle-adipose tissue triad represents a conceptual framework for predictive medicine in childhood obesity. By integrating adipose-derived signals, multi-organ proteomic signatures, and brain-body genetic links, we can move toward early identification of at-risk children and targeted preventive strategies. The Journal of Exercise & Organ Cross Talk is ideally positioned to advance this research agenda.
 

Abstract The pursuit of peak athletic performance is increasingly driven by technological innovation. This narrative review explores the role of emerging technologies in monitoring, analyzing, and enhancing the capabilities of athletes. We focus on the crosstalk between specific organ systems-the brain, the musculoskeletal system, and the cardiovascular system-and the technologies designed to interface with them. Key areas discussed include neurotechnology for cognitive training and recovery, wearable sensors and imaging for musculoskeletal assessment, and advanced biomonitoring for cardiovascular and metabolic optimization. A summary table synthesizes the technologies, their target organs, and primary applications. While these tools offer unprecedented insights, we also discuss challenges related to data interpretation, integration, and accessibility. The future of athletic performance lies in a holistic, technology-enabled understanding of the athlete as a complete, interconnected system.

Abstract Research indicates that a sedentary lifestyle significantly contributes to the development of post-COVID syndrome (PCS), characterized by persistent symptoms following acute COVID-19 infection. Engaging in regular physical activity is essential not only for mitigating these risks but also for enhancing recovery from COVID-19. Studies have shown that individuals who maintained high levels of PA before and after infection experienced fewer and less severe symptoms associated with PCS. Specifically, exercise training has been identified as a critical intervention for improving muscle function and modulating adipokine levels—signaling proteins released by adipose tissue that play a role in inflammation and metabolic regulation. Given the complex pathogenesis of PCS, which involves various physiological and psychological factors, it is imperative to incorporate structured exercise regimens into rehabilitation programs for affected individuals. Aerobic endurance training has demonstrated significant benefits in improving exercise capacity, reducing fatigue, and enhancing overall quality of life in PCS patients. Furthermore, high levels of PA are associated with improved immune function and lower rates of reinfection. In conclusion, promoting mandatory physical activity during and after pandemic conditions is vital for reducing the burden of post-COVID syndrome and enhancing public health outcomes. This review underscores the necessity for healthcare providers to advocate for exercise as a primary strategy in managing post-COVID symptoms and preventing future chronic diseases linked to sedentary behavior during different pandemics.

Abstract Most of the intracellular and extracellular factors that play a vital role in regulating energy metabolism and determining cell fate converge in the mitochondria. To promote or hinder cell survival through regulating the function and maintaining the mitochondrial structure. The decline of mitochondrial function and homeostasis with aging is the basis of the pathogenesis of aging-related diseases, especially in skeletal muscles. One of the important components of mitochondrial quality control that helps maintain the homeostasis of myocytes is autophagy, which is an important biological and evolutionary process, and its vital function is the removal of defective organelles. Although it has been proven that regular sports activities act as autophagy stimulators and play a role in maintaining the cellular homeostasis of skeletal muscle fibers and regulating intracellular metabolism. However, cellular autophagic responses to exercise in skeletal muscle appear to be different in different exercise protocols and disease models. How exercise activity modulates autophagy in skeletal muscle and how the effect of exercise is regulated by the autophagy signaling pathway are still poorly understood. The importance of understanding the obscure angles of this process can be an important goal in preventing the pathology of age-related diseases in skeletal muscle.

Abstract The presence of tetracycline in animal products has toxic and destructive effects on body tissues. In this study we investigate the potential protective mechanism of high-intensity interval training (HIIT) against tetracycline-induced hepatic steatosis (HS) and testicular apoptosis in male Wistar rat. In this study, forty-eight male Wistar rats (8-week, 220±10 gram) were randomly divaded into six groups of primary control (pre week one), primary HS (tetracycline-induced HS), secondary control (after week five), secondary HS, (5) HIIT, and HS+HIIT (after week five). Tetracycline was administered to rats 140 mg / kg for 7 days by gavage. HIIT was performed on rodent treadmill 5 days/week for 5 weeks.  Oral exposure of tetracycline for 7 days caused severe testis damage as indicated by significant alterations in histomorphological, apoptosis, increase Bax, P53 and decease Bcl2 (gene and protein, p=0.001) compared to primary control. But the changes of PARP1 were not significant (p>0.05). However, HIIT and HS+HIIT groups significantly increased spermatogonium counts, spermatocyte cell counts & spermatid cell counts (p=0.001 for all) in line with Bcl-2 and PARP1 (gene and protein, p=0.001) and decreasing apoptotic cells, Bax and p53 compared with secondary HS group (p=0.001). This research provides the first evidence that the beneficial anti-apoptosis effects of HIIT on testis of rats poisoned with tetracycline. This beneficial effect of HIIT on hepatic steatosis and testicular damage and toxicity due to tetracycline might be mediated by inhibiting P53-induced BAX upregulation and preventing apoptosis-mediated degradation of PARP-1.

Abstract Overweight and obesity are associated with an increased risk of cardiovascular disease, hypertension and type 2 diabetes. The purpose of this study was to determine the effect of two continuous aerobic training and high-intensity interval training on body weight, body mass index, waist to hip ratio, and body fat percentage in overweight and obese military people. In this quasi-experimental study, 30 overweight or obese military personnel stationed in a military center were divided into two equal groups of 15 subjects within continuous aerobic training group and high-intensity interval training group. The training protocol consisted of six weeks of continuous aerobic training and high intensity interval training performed every week for three sessions and each session for 60 minutes with equal intensity. The research variables included body weight, body mass index, waist to hip ratio and body fat percentage, which were measured in the same and standard conditions in two stages of pre-test and post-test. After 6 weeks of intervention, high-intensity interval training group showed a significant reduction in body mass index, waist-hip ratio and body fat percentage compared to the continuous aerobic training group(P<0.05). However, there was no significant change in the body weight of the subjects (P<0.05). The results of this study showed that the high-intensity interval training protocol had a greater effect on the body composition parameters of the subjects compared to the continuing aerobic exercise protocol, so it could be included in the training program for overweight or obese military persons.

Abstract Hepatic steatosis is increasingly being recognized as an important pathological feature of disease that commonly reported in patients with inflammatory bowel disease. This study aimed to investigate the effects of High-Intensity Interval Training (HIIT) on the expression of interleukin-10 and Signal transducer and activator of transcription 3 (STAT3) genes in intestinal tissue in an animal model of fatty liver. In this experimental study, 24 rats (weighing 200-250 gr) were selected and randomly divided into 3 groups including healthy control, fatty liver, and fatty liver + HIIT, groups. In order to induce fatty liver, oral tetracycline 140 mg/kg/day in 2 mL of water in form of a solution was given to the rats by gavage for 7 days. HIIT exercise program performed on treadmill five sessions per week for 5 weeks. Data were analyzed by one-way ANOVA and Tukey post hoc tests. P<0.05 was considered significant. The results showed that IL10 gene expression in HIIT groups was significantly lower than in the fatty liver group (p<0.0001). Also, the expression of the STAT3 gene in intestinal tissue was significantly upper in HIIT groups than that in the fatty liver group (p<0.0001). Regulation of IL-10 and STAT3 gene expression in fatty liver-induced adipose tissue can be modulated by HIIT exercise. Therefore, intense interval training can be considered as a non-pharmacological strategy in the treatment of fatty liver.

Abstract Dear Editor-in-Chief
In recent years, exercise has been called an ‘amazing’ medicine and a ‘miracle’ cure. Scientific research shows that regular exercise is effective in preventing and treating many common diseases, including type 2 diabetes, dementia, depression, heart disease, some cancers, and other common diseases (Fang et al., 2022). In fact, exercise in a specific dose and formula is prescribed for each patient who is diagnosed with the disease. The prescription should be very clear in terms of modality, intensity, frequency, and duration.
In this regard, the American College of Sports Medicine (ACSM) has launched the "Exercise is Medicine" project to recognize the myriad health benefits of exercise. These include reducing the incidence of a number of different cancers, lowering the risk of excessive weight gain (along with related health problems as well as diabetes), and improving cardiovascular health (as well as reducing the risk of high blood pressure in addition to heart stroke) (Ghardashi-Afousi et al., 2018).
The acute effect of exercise has been shown to lead to a transient decrease in triglyceride levels, an increase in HDL cholesterol levels, a decrease in blood pressure, a decrease in insulin resistance, and an improvement in glucose control. Regular exercise increases blood flow and oxygen to the brain which improves memory and mental function. It also increases the production of a number of hormones that stimulate the growth of brain cells (Ueno-Pardi et al., 2022).
In addition, some literature describes exercise even better than medicine. For example, a review of more than 300 randomized controlled trials found that exercise was as effective as drugs at risk for heart disease and diabetes, and more effective than post-stroke rehabilitation drugs (Naci & Ioannidis, 2013).
It has previously been suggested that vaccinating children with exercise can control the obesity epidemic in them. Recently, in the coronavirus outbreak, exercise has been referred to as a vaccine or vaccine adjuvant (Naci & Ioannidis, 2013). A recent study in the British Journal of Sports Medicine (BJSM) suggests that routine activities may protect people with COVID-19 from serious illness.
Evidence suggests that exercise and obesity are involved in the pathogenesis of COVID-19 disease and vaccine efficacy. Regular exercise has been shown to exert immune regulatory effects, control viral gateway, modulate inflammation, stimulate NO production pathways, and control oxidative stress. Adaptation to ordinary exercise seems to affect immune function, particularly innate and adaptive immunity, and ameliorate humoral immunity with enhanced vaccination responses. Exercise may at least partially reduce the detrimental effect of SARS-CoV-2 binding to the ECA2 receptor. Exercise training can activate anti-inflammatory signaling pathways (Shirvani & Rostamkhani, 2020). Today, COVID-19 vaccination has shown that individuals who exercise continuously and regularly may develop higher antibody titers to the SARS-CoV-2 strain contained in the vaccine compared to individuals who do not exercise (Hallam et al., 2022).
On the other hand, understanding how obesity and adiposity affect immunity and more specifically the production and function of antibodies is of great importance (Malavazos et al., 2020). Numerous studies have shown the effect of obesity on antibody properties. For example, adaptive immune responses to influenza virus are impaired during obesity, innate and adaptive immune responses to influenza are delayed in obese patients, and obesity was suggested to decline influenza antibody titers following influenza vaccination and reduce vaccine efficacy with poor vaccine immunization. In the same manner, lower COVID-19 mRNA vaccine-induced antibody titers have been related to central obesity and severe acute respiratory syndrome (Ghanemi et al., 2021).     
In general, recent research on the Covid-19 epidemic has shown that exercise is not only a wonderful medicine in the prevention and treatment of many diseases, but also regular exercise can act as an adjunct vaccine. Therefore, prescribing exercise will always help promote community health and is completely in line with the P4 medicine approach (predictive, preventative, personalized, and participatory).

Abstract The aim of this study was to investigate the influence of high intensity interval training on adipose tissue PAI-2 and MMP-2 mRNAs expression in rat with high-fat diet-induced metabolic syndrome. In this experimental study, 32 male Wistar rats (120 to 130 g) were selected and after 12 weeks of high-fat diet and modeling of metabolic syndrome were randomly divided into 4 groups: control, metabolic syndrome (Mets), high intensity interval training (HIIT) and Mets + HIIT. The HIIT program included 5 to 10 intense running on the treadmill with an intensity of 80 to 95% of the maximum speed and in slow running with a speed of 55% of the maximum speed with a zero slope of the treadmill for 8 weeks. Data were analyzed using one-way analysis of variance (ANOVA). The results of one-way analysis of variance showed that there was a difference between the mean expression of MMP-2 and PAI-2 mRNA in adipose tissue of male rats with metabolic syndrome in different groups (P = 0.001). However, HIIT improve this gene after Mets in adipose tissue (p<0.05). It seems that HIIT program improve metabolic syndrome with controlling PAI-2 mRNA and have an anti-inflammatory effect in adipose tissue. However, it need to more studies especially on human sample.

Abstract Toll-like receptor 4 (TLR4) is found in the membrane of skeletal muscle cells. A variety of factors can activate TLR4. It has been shown that TLR4 expression reduce after aerobic training, but more studies considering the influences of different types of training on TLR4 expression are necessary. The purpose of this study was to evaluate the influence of 8 weeks of aerobic training on muscle TLR4 Expression in rats. Twenty Male Wistar rats (200±20 g) divided into four groups: control, training, high fat diet (HFD) and HFD+exerise. High fat diet was made by adding 10% animal oil, 2% cholesterol and 0.5% colic acid to standard rodent chow. Training group performed a swimming training protocol (1 h/day, and 5 days/week for 8 weeks). Forty eight hours after the final session of training, the rats were sacrificed and their gastrocnemius muscle was removed for determination of TLR4 expression. Training significantly decreased TLR4 messenger RNA and protein expression (p<0.05). Levels of TLR4 expression in the HFD group was significantly (p<0.05) higher tahn control ones. Our result displayed that training in rats induceed a critical suppression in the TLR4 signaling in muscle. These data give noticeable progress in our knowledge of the events that link physical training to an improvement in inflammation.