Journal of Exercise & Organ Cross Talk

Abstract Western diet (WD) consumption promotes oxidative stress and inflammation and plays a central role in the development of fatty liver disease. This study investigated the effects of high-intensity interval training (HIIT), ketone ester supplementation, and their combination on hepatic Keap1, Nrf2, and NF-κB protein levels in WD-fed mice. Thirty male C57BL/6J mice were randomly assigned to five groups (n=6): normal diet (ND), WD, WD plus ketone ester (WD+KE), WD plus HIIT (WD+HIIT), and WD plus HIIT combined with ketone ester supplementation (WD+HIIT+KE). Except for the ND group, all animals consumed a WD for eight weeks. HIIT was performed for four weeks (three sessions/week), and ketone ester was administered daily by oral gavage. Hepatic protein levels of Keap1, Nrf2, and NF-κB were determined using Western blotting. WD feeding significantly increased hepatic Keap1 and NF-κB protein levels and reduced Nrf2 levels compared with the ND group. HIIT and ketone ester, both independently and in combination, significantly decreased NF-κB and increased Nrf2 protein levels compared with the WD group. In addition, HIIT alone and in combination with ketone ester supplementation significantly reduced hepatic Keap1 levels (p<0.05). Overall, both interventions alleviated WD-induced alterations in hepatic oxidative stress and inflammatory signaling. The combined intervention elicited the most pronounced molecular responses, suggesting potential synergistic effects of HIIT and ketone ester supplementation in attenuating Western diet-induced oxidative stress and inflammation.

Abstract Aerobic exercise has been proposed as a non-pharmacological intervention to modulate inflammatory gene expression, yet the molecular mechanisms remain incompletely understood. This study investigated the effects of a 12-week moderate-intensity aerobic exercise intervention on the mRNA expression levels of inflammation-related genes (TNF-α, IL-6, and IL-10) in peripheral blood mononuclear cells (PBMCs) of overweight individuals. Forty-five overweight adults (BMI 25-29.9 kg/m²) were randomly assigned to either an aerobic exercise group (n=30) or a sedentary control group (n=15). The exercise protocol consisted of supervised moderate-intensity aerobic training (60-75% HRmax) for 45-60 minutes, 5 days per week for 12 weeks. Blood samples were collected pre- and post- intervention for gene expression analysis using quantitative real-time PCR and protein quantification via ELISA. Following the 12-week intervention, the exercise group demonstrated significant reductions in TNF-α mRNA expression (−52.3%, p<0.001) and IL-6 expression (−47.8%, p<0.001) compared to baseline. Conversely, IL-10 expression increased significantly (+68.4%, p<0.001). Plasma protein concentrations paralleled these changes, with TNF-α decreasing from 8.6±2.1 to 4.9±1.3 pg/mL (p<0.001), IL-6 from 5.8±1.7 to 3.2±0.9 pg/mL (p<0.001), and IL-10 increasing from 3.1±0.8 to 5.6±1.2 pg/mL (p<0.001). Body mass index decreased significantly in the exercise group (−2.3 kg/m², p<0.001) with concurrent improvements in cardiorespiratory fitness (VO₂max increased by 18.7%, p<0.001). Moderate-intensity aerobic exercise effectively modulates the inflammatory gene expression profile in overweight individuals by downregulating pro-inflammatory genes (TNF-α and IL-6) and upregulating the anti- inflammatory gene (IL-10). These molecular adaptations may contribute to reduced inflammation and improved metabolic health in this population.

Abstract Exercise and the use of anti-inflammatory supplements are effective in controlling inflammation and tissue damage in diabetes. Therefore, the aim of the present study was to investigate the effect of 8 weeks of interval training and royal jelly on the expression of renal inflammatory genes and insulin resistance in diabetic rats. Thirty-two male Wistar rats were used in this study. Diabetes was induced by a high-fat diet for 20 weeks followed by intraperitoneal injection of freshly prepared STZ solution in saline (25 mg/kg). Then the rats were randomly divided into 4 groups: Diabetes (DI), DI+ HIIT, DI+ royal jelly (RJ), and DI+ HIIT+ RJ. Royal jelly groups were given royal jelly at a dose of 100 mg/kg diluted in distilled water and gavage 5 days a week. The exercise program consisted of eight weeks of HIIT training, five sessions per week with a gradual increase in intensity intervals from 22 to 38 meters per minute (80 to 90% of Vo2max) and rest intervals at a speed of 16 to 22 meters per minute (50 to 56% of Vo2max). At the end of the research, rats were euthanized and kidney tissue was removed to measure the expression of TNF-α and NF-κB genes. The DI+HIIT (p=0.0006), DI+RJ (p=0.0011) and DI+HIIT+RJ (p<0.0001) groups showed a significant decrease in HOMA-IR compared to the diabetes control group. The DI+HIIT, DI+RJ and DI+HIIT+RJ groups showed a significant decrease in TNF-α and NF-κB gene expression in kidney tissue compared to the diabetes control group. In conclusion, 8 weeks of HIIT and/or royal jelly supplementation significantly ameliorated insulin resistance and suppressed renal pro-inflammatory gene expression (TNF-α, NF-κB) in diabetic rats, with the combined approach showing the greatest efficacy.

Abstract This study investigated the combined efficacy of interval training and thyme honey in attenuating the expression of inflammatory genes (TNF-α and TGF-β) in renal tissue and improving insulin resistance in diabetic rats. In this experimental study, 32 young male Wistar rats were divided into 4 groups: diabetes mellitus control (DM), diabetes and interval training (DM+HIIT), diabetes and thyme honey (DM+TH), and diabetes and interval training-thyme honey (DM+HIIT+TH). Animals in the training group underwent 40 sessions of training over two months with a gradual increase in the number of intense intervals from 2 to 8 intervals and an intensity of 80 to 95% of maximum running speed. At the same time, the samples in the TH groups received thyme honey at a rate of g/kg 3 and 5 days per week. Insulin resistance index (HOMA-IR) was performed using the formula. TNF- α  and TGF-β gene expression in kidney tissue was evaluated using Real-Time PCR. Based on the results of the present study, DM+HIIT significantly reduced HOMA-IR compared to the diabetes group (p<0.05). However, the DM+HIIT+TH group did not yield a greater improvement in HOMA-IR than the DM+HIIT group alone. Also, TNF-α and TGF-β genes in the DM+HIIT, DM+TH and DM+HIIT+TH groups showed a significant decrease compared to the diabetes group (p<0.05). In conclusion, our findings provide strong evidence that both interval training and thyme honey supplementation independently ameliorate diabetic nephropathy by downregulating key pro-fibrotic and inflammatory mediators. While the combination therapy was highly effective at suppressing inflammatory genes, it did not provide a synergistic benefit for insulin sensitivity compared to exercise alone. These results suggest that interval exercise is the primary driver of improved insulin sensitivity in this model.

Abstract Intense and high-speed intermittent training is recognized as an effective method for achieving rapid and extensive physiological and functional adaptations. However, it is important to consider that a single session of such exercises can exert significant physiological stress, potentially leading to adverse effects. Therefore, this study investigated the effects of a repeated sprint training (RSA) session on serum adropin, inflammatory, and blood coagulation factors. Ten healthy young men (age: 23.60 ± 2.01 years, weight: 68.60 ± 7.21 kg, body mass index: 22.00 ± 2.10 kg/m2) participated in this study. Blood samples were collected before, immediately after, and 20 minutes following the exercise protocol for measuring of adropin protein, fibrinogen, CRP, WBC, RBC, Hgb, and Hct levels. The exercise protocol consisted of 20 repetitions of different running speeds in a distance of 20 meters, with a 20-second rest period after each repetition (20*20*20). A significant increase in adropin, fibrinogen, WBCs, RBC, Hgb and, Hct levels was observed immediately after the exercise (p < 0.05). But only Adropin levels remained significantly higher than before the exercise after 20 minutes following the exercise. Therefore, even after exercise, adropin levels can remain elevated, allowing for the continuation of its positive effects. However, it is important to note that the increase in fibrinogen levels may require further investigation, particularly in relation to the use of anticoagulant agents. Therefore, when considering the implementation of these intense activities for inactive individuals, it is crucial to exercise caution and carefully assess the potential risks involved.

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 Intense exercise training is associated with Lung inflammation. Fasl protein on the cell surface is responsible for the initiation of the inflammatory response that finally leads to cell death at the site of inflammation, and can be interpreted as Fasl induced apoptosis. Therefore, the aim of this study was to investigate the effects of increasing and intense interval exercise training on Fasl levels of mature rat lungs. 30 rats within three weeks of birth with mean weight 68±9 g were randomly divided into three basic, control, and exercise groups. Increasing interval training for 6 sessions per week, each session 30 minutes at a speed of 15 to 70 meters per min was employed and Fasl levels were measured using the kitby Elisa method. The data were analyzed with two-way ANOVA and LSD test was done at p≤0.05 significant level. The results showed that Fasl protein levels in the interval training group compared to baseline group increased by 23.75 % and was significant (p≤0/05). However, although the amount of this protein in the interval training group compared to the control group was high, this value was not significant. In addition, Fasl protein levels in the control group compared to the baseline group increased by13.58 % and was significant (p≤0.05). The findings indicated that intense and prolonged exercise training causes damage of the respiratory tract, and in turn, leads to the increased levels of Fasl.

Abstract Regular physical activity is the best defense against many diseases, illnesses, and abnormalities. Aerobic exercise and the consumption of herbal supplements strengthen the body's immune and defense systems. This study aimed to investigate the effect of a period of swimming endurance training with trachyspermum copticum (Ajwain) consumption on serum levels of some inflammatory factors in young men in a randomized clinical trial. The statistical population included all male students less than 25 years of age at the Islamic Azad University of Varamin Phishva, Iran. Among them, sample sizes of 60 people were selected by simple random sampling and were divided into four groups of 15 people each: trachyspermum copticum + training, trachyspermum copticum, training, and control. The training program included endurance swimming for 10 weeks either with or without the addition of trachyspermum copticum. Serum concentrations of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and heat shock protein 70 (HSP70) were measured in two-time stages before and after the study period. The level of CRP inflammatory index, TNF-α cytokine, and HSP70 were lower among the training + trachyspermum copticum than in the control group and other experimental groups. Endurance swimming training and trachyspermum copticum with anti-inflammatory properties strengthened the immune system, increased antioxidant defense, and decreased inflammatory markers. Also, the level of physical activity has improved this condition by improving endothelial function.

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.

Abstract Dear Editor-in-Chief
Overweight and obesity are considered as the most important lifestyle-related diseases today such that they are known as the fifth leading causes of death worldwide according to the published statistics. Moreover, as previous studies have shown, low-grade chronic inflammation is among the symptoms of these diseases and plays a key role in the pathogenesis of various physical problems and chronic diseases, such as cancer, diabetes, metabolic syndrome, cardiovascular, and neurodegenerative diseases (Safaei et al., 2021).
Meanwhile, new evidence suggests that leucine-rich α 2-glycoprotein 1 (LRG1) proinflammatory factor, an important upstream signaling pathway of transforming growth factor_⁃β (TGF_⁃β), will cause several pathological processes (Zou et al., 2022). In other words, it can be stated that LRG1, alone or in combination with other known factors, is considered as a potential biomarker for inflammation and obesity. There is a positive relationship between high levels of LRG1 and obesity, while low levels of plasma LRG1 predict weight loss in surgery for obesity and metabolic diseases (Pek et al., 2018). Investigation of the importance and the relationship of this issue in a broad study on 2,058 patients with type 2 diabetes showed that higher plasma LRG1 levels in women than men have a significant relationship with several risk factors for cardiovascular disease, namely arterial stiffness, endothelial dysfunction, systolic blood pressure, obesity, kidney disease, and high-sensitivity C-reactive protein (Pek et al., 2018; Zou et al., 2022). A recent 8-year longitudinal study also found that pigment epithelial-derived factor and plasma LRG1 mediated the inverse relationship between skeletal muscle mass and chronic kidney disease progression in patients with type 2 diabetes (Low et al., 2021). In other words, there is a positive correlation between high LRG1 levels in blood serum and adipose stores and high levels of body-mass-index (BMI), visceral adipose tissue, and waist circumference of obese people. According to these results and laboratory observations, LRG1 has been assumed to increase fat accumulation via suppression of fatty acids catabolism and inducing lipid biosynthesis through sterol regulatory element-binding transcription factor 1 activation or may enable hyperglycemia by decreasing expression of insulin receptor substrates (IRS1 and IRS2) (He et al., 2021).
On the other hand, consistent with the findings of studies showing the high serum levels of LRG1, it is possible that LRG1 binds preferentially to liver cells. With this assumption, LRG1 is considered a new adipokine that can play a role in obesity conditions by regulating an almost unique cross-talk between adipose tissue and the liver. More broad research is required to know whether LRG1 also exerts metabolic functions in physiological circumstances or not. However, the results of a study on LRG1 knockout mice with a high-fat diet revealed weight loss, smaller fat cell size, and preservation of brown adipose tissue in this type of mice. In other words, an increase in LRG1 gene expression during the process of fat lipogenesis can play an important role in regulating energy homeostasis (He et al., 2021; MacCannell et al., 2021). However, changing lifestyle by performing regular physical activity and a balanced diet have been introduced as a useful solution to prevent obesity. In this regard, a recent study on the elderly with an average BMI of 34 ± 1 kg / m2 showed that exercise combined with diet resulted in an 8-10 % weight loss in these individuals, indicating the possibility that molecular changes in peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) pathway can help transport fat and oxidize it in the skeletal muscles of older and obese people and in some ways regulate insulin resistance (Mulya et al., 2017).
Previous research studies have referred to the key role of PGC-1α in regulating mitochondrial function and helping regulate cellular energy status by enabling cellular energy in conditions 
when the body needs energy, such as fasting, performing exercise activities, or inhibiting it when the body has enough energy available. However, the evidence obtained regarding the role of PGC-1α and its relationship with LRG1 gene expression in obesity therapy showed that LRG1 expression in white adipose tissue reduced in mice model of insulin - resistant type II diabetes and obesity following treatment with PPARγ agonists (Muise et al., 2008). Moreover, evidence regarding the positive effects of exercise activity and the role of PGC-1α showed that probably five proteins, including interleukin 15 (IL-15), fibronectin type III domain- containing protein 5 (FNDC5), vascular endothelial growth factor B (VEGF-B), LRG1, and tissue inhibitor of metalloproteinase 4 (TIMP4), secreted in skeletal muscles, increase following endurance exercise activity and contribute to longevity as well (Boström et al., 2012).
Considering the evidence presented, LRG1 seems to play a key role in the pathogenesis of obesity. However, more broad research is required to better understand its relationship with other transcription factors, vital signaling pathways in this process, as well as the important effect of type, intensity, and duration of exercise activity, and type of diet in regulating its expression and its regulatory role in cross-talk with other organs to prevent obesity (Yang et al., 2021).