Journal of Exercise & Organ Cross Talk

Abstract The aim of this study was to investigate the effects of an exercise program (EP) in combination with functional electrical stimulation (FES) on bone mass density (BMD) and bone turnover markers (BTMs) in osteopenic postmenopausal women. In this semi-experimental study, 45 women aged 61.25 ± 4.1 years who were classified as osteopenic (-2.5 < T-score < -1) were divided into three groups: 1) EP + FES, 2) EP and 3) control. The EP + FES and EP groups participated in a combined aerobic (45-60% HRR) and strength program for 90 minutes three times a week for 12 weeks. In the EP + FES group, FES with a frequency of 45 Hz and a pulse width of 300 microseconds was applied to the lumbar and hip area. Blood samples were taken at the beginning of the study and again after 12 weeks to determine BMDs. BMD was measured using dual-energy X-ray absorptiometry (DXA). After 12 weeks, cross-linked type 1 collagen C-telopeptide (sCTX) (p=0.002) and pyridinoline (PYD) (p=0.001) levels decreased significantly, while vitamin D (p=0.002), PINP/PYD ratio (p=0,032), the ALP/PYD ratio (p=0.004) and the ALP/CTX-1 ratio (p=0.010) increased significantly in both the EP+FES and EP groups compared to the control group. The EP+FES group showed a significant increase in lumbar (p=0.048) and hip BMD (p=0.038) compared to the control group. Therefore, an exercise programme in combination with FES is recommended as the preferred intervention to maintain or improve bone formation, as FES has a synergistic effect on bone health in patients with osteopenia.

Abstract The present study evaluates the effects of aerobic exercise and ethanolic bitter orange peel extract on the expression of cardioprotective genes in female rats fed a high-fat diet (HFD). From the Islamic Azad University's Central Tehran Branch animal facility, 30 adult female rats of the Wistar strain were randomly assigned to five groups (six rats per group): 1) normal diet control (ND-C), 2) HFD control (HFD-C), 3) HFD aerobic exercise (HFD-AE), 4) HFD ethanolic bitter orange peel extract (HFD-BP), and 5) HFD aerobic exercise and ethanolic bitter orange peel extract (HFD-AE-BP). A normal diet was supplemented with 20% palm oil, 1.5% cholesterol, and 0.25 cholic acid to induce obesity. Before the intervention, the subjects received a HFD for four weeks, then continued it for another four weeks during the intervention. During the four-week aerobic exercise protocol, treadmill running was performed at a moderate intensity. An ethanol extract of bitter orange peel was administered orally to rats at a dose of 100 milligrams per kilogram of body weight for four weeks. After euthanasia, left ventricle myocardium was collected for real-time PCR analysis of CTRP9, LKB1, and AMPK gene expression. In the HFD-C, CTRP9 (P=0.001), LKB1 (P=0.001), and AMPK (P=0.001) genes were significantly lower than in the ND-C. Aerobic exercise significantly increased their expression compared with the HFD-C (P=0.001). Comparing HFD-C with ethanolic bitter orange peel extract, ethanolic bitter orange peel extract increased gene expression significantly (P=0.001). This indicates that the simultaneous use of these two interventions was able to add up the effects of each and did not have a synergistic effect. However, since the magnitude of change when these two interventions were combined was greater than the effect of each alone, the combination of AE and BP was greater than the effect of each alone, suggesting that these two interventions may be used to mitigate cardiac complications under HFD conditions.

Abstract Aging is associated with mitochondrial dysfunction, which leads to decreased cellular function and the development of age-related diseases. Exercise training is considered one of the most effective strategies for improving muscle cell function. The aim of the present study was to investigate the effect of six-week combined exercise on mitochondrial dynamics and biogenesis markers (MFN1, DRP1) as well as oxidative stress markers (MDA and SOD) in fast- and slow-twitch muscles of aged rats. In this study, 16 male Wistar rats (463.2 ± 9.3 g) were randomly divided into two groups (n=8 per group): control and resistance-endurance training. The training group underwent combined resistance-endurance training, 6 days a week for 6 weeks (3 resistance days, 3 endurance days). Forty-eight hours after the last training session, animals were sacrificed and fast-twitch (gastrocnemius) and slow-twitch (soleus) muscle tissues were collected. Gene expression levels of mitofusin 1 (MFN1), dynamin-related protein 1 (DRP1) were measured by real-time PCR (RT-PCR). In slow-twitch muscle, exercise training significantly increased mRNA expression levels of SOD genes, and significantly decreased mRNA expression of DRP1 and the concentration of MDA compared to the control group (p<0.05). Similarly, in fast-twitch muscle, six weeks of combined training significantly increased SOD gene expressions and decreased DRP1 mRNA and MDA levels compared to controls (p<0.05). Combined exercise training positively modulates mitochondrial biogenesis and dynamics markers (decreased DRP1 mRNA) and enhances antioxidant capacity (increased SOD gene expression and enzyme activity, decreased MDA levels) in both fast- and slow-twitch muscles of aged rats, highlighting its significant role in mitigating age-associated mitochondrial dysfunction. These findings reflect improvements in markers of mitochondrial quality control and oxidative stress rather than direct measurements of mitochondrial function.

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 Glioblastoma multiforme (GBM) exhibits dysregulated p53 tumor-suppressor signaling, driving therapeutic resistance; exercise and nutraceuticals represent promising adjuvants for pathway modulation. This study investigated resistance training and nanocurcumin in an orthotopic GBM rat model (n=40), with groups including healthy controls, cancer controls, nanocurcumin (80 mg/kg/day), resistance training (ladder climbing, 50% BW + 30g, 3×/week), and combined intervention. After 4 weeks, tumor tissue analysis revealed resistance training significantly reduced p53 mRNA expression versus cancer controls (1.8 ± 0.2 vs. 3.1 ± 0.3; p = 0.021), while all interventions suppressed p21 (combination group: 1.2 ± 0.1 vs. control 4.0 ± 0.4; p < 0.001), demonstrating 70% greater p21 inhibition in the combined group versus monotherapies (p < 0.01). The synergistic p21 downregulation indicates potent disruption of the G1/S cell-cycle checkpoint, likely mediated through inter-organ cross-talk along the muscle-liver-brain axis—where exercise-induced myokines (IL-6, BDNF) mitigate tumor oxidative stress, nanocurcumin suppresses hepatic inflammatory mediators, and hemodynamic adaptations enhance blood-brain barrier penetration. These findings position resistance training and nanocurcumin as a novel non-pharmacological adjuvant strategy to potentiate conventional glioma therapies by leveraging systemic physiological communication.

Abstract Skeletal muscle is a highly plastic organ that undergoes significant metabolic and structural stress during exercise, necessitating precise nutritional support for adaptation and recovery. While the roles of macronutrients are well-established, the complex interplay, or "crosstalk," between essential micronutrients is a critical yet dynamic facet of exercise physiology. This review synthesizes current evidence on the synergistic relationships between key vitamins and minerals—specifically vitamin D, calcium, magnesium, the B-vitamins, antioxidants, and iron—in supporting skeletal muscle function during and after exercise. We explore how these micronutrients co-operate in energy production, calcium handling, contraction coupling, antioxidant defense, and anabolic signaling. Recent research continues to elucidate the molecular mechanisms behind this crosstalk, highlighting the role of the gut-muscle axis and the impact of deficiencies on adaptive outcomes. Understanding this intricate network is paramount for developing targeted nutritional strategies that optimize athletic performance, enhance recovery, and support long-term musculoskeletal health.

Abstract Dear Editor-in-Chief
We are writing to highlight a rapidly advancing frontier at the intersection of exercise physiology, microbiology, and metabolism: the role of the gut microbiome as a critical endocrine organ regulating skeletal muscle function and adaptability
(1) The traditional paradigm of muscle regulation has centered on factors like mechanical load, neuronal input, and systemic hormones. However, cutting-edge research now positions the gut microbiome as a central modulator of muscle physiology. The latest findings move beyond correlation to establish causative mechanisms, primarily through microbial metabolites that serve as inter-organ signaling molecules.
 (2) A key advancement involves microbiota-derived metabolites as ergogenic agents. Butyrate and other short-chain fatty acids (SCFAs) are no longer viewed solely as colonocytes fuels. Recent studies demonstrate that butyrate supplementation enhances oxidative metabolism in muscle, improves mitochondrial function, and reduces exercise-induced fatigue in mouse models (Lahiri et al., 2019). This is mediated through the activation of AMPK and PGC-1α pathways, suggesting that gut bacteria can directly influence the molecular circuitry of muscle energy sensing and biogenesis.
(3) Furthermore, the microbial metabolism of dietary tryptophan into aryl hydrocarbon receptor (AhR) ligands (e.g., indole derivatives) is a breakthrough finding. These ligands are crucial for maintaining intestinal barrier integrity, thereby reducing endotoxemia and systemic inflammation. Furthermore, specific indole derivatives have been shown to directly activate AhR signaling in muscle, potentially influencing protein synthesis and mitigating atrophy pathways, presenting a novel gut-muscle axis.
(4) Perhaps the most direct link comes from microbiome-dependent purine metabolism. A groundbreaking study revealed that gut bacteria, notably Bifidobacterium species, can metabolize dietary purines into inosine. Systemically absorbed, inosine enhances aerobic capacity and exercise performance in mice by enhancing skeletal muscle metabolic activity, directly linking a specific bacterial metabolite to a functional exercise outcome (Besora-Moreno et al., 2025).
(5) Finally, this research is now yielding robust clinical translation, a fact confirmed by the highest level of evidence. A recent systematic review and meta-analysis of randomized controlled trials conclusively demonstrated that probiotic supplementation significantly improves muscle mass, muscle strength, and lean mass in human subjects across various populations (Prokopidis et al., 2023). This comprehensive analysis synthesizes data from multiple studies, including trials like that of Tsuchiya et al. (2023), to provide a definitive summary of the field's progress. The meta-analysis leaves little doubt that modulating the gut microbiome is a novel and viable therapeutic strategy for combating age-related and other forms of muscle loss.
These findings establish the gut microbiome as a potent endocrine organ that communicates with skeletal muscle. We believe this topic is of paramount importance to the readership of exercise and organ cross talk.