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 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 Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder associated with fat accumulation, sedentary lifestyle, and poor diet. This study examined the effects of aerobic exercise and mealworm protein supplementation on oxidative balance and the expression of FGF21 and mTOR genes in the soleus muscle of rats with NAFLD. Fifteen male Wistar rats (250 ± 50 g, aged 10–12 weeks) were randomly assigned to five groups: healthy control, fatty liver, fatty liver + supplement, fatty liver + exercise, and fatty liver + supplement + exercise. A high-fat diet was used to induce NAFLD. The exercise group performed moderate-intensity treadmill running (12–16 m/min) for eight weeks, five days per week. Mealworm protein (20 mg/kg) was administered via oral gavage. Liver and muscle tissues were analyzed using Real-Time PCR (FGF21, mTOR) and ELISA (TOS, TAC). Combined treatment significantly increased FGF21 expression (~130%; p = 0.022), reduced total oxidant status (~40%; p = 0.001), increased total antioxidant capacity (~45%; p = 0.009), and lowered SGPT and ALP levels (~32% and ~38%, respectively; p < 0.05). mTOR expression showed no significant change (p = 0.113), and the 18% SGOT reduction was not significant (p = 0.169). The combination had greater effects than either treatment alone. Aerobic exercise combined with mealworm protein supplementation improves oxidative balance and FGF21 expression in NAFLD. This integrative strategy may offer a novel therapeutic approach targeting liver-muscle metabolic interactions. Further human studies are recommended.

Abstract Recent studies highlight the role of molecular pathways, such as oxidative stress response and mitochondrial function, in COPD. This study explores the role of the PGC-1α gene, a key regulator of mitochondrial biogenesis and energy metabolism, using a rat model and bioinformatics analysis of human lung tissue samples. This study utilized a combined approach, analyzing gene expression in rat lung tissue alongside bioinformatics analysis of public human datasets. A total of 42 male Wistar rats were divided into seven groups, receiving treatments including cigarette smoke extract (CSE), nano-selenium (SeNPs), and aerobic interval training (AIT). PGC-1α expression levels were evaluated using quantitative Real-Time PCR (qRT-PCR) and analyzed using one-way ANOVA, followed by Dunnett’s post hoc test for multiple comparisons to determine significance across groups. The CSE+SeNPs+AIT group exhibited significantly higher PGC-1α expression compared to controls (p = 0.0289), indicating a potential protective role of SeNPs and exercise against oxidative stress. Bioinformatics analysis identified 250 differentially expressed genes (DEGs), with PGC-1α emerging as a critical hub gene associated with pathways like oxidative stress response and mitochondrial regulation. Protein-protein interaction (PPI) analysis further highlighted the centrality of PGC-1α in COPD pathophysiology. This study underscores the importance of PGC-1α in regulating mitochondrial function and oxidative stress in COPD. The findings suggest that PGC-1α could serve as a potential therapeutic target, offering insights into the development of interventions aimed at improving respiratory health in COPD patients. Future research should focus on validating these findings in clinical settings and exploring the therapeutic potential of PGC-1α modulation.