Background: High-fat diet (HFD)-induced obesity causes immune cells to infiltrate adipose tissue, leading to chronic inflammation and metabolic syndrome. Brown adipose tissue (BAT) can dissipate the energy produced by lipid oxidation as heat, thereby counteracting obesity. Aerobic exercise activates BAT, but the specific underlying mechanism is still unclear. Methods: Male C57BL/6 J mice were divided into a normal diet control group (NC group) and HFD group (H group). After becoming obese, the animals in the H group were subdivided into a control group (HC group) and an exercise group (HE group, with treadmill training). After 4 weeks, the mRNA profile of BAT was determined, and then differentially expressed key genes and pathways were verified in vitro. Results: Relative to the NC group, the genes upregulated in the HC group coded mainly for proteins involved in immune system progression and inflammatory and immune responses, while the downregulated genes regulated lipid metabolism and oxidation–reduction. Relative to the HC group, the genes upregulated in the HE group coded for glycolipid metabolism, while those that were downregulated were involved in cell death and apoptosis. VEGF and other signaling pathways were enhanced by aerobic exercise. Interaction analysis revealed that the gene encoding cyclooxygenase 2 (COX2) of the VEGF signaling pathway is central to this process, which was verified by a sympathetic activator (isoprenaline hydrochloride) and COX2 inhibitor (NS-398). Conclusions: In mice with HFD-induced obesity, four weeks of aerobic exercise elevated BAT mass and increased the expression of genes related to glycolipid metabolism and anti-inflammatory processes. Several pathways are involved, with COX2 in the VEGF signaling pathway playing a key role.

Background: Branched-chain amino acids (BCAAs, isoleucine, leucine, and valine) are commonly applied to promote muscle protein synthesis. However, the effects of BCAAs on exercise-induced substrate metabolism, performance and post-exercise fatigue during endurance exercise remain unclear. Methods: In a double-blind cross-over design, eleven active males completed 1 h of constant load exercise (CLE) at 60% VO₂max power followed by a time to exhaustion (TTE) test at 80% VO₂max power after supplementation with BCAAs or placebo on consecutive three days. During exercise, indirect calorimetry was used to measure the carbohydrate (CHO) and fat oxidation rate, as well as the cycling efficiency. In addition, rating of perceived exertion (RPE) and visual analogue scale (VAS) scores were obtained at interval times during the whole period. Fingertips and venous blood (n = 8) were collected for the measurement of metabolic responses at different time points during exercise. Results: Compared to the placebo group, the fat oxidation rate was significantly higher after 20 and 30 min of CLE (p < 0.05). The CHO oxidation rates showed a significant increase in the BCAA group during TTE (p < 0.05). Meanwhile, the cycling efficiency during TTE was significantly improved (p < 0.05). Interestingly, VAS significantly decreased post-exercise in the BCAA group (p < 0.05). Additionally, the levels of blood insulin between the two groups were significantly higher in the post-exercise period compared to the pre-exercise periods (p < 0.001), while insulin levels were significantly lower in the post-exercise period with supplemental BCAAs compared to the placebo (p < 0.001). BCAAs also enhanced the levels of blood ammonia in the post-exercise period compared to the fasting and pre-exercise periods (BCAA: p < 0.01; Placebo: p < 0.001). However, in the post-exercise period, blood ammonia levels were significantly lower in the BCAA group than in the placebo group (p < 0.05). Conclusions: This study shows the critical role of BCAAs during exercise in active males and finds that BCAA supplementation enhanced fat oxidation during the CLE, increased carbohydrate oxidation and exercise efficiency during the TTE, and reduced immediate post-exercise fatigue.

Diabetic muscle atrophy is an inflammation-related complication of type-2 diabetes mellitus (T2DM). Even though regular exercise prevents further deterioration of atrophic status, there is no effective mediator available for treatment and the underlying cellular mechanisms are less explored. In this study, we investigated the therapeutic potential of MCC950, a specific, small-molecule inhibitor of NLRP3, to treat pyroptosis and diabetic muscle atrophy in mice. Furthermore, we used MCC950 to intervene in the protective effects of aerobic exercise against muscle atrophy in diabetic mice. Blood and gastrocnemius muscle (GAS) samples were collected after 12 weeks of intervention and the atrophic state was assessed. We initially corroborated a diabetic muscle atrophy phenotype in db/db mice (D) by comparison with control m/m mice (W) by examining parameters such as fasting blood glucose (D vs. W: 24.47 ± 0.45 mmol L⁻¹ vs. 4.26 ± 0.6 mmol L⁻¹, p < 0.05), grip strength (D vs. W: 166.87 ± 15.19 g vs. 191.76 ± 14.13 g, p < 0.05), exercise time (D vs. W: 1082.38 ± 104.67 s vs. 1716 ± 168.55 s, p < 0.05) and exercise speed to exhaustion (D vs. W: 24.25 ± 2.12 m min⁻¹ vs. 34.75 ± 2.66 m min⁻¹, p < 0.05), GAS wet weight (D vs. W: 0.07 ± 0.01 g vs. 0.13 ± 0.01 g, p < 0.05), the ratio of GAS wet weight to body weight (D vs. W: 0.18 ± 0.01% vs. 0.54 ± 0.02%, p < 0.05), and muscle fiber cross-sectional area (FCSA) (D vs. W: 1875 ± 368.19 µm² vs. 2747.83 ± 406.44 µm², p < 0.05). We found that both MCC950 (10 mg kg⁻¹) treatment and exercise improved the atrophic parameters that had deteriorated in the db/db mice, inhibited serum inflammatory markers and significantly attenuated pyroptosis in atrophic GAS. In addition, a combined MCC950 treatment with exercise (DEI) exhibited a further improvement in glucose uptake capacity and muscle performance. This combined treatment also improved the FCSA of GAS muscle indicated by Laminin immunofluorescence compared to the group with the inhibitor treatment alone (DI) (DEI vs. DI: 2597 ± 310.97 vs. 1974.67 ± 326.15 µm², p < 0.05) or exercise only (DE) (DEI vs. DE: 2597 ± 310.97 vs. 2006.33 ± 263.468 µm², p < 0.05). Intriguingly, the combination of MCC950 treatment and exercise significantly reduced NLRP3-mediated inflammatory factors such as cleaved-Caspase-1, GSDMD-N and prevented apoptosis and pyroptosis in atrophic GAS. These findings for the first time demonstrate that targeting NLRP3-mediated pyroptosis with MCC950 improves diabetic muscle homeostasis and muscle function. We also report that inhibiting pyroptosis by MCC950 can enhance the beneficial effects of aerobic exercise on diabetic muscle atrophy. Since T2DM and muscle atrophy are age-related diseases, the young mice used in the current study do not seem to fully reflect the characteristics of diabetic muscle atrophy. Considering the fragile nature of db/db mice and for the complete implementation of the exercise intervention, we used relatively young db/db mice and the atrophic state in the mice was thoroughly confirmed. Taken together, the current study comprehensively investigated the therapeutic effect of NLRP3-mediated pyroptosis inhibited by MCC950 on diabetic muscle mass, strength and exercise performance, as well as the synergistic effects of MCC950 and exercise intervention, therefore providing a novel strategy for the treatment of the disease.

This study aims to explore the role of FoxO1 and its acetylation in the alleviation of hypoxia‐induced muscle atrophy by resistance training. Forty male Sprague–Dawley rats were randomly divided into four groups: normoxic control group (C), normoxic resistance training group (R), hypoxic control group (H) and hypoxic resistance training group (HR). Rats in R and HR groups were trained on an incremental weight‐bearing ladder every other day, while those in H and HR groups were kept in an environment containing 12.4% O₂. After 4 weeks, muscles were collected for analysis. Differentiated L6 myoblasts were analysed in vitro after hypoxia exposure and plasmids transfection (alteration in FoxO1 acetylation). The lean body mass loss, wet weight and fibre cross‐sectional area of extensor digitorum longus of rats were decreased after 4 weeks hypoxia, and the adverse reactions above was reversed by resistance training. At the same time, the increase in hypoxia‐induced autophagy was suppressed, which was accompanied by a decrease in the expression of nuclear FoxO1 and cytoplasmic Ac‐FoxO1 by resistance training. The L6 myotube diameter increased and the expression of autophagic proteins were inhibited under hypoxia via intervening by FoxO1 deacetylation. Overall, resistance training alleviates hypoxia‐induced muscle atrophy by inhibiting nuclear FoxO1 and cytoplasmic Ac‐FoxO1‐mediated autophagy.

Exposure to high altitude environment leads to skeletal muscle atrophy. As a hormone secreted by skeletal muscles after exercise, irisin contributes to promoting muscle regeneration and ameliorating skeletal muscle atrophy, but its role in hypoxia-induced skeletal muscle atrophy is still unclear. Our results showed that 4 w of hypoxia exposure significantly reduced body weight and gastrocnemius muscle mass of mice, as well as grip strength and the duration time of treadmill exercise. Hypoxic treatment increased HIF-1α expression and decreased both the circulation level of irisin and its precursor protein FNDC5 expression in skeletal muscle. In in vitro, CoCl₂-induced chemical hypoxia and 1% O₂ ambient hypoxia both reduced FNDC5, along with the increase in HIF-1α. Moreover, the decline in the area and diameter of myotubes caused by hypoxia were rescued by inhibiting HIF-1α via YC-1. Collectively, our research indicated that FNDC5/irisin was negatively regulated by HIF-1α and could participate in the regulation of muscle atrophy caused by hypoxia.

The purpose of this study is to observe the differences in precompetition diet structure, adaptability to training, gut microbiota, and metabolites of wrestlers with different weight control effects and analyze the correlation between them, aiming to provide scientific guidance and advice on weight control for wrestlers.