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.

Trimethylamine N-oxide (TMAO) has attracted interest because of its association with cardiovascular disease and diabetes, and evidence for the beneficial effects of TMAO is accumulating. This study investigates the role of TMAO in improving exercise performance and elucidates the underlying molecular mechanisms. Using C2C12 cells, we established an oxidative stress model and administered TMAO treatment. Our results indicate that TMAO significantly protects myoblasts from oxidative stress-induced damage by increasing the expression of Nrf2, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (NQO1), and catalase (CAT). In particular, suppression of Nrf2 resulted in a loss of the protective effects of TMAO and a significant decrease in the expression levels of Nrf2, HO-1, and NQO1. In addition, we evaluated the effects of TMAO in an exhaustive swimming test in mice. TMAO treatment significantly prolonged swimming endurance, increased glutathione and taurine levels, enhanced glutathione peroxidase activity, and increased the expression of Nrf2 and its downstream antioxidant genes, including HO-1, NQO1, and CAT, in skeletal muscle. These findings underscore the potential of TMAO to counteract exercise-induced oxidative stress. This research provides new insights into the ability of TMAO to alleviate exercise-induced oxidative stress via the Nrf2 signaling pathway, providing a valuable framework for the development of sports nutrition supplements aimed at mitigating oxidative stress.

There is often significant spatial heterogeneity in the factors influencing physical fitness in adolescents, yet less attention has been paid to this in established studies. Based on the 2018 Chinese National Student Physical Fitness Standard Test data, this study uses a multi-scale, geographically weighted regression (MGWR) model combined with a K-means clustering algorithm to construct a spatial regression model of the factors influencing adolescent physical fitness, and to investigate the degree of spatial variation in the physical fitness of Chinese adolescents from a socio-ecological perspective of health promotion. The following conclusions were drawn: the performance of the youth physical fitness regression model was significantly improved after taking spatial scale and heterogeneity into account. At the provincial scale, the non-farm output, average altitude, and precipitation of each region were strongly related to youth physical fitness, and each influencing factor generally showed a banded spatial heterogeneity pattern, which can be summarized into four types: N–S, E–W, NE–SW, and SE–NW. From the perspective of youth physical fitness, China can be divided into three regions of influence: the socio-economic-influenced region, mainly including the eastern region and some of the central provinces of China; the natural-environment-influenced region, which mainly includes the northwestern part of China and some provinces in the highland region; and the multi-factor joint-influenced region, which mainly includes the provinces in the central and northeastern regions of China. Finally, this study provides syndemic suggestions for physical fitness and health promotion for youths in each region.

To improve exercise performance, the supplement of nutrients has become a common practice before prolonged exercise. Trimethylamine N-oxide (TMAO) has been shown to ameliorate oxidative stress damage, which may be beneficial in improving exercise capacity. Here, we assessed the effects of TMAO on mice with exhaustive swimming, analyzed the metabolic changes, and identified significantly altered metabolic pathways of skeletal muscle using a nuclear magnetic resonance-based (NMR-based) metabolomics approach to uncover the effects of TMAO improving exercise performance of mice. We found that TMAO pre-administration markedly prolonged the exhaustive time in mice. Further investigation showed that TMAO pre-administration increased levels of 3-hydroxybutyrate, isocitrate, anserine, TMA, taurine, glycine, and glutathione and disturbed the three metabolic pathways related to oxidative stress and protein synthesis in skeletal muscle. Our results provide a metabolic mechanistic understanding of the effects of TMAO supplements on the exercise performance of skeletal muscle in mice. This work may be beneficial in exploring the potential of TMAO to be applied in nutritional supplementation to improve exercise performance. This work will lay a scientific foundation and be beneficial to exploring the potential of TMAO to apply in nutritional supplementation.

Aerobic capacity is important for speed skaters to achieve good results in middle–long distance events. The technical characteristics of speed skating cause intermittent blood flow blockage in the lower limbs. Therefore, an athlete’s aerobic capacity on ice may differ from that measured by cycling or running. Now, the on-ice aerobic capacity lacks methods for conducting aerobic capacity tests on ice. Objective: The objective of this study was to develop a method for measuring on-ice aerobic capacity for young athletes and to compare it with the VO_2max test on cycling. Methods: This study established a test method for the on-ice aerobic capacity of young, high-level speed skaters with incremental load (on-ice incremental skating test, OIST) through expert interviews and literature review. In the first part, OIST was used to test the aerobic abilities of 65 youth professional speed skaters (51 males and 14 females) on ice and to explore the correlation with their specific performance. The second part compares the relationship between aerobic capacity on ice and aerobic capacity on bicycle of 18 young high-level male athletes. The third part establishes the regression formula of ice ventilation threshold heart rate. The OIST established in this study can evaluate the on-ice aerobic capacity of athletes from National Level and Level 1&2 in China. The athletes’ on-ice aerobic capacity indicators were significantly lower than those of the cycling test. However, the values of absolute VO_2max and absolute ventilatory threshold had a high correlation (R = 0.532, p < 0.05; R = 0.584, p < 0.05). The regression formula of ventilatory threshold heart rate on ice = 0.921 × HRmax (Cycling test) −9.243. The OIST established in this study meets the characteristics and requirements of the VO_2max measurement method. The OIST seems to be able to better evaluate the aerobic capacity of athletes skating on ice. The indicators of maximum oxygen uptake and ventilation threshold in OIST were significantly lower than those in the aerobic cycling test, but there was a good correlation. The aerobic cycling test can be used as an important selection index of the ice aerobic capacity of speed skaters. The regression formula will provide an important basis for coaches to accurately monitor the intensity of ice training.