Yong Zhang

Exercise induces acute hepatic dysfunction and inflammation, a condition with currently limited treatment modalities. Dihydromyricetin (DHM) may protect the liver, but its role in exercise-related hepatic dysfunction and inflammation remains to be elucidated. In this work, we investigated whether DHM intervention is associated with the restoration of the T helper 17 (Th17)/regulatory T (Treg) balance in these exercise-induced hepatic disorders.Exhaustive treadmill running was performed on male C57BL/6 mice (8 weeks old, 20–22 g) to establish a mouse model of acute hepatic dysfunction and inflammation. Mice were then administered DHM (400 mg/kg/day by oral gavage for 6 consecutive days, concurrently with the exercise protocol), DHM + recombinant interleukin-17A (IL-17A) (rIL-17A; 100 ng/day, i.p., on Days 1–4 of the exercise protocol), or DHM + anti-CD25 monoclonal antibody (aCD25 mAb; 400 µg, i.p., on the second day of acclimatization and the third day of the exercise protocol). After acute exercise, livers were harvested for histopathological analysis, protein expression profiling, and immune cell population analysis. Acute exercise induced histological changes in the liver with infiltration of inflammatory cells, elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and increased hepatic Th17 cells and the Th17/Treg ratio, without significantly altering Treg cells, compared with the non-exercise group. DHM administration attenuated these changes, and this protective effect was associated with the restoration of the Th17/Treg balance. Administration of rIL-17A or aCD25 mAb blunted the protective effect of DHM. Our results suggest that DHM administration may serve as a potential protective strategy against exercise-induced transient hepatic dysfunction and inflammation, in association with the restoration of the Th17/Treg balance in mice.

Exhaustive exercise is known to induce muscle damage characterized by inflammation and oxidative stress. Although “regular” and “weekend warrior” exercise regimens have been shown to confer comparable health benefits in human studies, such as reduced risks of all-cause, cardiovascular disease (CVD), and cancer mortality, their differential impacts on muscle damage post-exhaustive exercise remain unclear. This study aimed to compare the effects of long-term, moderate-intensity (LTMI) and short-term, high-intensity (STHI) training modalities, matched for total exercise volume, on gut microbiota, short-chain fatty acids (SCFAs), and exhaustive exercise-induced muscle damage in mice, as well as to evaluate the correlation between these factors. LTMI is considered a regular exercise regimen, while STHI shares some similarities with the “weekend warrior” pattern, such as promoting exercise intensity and condensing training sessions into a short period. Our findings indicate that LTMI training significantly enhanced the abundance of SCFA-producing bacteria, including Akkermansia, Prevotellaceae_NK3B31_group, Odoribacter, Alistipes, and Lactobacillus, thereby increasing SCFA levels and attenuating muscle damage following exhaustive swimming. In contrast, STHI training increased the abundance of opportunistic pathogens such as Staphylococcus and Bilophila, without altering SCFA levels, and was associated with exacerbated muscle damage. Moreover, we observed a significant negative correlation between the abundance of SCFA-producing bacteria and SCFA levels with the expression of inflammatory cytokines in the muscle of mice post-exhaustive exercise. Conversely, the abundance of Staphylococcus and Bilophila showed a notable positive correlation with these cytokines. Additionally, the effects of LTMI and STHI on exhaustive exercise-induced muscle damage were transmissible to untrained mice via fecal microbiota transplantation, suggesting that gut microbiota changes induced by these training modalities may contribute to their contrasting impacts on muscle damage. These results underscore the significance of selecting an appropriate training modality prior to engaging in exhaustive exercise, with implications for athletic training and injury prevention.