BACKGROUND

The gradual rise in global temperatures can affect skeletal muscle development and intestinal microorganisms. However, the influence of microbial metabolites on skeletal muscle homeostasis under heat stress (HS) remains unclear.

METHODS

C57BL/6J mice were exposed to normal temperature or 40 °C conditions for 3 d, 7 d, or 14 d. The HS 7 d mice also were treated with sodium butyrate (NaB, 200 mg/kg, gavage).

RESULTS

Strikingly, the body weight, antioxidative ability (MDA, T-SOD, and GSH-Px), and average cross-sectional area decreased, but the blood glucose and core temperature increased under HS. However, the NaB treatment reversed these effects. Meanwhile, HS also increased the levels of TNF-α and CORT. Additionally, HS led to a reduction in the villus height and an increase in the crypt depth of the intestine. Microbial 16S rRNA sequencing analysis revealed that HS caused gut microbiota dysbiosis. NaB increased the expression of HSP70 under HS, to maintain skeletal muscle homeostasis. HS stimulated the expression of Pax7, which indicates that skeletal muscle homeostasis was disrupted. Meanwhile, the expressions of MyoG and MyoD were decreased under HS. The immunofluorescence results also show that HS triggered a shift from slow muscle fibers (MYH7) to fast muscle fibers (MYH1). However, NaB recovered the expressions of these muscle-related factors. HS inhibited autophagy initiation (mTOR, Beclin1, Atg5, Atg7, and Atg12), the formation (LC3 II/LC3 I) of autophagosomes, and the binding (p62 and LAMP1) of lysosomes to autophagosomes, which were activated by NaB. C2C12 cells were treated with HO to simulate skeletal muscle oxidative stress, and treated with NaB in advance. Oxidative stress disrupted the homeostasis of the C2C12 cells, characterized by an increase in Pax 7 and decreases in MyoG and MyoD, but these changes were reversed by the NaB treatment. Meanwhile, NaB was unable to maintain the stable expression of Pax7 when autophagy was inhibited.

CONCLUSIONS

This suggests that NaB can regulate oxidative stress induced by HS through autophagy to maintain skeletal muscle homeostasis.