Resistance Training Alleviates Skeletal Muscle Atrophy in Rats Exposed to Hypoxia by inhibiting Autophagy Mediated by Acetyl-FoxO1

Abstract

Background: Skeletal muscle atrophy induced by hypoxia could affect the physical fitness and training effect of the athletes in the rapid altitude, and also affect the production and life of the general public. Resistance training in a hypoxic environment could effectively alleviate the occurrence of muscular atrophy. Whether autophagy lysosomal pathway, as an important proteolysis pathway, is involved in this process, and whether FoxO1, the key gene of atrophy, plays a role by regulating autophagy is unclear. Methods: Male Sprague-Dawley (SD) rats were randomly divided into normoxic control group (group C), normoxic resistance-training group (group R), hypoxic control group (group H), and hypoxic resistance-training group (group HR). The H and HR groups were exposed to 12.4% oxygen for four weeks. The R and HR groups underwent incremental loaded training by climbing a ladder every other day for four weeks. Results: Compared to parameters in group H, resistance training increased lean body mass (LBM) and wet weight and decreased the expression of atrogin1 of the extensor digitorum longus (EDL) after four weeks ( P <0.05). Resistance training decreased the levels of FoxO1 and Ac-FoxO1 and the extent of their localization in the nucleus and cytoplasm, respectively ( P <0.05), as well as the LC3II/LC3I ratio, the integrated optical density (IOD) of LC3 and the levels of autophagy-related gene 7 (Atg7), and elevated the levels of sequestosome 1 (SQSTM1/p62) ( P <0.05). Most differentially expressed autophagy-related genes (ATGs) interacted with FoxO1, and the functions of these ATGs were mainly enriched in the early autophagy phase. Conclusions: Our findings demonstrate that resistance training lowers the levels of both nuclear FoxO1 and cytoplasmic Ac-FoxO1, as well as reduced autophagic flux in the EDL of rats exposed to hypoxia.