Resistance exercise preconditioning prevents disuse muscle atrophy by inhibiting apoptosis and protein degradation via SESN2 in C57BL/6J mice

Abstract

AimTo compare the effects of different exercise preconditioning in the context of skeletal muscle atrophy and to investigate the potential involvement of Sestrin2 (SESN2), a stress-inducible protein that can be regulated by exercise, in exercise preconditioning on preventing disuse muscle atrophy. MethodsEight-week-old male C57BL/6J mice were randomly assigned to sedentary groups (SD), aerobic exercise groups (AE), resistance exercise groups (RE), and combined exercise groups (CE) with or without 7 days of immobilization. The duration of the exercise intervention was 10 weeks. The effects of different exercise preconditioning to prevent muscle atrophy were analyzed by evaluating skeletal muscle function and mass. Additionally, to investigate the potential underlying mechanism of exercise-induced protection of skeletal muscle, wild-type and SESN2‐−/‐− mice were randomly divided into sedentary group and resistance exercise preconditioning group. C2C12 cells were treated with SESN2 adenoviruses and MK2206 (an AKT inhibitor) for 48 h to elucidate the underlined mechanism. ResultsRE was more effective in preserving skeletal muscle function, muscle mass and maintaining skeletal muscle protein homeostasis than AE and CE under immobilized condition. Importantly, exercise performance, muscle mass to body weight ratio, and the cross-sectional area of muscle fibers were significantly lower in SESN2−/− mice than wild-type mice after resistance exercise preconditioning. Mechanistically, the absence of SESN2 led to activation of the ubiquitin-proteasome system and induction of apoptosis. In vitro experiments showed that MK2206 treatment mitigated the regulatory effects of overexpression-SESN2 on protein hydrolysis and apoptosis. ConclusionRE was more effective than AE or CE in preventing disuse muscle atrophy. SESN2 mediated the protective effects of resistance exercise preconditioning on skeletal muscle atrophy.