Regulation of HiLo on AMPK/TSC2/mTOR Signaling pathway in Skeletal Muscle of Rats

• 1、College of P.E., Central China Normal University, WuHan 430079
• 2、College of Sport Science, Beijing Sport University, Beijing 100084, China

Abstract：Objective: The present study focused on the mechanism of hypoxia regulating skeletal muscle protein synthesis, and investigated the changing characteristics of AMPK/TSC2/mTOR signaling pathway in skeletal muscle after 4 weeks HiLo training programe. Methods: Male SD rats were randomly divided into groups: normoxia sedentary group, normoxia exercise group, hypoxia comparison group and HiLo group. A hypoxia exposure mode was used from 10 hours from 10 p.m. to 8 a.m. (oxygen concentration 13.6%). A normoxia exercise mode is defined as endurance exercise for 1 hour in a normoxia environment in the daytime. The HiLo group performs hypoxia exposure in the hypoxia room at night after endurance exercise in the daytime, the exercise mode and the hypoxia exposure mode of which are respectively identical to that of the normoxia exercise group and the hypoxia exposure group. AMP and ATP contents in extensor digitorum longus (EDL) of a rat were examined by HPLC analysis. The phosphorylation of LKB1 Ser428, AMPK Thr172, TSC2 Thr1462, mTOR Ser2448, p70S6K Thr389 and 4EBP1 Thr37/46 were examined by western blotting analysis. Results: (1) After 4 weeks hypoxia exposure, AMP content, AMP/ATP ratio and the phosphorylation of LKB1 and AMPK in skeletal muscle were increased remarkably, and phosphorylation of MHC, mTOR and downstream signals were inhibited remarkably. (2) After 4 weeks normoxia exercise, the phosphorylation of MHC, LKB1, AMPK, mTOR and downstream signals were increased remarkably, and the phosphorylation of TSC2 was inhibited. (3) After 4 weeks HiLo training programe, the effects of hypoxia on MHC, mTOR and downstream signals in skeletal muscle were attenuated by HiLo. Conclusions: (1) Hypoxia inhibits protein synthesis in skeletal muscle via AMPK/TSC2/mTOR signaling pathways, but exercise facilitates the synthesis by amplifying mTOR signal. (2) HiLo training can attenuate the inhibition effect of hypoxia on protein synthesis in skeletal muscle.

Keywords： HiLo LKB1 AMP/ATP AMPK mTOR