Resveratrol regulates skeletal muscle fibers switching through the AdipoR1-AMPK-PGC-1α pathway

Abstract

This study was conducted to investigate the effect and underlying mechanism of Resveratrol (RES) in regulating skeletal muscle fiber-type switching. We found that RES had no effect on the body weight and food intake of Kunming mice (KM mice) that were orally administered with 400 mg kg⁻¹ d⁻¹ RES for 12 weeks. Notably, the RES administration significantly increased the expression of myosin heavy chain (MyHC) 1, MyHC2a, and MyHC2x in the extensor digitorum longus (EDL) and soleus (SOL) muscles. Furthermore, the muscle immunostaining of the results showed that the RES treatment led to the myofiber type transition from glycolytic to oxidative in muscles. The mRNA and protein levels of the adiponectin receptor (AdipoR), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in EDL and SOL were drastically increased after RES treatment. Moreover, the plasma Adiponectin (AdipoQ) protein levels were higher in the RES-treated mice compared to the control mice. Moreover, the in vitro results further demonstrated that the 20 μM RES treatment increased the expression of AdipoR1, AdipoR2, AMPK, PGC-1α and MyHC1, but decreased the expression of MyHC2b in C2C12 myoblasts. Furthermore, mechanistic studies revealed that silencing the AdiopR1, not the AdiopR2, abolished the effect of RES on the expression of AMPK and PGC-1α in the C2C12 cells. These results indicated that RES could regulate skeletal fiber switching through the AdiopR1-AMPK-PGC-1α pathway. This work may provide a new strategy for enhancing endurance and relieving muscle diseases caused by oxidative muscle fiber deficiency.