Resveratrol prevents TNF-α-induced muscle atrophy via regulation of Akt/mTOR/FoxO1 signaling in C2C12 myotubes.

Abstract: Muscle atrophy poses a serious concern to patients inflicted with inflammatory diseases. There is now increasing evidence which suggests a vital role for tumor necrosis factor alpha (TNF-α) in muscle pathology associated with impairment of differentiation and muscle wasting. Resveratrol has been an ascribed inhibitory effect on glucocorticoid-induced muscle atrophy in vitro, but the influence of resveratrol on the growth of C2C12 myotubes exposed to TNF-α remains unclear. The present study aimed to investigate the involvement of TNF-α in the regulation of skeletal muscle hypertrophy and atrophy, and the possibility to interfere with such modulations by means of resveratrol supplementation. For this purpose, C2C12 myotubes were treated with TNF-α in the presence or absence of resveratrol. Myotube treatment with TNF-α contributes to both hyperexpression of the muscle-specific ubiquitin ligase MAFbx and MuRF1, and these alterations are linked to a decrease of anabolic targets (Akt, mTOR, p70S6k and 4E-BP1) and an increase of catabolic targets (FoxO1, FoxO3a, MAFbx and MuRF1). Resveratrol supplementation effectively counteracts TNF-α induced muscle protein loss and reverses declining expression of Akt, mTOR, p70S6K, 4E-BP1and FoxO1, but exerts no influence of FoxO3a expression. Our study demonstrates that resveratrol can reverse the muscle cell atrophy caused by TNF-α through regulation of the Akt/mTOR/FoxO1 signaling pathways, followed by inhibition of the atrophy-related ubiquitin ligase. Our findings suggested that resveratrol could represent a possible strategy to improve muscle mass. [Copyright &y& Elsevier]