Chronic Stress Induces Type 2b Skeletal Muscle Atrophy via the Inhibition of mTORC1 Signaling in Mice

Abstract

Chronic stress induces psychological and physiological changes that may have negative sequelae for health and well-being. In this study, the skeletal muscles of male C57BL/6 mice subjected to repetitive water-immersion restraint stress to model chronic stress were examined. In chronically stressed mice, serum corticosterone levels significantly increased, whereas thymus volume and bone mineral density decreased. Further, body weight, skeletal muscle mass, and grip strength were significantly decreased. Histochemical analysis of the soleus muscles revealed a significant decrease in the cross-sectional area of type 2b muscle fibers. Although type 2a fibers also tended to decrease, chronic stress had no impact on type 1 muscle fibers. Chronic stress increased the expression of REDD1, FoxO1, FoxO3, KLF15, Atrogin1, and FKBP5, but did not affect the expression of myostatin or myogenin. In contrast, chronic stress resulted in a decrease in p-S6 and p-4E-BP1 levels in the soleus muscle. Taken together, these results indicate that chronic stress promotes muscle atrophy by inhibiting mammalian targets of rapamycin complex 1 activity due to the upregulation of its inhibitor, REDD1.

The Influence of Stress and Binge-Patterned Alcohol Drinking on Mouse Skeletal Muscle Protein Synthesis and Degradation Pathways

“…In contrast to stress exposure, ten days of binge-patterned alcohol ingestion did not influence puromycin incorporation in mouse gastrocnemius muscle. However, notable disruptions were observed along the Akt-mTOR pathway that could be consistent with the impaired MPS reported by other studies [46,69]. Alcohol access decreased the phosphorylation of p70S6K and p-mTOR levels.…”

“…Repeated exposure to restraint stress can result in muscle atrophy [11,15,46,69], yet whether rates of MPS are sensitive to stress exposure versus repeated bouts of immobility is less clear. Our data, in which MPS was suppressed nearly two weeks after stress, suggest that stress per se may contribute to a possible long-term disruption in muscle protein balance, although the immobility may further promote muscle atrophy, as observed in chronic restraint models [11,46], that was not observed here.…”