Altered signaling pathway governing protein metabolism in skeletal muscle of the Japanese black bear during hibernation

Hibernating mammals experience prolonged periods of torpor and starvation during winter survival. While continued physical inactivity and malnutrition lead to profound loss of skeletal muscle in most mammals, hibernating animals show limited muscle atrophy and can successfully maintain physical function following hibernation. Since net balance between protein synthesis and degradation determines total mass of skeletal muscle, we hypothesized that hibernating animals uniquely alter the regulatory mechanisms governing protein metabolism to prevent muscle atrophy during hibernation. In this study, alteration of signaling pathways regulating protein metabolism was examined in skeletal muscle of the Japanese black bear ( Ursus thibetanus japonicus ). Sartorius muscle samples were collected from bear leg on late November and early April (pre/post‐hibernation). Ubiquitin‐proteasome pathway (as assessed by increased expression of Atrogin1 and MuRF1 mRNA) was significantly activated in skeletal muscle following hibernation. In contrast, as indicated by a significant increase in S6K1 phosphorylation, activation state of mTOR signaling which functions as a central regulator of protein synthesis was increased following hibernation. Additionally, gene expression of myostatin, a negative regulator of muscle mass, was significantly decreased on post‐hibernation. These observations suggest that protein synthesis rate may be enhanced in skeletal muscle of hibernating bear, which then lead to limited loss of muscle mass and maintenance of physical performance. This work was supported by JSPS KAKENHI Grant Number 25702041 and 26560369.