Active bile acid metabolism could contribute to muscle preservation in hibernating bears via the TGR5 pathway.

Hibernation is an adaptive strategy that enables certain mammals to survive prolonged periods of starvation and physical inactivity, while maintaining muscle mass. Although some bile acids (BA) have been shown to regulate proteostasis in cell models, their possible role during hibernation has not yet been examined in detail. In the present study, we comprehensively compared serum and feces BA profiles in brown bears (Ursus arctos) during hibernation and the active season and examined bear muscle expression levels of main actors in the BA-mediated signaling pathways and bear microbiota composition. Total serum BA concentration was significantly reduced in hibernating bears; however, the ratio of concentrations of secondary BA to primary BA was higher during hibernation. This indicates that BA metabolism remains active during hibernation, the mechanisms of which we were able to link to both hepatic pathways (transcriptomics) and bear microbiota. Nevertheless, we noted a drastic increase in taurolithocholic acid (TLCA) levels in hibernating bears. Analysis of BA signaling pathways in bear muscle enabled us to show that the BA/TGR5 axis appears to be maintained, presumably to help maintain mitochondrial biogenesis and preserve muscle cell differentiation capacity. This study investigates and suggests potential new mechanisms for the preservation of skeletal muscle during hibernation, which builds the foundation for the development of future treatments for muscle atrophy in humans.