Alteration of bile acid metabolism in mice under thermoneutral conditions

Metabolic responses in mice at thermoneutrality (TN; 30°C) closely reflect those in humans rather than at conventional ambient temperature (CT; 22°C). However, the effect of TN on bile acid (BA) metabolism remains unclear. In this study, mice were maintained at CT or TN for 6 weeks, and BA profiles were quantitatively assessed at several sites, including enterohepatic and systemic circulation. TN markedly increased feed efficiency, adipose tissue mass, and hepatic and circulating triglyceride levels. Moreover, the ratio of 12-hydroxylated to non-12-hydroxylated BAs was elevated in the liver, small intestinal contents, and feces in mice maintained at TN. The ratios of primary to secondary BAs and of conjugated to unconjugated BAs were consistently reduced across sites, suggesting enhanced microbiota-dependent BA metabolism at TN. Collectively, these findings indicate that TN shifts murine BA composition toward a more human-like profile, highlighting the significance of TN models in terms of BA metabolism.