Cold exposure remodels bile acid metabolism in a mouse strain- and tissue-specific manner.

Cold exposure remodels bile acid metabolism, but whether these changes are conserved across mouse strains and biological compartments is unclear. We profiled bile acid composition in C57BL/6J (C57) and C3H/HeJ (C3H) mice housed at 30°C or exposed to 10°C for 6, 24, or 72 h. Total, conjugated, and unconjugated bile acids were quantified in liver, plasma, and feces. In the liver, Cyp7a1 and Cyp8b1 increased after 24 h of cold in both strains, and Cyp2c70 and Cyp7b1 increased with higher levels in C3H. C57 showed decreases in taurine-conjugated muricholic acids (T-α-MCA, T-β-MCA, and T-ω-MCA) after 72 h of cold exposure, whereas C3H maintained or increased hepatic TCA, TUDCA, and β-MCA. In plasma, C57 accumulated conjugated bile acids at 72 h (TCA, TCDCA, TUDCA, and THDCA), while levels in C3H remained largely unchanged. In feces, total bile acids fell at 6 h in both strains, and conjugated species were consistently higher in C3H across conditions. C57 mice showed hepatic depletion and systemic accumulation of conjugated bile acids, while C3H maintained higher hepatic and fecal conjugates, consistent with enhanced excretory flux. These distinct profiles highlight TCA, TUDCA, β-MCA, and TCDCA as candidate bile acid species associated with cold-induced thermogenic adaptation. Together, our findings reveal that genetic background and temperature interact to shape bile acid handling and signaling, providing a framework to interpret variability in the metabolic outcomes of bile acid-based interventions.