Abstract
It has been proposed that diet-induced obesity at thermoneutrality (TN; 29°C) is reduced by a UCP1-dependent thermogenesis; however, it has not been shown how UCP1-dependent thermogenesis can be activated in the absence of sympathetic activity. A recent study provides such a mechanism by showing that dietary bile acids (BAs) suppress obesity in mice fed a high-fat diet (HFD) by a mechanism dependent on type 2 deiodinase (DIO2); however, neither a role for UCP1 nor the influence of sympathetic activity was properly assessed. To test whether the effects of BAs on adiposity are independent of Ucp1 and cold-activated thermogenesis, obesity phenotypes were determined in C57BL6/J.(+)/(+) (WT) and C57BL6/J.Ucp1.(-)/(-) mice (Ucp1-KO) housed at TN and fed a HFD with or without 0.5% (wt/wt) cholic acid (CA) for 9 wk. CA in a HFD reduced adiposity and hepatic lipogenesis and improved glucose tolerance in WT but not in Ucp1-KO mice and was accompanied by increases in food intake and energy expenditure (EE). In iBAT, CA increased Ucp1 mRNA and protein levels 1.5- and twofold, respectively, and increased DIO2 and TGR5 protein levels in WT mice. Despite enhanced Dio2 expression in Ucp1-KO and Ucp1-KO-CA treated mice, this did not enhance the ability of BAs to reduce obesity. By comparing the effects of BAs on WT and Ucp1-KO mice at TN, our study showed that BAs suppress diet-induced obesity by increasing EE through a mechanism dependent on Ucp1 expression, which is likely independent of adrenergic signaling.