title: Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice.
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.
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
authors.forename: Marika
authors.initials: M
authors.lastname: Zietak
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland l.kozak@pan.olsztyn.pl.
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Kozak
mesh_terms: D050154:Adiposity / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D019826:Cholic Acid / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects* / Q000235:genetics; D005951:Glucose Tolerance Test; D007453:Iodide Peroxidase / Q000187:drug effects / Q000235:genetics; D007473:Ion Channels / Q000235:genetics*; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects* / Q000235:genetics; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D001647:Bile Acids and Salts; D019826:Cholic Acid; D007453:Iodide Peroxidase; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II; C000604372:Ucp1 protein, mouse
keywords: bile acids; brown adipose tissue; diet-induced obesity; mitochondrial uncoupling protein 1; thermogenesis; type 2 deidodinase