Chenodeoxycholic acid attenuates high-fat diet-induced obesity and hyperglycemia via the G protein-coupled bile acid receptor 1 and proliferator-activated receptor [gamma] pathway

G protein-coupled bile acid receptor 1 (TGR5) serves a key function in regulating glycometabolism. TGR5 is highly expressed in the mitochondria of brown adipose tissue (BAT) and downregulates adenosine triphosphate synthesis via the bile acid-TGR5-cyclic adenosine monophosphate-2-iodothyronine deiodinase (D2)-triiodothyronine-uncoupling protein pathway, thus regulating energy homeostasis and reducing body weight. Chenodeoxycholic acid (CDCA), the primary bile acid, is a natural ligand of TGR5. The present study aimed to characterize the ability of CDCA to reduce high-fat diet-induced obesity and improve glucose tolerance. A mouse model of diet-induced obesity was constructed. The results demonstrated that a high-fat diet significantly increased the weight of mice after 10 weeks (P