RT Journal Article SR Electronic T1 MOLECULAR REGULATION OF BILE ACID HOMEOSTASIS JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP DMD-MR-2021-000643 DO 10.1124/dmd.121.000643 A1 Supratim Choudhuri A1 Curtis D. Klaassen YR 2021 UL http://dmd.aspetjournals.org/content/early/2021/10/22/dmd.121.000643.1.abstract AB Bile acids have been known for decades to aid in the digestion and absorption of dietary fats and fat-soluble vitamins in the intestine. The development of gene knockout mice models and transgenic humanized mouse models have helped us understand other function of bile acids, such as their role in modulating fat, glucose, and energy metabolism, and in the molecular regulation of the synthesis, transport, and homeostasis of bile acids. The G-protein coupled receptor TGR5 regulates the bile acid induced alterations of intermediary metabolism, while the nuclear receptor FXR regulates bile acid synthesis and homeostasis. However, this review indicates that unidentified factors in addition to FXR must exist to aid in the regulation of bile acid synthesis and homeostasis. Significance Statement This review captures the present understanding of bile acid synthesis, the role of bile acid transporters in the enterohepatic circulation of bile acids, the role of the nuclear receptor FXR on the regulation of bile acid synthesis and bile acid transporters, and the importance of bile acids in activating GPCR signaling via TGR5 to modify intermediary metabolism. This information is useful for developing drugs for the treatment of various hepatic and intestinal diseases, as well as the metabolic syndrome.