Roles of Ileal ASBT and OSTα-OSTß in Regulating Bile Acid Signaling.

ABSTRACT

BACKGROUND: In addition to their classical role as detergents, bile acids function as signaling molecules to regulate gastrointestinal physiology, carbohydrate and lipid metabolism, and energy expenditure. The pharmacodynamic potential of bile acids is dependent in part on the tight pharmacokinetic control of their concentration and metabolism, properties governed by their hepatic synthesis, enterohepatic cycling, and biotransformation via host and gut microbiota-catalyzed pathways. Key Messages By altering the normal cycling and compartmentalization of bile acids, changes in hepatobiliary or intestinal transport can affect signaling and lead to the retention of cytotoxic hydrophobic bile acids and cell injury. This review discusses advances in our understanding of the intestinal transporters that maintain the enterohepatic cycling of bile acids, signaling via bile acid-activated nuclear and G protein receptors, and mechanisms of bile acid-induced cell injury. CONCLUSIONS: Dysregulated expression of the Asbt and Ostα-Ostß alters bile acid signaling via the gut-liver farnesoid X receptor-fibroblast growth factor 15/19 axis and may contribute to other bile acid-regulated metabolic and cell injury pathways.