Fig. 1.

FXR controls the enterohepatic cycle of bile acids. FXR activation by BAs protects the liver against BAs’ accumulation through a multistep mechanism involving a communication between the liver and intestine. In the intestine, FXR activation by BAs reduces bile acid uptake from the intestinal lumen and increases BAs’ cellular trafficking and export into the portal circulation. In addition, FXR activation in the intestine (distal ileum) increases FGF15 synthesis and export into the portal system. FGF15 through its membrane receptor FGFR4 decreases hepatic bile acid biosynthesis through SHP-dependent and SHP-independent mechanisms, mostly affecting Cyp7a1 activity, and hence CDCA synthesis. Hepatic FXR activation increases bile acid efflux from hepatocytes through the regulation of transporters’ expression (OSTα/β, BSEP and MDR3). FXR represses bile acid uptake into the hepatocyte through the repression of the NTCP transporter. This figure has been made using Servier Medical Art according to the license Creative Commons Attribution 3.0 France