Targeting the FXR Nuclear Receptor to Treat Liver Disease Brent A. Neuschwander-Tetri  Gastroenterology  Volume 148, Issue 4, Pages 704-706 (April 2015) DOI: 10.1053/j.gastro.2015.02.037 Copyright © 2015 AGA Institute Terms and Conditions

Figure 1 Obeticholic acid (OCA), a synthetic variant of the natural bile acid chenodeoxycholic acid, is a potent activator of the nuclear receptor farnesoid X receptor (FXR). Bile acids are the natural ligands for FXR and FXR activation decreases hepatocyte bile acid levels by decreasing hepatocyte uptake and synthesis of bile acids while increasing their biliary secretion, thus tightly regulating the bile acid pool. By decreasing the endogenous bile acid pool in patients on ursodeoxycholic acid (UDCA) for primary biliary cirrhosis, OCA decreased the potentially toxic endogenous bile acid pool which may reduce injury of the of biliary epithelium. FXR activation may also decrease lipogenesis and through this mechanism may have beneficial effects for nonalcoholic steatohepatitis (NASH). In both primary biliary cirrhosis (PBC) and NASH, decreasing the synthesis of bile acids from cholesterol also changed the serum cholesterol pool, but it is not clear if these changes are associated with an increased risk of cardiovascular disease. Gastroenterology 2015 148, 704-706DOI: (10.1053/j.gastro.2015.02.037) Copyright © 2015 AGA Institute Terms and Conditions