Benefit of farnesoid X receptor inhibition in obstructive cholestasis.

ABSTRACT: The nuclear hormone receptors farnesoid X receptor (FXR) and pregnane X receptor have been implicated in regulating bile acid, lipid, carbohydrate, and xenobiotic metabolism. Bile duct ligation was used to increase endogenous bile acids and evaluate the roles of these receptors in modulating cholestatic liver injury. FXR knockout (KO) mice were found to be protected from obstructive cholestasis. Concurrent deletion of FXR also could ameliorate an increase in liver injury that is seen usually in pregnane X receptor KO mice with cholestasis. Mechanisms proposed for this protection include the lowering of bile acid concentrations and altered expression of the hepatic transporters Mdr1, Mdr2, BSEP, and Mrp4. FXR KO mice also exhibit a biphasic lipid profile after bile duct ligation, with an in

SUBMITTER: Stedman C 

PROVIDER: S-EPMC1544085 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature