The farnesoid X receptor (FXR) as a new target in non-alcoholic steatohepatitis

Abstract

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is mainly expressed in liver, intestine, kidney and adipose tissue. On activation by bile acids, FXR regulates a wide variety of target genes that are critically involved in the control of bile acid, lipid and glucose homeostasis. Thus, FXR appears to be a promising target for the treatment of non-alcoholic steatohepatitis (NASH). Notably, FXR activation inhibits hepatic de novo lipogenesis, increases insulin sensitivity and protects hepatocytes against bile acid-induced cytotoxicity. More recent data also indicate a critical role of FXR in liver regeneration and hepatocarcinogenesis. For this reason, the development of FXR agonists and/or modulators (SBARMs) may prove to be clinically useful for treating NASH. While preclinical studies in rodents support this hypothesis, clinical studies are still warranted in humans.