Targeting nuclear bile acid receptors for liver disease

Abstract

Bile acids (BAs) are able to activate a range of dedicated nuclear receptors (NRs) which play a key role in the transcriptional control of critical steps of a wide range of hepatic functions ranging from BA homeostasis and bile formation, phase I/II metabolism of endo- and xenobiotics such as BAs and drugs, respectively, to hepatic lipids and glucose metabolism. Apart from these metabolic roles, BA-activated nuclear receptors also play a key role in the control of hepatic inflammation, fibrogenesis, replication of hepatitis B and C virus, liver regeneration and carcinogenesis. As such, several physiological and pathophysiological effects of BAs can now be explained through activation of regulatory NR networks. Moreover, BA-activated NRs are key for understanding the pathogenesis of several liver diseases and represent attractive drug targets. This article will provide a brief overview on the role of BA-activated NRs in cholestatic and fatty liver disease.