Advances in the Regulation of Hepatic Lipid Metabolism by the Nuclear Receptor FXR

Hepatic steatosis is a consequence of lipid acquisition (i.e. increased free fatty acid uptake and de novo lipogenesis) exceeding lipid disposal (i.e. decreased fatty acid β-oxidation and relatively inadequate lipoprotein output). Restoration of hepatic lipid homeostasis, therefore, is currently the main therapeutic strategy for liver diseases in which steatosis is the main pathological manifestation. Farnesoid X receptor (FXR) is a major member of the ligand-activated nuclear receptor superfamily, and numerous studies have shown its important role in regulating bile acid homeostasis, glucose and lipid metabolism, inflammation, intestinal bacterial growth, and hepatic regeneration. This paper reviews the regulatory roles of FXR and its post-translational modifications on various pathways of hepatic lipid uptake, synthesis, oxidation and transport, and outlines the current status of development of small molecule ligand drugs targeting FXR, with the aim of providing insights to further elucidate the molecular mechanisms of liver diseases characterized by hepatic steatosis.