Role of farnesoid X receptor in hepatic steatosis in nonalcoholic fatty liver disease

With the increased incidence of obesity, nonalcoholic fatty liver disease (NAFLD) has become a major global health concern. The pathogenesis of NAFLD has not yet been fully elucidated, and as few efficient pharmaceutical treatments are available for the condition, economic and medical burdens are heavy. Hepatic steatosis, as a precursor of NAFLD, plays a vital role in the pathological process of NAFLD. Hepatic steatosis is a consequence of lipid acquisition (i.e. free fatty acid uptake and de novo lipogenesis) exceeding lipid disposal (i.e. fatty acid oxidation and export as very-low-density lipoproteins). Therefore, restoring lipid homeostasis in the liver is an important therapeutic strategy of NAFLD. Farnesoid X receptor (FXR) is a major member of the ligand-activated nuclear receptor superfamily. Previous reviews have shown that FXR is a multipurpose receptor that plays an important role in regulating bile acid homeostasis, glucose and lipid metabolism, intestinal bacterial growth, and hepatic regeneration. This review focuses on the role of FXR in individual pathways that contribute to hepatic steatosis; it further demonstrates the molecular function of FXR in the pathogenesis of NAFLD.