Farnesoid X receptor (FXR) as a potential therapeutic target in nonalcoholic fatty liver disease and associated syndromes

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a group of obesity-associated pathological changes characterized by abnormal accumulation of lipids in cells of the liver parenchyma. NAFLD and associated conditions, namely insulin resistance and type II diabetes mellitus (DM2), as well as the possible risks of developing fibrosis and cirrhosis with a potential outcome in hepatocellular carcinoma, represent the primary health problems in developed countries, gradually replacing the importance of similar pathologies caused by the regular use of hepatotoxic doses of alcoholic beverages. Recent fundamental and clinical studies demonstrated the important role of the farnesoid receptor (FXR, NR1H4) in the regulation of the metabolism of glucose, lipids and bile acids. This review focuses on the molecular aspects of the pathogenesis of NAFLD, the role of FXR (NR1H4) in the biology of this disease, and the prospects for using different FXR (NR1H4) modulators for therapy of NAFLD and associated conditions such as metabolic syndrome and DM2, as well as a number of other FXR (NR1H4) mediated diseases.