title: Pleiotropic functions of bile acids mediated by the farnesoid X receptor.
abstract: In addition to their well-established role in the digestion and absorption of dietary lipids, bile acids (BAs) are recognized as signalling molecules in a wide range of metabolic processes. Bile acids regulate their own metabolism and enterohepatic circulation by activating the farnesoid X receptor (FXR). BAs have been shown to affect lipid metabolism, to decrease levels of circulating triglycerides, improve hyperglycemia and insulin signalling, directly act on the arterial wall and protect hepatocytes against cholestatic liver injury. Given that BAs are an integrated part of the complex metabolic network regulated by FXR, acting as a major underlying pathway, specific therapeutic targeting of this nuclear receptor represents an attractive therapeutic approach for a wide range of disorders. During a phase II clinical trial, the administration of a semisynthetic BA derivative 6-ethyl-chenodeoxycholic acid (6-ECDCA) to patients with diabetes, non-alcoholic fatty liver disease (NAFLD) and primary biliary cirrhosis (PBC), led to encouraging results, despite side effects being observed in pre-clinical studies. Chemical manipulations of the side chain and the steroid nucleus of BAs could lead to the discovery of novel semisynthetic BA derivatives that are more specific and selective FXR activators.
authors: Department of Pharmacology, Toxicology and Clinical Pharmacology, Medical Faculty Novi Sad, University of Novi Sad, Hajduk Veljkova 3, Serbia. bojanstanimirov@yahoo.com
authors: B
authors: B
authors: Stanimirov
authors: K
authors: K
authors: Stankov
authors: M
authors: M
authors: Mikov
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D002779:Cholestasis / Q000188:drug therapy / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002986:Clinical Trials as Topic; D004041:Dietary Fats / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004764:Enterohepatic Circulation; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D002784:Cholesterol; D004041:Dietary Fats; D005947:Glucose; D018160:Receptors, Cytoplasmic and Nuclear; D014280:Triglycerides; D000099150:Receptor, Farnesoid X-Activated