Bile acid-activated receptors in the treatment of dyslipidemia and related disorders.

摘要: Dyslipidemia is a metabolic disorder that constitutes major risk factor for cardiovascular diseases and stroke often associated with diabetes mellitus atherosclerosis. In recent years number of ligand-activated receptors have been found to exert role in integrating essential steps lipid glucose metabolism. Bile acid-activated are defined subset nuclear G-protein coupled mainly expressed entero-hepatic tissues which bile acids function as signaling molecules. Primary (chenodeoxycholic acid cholic acid) physiological ligands/activators farnesoid-X-receptor (FXR), pregnane-X-receptor (PXR) constitutive androstane receptor (CAR), while litocholic ligand the Vitamin D (VDR) TGR5. Despite FXR demonstrates high selectivity acids, PXR CAR relatively promiscuous homeostasis xenobiotic FXR, PXR, TGR synergistic activities regulating energy expenditure liver peripheral insulin sensitivity. Ligands these hold promise treatment dyslipidemic conditions revealed by results preclinical models but carry potential side effects.