Nuclear receptor regulation of lipid metabolism: potential therapeutics for dyslipidemia, diabetes, and chronic heart and liver diseases.
Lipids are essential components of biological membranes, fuel molecules and metabolic regulators that control cellular functions, metabolism and homeostasis. The liver plays a central role in regulating lipid metabolism and whole body lipid homeostasis. Sterols, bile acids and fatty acids are the endogenous ligands of the liver orphan receptor, farnesoid X receptor, peroxisome proliferator-activated receptor, vitamin D receptor, constitutive androstane receptor and pregnane X receptor. These metabolic receptors coordinately regulate lipid, glucose, energy and drug metabolism. Alteration of lipid homeostasis causes dyslipidemia, which is a major risk factor contributing to atherosclerotic cardiovascular diseases, diabetes, obesity and liver diseases. Advances in the understanding of the mechanisms of nuclear receptor regulation of lipid homeostasis have provided an opportunity to investigate potential therapeutic drugs targeted to nuclear receptors. This could be useful for the treatment of diabetes, and cardiovascular and chronic liver diseases.
Chiang
John Y L
JY
Northeastern Ohio University's College of Medicine, Department of Biochemistry & Molecular Pathology, Rootstown, OH 44272, USA. jchiang@neoucom.edu
D000818:Animals; D002908:Chronic Disease; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism; D006331:Heart Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D050356:Lipid Metabolism; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D018160:Receptors, Cytoplasmic and Nuclear