Endogenous ligand for an orphan receptor.
The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) can be activated pharmacologically by fibrate drugs, lowering triglycerides and raising high-density lipoprotein. However, until recently, the endogenous ligand of PPARalpha had been unknown. A new study reports the identity of a physiologically relevant endogenous PPARalpha ligand as a phospholipid that is dependent upon a nutritionally responsive enzyme, fatty acid synthase. Mass spectrometry identified this phospholipid as 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16/18-GPC) and as the endogenous ligand of PPARalpha. In vivo experiments involving portal vein infusion of 16/18-GPC induced PPARalpha-dependent expression of the fatty acid metabolism genes acyl CoA oxidase and carnitine palmitoyl transferase.
Wolf
George
G
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California, USA. nutritionreviews@ilsi.org
D000818:Animals; D050260:Carbohydrate Metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism; D047493:PPAR alpha / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*
D008024:Ligands; D047493:PPAR alpha; D010713:Phosphatidylcholines; C028694:1-palmitoyl-2-oleoylphosphatidylcholine