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Publication : Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis.

First Author  Lefebvre P Year  2006
Journal  J Clin Invest Volume  116
Issue  3 Pages  571-80
PubMed ID  16511589 Mgi Jnum  J:106488
Mgi Id  MGI:3618655 Doi  10.1172/JCI27989
Citation  Lefebvre P, et al. (2006) Sorting out the roles of PPARalpha in energy metabolism and vascular homeostasis. J Clin Invest 116(3):571-80
abstractText  PPARalpha is a nuclear receptor that regulates liver and skeletal muscle lipid metabolism as well as glucose homeostasis. Acting as a molecular sensor of endogenous fatty acids (FAs) and their derivatives, this ligand-activated transcription factor regulates the expression of genes encoding enzymes and transport proteins controlling lipid homeostasis, thereby stimulating FA oxidation and improving lipoprotein metabolism. PPARalpha also exerts pleiotropic antiinflammatory and antiproliferative effects and prevents the proatherogenic effects of cholesterol accumulation in macrophages by stimulating cholesterol efflux. Cellular and animal models of PPARalpha help explain the clinical actions of fibrates, synthetic PPARalpha agonists used to treat dyslipidemia and reduce cardiovascular disease and its complications in patients with the metabolic syndrome. Although these preclinical studies cannot predict all of the effects of PPARalpha in humans, recent findings have revealed potential adverse effects of PPARalpha action, underlining the need for further study. This Review will focus on the mechanisms of action of PPARalpha in metabolic diseases and their associated vascular pathologies.
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