Sorting out the roles of PPARα in energy metabolism and vascular horneostasis

PPAR alpha 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 figand-activated transcription factor regulates the expression of genes encoding enzymes and transport proteins controlling lipid homeostasis, thereby stimulating FA oxidation and improving lipoprotein metabolism. PPAR alpha also exerts pleiotropic antiinflammatory and and proliferative effects and prevents the proatherogenic effects of cholesterol accumulation in macrophages by stimulating cholesterol efflux. Cellular and animal models of PPAR alpha help explain the clinical actions of fibrates, synthetic PPAR alpha 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 PPAR alpha in humans, recent findings have revealed potential adverse effects of PPAR alpha action, underlining the need for further study. This Review will focus on the mechanisms of action of PPAR alpha. in metabolic diseases and their associated vascular pathologies.