Peroxisome proliferator-activated receptor alpha in metabolic disease, inflammation, atherosclerosis and aging

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors w hich are activated by fatty acids and derivatives. The PPAR alpha form has been shown to mediate the action of the hypolipidemic drugs of the fibrate class on lipid and lipoprotein metabolism. PPAR alpha activators furthermor e improve glucose homeostasis and influence body weight and energy homeosta sis. It is likely that these actions of PPAR alpha activators on lipid, glu cose and energy metabolism are, at least in part, due to the increase of he patic fatty acid beta-oxidation resulting in an enhanced fatty acid flux an d degradation in the liver. Moreover, PPARs are expressed in different immu nological and vascular wall cell types where they exert antiinflammatory an d proapoptotic activities. The observation that these receptors are also ex pressed in atherosclerotic lesions suggests a role in atherogenesis, Finall y, PPAR alpha activators correct age-related dysregulations in redox balanc e. Taken together, these data indicate a modulatory role for PPAR alpha in the pathogenesis of age-related disorders, such as dyslipidemia, insulin re sistance and chronic inflammation, predisposing to atherosclerosis. Curr Op in Lipidol 10:151-159. (C) 1999 Lippincott Williams & Wilkins.