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

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Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors which are activated by fatty acids and derivatives. The PPARα form has been shown to mediate the action of the hypolipidemic drugs of the fibrate class on lipid and lipoprotein metabolism. PPARα activators furthermore improve glucose homeostasis and influence body weight and energy homeostasis. It is likely that these actions of PPARα activators on lipid, glucose and energy metabolism are, at least in part, due to the increase of hepatic fatty acid β-oxidation resulting in an enhanced fatty acid flux and degradation in the liver. Moreover, PPARs are expressed in different immunological and vascular wall cell types where they exert anti-inflammatory and proapoptotic activities. The observation that these receptors are also expressed in atherosclerotic lesions suggests a role in atherogenesis. Finally, PPARα activators correct age-related dysregulations in redox balance. Taken together, these data indicate a modulatory role for PPARα in the pathogenesis of age-related disorders, such as dyslipidemia, insulin resistance and chronic inflammation, predisposing to atherosclerosis.

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