PPARs: transcription factors controlling lipid and lipoprotein metabolism

Abstract

Nuclear receptors are transcription factors that are activated by ligands and subsequently bind to regulatory regions in target genes, thereby modulating their expression. Nuclear receptors thus allow the organism to integrate signals coming from the environment and to adapt by modifying the expression levels of relevant genes. The peroxisome proliferator-activated receptors (PPARs) alpha, beta/delta, and gamma constitute a subfamily of nuclear receptors. PPARalpha has been shown to bind and to be activated by leukotriene B4 and the hypolipidemic drugs of the fibrate class; PPARbeta/delta ligands are polyunsaturated fatty acids and prostaglandins; while prostaglandin J2 derivatives and the antidiabetic glitazones are, respectively, natural and synthetic ligands for PPARgamma. Upon binding and activation by their ligands, they regulate the transcription of numerous genes involved in intracellular lipid metabolism, lipoprotein metabolism, and reverse cholesterol transport in a subtype- and tissue-specific manner. PPARs therefore constitute interesting targets for the development of therapeutic compounds useful in the treatment of disorders of lipid and lipoprotein metabolism.