Peroxisome proliferator-activated receptors: a nuclear hormone receptor involved in adipocyte differentiation and lipid homeostasis

The peroxisome proliferator-activated receptors (PPARs) were, until recently, orphan receptors with no known ligand and an unclear physiological role. Since the recent discovery of PPAR ligands and their effect on adipocyte differentiation, this receptor is now speculated to be possibly implicated in the pathogenesis of insulin resistance and obesity. The PPARs belong to the superfamily of nuclear hormone receptors (together with steroid, thyroid hormone, retinoid and vitamin D receptors) which act as transcription factors. PPARs recognize and bind to specific DNA sequences (response elements) in the promoter region of target genes as a heterodimer with the 9-cis-retinoic acid receptor RXR. While PPAR can bind to DNA in the unliganded state, ligand binding is essential for activation of the PPAR and the resulting induction of target gene expression. The known target genes are mostly coding for lipolytic enzymes involved in peroxisomal fatty acid β-oxidation.