The role of PPARs in the transcriptional control of cellular processes

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the nuclear hormone receptor superfamily. PPAR has three isoforms designated PPARα, PPARβ/δ and PPARγ. Although all three isoforms share similar protein sequence and structure, they differ in tissue distribution, ligand selectivity and biological actions. As ligand-activated transcription factors, PPARs participate in a broad spectrum of biological processes, including cell differentiation, energy balance, lipid metabolism, insulin sensitivity, bone formation, inflammation and tissue remodeling. PPARα is the molecular target of the hypolipidemic fibrates including benzafibrate and clofibrate. In general, PPARα is expressed in tissues with high mitochondrial and β- oxidation activity corresponding to its role in regulating lipid metabolism. In contrast, PPARβ/δ is ubiquitously expressed and has been suggested to be involved in bone formation, oocyte implantation and lipid catabolism. PPARβ/δ ligands have been found to effectively improve lipid profile and insulin resistance. PPARγ is a key player in adipogenesis and plays an important role in diverse cellular processes such as cell cycle regulation, cell differentiation and insulin sensitivity. Synthetic PPARγ ligands, including thiazolidinediones and non-thiazolidinedione compounds, have been shown to increase insulin sensitivity and improve hyperglycemia in insulin resistance and non- insulin dependent diabetes mellitus. The biological effects of PPARs indicate that both agonists and antagonists for PPARs may provide new therapeutic options in a variety of human diseases.