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 PPARalpha, PPARbeta/delta and PPARgamma. 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. PPARalpha is the molecular target of the hypolipidemic fibrates including benzafibrate and clofibrate. In general, PPARalpha is expressed in tissues with high mitochondrial and beta-oxidation activity corresponding to its role in regulating lipid metabolism. In contrast, PPARbeta/delta is ubiquitously expressed and has been suggested to be involved in bone formation, oocyte implantation and lipid catabolism. PPARbeta/delta ligands have been found to effectively improve lipid profile and insulin resistance. PPARgamma 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 PPARgamma ligands, including thiazolidinediones and non-thiazolidinedione compounds, have been shown to increase insulin sensitivity and improve hyperglycemia in insulin resistance and noninsulin 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. (c) 2002 Prous Science. All rights reserved.