Peroxisome Proliferator-Activated Receptors (PPARs): Choreographers of Metabolic Gene Transcription

Nuclear receptors are ligand-activated transcription factors that regulate gene expression in response to small lipophilic compounds such as testosterone [androgen receptor (AR)], oxysterols [liver X receptor (LXR)], estrogen (ER), xenobiotics [pregnane X receptor (PXR)], retinoic acid (RAR), thyroid hormone (TR), bile acids [farnesoid X receptor (FXR)] and vitamin D (VDR). The peroxisome proliferatoractivated receptors (PPARs) are members of the nuclear receptor supergene family that play a central role in the regulation of storage and catabolism of dietary fats [1-4]. The three subtypes of PPAR (designated α, δ and γ) bind to fatty acids and fatty acid metabolites and regulate the expression of genes involved in the transport, metabolism and buffering of these ligands within cells. Each of the three PPAR subtypes exhibits a unique expression pattern within vertebrate tissues. In rats, PPARα is most highly expressed in brown adipose tissue, followed by liver, kidney, heart and skeletal muscle [2]. PPARγ is most highly expressed in white and brown adipose tissue, but is also expressed in muscle, colon and liver. PPARδ is expressed in all tissues studied to date.