Peroxisome proliferator-activated receptors, orphans with ligands and functions

The three peroxisome proliferator-activated receptors (PPARs), PPAR alpha, delta and gamma, form a subfamily of the nuclear hormone receptor gene family. PPAR alpha has been shown to bind and be activated by leukotriene B-4 and fibrates, whereas prostaglandin J(2) derivatives and the antidiabetic thiazolidinediones, respectively, are natural and synthetic ligands for PPAR gamma. The availability of ligands and activators for PPAR alpha and PPAR gamma allowed an initial assessment of their respective functions. PPAR alpha and PPAR gamma are shown to function as important regulators in lipid and glucose metabolism, adipocyte differentiation, inflammatory response and energy homeostasis. PPAR alpha seems to mediate its pleiotropic effects mainly through the stimulation of oxidation of lipids, whereas PPAR gamma is a key mediator of lipid storage. The next few years will be very exciting as additional studies will refine our current knowledge about PPAR alpha and PPAR gamma and may reveal a ligand and role for the lonesome: orphan among the PPARs, PPAR delta.