Peroxisome proliferator-activated receptor gamma and metabolic disease

The nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) i s a transcription factor that is activated by polyunsaturated fatty acids a nd their metabolites and is essential for fat cell formation. Although obes ity is a strong risk factor for type 2 diabetes mellitus and other metaboli c diseases, potent PPAR gamma activators such as the glitazone drugs lower glucose and lipid levels in patients with type 2 diabetes and also have ant iatherosclerotic and antihypertensive effects. We review recent studies pro viding insight into the paradoxical relationship between PPAR gamma and met abolic disease. We also review recent advances in understanding the structu ral basis for PPAR gamma activation by ligands. The unusual ligand-binding properties of PPAR gamma suggest that it will be possible to discover new c hemical classes of receptor "modulators" with distinct pharmacological acti vities for the treatment of type 2 diabetes and other metabolic diseases.