PPAR gamma as a metabolic regulator: insights from genomics and pharmacology

Abstract

Since its identification in the early 1990 s, peroxisome-proliferator-activated receptor gamma (PPAR gamma), a nuclear hormone receptor, has attracted tremendous scientific and clinical interest. The role of PPAR gamma in macronutrient metabolism has received particular attention, for three main reasons: first, it is the target of the thiazolidinediones (TZDs), a novel class of insulin sensitisers widely used to treat type 2 diabetes; second, it plays a central role in adipogenesis; and third, it appears to be primarily involved in regulating lipid metabolism with predominantly secondary effects on carbohydrate metabolism, a notion in keeping with the currently in vogue 'lipocentric' view of diabetes. This review summarises in vitro studies suggesting that PPAR gamma is a master regulator of adipogenesis, and then considers in vivo findings from use of PPAR gamma agonists, knockout studies in mice and analysis of human PPAR gamma mutations/polymorphisms.