PPAR[gamma] as a metabolic regulator: insights from genomics and pharmacology
Since its identification in the early 1990s, 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.
Key Words: PPAR[gamma]; nuclear receptor; metabolic syndrome; diabetes; insulin resistance; lipodystrophy.
c1 Yale University School of Medicine, S260 TAC, 1 Gilbert Street, New Haven, CT 06520-8020, USA. Tel: +1 203 737 5679; Fax: +1 203 785 3823; E-mail: [email protected]
p1 Present address: Yale University School of Medicine, S260 TAC, 1 Gilbert Street, New Haven, CT 06520-8020, USA.