PPAR gamma as a metabolic regulator: insights from genomics and pharmacology.
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.
Savage
David B
DB
Department of Medicine, University of Cambridge, UK. david.savage@yale.edu
D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D050260:Carbohydrate Metabolism / Q000235:genetics / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D008060:Lipodystrophy / Q000150:complications / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009765:Obesity / Q000150:complications / Q000378:metabolism; D009928:Organ Specificity; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism
D047495:PPAR gamma; D020033:Protein Isoforms; D045162:Thiazolidinediones; D014280:Triglycerides