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

Expert Rev Mol Med. 2005 Jan 25;7(1):1-16. doi: 10.1017/S1462399405008793.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipocytes / metabolism
  • Adipogenesis / genetics
  • Adipogenesis / physiology*
  • Animals
  • Carbohydrate Metabolism / genetics
  • Carbohydrate Metabolism / physiology*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism
  • Energy Metabolism
  • Humans
  • Insulin Resistance
  • Lipid Metabolism / genetics
  • Lipid Metabolism / physiology*
  • Lipodystrophy / complications
  • Lipodystrophy / metabolism
  • Mice
  • Mice, Knockout
  • Mutation
  • Obesity / complications
  • Obesity / metabolism
  • Organ Specificity
  • PPAR gamma / agonists
  • PPAR gamma / genetics
  • PPAR gamma / physiology*
  • Protein Isoforms / genetics
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use
  • Transcription, Genetic
  • Triglycerides / metabolism

Substances

  • PPAR gamma
  • Protein Isoforms
  • Thiazolidinediones
  • Triglycerides