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PPARγ as a metabolic regulator: insights from genomics and pharmacology

Published online by Cambridge University Press:  25 January 2005

David B. Savage
Affiliation:
Departments of Medicine and Clinical Biochemistry, University of Cambridge, UK. Present address: Yale University School of Medicine, S260 TAC, 1 Gilbert Street, New Haven, CT 06520-8020, USA.

Abstract

Since its identification in the early 1990s, peroxisome-proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor, has attracted tremendous scientific and clinical interest. The role of PPARγ 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 PPARγ is a master regulator of adipogenesis, and then considers in vivo findings from use of PPARγ agonists, knockout studies in mice and analysis of human PPARγ mutations/polymorphisms.

Type
Review Article
Copyright
© Cambridge University Press 2005

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