Selective Modulators of PPAR-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>γ</mml:mi></mml:math> Activity: Molecular Aspects Related to Obesity and Side-Effects

Zhang, Fang; Lavan, Brian E.; Gregoire, Francine M.

doi:https://doi.org/10.1155/2007/32696

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Volume 2007 | Article ID 032696 | https://doi.org/10.1155/2007/32696

Selective Modulators of PPAR-γ Activity: Molecular Aspects Related to Obesity and Side-Effects

Fang Zhang,¹Brian E. Lavan,¹and Francine M. Gregoire¹

Academic Editor: Sander Kersten

Received03 Oct 2006

Revised21 Nov 2006

Accepted22 Nov 2006

Published08 Jan 2007

Abstract

Peroxisome proliferator-activated receptor γ (PPAR-γ) is a key regulator of lipid metabolism and energy balance implicated in the development of insulin resistance and obesity. The identification of putative natural and synthetic ligands and activators of PPAR-γ has helped to unravel the molecular basis of its function, including molecular details regarding ligand binding, conformational changes of the receptor, and cofactor binding, leading to the emergence of the concept of selective PPAR-γ modulators (SPPARγMs). SPPARγMs bind in distinct manners to the ligand-binding pocket of PPAR-γ, leading to alternative receptor conformations, differential cofactor recruitment/displacement, differential gene expression, and ultimately differential biological responses. Based on this concept, new and improved antidiabetic agents for the treatment of diabetes are in development. This review summarizes the current knowledge on the mechanism of action and biological effects of recently characterized SPPARγMs, including metaglidasen/halofenate, PA-082, and the angiotensin receptor antagonists, recently characterized as a new class of SPPARγMs.

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Copyright © 2007 Fang Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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