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PPAR Research
Volume 2007, Article ID 12781, 12 pages
Review Article

Genetic Manipulations of PPARs: Effects on Obesity and Metabolic Disease

The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA

Received 7 August 2006; Revised 10 November 2006; Accepted 16 November 2006

Academic Editor: Wallace Harrington

Copyright © 2007 Yaacov Barak and Suyeon Kim. 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.


The interest in genetic manipulations of PPARs is as old as their discovery as receptors of ligands with beneficial clinical activities. Considering the effects of PPAR ligands on critical aspects of systemic physiology, including obesity, lipid metabolism, insulin resistance, and diabetes, gene knockout (KO) in mice is the ideal platform for both hypothesis testing and discovery of new PPAR functions in vivo. With the fervent pursuit of the magic bullet to eradicate the obesity epidemic, special emphasis has been placed on the impacts of PPARs on obesity and its associated diseases. As detailed in this review, understanding how PPARs regulate gene expression and basic metabolic pathways is a necessary intermediate en route to deciphering their effects on obesity. Over a decade and dozens of genetic modifications of PPARs into this effort, valuable lessons have been learned, but we are left with more questions to be answered. These lessons and future prospects are the subject of this review.