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J. Biol. Chem. 283 (36): 24290-24294

© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

A Functional Peroxisome Proliferator-activated Receptor-{gamma} Ligand-binding Domain Is Not Required for Adipogenesis*

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Christopher J. Walkey, and Bruce M. Spiegelman1

Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115

Abstract: The nuclear hormone receptor peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) is the central regulator of adipogenesis. Although it is the target for several drugs that function as agonist activators, a high affinity endogenous ligand for this receptor that is involved in regulating adipogenesis has yet to be identified. Here, we investigated the requirement for ligand activation of PPAR{gamma} in fat cell differentiation, taking advantage of a natural mutant of this receptor that does not bind or become activated by any known natural or synthetic ligand. When ectopically expressed in PPAR{gamma}-null fibroblasts, this Q286P allele was able to strongly promote morphological adipogenesis, without any significant difference compared with wild-type PPAR{gamma}. In addition, no significant differences were found in the expression of several adipogenic genes between the wild-type and Q286P mutant alleles. To extend our studies to an in vivo setting, we performed subcutaneous injections of PPAR{gamma}-expressing fibroblasts into nude mice. We found that both wild-type and Q286P mutant-expressing fibroblasts were able to generate fat pads in the mice. These results suggest that the binding and activation of PPAR{gamma} by agonist ligands may not be required for adipogenesis under physiological conditions.

Received for publication July 8, 2008.

* This work was supported, in whole or in part, by National Institutes of Health Grant DK31405. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


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The on-line version of this article (available at http://www.jbc.org) contains a supplemental table.

1 To whom correspondence should be addressed: Dana-Farber Cancer Inst., SM958, 44 Binney St., Boston, MA 02115. E-mail: Bruce_Spiegelman{at}dfci.harvard.edu.

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