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Molecular and Cellular Biology, August 1999, p. 5495-5503, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Regulation of Peroxisome Proliferator-Activated Receptor gamma  Expression by Adipocyte Differentiation and Determination Factor 1/Sterol Regulatory Element Binding Protein 1: Implications for Adipocyte Differentiation and Metabolism

Lluis Fajas,1,dagger Kristina Schoonjans,1 Laurent Gelman,1 Jae B. Kim,2 Jamila Najib,1 Genevieve Martin,1 Jean-Charles Fruchart,1 Michael Briggs,3,Dagger Bruce M. Spiegelman,2 and Johan Auwerx1,*

LBRE, U 325 INSERM, Institut Pasteur, F-59019 Lille, France1; Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 021152; and Ligand Pharmaceuticals, San Diego, California 921213

Received 28 October 1998/Returned for modification 3 December 1998/Accepted 12 May 1999

Peroxisome proliferator-activated receptor gamma  (PPARgamma ) is a nuclear receptor implicated in adipocyte differentiation and insulin sensitivity. We investigated whether PPARgamma expression is dependent on the activity of adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1 (ADD-1/SREBP-1), another transcription factor associated with both adipocyte differentiation and cholesterol homeostasis. Ectopic expression of ADD-1/SREBP-1 in 3T3-L1 and HepG2 cells induced endogenous PPARgamma mRNA levels. The related transcription factor SREBP-2 likewise induced PPARgamma expression. In addition, cholesterol depletion, a condition known to result in proteolytic activation of transcription factors of the SREBP family, induced PPARgamma expression and improved PPRE-driven transcription. The effect of the SREBPs on PPARgamma expression was mediated through the PPARgamma 1 and -3 promoters. Both promoters contain a consensus E-box motif that mediates the regulation of the PPARgamma gene by ADD-1/SREBP-1 and SREBP-2. These results suggest that PPARgamma expression can be controlled by the SREBP family of transcription factors and demonstrate new interactions between transcription factors that can regulate different pathways of lipid metabolism.

* Corresponding author. Mailing address: LBRE, U 325 INSERM, Département d'Athérosclérose, Institut Pasteur, 1 Rue Calmette, F-59019 Lille, France. Phone: (33)-320-87 77 88. Fax: (33)-320-87 73 60. E-mail: Johan.Auwerx{at}pasteur-lille.fr.

dagger Present address: Institut de Génétique Moleculaire de Montpellier, F-34000 Montpellier, France.

Dagger Present address: Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.

Molecular and Cellular Biology, August 1999, p. 5495-5503, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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