Previous Article | Next Article ![]()
Molecular and Cellular Biology, August 1999, p. 5495-5503, Vol. 19, No. 8
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
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Regulation of Peroxisome Proliferator-Activated Receptor
Expression by Adipocyte Differentiation and Determination
Factor 1/Sterol Regulatory Element Binding Protein 1: Implications
for Adipocyte Differentiation and Metabolism


(PPAR
) is a
nuclear receptor implicated in adipocyte differentiation and insulin sensitivity. We investigated whether PPAR
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 PPAR
mRNA levels. The related transcription factor
SREBP-2 likewise induced PPAR
expression. In addition, cholesterol
depletion, a condition known to result in proteolytic activation of
transcription factors of the SREBP family, induced PPAR
expression
and improved PPRE-driven transcription. The effect of the SREBPs on
PPAR
expression was mediated through the PPAR
1 and -3 promoters.
Both promoters contain a consensus E-box motif that
mediates the regulation of the PPAR
gene by ADD-1/SREBP-1 and
SREBP-2. These results suggest that PPAR
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.
Present address: Institut de Génétique Moleculaire de
Montpellier, F-34000 Montpellier, France.
Present address: Cardiovascular Pharmacology,
SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|