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PMID: 10409739 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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.

Molecular and cellular biology ·Vol. 19 ·No. 8 ·1999-08-00 ·Pages 5495-503

Fajas L, Schoonjans K, Gelman L, Kim JB, Najib J, Martin G, Fruchart JC, Briggs M, Spiegelman BM, Auwerx J

Abstract

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 PPARgamma1 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.

MeSH Terms
Adipocytes/cytology,metabolism CCAAT-Enhancer-Binding Proteins Cell Differentiation/genetics Cholesterol/metabolism,pharmacology Consensus Sequence DNA-Binding Proteins/physiology Fatty Acids/pharmacology Gene Expression Regulation, Developmental/drug effects Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology Lipid Metabolism Multigene Family Nuclear Proteins/physiology Peroxisome Proliferators/pharmacology Promoter Regions, Genetic Receptors, Cytoplasmic and Nuclear/biosynthesis,genetics Simvastatin/pharmacology Sterol Regulatory Element Binding Protein 1 Transcription Factors/biosynthesis,genetics,physiology
Chemicals
CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins Fatty Acids Hydroxymethylglutaryl-CoA Reductase Inhibitors Nuclear Proteins Peroxisome Proliferators Receptors, Cytoplasmic and Nuclear SREBF1 protein, human Sterol Regulatory Element Binding Protein 1 Transcription Factors Cholesterol Simvastatin
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Fajas L
LBRE, U 325 INSERM, Institut Pasteur, F-59019 Lille, France.
Schoonjans K
Gelman L
Kim J B
Najib J
Martin G
Fruchart J C
Briggs M
Spiegelman B M
Auwerx J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.8.5495
Published
1999-08-00
Pages
5495-503
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84391
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.19.8.5495 PMC Full Text View journal details
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