Peroxisome Proliferator-activated Receptor (PPAR)-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the retinoid X receptor/PPARγ heterodimer

Péter Bai, Sander M. Houten, Aline Huber, Valérie Schreiber, Mitsuhiro Watanabe, Borbála Kiss, Gilbert De Murcia, Johan Auwerx, Josiane Ménissier-De Murcia

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The peroxisome proliferator-activated receptor-γ (PPARγ, NR1C3) in complex with the retinoid X receptor (RXR) plays a central role in white adipose tissue (WAT) differentiation and function, regulating the expression of key WAT proteins. In this report we show that poly(ADP-ribose) polymerase-2 (PARP-2), also known as an enzyme participating in the surveillance of the genome integrity, is a member of the PPARγ/RXR transcription machinery. PARP-2-/- mice accumulate less WAT, characterized by smaller adipocytes. In the WAT of PARP-2-/- mice the expression of a number of PPARγ target genes is reduced despite the fact that PPARγ1 and -γ2 are expressed at normal levels. Consistent with this, PARP-2 -/- mouse embryonic fibroblasts fail to differentiate to adipocytes. In transient transfection assays, PARP-2 small interference RNA decreases basal activity and ligand-dependent activation of PPARγ, whereas PARP-2 overexpression enhances the basal activity of PPARγ, although it does not change the maximal ligand-dependent activation. In addition, we show a DNA-dependent interaction of PARP-2 and PPARγ/RXR heterodimer by chromatin immunoprecipitation. In combination, our results suggest that PARP-2 is a novel cofactor of PPARγ activity.

Original languageEnglish
Pages (from-to)37738-37746
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number52
DOIs
Publication statusPublished - 2007 Dec 28
Externally publishedYes

Fingerprint

Retinoid X Receptors
Peroxisome Proliferator-Activated Receptors
Adipocytes
Adipose Tissue
Poly(ADP-ribose) Polymerases
Tissue
White Adipose Tissue
Genes
Chemical activation
Ligands
Chromatin Immunoprecipitation
Transcription
Fibroblasts
RNA Interference
Chromatin
Machinery
Transfection
Assays
Genome
RNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Peroxisome Proliferator-activated Receptor (PPAR)-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the retinoid X receptor/PPARγ heterodimer. / Bai, Péter; Houten, Sander M.; Huber, Aline; Schreiber, Valérie; Watanabe, Mitsuhiro; Kiss, Borbála; De Murcia, Gilbert; Auwerx, Johan; Ménissier-De Murcia, Josiane.

In: Journal of Biological Chemistry, Vol. 282, No. 52, 28.12.2007, p. 37738-37746.

Research output: Contribution to journalArticle

Bai, Péter ; Houten, Sander M. ; Huber, Aline ; Schreiber, Valérie ; Watanabe, Mitsuhiro ; Kiss, Borbála ; De Murcia, Gilbert ; Auwerx, Johan ; Ménissier-De Murcia, Josiane. / Peroxisome Proliferator-activated Receptor (PPAR)-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the retinoid X receptor/PPARγ heterodimer. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 52. pp. 37738-37746.
@article{11e7b46269ea406285c0925c6a9f62b4,
title = "Peroxisome Proliferator-activated Receptor (PPAR)-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the retinoid X receptor/PPARγ heterodimer",
abstract = "The peroxisome proliferator-activated receptor-γ (PPARγ, NR1C3) in complex with the retinoid X receptor (RXR) plays a central role in white adipose tissue (WAT) differentiation and function, regulating the expression of key WAT proteins. In this report we show that poly(ADP-ribose) polymerase-2 (PARP-2), also known as an enzyme participating in the surveillance of the genome integrity, is a member of the PPARγ/RXR transcription machinery. PARP-2-/- mice accumulate less WAT, characterized by smaller adipocytes. In the WAT of PARP-2-/- mice the expression of a number of PPARγ target genes is reduced despite the fact that PPARγ1 and -γ2 are expressed at normal levels. Consistent with this, PARP-2 -/- mouse embryonic fibroblasts fail to differentiate to adipocytes. In transient transfection assays, PARP-2 small interference RNA decreases basal activity and ligand-dependent activation of PPARγ, whereas PARP-2 overexpression enhances the basal activity of PPARγ, although it does not change the maximal ligand-dependent activation. In addition, we show a DNA-dependent interaction of PARP-2 and PPARγ/RXR heterodimer by chromatin immunoprecipitation. In combination, our results suggest that PARP-2 is a novel cofactor of PPARγ activity.",
author = "P{\'e}ter Bai and Houten, {Sander M.} and Aline Huber and Val{\'e}rie Schreiber and Mitsuhiro Watanabe and Borb{\'a}la Kiss and {De Murcia}, Gilbert and Johan Auwerx and {M{\'e}nissier-De Murcia}, Josiane",
year = "2007",
month = "12",
day = "28",
doi = "10.1074/jbc.M701021200",
language = "English",
volume = "282",
pages = "37738--37746",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "52",

}

TY - JOUR

T1 - Peroxisome Proliferator-activated Receptor (PPAR)-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the retinoid X receptor/PPARγ heterodimer

AU - Bai, Péter

AU - Houten, Sander M.

AU - Huber, Aline

AU - Schreiber, Valérie

AU - Watanabe, Mitsuhiro

AU - Kiss, Borbála

AU - De Murcia, Gilbert

AU - Auwerx, Johan

AU - Ménissier-De Murcia, Josiane

PY - 2007/12/28

Y1 - 2007/12/28

N2 - The peroxisome proliferator-activated receptor-γ (PPARγ, NR1C3) in complex with the retinoid X receptor (RXR) plays a central role in white adipose tissue (WAT) differentiation and function, regulating the expression of key WAT proteins. In this report we show that poly(ADP-ribose) polymerase-2 (PARP-2), also known as an enzyme participating in the surveillance of the genome integrity, is a member of the PPARγ/RXR transcription machinery. PARP-2-/- mice accumulate less WAT, characterized by smaller adipocytes. In the WAT of PARP-2-/- mice the expression of a number of PPARγ target genes is reduced despite the fact that PPARγ1 and -γ2 are expressed at normal levels. Consistent with this, PARP-2 -/- mouse embryonic fibroblasts fail to differentiate to adipocytes. In transient transfection assays, PARP-2 small interference RNA decreases basal activity and ligand-dependent activation of PPARγ, whereas PARP-2 overexpression enhances the basal activity of PPARγ, although it does not change the maximal ligand-dependent activation. In addition, we show a DNA-dependent interaction of PARP-2 and PPARγ/RXR heterodimer by chromatin immunoprecipitation. In combination, our results suggest that PARP-2 is a novel cofactor of PPARγ activity.

AB - The peroxisome proliferator-activated receptor-γ (PPARγ, NR1C3) in complex with the retinoid X receptor (RXR) plays a central role in white adipose tissue (WAT) differentiation and function, regulating the expression of key WAT proteins. In this report we show that poly(ADP-ribose) polymerase-2 (PARP-2), also known as an enzyme participating in the surveillance of the genome integrity, is a member of the PPARγ/RXR transcription machinery. PARP-2-/- mice accumulate less WAT, characterized by smaller adipocytes. In the WAT of PARP-2-/- mice the expression of a number of PPARγ target genes is reduced despite the fact that PPARγ1 and -γ2 are expressed at normal levels. Consistent with this, PARP-2 -/- mouse embryonic fibroblasts fail to differentiate to adipocytes. In transient transfection assays, PARP-2 small interference RNA decreases basal activity and ligand-dependent activation of PPARγ, whereas PARP-2 overexpression enhances the basal activity of PPARγ, although it does not change the maximal ligand-dependent activation. In addition, we show a DNA-dependent interaction of PARP-2 and PPARγ/RXR heterodimer by chromatin immunoprecipitation. In combination, our results suggest that PARP-2 is a novel cofactor of PPARγ activity.

UR - http://www.scopus.com/inward/record.url?scp=38049129655&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38049129655&partnerID=8YFLogxK

U2 - 10.1074/jbc.M701021200

DO - 10.1074/jbc.M701021200

M3 - Article

VL - 282

SP - 37738

EP - 37746

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 52

ER -