Noradrenaline represses PPAR (peroxisome-proliferator-activated receptor) γ2 gene expression in brown adipocytes: intracellular signalling and effects on PPARγ2 and PPARγ1 protein levels

Eva M Lindgren, Ronni Nielsen, Natasa Petrovic, Anders Jacobsson, Susanne Mandrup, Barbara Cannon, Jan Nedergaard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2004-Sep-1
OriginalsprogEngelsk
TidsskriftBiochemical Journal
Vol/bind382
Udgave nummerPt 2
Sider (fra-til)597-606
Antal sider9
ISSN0264-6021
DOI
StatusUdgivet - 2004

Fingeraftryk

Brown Adipocytes
Peroxisome Proliferator-Activated Receptors
PPAR gamma
Gene expression
Norepinephrine
Proteins
Down-Regulation
Messenger RNA
Cyclic AMP-Dependent Protein Kinases
White Adipose Tissue
Protein Synthesis Inhibitors
1-Phosphatidylinositol 4-Kinase
Mitogen-Activated Protein Kinase 3
src-Family Kinases
Mitogen-Activated Protein Kinase 1

Citer dette

@article{09d7d610f19611db821c000ea68e967b,
title = "Noradrenaline represses PPAR (peroxisome-proliferator-activated receptor) γ2 gene expression in brown adipocytes: intracellular signalling and effects on PPARγ2 and PPARγ1 protein levels",
abstract = "PPAR (peroxisome-proliferator-activated receptor) gamma is expressed in brown and white adipose tissues and is involved in the control of differentiation and proliferation. Noradrenaline stimulates brown pre-adipocyte proliferation and brown adipocyte differentiation. The aim of the present study was thus to investigate the influence of noradrenaline on PPARgamma gene expression in brown adipocytes. In primary cultures of brown adipocytes, PPARgamma2 mRNA levels were 20-fold higher than PPARgamma1 mRNA levels. PPARgamma expression occurred during both the proliferation and the differentiation phases, with the highest mRNA levels being found at the time of transition between the phases. PPARgamma2 mRNA levels were downregulated by noradrenaline treatment (EC50, 0.1 microM) in both proliferative and differentiating cells, with a lagtime of 1 h and lasting up to 4 h, after which expression gradually recovered. The down-regulation was beta-adrenoceptor-induced and intracellularly mediated via cAMP and protein kinase A; the signalling pathway did not involve phosphoinositide 3-kinase, Src, p38 mitogen-activated protein kinase or extracellular-signal-regulated kinases 1 and 2. Treatment of the cells with the protein synthesis inhibitor cycloheximide not only abolished the noradrenaline-induced down-regulation of PPARgamma2 mRNA, but also in itself induced PPARgamma2 hyperexpression. The down-regulation was probably the result of suppression of transcription. The down-regulation of PPARgamma2 mRNA resulted in similar down-regulation of PPARgamma2 and phosphoPPARgamma2 protein levels. Remarkably, the level of PPARgamma1 protein was similar to that of PPARgamma2 (despite almost no PPARgamma1 mRNA), and the down-regulation by noradrenaline demonstrated similar kinetics to that of PPARgamma2; thus PPARgamma1 was apparently translated from the PPARgamma2 template. It is suggested that beta-adrenergic stimulation via cAMP and protein kinase A represses PPARgamma gene expression, leading to reduction of PPARgamma2 mRNA levels, which is then reflected in down-regulated levels of PPARgamma2, phosphoPPARgamma2 and PPARgamma1.",
keywords = "Adipocytes, Adipose Tissue, Brown, Animals, Cells, Cultured, Gene Expression Regulation, Intracellular Space, Male, Mice, Mice, Inbred Strains, Norepinephrine, PPAR gamma, RNA, Messenger, Signal Transduction",
author = "Lindgren, {Eva M} and Ronni Nielsen and Natasa Petrovic and Anders Jacobsson and Susanne Mandrup and Barbara Cannon and Jan Nedergaard",
year = "2004",
doi = "10.1042/BJ20031622",
language = "English",
volume = "382",
pages = "597--606",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "Pt 2",

}

Noradrenaline represses PPAR (peroxisome-proliferator-activated receptor) γ2 gene expression in brown adipocytes: intracellular signalling and effects on PPARγ2 and PPARγ1 protein levels. / Lindgren, Eva M; Nielsen, Ronni; Petrovic, Natasa; Jacobsson, Anders; Mandrup, Susanne; Cannon, Barbara; Nedergaard, Jan.

I: Biochemical Journal, Bind 382, Nr. Pt 2, 2004, s. 597-606.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Noradrenaline represses PPAR (peroxisome-proliferator-activated receptor) γ2 gene expression in brown adipocytes: intracellular signalling and effects on PPARγ2 and PPARγ1 protein levels

AU - Lindgren, Eva M

AU - Nielsen, Ronni

AU - Petrovic, Natasa

AU - Jacobsson, Anders

AU - Mandrup, Susanne

AU - Cannon, Barbara

AU - Nedergaard, Jan

PY - 2004

Y1 - 2004

N2 - PPAR (peroxisome-proliferator-activated receptor) gamma is expressed in brown and white adipose tissues and is involved in the control of differentiation and proliferation. Noradrenaline stimulates brown pre-adipocyte proliferation and brown adipocyte differentiation. The aim of the present study was thus to investigate the influence of noradrenaline on PPARgamma gene expression in brown adipocytes. In primary cultures of brown adipocytes, PPARgamma2 mRNA levels were 20-fold higher than PPARgamma1 mRNA levels. PPARgamma expression occurred during both the proliferation and the differentiation phases, with the highest mRNA levels being found at the time of transition between the phases. PPARgamma2 mRNA levels were downregulated by noradrenaline treatment (EC50, 0.1 microM) in both proliferative and differentiating cells, with a lagtime of 1 h and lasting up to 4 h, after which expression gradually recovered. The down-regulation was beta-adrenoceptor-induced and intracellularly mediated via cAMP and protein kinase A; the signalling pathway did not involve phosphoinositide 3-kinase, Src, p38 mitogen-activated protein kinase or extracellular-signal-regulated kinases 1 and 2. Treatment of the cells with the protein synthesis inhibitor cycloheximide not only abolished the noradrenaline-induced down-regulation of PPARgamma2 mRNA, but also in itself induced PPARgamma2 hyperexpression. The down-regulation was probably the result of suppression of transcription. The down-regulation of PPARgamma2 mRNA resulted in similar down-regulation of PPARgamma2 and phosphoPPARgamma2 protein levels. Remarkably, the level of PPARgamma1 protein was similar to that of PPARgamma2 (despite almost no PPARgamma1 mRNA), and the down-regulation by noradrenaline demonstrated similar kinetics to that of PPARgamma2; thus PPARgamma1 was apparently translated from the PPARgamma2 template. It is suggested that beta-adrenergic stimulation via cAMP and protein kinase A represses PPARgamma gene expression, leading to reduction of PPARgamma2 mRNA levels, which is then reflected in down-regulated levels of PPARgamma2, phosphoPPARgamma2 and PPARgamma1.

AB - PPAR (peroxisome-proliferator-activated receptor) gamma is expressed in brown and white adipose tissues and is involved in the control of differentiation and proliferation. Noradrenaline stimulates brown pre-adipocyte proliferation and brown adipocyte differentiation. The aim of the present study was thus to investigate the influence of noradrenaline on PPARgamma gene expression in brown adipocytes. In primary cultures of brown adipocytes, PPARgamma2 mRNA levels were 20-fold higher than PPARgamma1 mRNA levels. PPARgamma expression occurred during both the proliferation and the differentiation phases, with the highest mRNA levels being found at the time of transition between the phases. PPARgamma2 mRNA levels were downregulated by noradrenaline treatment (EC50, 0.1 microM) in both proliferative and differentiating cells, with a lagtime of 1 h and lasting up to 4 h, after which expression gradually recovered. The down-regulation was beta-adrenoceptor-induced and intracellularly mediated via cAMP and protein kinase A; the signalling pathway did not involve phosphoinositide 3-kinase, Src, p38 mitogen-activated protein kinase or extracellular-signal-regulated kinases 1 and 2. Treatment of the cells with the protein synthesis inhibitor cycloheximide not only abolished the noradrenaline-induced down-regulation of PPARgamma2 mRNA, but also in itself induced PPARgamma2 hyperexpression. The down-regulation was probably the result of suppression of transcription. The down-regulation of PPARgamma2 mRNA resulted in similar down-regulation of PPARgamma2 and phosphoPPARgamma2 protein levels. Remarkably, the level of PPARgamma1 protein was similar to that of PPARgamma2 (despite almost no PPARgamma1 mRNA), and the down-regulation by noradrenaline demonstrated similar kinetics to that of PPARgamma2; thus PPARgamma1 was apparently translated from the PPARgamma2 template. It is suggested that beta-adrenergic stimulation via cAMP and protein kinase A represses PPARgamma gene expression, leading to reduction of PPARgamma2 mRNA levels, which is then reflected in down-regulated levels of PPARgamma2, phosphoPPARgamma2 and PPARgamma1.

KW - Adipocytes

KW - Adipose Tissue, Brown

KW - Animals

KW - Cells, Cultured

KW - Gene Expression Regulation

KW - Intracellular Space

KW - Male

KW - Mice

KW - Mice, Inbred Strains

KW - Norepinephrine

KW - PPAR gamma

KW - RNA, Messenger

KW - Signal Transduction

U2 - 10.1042/BJ20031622

DO - 10.1042/BJ20031622

M3 - Journal article

VL - 382

SP - 597

EP - 606

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - Pt 2

ER -