ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes

Qin Hao; Jacob B Hansen; Rasmus K Petersen; Philip Hallenborg; Claus Jørgensen; Saverio Cinti; Philip J Larsen; Knut R Steffensen; Haibo Wang; Sheila Collins; Jun Wang; Jan-Ake Gustafsson; Lise Madsen; Karsten Kristiansen

doi:10.1016/j.bbalip.2009.11.008

ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes

Qin Hao, Jacob B Hansen, Rasmus K Petersen, Philip Hallenborg, Claus Jørgensen, Saverio Cinti, Philip J Larsen, Knut R Steffensen, Haibo Wang, Sheila Collins, Jun Wang, Jan-Ake Gustafsson, Lise Madsen, Karsten Kristiansen

Research output: Contribution to journal › Journal article › Research › peer-review

24 Citations (Scopus)

Abstract

Cold adaptation elicits a paradoxical simultaneous induction of fatty acid synthesis and beta-oxidation in brown adipose tissue. We show here that cold exposure coordinately induced liver X receptor alpha (LXRalpha), adipocyte determination and differentiation-dependent factor 1 (ADD1)/sterol regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) in brown and inguinal white adipose tissues, but not in epididymal white adipose tissue. Using in vitro models of white and brown adipocytes we demonstrate that beta-adrenergic stimulation induced expression of LXRalpha, ADD1/SREBP1c and PGC1alpha in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1alpha expression via a conserved E box in the proximal promoter and that beta-adrenergic stimulation led to recruitment of ADD1/SREBP1c to this E box. The ability of ADD1/SREBP1c to activate the PGC1alpha promoter exhibited a striking cell type dependency, suggesting that additional cell type-restricted factors contribute to ADD1/SREBP1c-mediated activation. In conclusion, our data demonstrate a novel role of ADD1/SREBP1c as a regulator of PGC1alpha expression in brown adipose tissue.

Original language	English
Journal	BBA General Subjects
Volume	1801
Issue number	4
Pages (from-to)	421-9
Number of pages	8
ISSN	0304-4165
DOIs	https://doi.org/10.1016/j.bbalip.2009.11.008
Publication status	Published - 2010

Bibliographical note

Keywords: Adipocytes, Brown; Animals; Cell Differentiation; Cells, Cultured; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Electroporation; Male; Mice; Mice, Inbred C57BL; Orphan Nuclear Receptors; Promoter Regions, Genetic; RNA, Messenger; Regulatory Sequences, Nucleic Acid; Reverse Transcriptase Polymerase Chain Reaction; Sterol Regulatory Element Binding Protein 1; Trans-Activators

Access to Document

10.1016/j.bbalip.2009.11.008

Cite this

ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes. / Hao, Qin; Hansen, Jacob B; Petersen, Rasmus K; Hallenborg, Philip; Jørgensen, Claus; Cinti, Saverio; Larsen, Philip J; Steffensen, Knut R; Wang, Haibo; Collins, Sheila; Wang, Jun; Gustafsson, Jan-Ake; Madsen, Lise; Kristiansen, Karsten.

In: BBA General Subjects, Vol. 1801, No. 4, 2010, p. 421-9.

Research output: Contribution to journal › Journal article › Research › peer-review

Hao, Qin ; Hansen, Jacob B ; Petersen, Rasmus K ; Hallenborg, Philip ; Jørgensen, Claus ; Cinti, Saverio ; Larsen, Philip J ; Steffensen, Knut R ; Wang, Haibo ; Collins, Sheila ; Wang, Jun ; Gustafsson, Jan-Ake ; Madsen, Lise ; Kristiansen, Karsten. / ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes. In: BBA General Subjects. 2010 ; Vol. 1801, No. 4. pp. 421-9.

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title = "ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes",

abstract = "Cold adaptation elicits a paradoxical simultaneous induction of fatty acid synthesis and beta-oxidation in brown adipose tissue. We show here that cold exposure coordinately induced liver X receptor alpha (LXRalpha), adipocyte determination and differentiation-dependent factor 1 (ADD1)/sterol regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) in brown and inguinal white adipose tissues, but not in epididymal white adipose tissue. Using in vitro models of white and brown adipocytes we demonstrate that beta-adrenergic stimulation induced expression of LXRalpha, ADD1/SREBP1c and PGC1alpha in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1alpha expression via a conserved E box in the proximal promoter and that beta-adrenergic stimulation led to recruitment of ADD1/SREBP1c to this E box. The ability of ADD1/SREBP1c to activate the PGC1alpha promoter exhibited a striking cell type dependency, suggesting that additional cell type-restricted factors contribute to ADD1/SREBP1c-mediated activation. In conclusion, our data demonstrate a novel role of ADD1/SREBP1c as a regulator of PGC1alpha expression in brown adipose tissue.",

author = "Qin Hao and Hansen, {Jacob B} and Petersen, {Rasmus K} and Philip Hallenborg and Claus J{\o}rgensen and Saverio Cinti and Larsen, {Philip J} and Steffensen, {Knut R} and Haibo Wang and Sheila Collins and Jun Wang and Jan-Ake Gustafsson and Lise Madsen and Karsten Kristiansen",

note = "Keywords: Adipocytes, Brown; Animals; Cell Differentiation; Cells, Cultured; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Electroporation; Male; Mice; Mice, Inbred C57BL; Orphan Nuclear Receptors; Promoter Regions, Genetic; RNA, Messenger; Regulatory Sequences, Nucleic Acid; Reverse Transcriptase Polymerase Chain Reaction; Sterol Regulatory Element Binding Protein 1; Trans-Activators",

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T1 - ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes

AU - Hao, Qin

AU - Hansen, Jacob B

AU - Petersen, Rasmus K

AU - Hallenborg, Philip

AU - Jørgensen, Claus

AU - Cinti, Saverio

AU - Larsen, Philip J

AU - Steffensen, Knut R

AU - Wang, Haibo

AU - Collins, Sheila

AU - Wang, Jun

AU - Gustafsson, Jan-Ake

AU - Madsen, Lise

AU - Kristiansen, Karsten

N1 - Keywords: Adipocytes, Brown; Animals; Cell Differentiation; Cells, Cultured; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Electroporation; Male; Mice; Mice, Inbred C57BL; Orphan Nuclear Receptors; Promoter Regions, Genetic; RNA, Messenger; Regulatory Sequences, Nucleic Acid; Reverse Transcriptase Polymerase Chain Reaction; Sterol Regulatory Element Binding Protein 1; Trans-Activators

PY - 2010

Y1 - 2010

N2 - Cold adaptation elicits a paradoxical simultaneous induction of fatty acid synthesis and beta-oxidation in brown adipose tissue. We show here that cold exposure coordinately induced liver X receptor alpha (LXRalpha), adipocyte determination and differentiation-dependent factor 1 (ADD1)/sterol regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) in brown and inguinal white adipose tissues, but not in epididymal white adipose tissue. Using in vitro models of white and brown adipocytes we demonstrate that beta-adrenergic stimulation induced expression of LXRalpha, ADD1/SREBP1c and PGC1alpha in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1alpha expression via a conserved E box in the proximal promoter and that beta-adrenergic stimulation led to recruitment of ADD1/SREBP1c to this E box. The ability of ADD1/SREBP1c to activate the PGC1alpha promoter exhibited a striking cell type dependency, suggesting that additional cell type-restricted factors contribute to ADD1/SREBP1c-mediated activation. In conclusion, our data demonstrate a novel role of ADD1/SREBP1c as a regulator of PGC1alpha expression in brown adipose tissue.

AB - Cold adaptation elicits a paradoxical simultaneous induction of fatty acid synthesis and beta-oxidation in brown adipose tissue. We show here that cold exposure coordinately induced liver X receptor alpha (LXRalpha), adipocyte determination and differentiation-dependent factor 1 (ADD1)/sterol regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) in brown and inguinal white adipose tissues, but not in epididymal white adipose tissue. Using in vitro models of white and brown adipocytes we demonstrate that beta-adrenergic stimulation induced expression of LXRalpha, ADD1/SREBP1c and PGC1alpha in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1alpha expression via a conserved E box in the proximal promoter and that beta-adrenergic stimulation led to recruitment of ADD1/SREBP1c to this E box. The ability of ADD1/SREBP1c to activate the PGC1alpha promoter exhibited a striking cell type dependency, suggesting that additional cell type-restricted factors contribute to ADD1/SREBP1c-mediated activation. In conclusion, our data demonstrate a novel role of ADD1/SREBP1c as a regulator of PGC1alpha expression in brown adipose tissue.

U2 - 10.1016/j.bbalip.2009.11.008

DO - 10.1016/j.bbalip.2009.11.008

M3 - Journal article

C2 - 19962449

VL - 1801

SP - 421

EP - 429

JO - B B A - General Subjects

JF - B B A - General Subjects

SN - 0304-4165

IS - 4

ER -