ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes
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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
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TY - JOUR
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 -
ID: 19664243