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

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 - 2010/4

Y1 - 2010/4

N2 - Cold adaptation elicits a paradoxical simultaneous induction of fatty acid synthesis and β-oxidation in brown adipose tissue. We show here that cold exposure coordinately induced liver X receptor α (LXRα), adipocyte determination and differentiation-dependent factor 1 (ADD1)/sterol regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) 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 β-adrenergic stimulation induced expression of LXRα, ADD1/SREBP1c and PGC1α in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1α expression via a conserved E box in the proximal promoter and that β-adrenergic stimulation led to recruitment of ADD1/SREBP1c to this E box. The ability of ADD1/SREBP1c to activate the PGC1α 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 PGC1α expression in brown adipose tissue.

AB - Cold adaptation elicits a paradoxical simultaneous induction of fatty acid synthesis and β-oxidation in brown adipose tissue. We show here that cold exposure coordinately induced liver X receptor α (LXRα), adipocyte determination and differentiation-dependent factor 1 (ADD1)/sterol regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) 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 β-adrenergic stimulation induced expression of LXRα, ADD1/SREBP1c and PGC1α in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1α expression via a conserved E box in the proximal promoter and that β-adrenergic stimulation led to recruitment of ADD1/SREBP1c to this E box. The ability of ADD1/SREBP1c to activate the PGC1α 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 PGC1α 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

SN - 0304-4165

VL - 1801

SP - 421

EP - 429

JO - B B A - General Subjects

JF - B B A - General Subjects

IS - 4

ER -