ADD1/SREBP1c activates the PGC1-α 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 Åke Gustafsson, Lise Madsen, Karsten Kristiansen

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)421-429
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1801
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

  • ADD1/SREBP1c
  • Adipogenesis
  • Brown adipocytes
  • LXR
  • PGC1α

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'ADD1/SREBP1c activates the PGC1-α promoter in brown adipocytes'. Together they form a unique fingerprint.

Cite this