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 journalArticlepeer-review

    24 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

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