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-Åke Gustafsson, Lise Madsen, Karsten Kristiansen

Research output: Contribution to journalJournal articleResearchpeer-review


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 languageEnglish
JournalBBA General Subjects
Issue number4
Pages (from-to)421-429
Publication statusPublished - 2. Dec 2009

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