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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Qin Hao
  • Hansen, Jacob B.
  • Rasmus K Petersen
  • Philip Hallenborg
  • Claus Jørgensen
  • Saverio Cinti
  • Philip J Larsen
  • Knut R Steffensen
  • Haibo Wang
  • Sheila Collins
  • Jun Wang
  • Jan-Ake Gustafsson
  • Lise Madsen
  • Kristiansen, Karsten
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
Volume1801
Issue number4
Pages (from-to)421-9
Number of pages8
ISSN0304-4165
DOIs
Publication statusPublished - 2010

Bibliographical note

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

ID: 19664243