Identification of the promoter region required for human adiponectin gene transcription: Association with CCAAT/enhancer binding protein-beta and tumor necrosis factor-alpha

Biochem Biophys Res Commun. 2005 Jun 3;331(2):484-90. doi: 10.1016/j.bbrc.2005.03.205.


Adiponectin, an adipose tissue-specific plasma protein, is involved in insulin sensitizing and has anti-atherosclerotic properties. Plasma levels of adiponectin are decreased in obese individuals and patients with type 2 diabetes with insulin resistance. Tumor necrosis factor-alpha (TNF-alpha) decreases the expression of adiponectin in adipocytes. The aims of the present study were: (1) to identify the promoter region responsible for basal transcription of the human adiponectin gene, and (2) to investigate the mechanism by which adiponectin was regulated by TNF-alpha. The human adiponectin promoter (2.1kb) was isolated and used for luciferase reporter analysis by transient transfection into 3T3-L1 adipocytes. Deletion analysis demonstrated that the promoter region from -676 to +41 was sufficient for basal transcriptional activity. Mutation analysis of putative response elements for sterol regulatory element binding protein (SREBP) (-431 to -423) and CCAAT/enhancer binding protein (C/EBP) (-230 to -224) showed that both elements were required for basal promoter activity. Adiponectin transcription was increased 3-fold in cells that over-expressed constitutively active C/EBP-beta. Electrophoretic mobility shift assay, using nuclear extract from 3T3-L1 cells and the -258 to -199 region as a probe, demonstrated specific DNA-protein binding, which was abolished by TNF-alpha treatment. The present data indicate that the putative response elements for SREBP and C/EBP are required for human adiponectin promoter activity, and that suppression by TNF-alpha may, at least in part, be associated with inactivation of C/EBP-beta.

MeSH terms

  • 3T3-L1 Cells
  • Adiponectin
  • Animals
  • Base Sequence
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Enhancer Elements, Genetic / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Promoter Regions, Genetic / genetics*
  • Response Elements / genetics
  • Sequence Deletion / genetics
  • Transcription, Genetic / drug effects*
  • Transcription, Genetic / genetics
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Adiponectin
  • CCAAT-Enhancer-Binding Protein-beta
  • Intercellular Signaling Peptides and Proteins
  • Tumor Necrosis Factor-alpha