Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes

Biochem Biophys Res Commun. 2003 Feb 21;301(4):1045-50. doi: 10.1016/s0006-291x(03)00090-1.


Recently, it has been shown that adiponectin is an important insulin-sensitizing fat-derived protein which is downregulated in insulin resistance and obesity, and replenishment of which improves insulin sensitivity. In contrast, interleukin (IL)-6 appears as an adipocytokine serum concentrations of which are elevated in these states. However, it has not been determined whether IL-6 might impact on expression and secretion of adiponectin. To clarify this, 3T3-L1 adipocytes were treated with different concentrations of IL-6 for various periods of time. Adiponectin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction and secretion was determined by radioimmunoassays. Interestingly, treatment of 3T3-L1 cells with 30 ng/ml IL-6 significantly decreased adiponectin secretion to 75% of control levels. Adiponectin secretion was also inhibited between 25% and 45% by chronic treatment with forskolin (50 microM), tumor necrosis factor alpha (100 ng/ml), and dexamethasone (100 nM). Furthermore, adiponectin mRNA expression was downregulated by up to 50% in a time- and dose-dependent manner, with significant inhibition detectable at concentrations as low as 3 ng/ml IL-6 and as early as 8h after effector addition. The inhibitory effect of IL-6 was partially reversed by pretreatment of 3T3-L1 cells with pharmacological inhibitors of a p44/42 mitogen-activated protein (MAP) kinase. Moreover, the negative effect of IL-6 on adiponectin mRNA expression could be reversed by withdrawal of the hormone for 24h. Taken together, our results suggest that adiponectin gene expression is reversibly downregulated by IL-6 and support the concept of adiponectin being an important selectively controlled modulator of insulin sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism*
  • Adiponectin
  • Animals
  • Colforsin / pharmacology
  • Dexamethasone / pharmacology
  • Down-Regulation / drug effects
  • Gene Expression / drug effects
  • Insulin Resistance / physiology
  • Intercellular Signaling Peptides and Proteins*
  • Interleukin-6 / pharmacology*
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Protein Biosynthesis*
  • Proteins / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology


  • Adiponectin
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-6
  • Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Colforsin
  • Dexamethasone
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases