MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirT1

Mol Endocrinol. 2009 Nov;23(11):1876-84. doi: 10.1210/me.2009-0117. Epub 2009 Oct 9.


Human adipose tissue secretes a number of proinflammatory mediators that may contribute to the pathophysiology of obesity-related disorders. Understanding the regulatory pathways that control their production is paramount to developing effective therapeutics to treat these diseases. Using primary human adipose-derived stem cells as a source of preadipocytes and in vitro differentiated adipocytes, we found IL-8 and monocyte chemoattractant protein-1 (MCP-1) are constitutively secreted by both cell types and induced in response to serum deprivation. MicroRNA profiling revealed the rapid induction of microRNA 132 (miR-132) in these cells when switched to serum-free medium. Furthermore, miR-132 overexpression was sufficient to induce nuclear factor-kappaB translocation, acetylation of p65, and production of IL-8 and MCP-1. Inhibitors of miR-132 decreased acetylated p65 and partially inhibited the production of IL-8 and MCP-1 induced by serum deprivation. MiR-132 was shown to inhibit silent information regulator 1 (SirT1) expression through a miR-132 binding site in the 3'-untranslated region of SirT1. Thus, in response to nutritional availability, induction of miR-132 decreases SirT1-mediated deacetylation of p65 leading to activation of nuclear factor-kappaB and transcription of IL-8 and MCP-1 in primary human preadipocytes and in vitro differentiated adipocytes.

MeSH terms

  • 3' Untranslated Regions
  • Adipocytes / metabolism
  • Adipose Tissue / cytology
  • Adult
  • Binding Sites
  • Chemokine CCL2 / metabolism
  • Chemokines / metabolism*
  • Female
  • Gene Expression Regulation*
  • Humans
  • Interleukin-8 / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nutritional Sciences*
  • Sirtuin 1 / metabolism
  • Sirtuin 1 / physiology*
  • Stem Cells / cytology


  • 3' Untranslated Regions
  • Chemokine CCL2
  • Chemokines
  • Interleukin-8
  • MIRN132 microRNA, human
  • MicroRNAs
  • SIRT1 protein, human
  • Sirtuin 1