TNFα-induced up-regulation of miR-155 inhibits adipogenesis by down-regulating early adipogenic transcription factors

Biochem Biophys Res Commun. 2011 Oct 28;414(3):618-24. doi: 10.1016/j.bbrc.2011.09.131. Epub 2011 Oct 2.

Abstract

Tumor necrosis factor α (TNFα) is known to inhibit adipogenesis, but the molecular mechanism of this inhibition remains elusive. In the present study, we found that TNFα-induced inhibition of adipogenesis mainly occurs when 3T3-L1 preadipocytes are treated with TNFα within 2h induction of adipogenesis. We revealed that TNFα treatment results in the up-regulation of miR-155 through the NFκB pathway in 3T3-L1 cells. This overexpression of miR-155 may suppress the expression of C/EBPβ and CREB by directly targeting their 3' untranslated regions (3' UTRs). Importantly, anti-miR-155 reduces the TNFα-induced inhibition of adipogenesis, whereas exogenous expression of mir-155 inhibits adipogenesis. Taken together, these findings reveal a novel role for TNFα in the regulation of anti-adipogenic miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3T3-L1 Cells
  • Adipogenesis / genetics*
  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Down-Regulation
  • Mice
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • CCAAT-Enhancer-Binding Protein-beta
  • Cyclic AMP Response Element-Binding Protein
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • NF-kappa B
  • Transcription Factors
  • Tumor Necrosis Factor-alpha