Regulation of PPARgamma function by TNF-alpha

Biochem Biophys Res Commun. 2008 Sep 26;374(3):405-8. doi: 10.1016/j.bbrc.2008.07.068. Epub 2008 Jul 23.


The nuclear receptor PPARgamma is a lipid sensor that regulates lipid metabolism through gene transcription. Inhibition of PPARgamma activity by TNF-alpha is involved in pathogenesis of insulin resistance, atherosclerosis, inflammation, and cancer cachexia. PPARgamma activity is regulated by TNF-alpha at pre-translational and post-translational levels. Activation of serine kinases including IKK, ERK, JNK, and p38 may be involved in the TNF-regulation of PPARgamma. Of the four kinases, IKK is a dominant signaling molecule in the TNF-regulation of PPARgamma. IKK acts through at least two mechanisms: inhibition of PPARgamma expression and activation of PPARgamma corepressor. In this review article, literature is reviewed with a focus on the mechanisms of PPARgamma inhibition by TNF-alpha.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Nucleus / metabolism*
  • Histone Deacetylases / metabolism
  • Humans
  • I-kappa B Kinase / metabolism
  • Mice
  • PPAR gamma / antagonists & inhibitors*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism*


  • PPAR gamma
  • Tumor Necrosis Factor-alpha
  • I-kappa B Kinase
  • Histone Deacetylases
  • histone deacetylase 3