Regulation of PPARgamma function by TNF-alpha.
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.
Ye
Jianping
J
Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA. yej@pbrc.edu
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000099186:Histone Deacetylase 3
D006655:Histone Deacetylases; D051550:I-kappa B Kinase; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D000099186:Histone Deacetylase 3