PKCζ-regulated inflammation in the nonhematopoietic compartment is critical for obesity-induced glucose intolerance Academic Article uri icon


MeSH Major

  • Glucose Intolerance
  • Inflammation
  • Obesity
  • Protein Kinase C


  • Obesity-induced inflammation is critical for the development of insulin resistance. Here, we show that genetic inactivation of PKCzeta in vivo leads to a hyperinflammatory state in obese mice that correlates with a higher glucose intolerance and insulin resistance. Previous studies implicated PKCzeta in the regulation of type 2 inflammatory responses in T cells. By using ex vivo and in vivo experiments, we demonstrate that although PKCzeta is involved in the alternative (M2) activation of macrophages, surprisingly, PKCzeta ablation in the nonhematopoietic compartment but not in the hematopoietic system is sufficient to drive inflammation and IL-6 synthesis in the adipose tissue, as well as insulin resistance. Experiments using PKCzeta/IL-6 double-knockout mice demonstrated that IL-6 production accounts for obesity-associated glucose intolerance induced by PKCzeta deficiency. These results establish PKCzeta as a critical negative regulator of IL-6 in the control of obesity-induced inflammation in adipocytes.

publication date

  • July 7, 2010



  • Academic Article



  • eng

PubMed Central ID

  • PMC2907185

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2010.05.003

PubMed ID

  • 20620996

Additional Document Info

start page

  • 65

end page

  • 77


  • 12


  • 1