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Lee, S.J.* ; Kim, J.Y.* ; Nogueiras, R.* ; Linares, J.F.* ; Perez-Tilve, D.* ; Jung, D.Y.* ; Ko, H.J.* ; Hofmann, S.M.* ; Drew, A.* ; Leitges, M.* ; Kim, J.K.* ; Tschöp, M.H.* ; Diaz-Meco, M.T.* ; Moscat, J.*

PKCzeta-regulated inflammation in the nonhematopoietic compartment is critical for obesity-induced glucose intolerance.

Cell Metab. 12, 65-77 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Journal Cell Metabolism
Quellenangaben Volume: 12, Issue: 1, Pages: 65-77 Article Number: , Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)