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

TitlePKCzeta-regulated inflammation in the nonhematopoietic compartment is critical for obesity-induced glucose intolerance.
Publication TypeJournal Article
Year of Publication2010
AuthorsLee SJun, Kim JYoung, Nogueiras R, Linares JF, Perez-Tilve D, Jung DYoung, Ko HJin, Hofmann SM, Drew A, Leitges M, Kim JK, Tschöp MH, Diaz-Meco MT, Moscat J
JournalCell Metab
Volume12
Issue1
Pagination65-77
Date Published2010 Jul 07
ISSN1932-7420
KeywordsAdipose Tissue, Animals, Glucose Intolerance, Inflammation, Insulin Resistance, Interleukin-6, Macrophages, Mice, Mice, Knockout, Obesity, Protein Kinase C
Abstract

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.

DOI10.1016/j.cmet.2010.05.003
Alternate JournalCell Metab
PubMed ID20620996
PubMed Central IDPMC2907185
Grant ListR01AI072581 / AI / NIAID NIH HHS / United States
R01DK088107 / DK / NIDDK NIH HHS / United States
R01CA134530 / CA / NCI NIH HHS / United States
R01CA132847 / CA / NCI NIH HHS / United States
DK59630 / DK / NIDDK NIH HHS / United States
DK32520 / DK / NIDDK NIH HHS / United States
DK56863 / DK / NIDDK NIH HHS / United States
R01DK80756 / DK / NIDDK NIH HHS / United States
DK69987 / DK / NIDDK NIH HHS / United States
Related Faculty: 
Jorge Moscat, Ph.D. Juan Francisco Linares Rodriguez, Ph.D. Maria Diaz-Meco Conde, Ph.D.

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