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

Cell Metabolism
Sang Jun LeeJorge Moscat

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.

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Citations

Sep 7, 2011·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Y-H ChangM-Y Shiau
Mar 8, 2012·Nature Medicine·Olivia Osborn, Jerrold M Olefsky
Jan 24, 2013·PloS One·Sonia Perez-SieiraCarlos Dieguez
Sep 14, 2012·The Review of Diabetic Studies : RDS·Mariana MureaBarry I Freedman
Feb 22, 2014·Age·Alessandro BittoChristian Sell
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Feb 3, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Jacqueline GürkeAnne Navarrete Santos
Jan 12, 2017·Diabetes·Mauricio D DorfmanJoshua P Thaler
Jun 21, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hui-Hui FanFan Deng
Nov 12, 2014·The Journal of Endocrinology·Xiao-Bing CuiShi-You Chen
Nov 9, 2014·Journal of Molecular Endocrinology·Jun ZhouMing-Hui Zou
Mar 23, 2012·Immunological Reviews·Maria T Diaz-Meco, Jorge Moscat

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