PKCζ-Regulated Inflammation in the Nonhematopoietic Compartment Is Critical for Obesity-Induced Glucose Intolerance
| Autor: | Angela F. Drew, Sang Jun Lee, Michael Leitges, Jason K. Kim, Jorge Moscat, Diego Perez-Tilve, Maria T. Diaz-Meco, Susanna M. Hofmann, Hwi Jin Ko, Dae Young Jung, Juan F. Linares, Ji Young Kim, Rubén Nogueiras, Matthias H. Tschöp |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Physiology HUMDISEASE Adipose tissue Inflammation Article 03 medical and health sciences Mice 0302 clinical medicine Insulin resistance In vivo Internal medicine Glucose Intolerance medicine Animals Obesity Interleukin 6 Molecular Biology Protein kinase C Protein Kinase C 030304 developmental biology Mice Knockout 0303 health sciences biology Interleukin-6 Macrophages Cell Biology medicine.disease Haematopoiesis Endocrinology Adipose Tissue 030220 oncology & carcinogenesis biology.protein medicine.symptom Insulin Resistance Ex vivo |
| Zdroj: | Cell Metabolism. 12(1):65-77 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2010.05.003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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