1. Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal Ccl2/Ccr2-Dependent Manner.
- Author
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Kawano Y, Nakae J, Watanabe N, Kikuchi T, Tateya S, Tamori Y, Kaneko M, Abe T, Onodera M, and Itoh H
- Subjects
- Adipose Tissue metabolism, Adipose Tissue pathology, Animals, Diet, High-Fat, Epithelial Cells drug effects, Epithelial Cells metabolism, Gastrointestinal Microbiome drug effects, Gene Deletion, Inflammasomes metabolism, Insulin pharmacology, Macrophages drug effects, Mice, Inbred C57BL, Mice, Knockout, Organ Specificity drug effects, Permeability, Chemokine CCL2 metabolism, Colon pathology, Inflammation pathology, Insulin Resistance, Macrophages metabolism, Macrophages pathology, Receptors, CCR2 metabolism
- Abstract
High-fat diet (HFD) induces low-grade chronic inflammation and insulin resistance. However, little is known about the mechanism underlying HFD-induced chronic inflammation in peripheral insulin-responsive tissues. Here, we show that colonic pro-inflammatory macrophages regulate insulin sensitivity under HFD conditions. To investigate the pathophysiological role of colonic macrophages, we generated macrophage-specific chemokine (C-C Motif) receptor 2 (Ccr2) knockout (M-Ccr2KO) and intestinal epithelial cell-specific tamoxifen-inducible Ccl2 knockout (Vil-Ccl2KO) mice. Both strains exhibited similar body weight to control under HFD. However, they exhibited decreased infiltration of colonic pro-inflammatory macrophages, decreased intestinal permeability, and inactivation of the colonic inflammasome. Interestingly, they showed significantly improved glucose tolerance and insulin sensitivity with decreased chronic inflammation of adipose tissue. Therefore, inhibition of pro-inflammatory macrophage infiltration prevents HFD-induced insulin resistance and could be a novel therapeutic approach for type 2 diabetes., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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