| Literature DB >> 27508875 |
Yoshinaga Kawano1, Jun Nakae2, Nobuyuki Watanabe3, Tetsuhiro Kikuchi1, Sanshiro Tateya4, Yoshikazu Tamori5, Mari Kaneko6, Takaya Abe7, Masafumi Onodera3, Hiroshi Itoh1.
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.Entities:
Mesh：
Substances：
Year: 2016 PMID： 27508875 DOI： 10.1016/j.cmet.2016.07.009
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287