胰岛素抵抗
CCR2型
炎症
脂肪组织
内分泌学
炎症体
内科学
四氯化碳
趋化因子
肠道通透性
基因剔除小鼠
胰岛素
医学
受体
趋化因子受体
作者
Yusuke Kawano,Jun Nakae,Nobuyuki Watanabe,Tetsuhiro Kikuchi,Sanshiro Tateya,Yoshikazu Tamori,Mari Kaneko,Takaya Abe,Masafumi Onodera,Hiroshi Itoh
标识
DOI:10.1016/j.cmet.2016.07.009
摘要
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.
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