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首页> 外文期刊>Cell metabolism >Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal Ccl2/Ccr2-Dependent Manner
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Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal Ccl2/Ccr2-Dependent Manner

机译:结肠促炎性巨噬细胞以肠道Ccl2 / Ccr2依赖性方式引起胰岛素抵抗

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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.
机译:高脂饮食(HFD)会诱发低度慢性炎症和胰岛素抵抗。但是,关于外周胰岛素应答组织中HFD诱导的慢性炎症的潜在机制了解甚少。在这里,我们显示结肠促炎性巨噬细胞在HFD条件下调节胰岛素敏感性。为了研究结肠巨噬细胞的病理生理作用,我们生成了巨噬细胞特异性趋化因子(C-C母题)受体2(Ccr2)敲除(M-Ccr2KO)和肠上皮细胞特异性他莫昔芬诱导的Ccl2敲除(Vil-Ccl2KO)小鼠。两种菌株均显示出与HFD控制下相似的体重。然而,它们表现出结肠炎性巨噬细胞浸润减少,肠通透性降低和结肠炎性小体失活。有趣的是,它们显示出显着改善的葡萄糖耐量和胰岛素敏感性,同时减少了脂肪组织的慢性炎症。因此,抑制促炎性巨噬细胞浸润可防止HFD诱导的胰岛素抵抗,并且可能是2型糖尿病的新型治疗方法。

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