CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages.
CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages.
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CD11b 通过限制脂肪组织巨噬细胞的选择性激活和增殖来调节肥胖引起的胰岛素抵抗。
DOI：
10.1073/pnas.1500396113
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发表时间：
2015
影响因子：
11.1
通讯作者：
Wang Ying
中科院分区：
文献类型：
--
作者：
Zheng Chunxing;Yang Qian;Xu Chunliang;Shou Peishun;Cao Jianchang;Jiang Menghui;Chen Qing;Cao Gang;Han Yanyan;Li Fengying;Cao Wei;Zhang Liying;Zhang Li;Shi Yufang;Wang Ying
肥胖相关炎症伴随着脂肪组织巨噬细胞（ATM）的积累，这被认为会使肥胖个体容易产生胰岛素抵抗。 CD11b（整合素 αM）在单核细胞和巨噬细胞上高度表达，对其迁移和功能至关重要。我们在这里发现，高脂肪饮食诱导的胰岛素抵抗在 CD11b 缺陷小鼠中显着降低。有趣的是，当 CD11b 缺陷时，单核细胞向脂肪组织的募集会受到损害，尽管 CD11b 缺陷小鼠中 ATM 的细胞结构高于野生型小鼠。我们进一步发现ATMs的增加主要是由于它们在CD11b缺失的情况下的旺盛增殖所致。此外，ATM 的增殖和选择性激活受到 IL-4/STAT6 轴的调节，而 IL-4/STAT6 轴又通过磷酸酶 SHP-1 的活性受到 CD11b 的抑制。因此，CD11b 通过限制 ATM 的增殖和替代激活，在肥胖引起的胰岛素抵抗中发挥着关键作用。
Obesity-associated inflammation is accompanied by the accumulation of adipose tissue macrophages (ATMs), which is believed to predispose obese individuals to insulin resistance. CD11b (integrin αM) is highly expressed on monocytes and macrophages and is critical for their migration and function. We found here that high-fat diet–induced insulin resistance was significantly reduced in CD11b-deficient mice. Interestingly, the recruitment of monocytes to adipose tissue is impaired when CD11b is deficient, although the cellularity of ATMs in CD11b-deficient mice is higher than that in wild-type mice. We further found that the increase in ATMs is caused mainly by their vigorous proliferation in the absence of CD11b. Moreover, the proliferation and alternative activation of ATMs are regulated by the IL-4/STAT6 axis, which is inhibited by CD11b through the activity of phosphatase SHP-1. Thus, CD11b plays a critical role in obesity-induced insulin resistance by limiting the proliferation and alternative activation of ATMs.