Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase.
Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase.
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DOI：
10.1038/nm.2885
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发表时间：
2012-09
期刊：
影响因子：
82.9
通讯作者：
Olefsky, Jerrold M.
中科院分区：
文献类型：
--
作者：
Talukdar, Saswata;Oh, Da Young;Bandyopadhyay, Gautam;Li, Dongmei;Xu, Jianfeng;McNelis, Joanne;Lu, Min;Li, Pingping;Yan, Qingyun;Zhu, Yimin;Ofrecio, Jachelle;Lin, Michael;Brenner, Martin B.;Olefsky, Jerrold M.
慢性低度脂肪组织和肝脏炎症是全身胰岛素抵抗的主要原因，也是肥胖和2型糖尿病中存在的低胰岛素敏感性的关键组成部分。免疫细胞，如巨噬细胞、T 细胞、B 细胞、肥大细胞和嗜酸性粒细胞，都被认为在此过程中发挥着作用,,,,,。中性粒细胞通常是第一个对炎症做出反应的免疫细胞，并且可以通过帮助招募巨噬细胞并通过与抗原呈递细胞相互作用来加剧慢性炎症状态。中性粒细胞分泌多种蛋白酶，其中一种是中性粒细胞弹性蛋白酶，它可以促进多种疾病模型中的炎症反应。在这里，我们表明，用中性粒细胞弹性蛋白酶处理肝细胞会导致细胞胰岛素抵抗，并且在高脂饮食诱导的肥胖（DIO）小鼠中删除中性粒细胞弹性蛋白酶会导致较少的组织炎症，这与较低的脂肪组织中性粒细胞和巨噬细胞含量有关。这些变化伴随着葡萄糖耐量的改善和胰岛素敏感性的增加。综上所述，我们发现中性粒细胞可以添加到参与炎症诱导的代谢疾病的广泛免疫细胞库中。
Chronic low-grade adipose tissue and liver inflammation is a major cause of systemic insulin resistance and is a key component of the low degree of insulin sensitivity that exists in obesity and type 2 diabetes,. Immune cells, such as macrophages, T cells, B cells, mast cells and eosinophils, have all been implicated as having a role in this process,,,,,. Neutrophils are typically the first immune cells to respond to inflammation and can exacerbate the chronic inflammatory state by helping to recruit macrophages and by interacting with antigen-presenting cells,,. Neutrophils secrete several proteases, one of which is neutrophil elastase, which can promote inflammatory responses in several disease models. Here we show that treatment of hepatocytes with neutrophil elastase causes cellular insulin resistance and that deletion of neutrophil elastase in high-fat-diet–induced obese (DIO) mice leads to less tissue inflammation that is associated with lower adipose tissue neutrophil and macrophage content. These changes are accompanied by improved glucose tolerance and increased insulin sensitivity. Taken together, we show that neutrophils can be added to the extensive repertoire of immune cells that participate in inflammation-induced metabolic disease.
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影响因子：
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