EGFR-mediated activation of adipose tissue macrophages promotes obesity and insulin resistance.
EGFR-mediated activation of adipose tissue macrophages promotes obesity and insulin resistance.
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EGFR 介导的脂肪组织巨噬细胞激活促进肥胖和胰岛素抵抗。
DOI：
10.1038/s41467-022-32348-3
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发表时间：
2022-08-10
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
肥胖症和与肥胖症有关的健康并发症的发病率正在上升。来自肥胖受试者的脂肪组织具有低度慢性炎症，导致胰岛素抵抗。脂肪组织巨噬细胞（ATM）是促炎细胞因子的来源，其进一步加重脂肪细胞功能障碍。响应于高脂肪饮食（HFD），ATM数目最初通过驻留巨噬细胞的增殖而增加，但随后的增加也是响应于来自发炎脂肪组织的趋化信号的浸润所致。为了阐明调节ATM及其促炎表型增加的潜在机制，我们研究了ATM表皮生长因子受体（EGFR）活化的作用。高脂饮食增加ATM中EGFR及其配体双调蛋白的表达。ATM中EGFR的选择性缺失抑制了常驻ATM增殖和单核细胞向脂肪组织的浸润，并减少了肥胖和胰岛素抵抗的发展。因此，ATM EGFR活化在脂肪组织功能障碍中起重要作用。在肥胖症中，脂肪组织慢性发炎，导致胰岛素抵抗，并且脂肪组织巨噬细胞（ATM）是加重脂肪细胞功能障碍的细胞因子的主要来源。在这里，作者表明，选择性删除表皮生长因子受体在ATM减少肥胖和胰岛素抵抗的发展。
Obesity and obesity-related health complications are increasing in prevalence. Adipose tissue from obese subjects has low-grade, chronic inflammation, leading to insulin resistance. Adipose tissue macrophages (ATMs) are a source of proinflammatory cytokines that further aggravate adipocyte dysfunction. In response to a high fat diet (HFD), ATM numbers initially increase by proliferation of resident macrophages, but subsequent increases also result from infiltration in response to chemotactic signals from inflamed adipose tissue. To elucidate the underlying mechanisms regulating the increases in ATMs and their proinflammatory phenotype, we investigated the role of activation of ATM epidermal growth factor receptor (EGFR). A high fat diet increased expression of EGFR and its ligand amphiregulin in ATMs. Selective deletion of EGFR in ATMs inhibited both resident ATM proliferation and monocyte infiltration into adipose tissue and decreased obesity and development of insulin resistance. Therefore, ATM EGFR activation plays an important role in adipose tissue dysfunction. In obesity, adipose tissue is chronically inflamed, leading to insulin resistance, and adipose tissue macrophages (ATMs) are a major source of cytokines that aggravate adipocyte dysfunction. Here, the authors show that selective deletion of the epidermal growth factor receptor in ATMs decreased obesity and development of insulin resistance.
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巨噬细胞的局部扩散有助于与肥胖相关的脂肪组织炎症。
影响因子：
29
作者：
Amano SU;Cohen JL;Vangala P;Tencerova M;Nicoloro SM;Yawe JC;Shen Y;Czech MP;Aouadi M
通讯作者：
Aouadi M
影响因子：
5.3
作者：
Chen, Jianchun;Chen, Jian-Kang;Harris, Raymond C.
通讯作者：
Harris, Raymond C.
影响因子：
13.6
作者：
Chen, Jianchun;Chen, Jian-Kang;Harris, Raymond C.
通讯作者：
Harris, Raymond C.
影响因子：
13.6
作者：
Chen, Jianchun;Harris, Raymond C.
通讯作者：
Harris, Raymond C.
影响因子：
29.4
作者：
Berasain, C;García-Trevijano, ER;Avila, MA
通讯作者：
Avila, MA