Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.
Nat Commun. 2022 Aug 10;13(1):4684. doi: 10.1038/s41467-022-32348-3.
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.
肥胖症和与之相关的健康并发症的发病率正在上升。肥胖症患者的脂肪组织存在低度、慢性炎症，导致胰岛素抵抗。脂肪组织巨噬细胞（ATMs）是促炎细胞因子的来源，进一步加重脂肪细胞功能障碍。对高脂肪饮食（HFD）的反应，ATMs 数量最初通过常驻巨噬细胞的增殖增加，但随后的增加也来自于对来自发炎脂肪组织的趋化信号的浸润。为了阐明调节 ATMs 及其促炎表型增加的潜在机制，我们研究了激活 ATMs 表皮生长因子受体（EGFR）的作用。高脂肪饮食增加了 ATMs 中 EGFR 及其配体 Amphiregulin 的表达。ATMs 中 EGFR 的选择性缺失抑制了常驻 ATMs 的增殖和单核细胞浸润到脂肪组织中，并减少了肥胖症和胰岛素抵抗的发展。因此，ATMs EGFR 的激活在脂肪组织功能障碍中发挥重要作用。
