脂肪组织
白色脂肪组织
微泡
巨噬细胞极化
炎症
脂肪组织巨噬细胞
内分泌学
外体
内科学
生物
葡萄糖稳态
干细胞
巨噬细胞
胰岛素抵抗
细胞生物学
医学
胰岛素
小RNA
基因
体外
生物化学
作者
Hui Zhao,Qianwen Shang,Zhenzhen Pan,Yang Bai,Zequn Li,Huiying Zhang,Qiu Zhang,Chun Guo,Lining Zhang,Qun Wang
出处
期刊:Diabetes
[American Diabetes Association]
日期:2017-11-13
卷期号:67 (2): 235-247
被引量:447
摘要
Adipose-derived stem cells (ADSCs) play critical roles in controlling obesity-associated inflammation and metabolic disorders. Exosomes from ADSCs exert protective effects in several diseases, but their roles in obesity and related pathological conditions remain unclear. In this study, we showed that treatment of obese mice with ADSC-derived exosomes facilitated their metabolic homeostasis, including improved insulin sensitivity (27.8% improvement), reduced obesity, and alleviated hepatic steatosis. ADSC-derived exosomes drove alternatively activated M2 macrophage polarization, inflammation reduction, and beiging in white adipose tissue (WAT) of diet-induced obese mice. Mechanistically, exosomes from ADSCs transferred into macrophages to induce anti-inflammatory M2 phenotypes through the transactivation of arginase-1 by exosome-carried active STAT3. Moreover, M2 macrophages induced by ADSC-derived exosomes not only expressed high levels of tyrosine hydroxylase responsible for catecholamine release, but also promoted ADSC proliferation and lactate production, thereby favoring WAT beiging and homeostasis in response to high-fat challenge. These findings delineate a novel exosome-mediated mechanism for ADSC–macrophage cross talk that facilitates immune and metabolic homeostasis in WAT, thus providing potential therapy for obesity and diabetes.
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