巨噬细胞极化
炎症
脂肪组织
免疫学
胰岛素抵抗
糖蛋白130
医学
代谢综合征
全身炎症
巨噬细胞
内分泌学
内科学
生物
肥胖
白细胞介素6
生物化学
体外
作者
Hongxia Duan,Linhai Jing,Jianquan Xiang,Chenhui Ju,Zhenzhen Wu,Jingyu Liu,Xinran Ma,Xuehui Chen,Zheng Liu,Jing Feng,Xiyun Yan
标识
DOI:10.1002/advs.202103719
摘要
Abstract The mechanism of obesity‐related metabolic dysfunction involves the development of systemic inflammation, largely mediated by macrophages. Switching of M1‐like adipose tissue macrophages (ATMs) to M2‐like ATMs, a population of macrophages associated with weight loss and insulin sensitivity, is considered a viable therapeutic strategy for obesity‐related metabolic syndrome. However, mechanisms for reestablishing the polarization of ATMs remain elusive. This study demonstrates that CD146 + ATMs accumulate in adipose tissue during diet‐induced obesity and are associated with increased body weight, systemic inflammation, and obesity‐induced insulin resistance. Inactivating the macrophage CD146 gene or antibody targeting of CD146 alleviates obesity‐related chronic inflammation and metabolic dysfunction. Macrophage CD146 interacts with Glycoprotein 130 (Gp130), the common subunit of the receptor signaling complex for the interleukin‐6 family of cytokines. CD146/Gp130 interaction promotes pro‐inflammatory polarization of ATMs by activating JNK signaling and inhibiting the activation of STAT3, a transcription factor for M2‐like polarization. Disruption of their interaction by anti‐CD146 antibody or interleukin‐6 steers ATMs toward anti‐inflammatory polarization, thus attenuating obesity‐induced chronic inflammation and metabolic dysfunction in mice. The results suggest that macrophage CD146 is an important determinant of pro‐inflammatory polarization and plays a pivotal role in obesity‐induced metabolic dysfunction. CD146 could constitute a novel therapeutic target for obesity complications.
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