Wu Zhenzhen, Liu Jingyu, Chen Gang, Du Junfeng, Cai Huiyun, Chen Xuehui, Ye Gaoqi, Luo Yongting, Luo Yiyi, Zhang Liwen, Duan Hongxia, Liu Zheng, Yang Sai, Sun Hongwei, Cui Yan, Sun Lei, Zhang Hongjie, Shi Guizhi, Wei Taotao, Liu Pingsheng, Yan Xiyun, Feng Jing, Bu Pengcheng
Key Laboratory of RNA Biology Key Laboratory of Protein and Peptide Pharmaceuticals Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China.
College of Life Sciences University of Chinese Academy of Sciences Beijing 100049 China.
Adv Sci (Weinh). 2021 Jan 27;8(6):2004032. doi: 10.1002/advs.202004032. eCollection 2021 Mar.
Obesity and its related complications pose an increasing threat to human health; however, targetable obesity-related membrane receptors are not yet elucidated. Here, the membrane receptor CD146 is demonstrated to play an essential role in obesity. In particular, CD146 acts as a new adipose receptor for angiopoietin-like protein 2 (ANGPTL2), which is thought to act on endothelial cells to activate adipose inflammation. ANGPTL2 binds to CD146 to activate cAMP response element-binding protein (CREB), which then upregulates CD146 during adipogenesis and adipose inflammation. CD146 is present in preadipocytes and mature adipocytes, where it is mediated by its ligands ANGPTL2 and galectin-1. In preadipocytes, CD146 ablation suppresses adipogenesis, whereas the loss of CD146 in mature adipocytes suppresses lipid accumulation and enhances energy expenditure. Moreover, anti-CD146 antibodies inhibit obesity by disrupting the interactions between CD146 and its ligands. Together, these findings demonstrate that ANGPTL2 directly affects adipocytes via CD146 to promote obesity, suggesting that CD146 can be a potential target for treating obesity.
肥胖及其相关并发症对人类健康构成了日益严重的威胁；然而，尚未阐明可靶向的肥胖相关膜受体。在此，膜受体CD146被证明在肥胖中起关键作用。具体而言，CD146作为血管生成素样蛋白2（ANGPTL2）的一种新的脂肪受体，据认为ANGPTL2作用于内皮细胞以激活脂肪炎症。ANGPTL2与CD146结合以激活环磷酸腺苷反应元件结合蛋白（CREB），然后在脂肪生成和脂肪炎症过程中上调CD146。CD146存在于前脂肪细胞和成熟脂肪细胞中，其由配体ANGPTL2和半乳糖凝集素-1介导。在前脂肪细胞中，CD146缺失会抑制脂肪生成，而在成熟脂肪细胞中CD146的缺失会抑制脂质积累并增加能量消耗。此外，抗CD146抗体通过破坏CD146与其配体之间的相互作用来抑制肥胖。总之，这些发现表明ANGPTL2通过CD146直接影响脂肪细胞以促进肥胖，提示CD146可能成为治疗肥胖的潜在靶点。
