Open AccessCD146 is a Novel ANGPTL2 Receptor that Promotes Obesity by Manipulating Lipid Metabolism and Energy Expenditure
Author(s) -
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
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202004032
Subject(s) - adipogenesis , cd146 , adipose tissue , endocrinology , receptor , inflammation , medicine , microbiology and biotechnology , chemistry , lipid metabolism , biology , stem cell , cd34
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.