Function and mechanism study of CD146 which is the receptor of ANGPTL2 in obesity. Mus musculus

Obesity and its complications are increasingly becoming a major threat to human health. At present, the research on obesity mainly focuses on intracellular transcription factors and extracellular cytokines, and there is still a lack of membrane receptor molecules which can be targeted to treat obesity. For example, ANGPTL2 is one of the important adipocytokines, which promotes obesity and its complications. However, the mechanism that ANGPTL2 promotes obesity is not clear. Recently, when we study the function of CD146 which is high expressed in adipocyte, we find that ANGPTL2 interacts with CD146 directly in adipocytes, and anti-CD146 antibody blocked CD146-ANGPTL2 interaction. Systemic or adipose tissue-specific knockout of CD146 protects mice from obesity and related detrimental effects. Thus, we propose that CD146 is the key receptor for transmitting ANGPTL2 signaling from extracellular to intracellular in the development of obesity and related diseases. In this study, we will take advantage of various CD146 knockout mouse models and clinical samples to study the function and molecular mechanism of ANGPTL2-CD146 in promoting obesity systematically and the therapy effects of targeting CD146 in obesity. This study will provide a new molecular mechanism for obesity and provide a new target for obesity treatment.