B淋巴细胞分泌致病性抗体在HHcy引起早期脂肪组织胰岛素抵抗发病中的作用

Our previous studies revealed that HHcy initiates adipose inflammation and insulin resistance. The recent results further showed that Hcy promotes LPC generation in adipocytes, induces inflammation in macrophages and increases the secretion of anti-phospholipid antibody in B cells. Therefore, we hypothesized that adipocyte-derived LPC promotes anti-phospholipid antibody generation in B cells, which is involved in the HHcy-induced adipose inflammation and insulin resistance. In the project, the B cell-null mice and lipidomics will be employed to clarify 1. The involvement of anti-phospholipid antibody in the Hcy-induced insulin resistance; 2. Whether adipocyte-derived LPC mediates anti-phospholipid antibody secretion in B cells; 3. The improving effect of inhibiting antibody secretion on the Hcy-induced insulin resistance. The project will provide new strategy against metabolic disorders.

课题组之前的研究发现高同型半胱氨酸血症（HHcy）可引起脂肪组织炎症与胰岛素抵抗。我们近期结果表明Hcy能促进脂肪细胞产生溶血磷脂酰胆碱（LPC），诱导巨噬细胞炎症并促进B淋巴细胞产生抗磷脂抗体。据此我们提出如下假说，脂肪细胞来源的LPC通过促进B淋巴细胞产生抗磷脂抗体，进而促进脂肪组织炎症和胰岛素抵抗。本项目拟利用B淋巴细胞特异敲除小鼠，B淋巴细胞移植回输小鼠结合脂质组学等新技术重点研究：1. B细胞分泌的抗磷脂抗体是否参与HHcy诱导的脂肪组织胰岛素抵抗；2. 通过细胞共培养实验，研究Hcy引起脂肪细胞源的LPC释放是否引起B淋巴细胞分泌抗磷脂抗体；3. 明确在体干预B细胞分泌抗磷脂抗体能否改善Hcy诱导的脂肪组织胰岛素抵抗。本项目将为代谢相关疾病提供新的干预新策略。