Sema4D在肥胖诱导的脂肪炎症和胰岛素抵抗中的作用和机制研究

项目名称： Sema4D在肥胖诱导的脂肪炎症和胰岛素抵抗中的作用和机制研究

项目编号： No.81500653

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 卢穹宇

作者单位： 苏州大学

项目金额： 18万元

中文摘要： 肥胖诱导的脂肪组织炎症及胰岛素抵抗在2型糖尿病乃至心血管疾病的发病过程中起重要作用。轴突导向分子Sema4D广泛表达于免疫细胞，并参与多种炎症相关疾病。我们最近发现Sema4D在2型糖尿病病人血浆中和高脂诱导的肥胖小鼠脂肪组织中的表达显著增加，更为重要的是我们利用模式动物证实了敲除Sema4D能够改善高脂饮食诱导的炎症因子分泌和脂肪组织胰岛素抵抗，但Sema4D如何介导肥胖诱导的脂肪组织炎症及胰岛素抵抗尚不清楚。本项目将研究Sema4D促进肥胖诱导的脂肪炎症的细胞特性，探明Sema4D及其受体介导脂肪组织炎症反应中细胞之间相互作用的分子机制，尝试利用可溶性Sema4D及其抗体对脂肪炎症和胰岛素抵抗进行实验性干预研究。研究成果可为预防、诊断和治疗肥胖相关疾病包括2型糖尿病、心血管疾病等提供重要的理论依据。

中文关键词： 肥胖；脂肪炎症；Sema4D；胰岛素抵抗

英文摘要： Obesity-induced adipose tissue inflammation and insulin resistance play an important role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Axonal guidance molecule Semaphorin 4D (Sema4D) is widely expressed on immune cells and participates in many inflammation-associated diseases. We recently found that the plasma level of soluble Sema4D is elevated in type 2 diabetes patients and that the expression of Sema4D is increased in the adipose tissue of C57/BL6 mice on high fat diet. The most convincing finding using genetic-engineering animal models was that Sema4D knockout improved insulin resistance and cytokine release in C57/BL6 on high fat diet. However, the cellular and molecular mechanisms by which Sema4D mediate adipose tissue inflammation and insulin resistance have not been clear. Therefore, in this proposal, we will study the cellular mechanism of Sema4D in mediating adipose tissue inflammation and insulin resistance, investigate the molecular mechanism of Sema4D and its receptors in mediating the interaction between immune cells and immune cells with adipocytes, and perform the experimental studies on the modulation of obesity-associated adipose tissue inflammation and insulin resistance. The data will potentially supply better approaches for prophylaxis, diagnosis and treatment of type 2 diabetes and cardiovascular diseases using Sema4D and its antibodies.

英文关键词： obesity;adipose inflammation;Sema4D;insulin resistance