长期饮食诱导的肥胖小鼠中肥大细胞调控附睾脂肪组织萎缩阶段血管化的机制

项目名称： 长期饮食诱导的肥胖小鼠中肥大细胞调控附睾脂肪组织萎缩阶段血管化的机制

项目编号： No.31471320

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 刘健

作者单位： 合肥工业大学

项目金额： 80万元

中文摘要： 脂肪组织血管化在肥胖及其并发症的发展中起重要作用。在小鼠长期高脂饮食诱导的肥胖中，附睾脂肪组织（EAT）具有先扩张再萎缩的独特重构过程，引起脂肪肝的发生。我们前期研究显示，肥大细胞通过启动脂肪组织血管化，导致饮食诱导肥胖的发生，而肥大细胞的EAT聚集，与EAT萎缩阶段血管化及肝脏并发症的发生密切相关，但是对于其细节细胞生物学调控并不了解。本项目拟在此基础上，以肥大细胞调控EAT萎缩阶段血管化作用为研究主体；利用流式细胞分选技术，分离三对在此方面具有相似功能差异性的EAT肥大细胞为材料；通过基因芯片、RNA 干涉等分子和细胞生物学方法，筛选、确认肥大细胞中调控EAT萎缩阶段血管化的关键因子；再从体外和体内水平，对关键因子产生和作用的细节通路进行初步的研究。该项目的执行,不仅能丰富肥大细胞调控肥胖及相关肝脏疾病的细胞生物学理论，而且也能为相关疾病治疗方法的发展提供新的思路。

中文关键词： 肥大细胞；血管化；附睾脂肪组织；饮食诱导的肥胖；调控机制

英文摘要： Adipose tissue angiogenesis plays an important role in the development of obesity and associated complications.During the developmest of long-standing diet-induced obesity in mice, epididymal adipose tissues (EAT) possess a typical remodeling process from extension to atrophy, intiating hepatic steatosis.Our previous studies showed that mast cells could promote adipose tissue angiogenesis and finally lead to diet-induced obesity. Meanwhile, the accumulation of mast cells into EAT is closely related to EAT angiogenesis and liver complication during EAT atrophy.However,it is unclear which and how cell biological mechasims are invloved in the processes.Therefore, we are plan to investigate the regulatory role of mast cells in angiogenesis during EAT atrophy. Flow cytometry will be used to isolate three pairs of mast cell samples, which possess similar functional differences in mast cell associated EAT angiogenesis, from EAT in mice. Using gene microarray and RNA interference，we are able to screen and affirm the essential molecules in mast cells, which can regulate EAT angiogenesis during EAT atrophy. Further, in vitro and in vivo studies will help us understand the basic functional mechanisms of mast cells in the processes. The proposal will not only give us more cell biological knowledge about role of mast cells in obesity and associated hepatic steatosis, but also suggest a new therapeutic approach for these common diseases.

英文关键词： mast cell;angiogenesis;epididymal adipose tissues (EAT);diet-induced obesity;regulatory mechanism