Cidea和Fsp27蛋白调控机体脂代谢的功能研究

项目名称： Cidea和Fsp27蛋白调控机体脂代谢的功能研究

项目编号： No.31771303

项目类型： 面上项目

立项/批准年度： 2018

项目学科： 生理学与整合生物学

项目作者： 周林康

作者单位： 清华大学

项目金额： 25万元

中文摘要： 生物体的脂代谢稳态平衡是各个组织协调作用的结果，脂稳态的紊乱会导致代谢综合征如肥胖、糖尿病、脂肪肝的发生。Cidea和Fsp27是最近发现的在脂类代谢中起着重要作用的蛋白。之前的研究都关注在单个蛋白Cidea或者Fsp27在脂肪组织中的功能研究，但在褐色脂肪组织及脂肪性肝脏中同时有Cidea和Fsp27的表达，并且Cidea蛋白在Fsp27缺失的白色脂肪组织中也有表达。Cidea和Fsp27两个蛋白是如何共同作用调控肥胖小鼠脂肪组织和肝脏脂类代谢的尚不清楚。我们拟利用ob/ob/Fsp27-/-/Cidea-/-小鼠，研究在肥胖状态下脂肪组织和肝脏中Cidea和Fsp27对脂积累的影响，以及Cidea和Fsp27缺失后的脂肪组织和肝脏对机体整体代谢状态的影响。并在细胞和分子水平上研究Cidea和Fsp27双缺失对脂储存的影响。

中文关键词： 脂质代谢；脂肪细胞；肝脏脂代谢；脂滴；脂解

英文摘要： Lipid homeostasis represents the relatively stable levels of lipids in circulation and in various tissues including liver, muscle and adipocytes . Lipid homeostasis is a result of the coordination of various tissues. Disrupt lipid homeostasis will lead to metablic diseases such as diabetes obesity and hepatic steatosis. Cidea and Fsp27, members of the Cide family proteins, are lipid-droplet-associated proteins that has emerged as important regulator of lipid storage in adipocyte. Both Cidea and Fsp27 knockout mice has lean phenotype and reduced adipose tissue. Previous research mainly focus on the function of either Cidea or Fsp27. However,. Cidea and Fsp27 are both highly expressed in brown adipose tissue and steatotic liver. Cidea is also upregulated in the white fat tissue of Fsp27 deficient mice. It is important to study the function of both Cidea and Fsp27 in lipid metabolism. In this proposal, we will investigate the mechanism of Cidea and Fsp27 in lipid metabolism using ob/ob、ob/ob/Fsp27-/-、ob/ob/Cidea-/- and ob/ob/Fsp27-/-/Cidea-/- mice. We will use techniques such as molecular and cellular biology to further elucidate the role of Cidea and Fsp27 in liver and adipocyte lipid metabolism.Furthermore, We will investigate the interaction between Cidea/Fsp27 and ATGL in regulating lipid storage. Overall, our study will provide sigificant insight in Cidea and Fsp27-controlled lipid homostasis and the mechaism of the development of metabolic disease.

英文关键词： lipid metabolism;fat cell;liver lipid metabolism;lipid droplets;lipolysis