Rabif基因在肥胖发生中的作用及其机制研究

项目名称： Rabif基因在肥胖发生中的作用及其机制研究

项目编号： No.31701031

项目类型： 青年科学基金项目

立项/批准年度： 2018

项目学科： 生理学与整合生物学

项目作者： 宋海昭

作者单位： 清华大学

项目金额： 10万元

中文摘要： Rabif是一种在进化上高度保守的基因，在哺乳类动物的组织与器官中广泛表达。目前关于Rabif基因功能的研究较少，且未见其与肥胖发生关系的研究报道。本实验室首次成功构建出脂肪组织特异性Rabif基因敲除小鼠，前期研究发现该小鼠可以抵抗由高脂膳食所诱导的肥胖的发生，提高胰岛素的敏感性。本课题拟进一步完成脂肪组织特异性Rabif敲除小鼠生理学变化的研究，同时繁育肝脏特异性Rabif基因敲除小鼠，并通过生物化学与分子生物学等方法从动物、细胞和分子水平多方面研究Rabif基因对肥胖的发生和脂代谢的影响，初步探究Rabif影响脂代谢的分子机制。本课题的开展将揭示Rabif基因与肥胖的关系及其调控肥胖发生的分子机制，为肥胖的防治提供一种新思路和药物作用新靶点，具有重要的理论意义和实际应用价值。

中文关键词： 肥胖；脂肪细胞；脂质代谢；脂滴；甘油三酯合成

英文摘要： Rabif is an evolutionarily highly conserved gene and is expressed in all mammalian tissues. Its precise biological function was still elusive, and no studies related to obesity were reported. In our lab, adipose tissue-specific Rabif knockout mice were generated, and the Rabif -/- mice had decreased high-fat diet-induced body weight gain and lipid accumulation. Furthermore, the insulin sensitivity was also increased in Rabif -/- mice. This model provides direct evidence for a role of Rabif in obesity. In this study, we will continue to study the physiological changes that occur in Rabif -/- mice. Moreover, we will focus on understanding the impact of Rabif on lipid metabolism and how it occurs at the cellular and molecular level by using the laboratory techniques in biochemistry and molecular biology. This study will reveal the crucial role of Rabif in obesity and the underlying mechanism. The research will also bring a new understanding of the anti-obesity strategy and could make a base for protocol implementation in the screening of anti-obesity compounds.

英文关键词： Obesity;Adipocyte;Lipid metabolism;Lipid droplet;Triglyceride synthesis