一种新的长链非编码RNA调控CHCHD3基因对白色脂肪棕色化的机制研究

项目名称： 一种新的长链非编码RNA调控CHCHD3基因对白色脂肪棕色化的机制研究

项目编号： No.81670783

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 孙嘉

作者单位： 南方医科大学

项目金额： 25万元

中文摘要： 能量失衡是肥胖发生的主要原因，线粒体形态及功能异常影响能量代谢是肥胖发生的中心环节。课题组前期通过基因芯片筛选发现：lncRNA P19461在肥胖人群中表达下调，低脂饮食促进其表达上调；生物信息学分析显示lncRNA P19461和线粒体稳定蛋白复合体的核心基因CHCHD3共表达,CHCHD3是其潜在的作用靶点。由此我们提出，lncRNA P19461可能通过参与调控线粒体的结构、功能及白色脂肪棕色化过程参与肥胖进程,其中mtNOS/NO/cGMP/MAPK信号通路可能发挥重要作用。本课题拟应用3T3-L1前脂肪细胞模型，通过质粒/siRNA转染、分子生物学等技术，探讨lncRNA P19461/CHCHD3对高脂诱导线粒体损伤的调控及影响白色脂肪棕色化参与肥胖的发生发展的可能机制，以期为肥胖防治提供新策略。

中文关键词： 长链非编码RNA；线粒体；含卷曲螺旋螺旋卷曲螺旋螺旋域3蛋白；白色脂肪棕色化

英文摘要： Energy imbalance is the main cause of obesity. The paramorphia and dysfunction of mitochondria are the central part of obesity. With microarrays analysis, we previously found that lncRNA p19461 was down-regulated in obese patients while low-fat diet can promote its expression. Bioinformatics analysis showed that lncRNA p19461 was co-expressed with CHCHD3 gene, which helped to stabalize protein complex in mitochondria. Therefore, we proposed that lncRNA p19461 might play an important role in obesity through regulating the structure and function of mitochondria as well as the process of white fat brown through mtNOS/NO/cGMP/MAPK signaling pathway. 3T3-L1 preadipocytes will be used in our study. With technique including plasmid/siRNA transfection and other molecular biology techniques, we plan to verify that lncRNA P19461/CHCHD3 contribute to the pathogenesis and development of obesity by regulating the mitochondria dysfunction as well as the process of white fat brown, which may provide a new strategy and treatment for obesity.

英文关键词： long noncoding RNA;mitochondrion;CHCHD3;white adipocyte browning