SREBP-1c/lncRNA BC158825在高脂致骨骼肌胰岛素抵抗中的作用研究

项目名称： SREBP-1c/lncRNA BC158825在高脂致骨骼肌胰岛素抵抗中的作用研究

项目编号： No.81500630

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： 吴文君

作者单位： 南京医科大学

项目金额： 18万元

中文摘要： 固醇调节元件结合蛋白1c（SREBP-1c）在脂毒性骨骼肌胰岛素抵抗（IR）中发挥重要作用，是否存在其他机制尚不明确。我们发现：骨骼肌SREBP-1c表达升高同时肿瘤坏死因子α（TNF-α）表达升高；lncRNA芯片示SREBP-1c上调lncRNA BC158825与TNF通路相关基因表达升高相关；过表达lncRNA BC158825，TNF-α表达升高，提示SREBP-1c可能通过lncRNA BC158825激活炎症通路在高脂致骨骼肌IR中起作用。本课题拟建立SREBP-1c/lncRNA BC158825不同表达状态细胞模型，深入研究SREBP-1c对炎症通路的影响、SREBP-1c/lncRNA BC158825的靶向调控关系及胰岛素是否通过SREBP-1c诱导lncRNA BC158825表达。本研究有助明确SREBP-1c在骨骼肌IR中的作用机制，为防治2型糖尿病提供新靶点。

中文关键词： 固醇调节元件结合蛋白1c；长链非编码RNA；炎症；胰岛素抵抗；骨骼肌

英文摘要： Sterol regulatory element binding protein 1c（SREBP-1c）play a major role involved in lipotoxicity of skeletal muscle insulin resistance, but whether there is other mechanism is not clear. We found that augmentation of SREBP-1c expression in skeletal muscle cells was accompanied by increased tumor necrosis factor-α (TNF-α) expression. The results of lncRNA chips showed that lncRNA BC158825 upregulated by SREBP-1c was associated with elevated gene expressions related to TNF signaling pathway. Overexpression of lncRNA BC158825 in L6 cells increased TNF-α expression. Taken together, we speculated that SREBP-1c activated inflammatory signaling by upregulation of lncRNA BC158825 and played a role in lipid-induced skeletal muscle insulin resistance. The study was undertaken to explore the role of SREBP-1c on inflammatory signaling, SREBP-1c/lncRNA BC158825 targeted regulation and insulin-induced expression of lncRNA BC158825 through SREBP-1c using different SREBP-1c/lncRNA BC158825 expression cell models. The study could help to clarify the mechanism of SREBP-1c action in skeletal muscle insulin resistance, and provide a new target for the prevention and treatment of type 2 diabetes.

英文关键词： sterol regulatory element binding protein 1c;long noncoding RNA;inflammation;insulin resistance;skeletal muscle