Lnc-Fat1在高脂饮食诱导的2型糖尿病中的功能及作用机制研究

Diabetes mellitus (DM), commonly referred to as diabetes, it is one of the important disease severe impact on human life and health. The molecular regulatory mechanisms of diabetes is one of the important scientific problem. Long non-coding RNAs (Lnc-RNAs) involved in a variety of physiological and pathological process, and its expression specificity related to many diseases, but its regulatory role in the generation and development of diabetes is unknown. We used gene microarray analysis, draw up the diabetes related LncRNAs expression map of high-fat diet induced mouse adipose tissue，screened one of the significant differentially expressed LncRNAs and named as Lnc-Fat1. We further confirmed the expression of Lnc-Fat1 was up-regulated in high-fat diet induced mice in adipose tissue, moreover, GO, pathway analysis and co-expression network map suggested that Lnc-Fat1 was closely related to the insulin signaling pathway and diabetes. The preliminary results indicate that Lnc-Fat1 may play an important regulating role in the process of generation and development of diabetes. In this project, we will observe the role of Lnc-Fat1 in glycometabolism, lipid metabolism and insulin signaling transduction, to expound the functions of Lnc-Fat1. The target genes and molecular of Lnc-Fat1 will be screened to reveal the molecular mechanisms of Lnc-Fat1 involving in diabetes process regulation. The regulatory role and molecular mechanism of Lnc-Fat1 in the generation and development of diabetes will lay a foundation for LncRNAs research in diabetes, propose a new theory for the diagnosis and treatment of diabetes.

糖尿病是危害人类健康的重要疾病，研究其发生发展分子调控机制是重大的科学问题。LncRNAs参与多种生理病理过程，其表达特异性与多种疾病密切相关，而LncRNAs在糖尿病发生发展中的调控作用并不清楚。我们利用基因芯片技术，绘制糖尿病脂肪组织相关LncRNAs表达谱，筛选出差异表达显著LncRNA（Lnc-Fat1），证明其在糖尿病小鼠脂肪组织内高表达，GO、pathway分析和共表达网络提示Lnc-Fat1与胰岛素信号通路及糖尿病密切相关，推测其在糖尿病发生发展过程中起重要调控作用。本项目拟通过研究Lnc-Fat1对糖、脂代谢及胰岛素相关信号通路的影响，阐明其功能；通过研究Lnc-Fat1的靶基因和靶分子揭示Lnc-Fat1参与调控糖尿病过程的分子机制。研究Lnc-Fat1在糖尿病发生发展中的作用机制，为LncRNAs在糖尿病中的研究奠定基础，为糖尿病的诊断及治疗提供新的理论依据和研究方向。

糖尿病是一组以高血糖为特征的代谢性疾病。长链非编码RNA涉及多种生理和病理过程，其表达特异性与多种疾病有关，但其在糖尿病发生发展中的调控作用尚未阐明。本研究采用高脂饮食诱导的肥胖2型糖尿病小鼠模型，利用芯片技术在脂肪组织中绘制mRNA和lncRNA表达图谱。通过功能分析、途径分析，发现与代谢相关的基因相关性最强。转录组分析筛选到差异表达1606个mRNA和124个lncRNA，在此基础上我们构建了mRNA-lncRNA共表达网络，筛选出15个候选lncRNA。从中确定了研究靶标Lnc-Fat1，证明其在成脂分化过程中表达改变显著，通过调控靶基因MEST间接参与糖尿病的发生与发展。本研究为LncRNAs在糖尿病中的研究奠定了基础，为糖尿病的诊断提供新的候选靶标，为糖尿病的治疗提供新的理论依据和研究方向。