脂肪组织慢性炎症反应是造成妊娠期糖尿病（GDM）胰岛素抵抗的关键因素之一。我们前期发现，新的人lnc-GAT1在GDM患者皮下脂肪组织中低表达，而其调节炎症反应的靶基因TNFSF12高表达，推测lnc-GAT1通过TNFSF12参与GDM脂肪组织慢性炎症反应。为阐明其分子机制，本项目拟采用GDM患者脂肪组织，利用RT-qPCR 、斑点杂交、FISH等技术观察lnc-GAT1的表达及定位情况，明确其生物学特性；采用lnc-GAT1和/或TNFSF12稳定高/低表达的SGBS细胞株和人原代前体脂肪细胞，通过检测细胞及培养液中炎性相关脂肪细胞因子的表达，分析lnc-GAT1的功能及其与TNFSF12的靶向调节关系；最后采用RNA pull down、MS、RIP等技术阐明lnc-GAT1调控TNFSF12基因表达的分子机制。结果将丰富lncRNA对GDM作用的认识，为GDM的防治提供新思路。

Gestational diabetes mellitus (GDM) is defined as a glucose intolerance of varying severity with onset or first recognition during pregnancy. Insulin resistance is currently linked to the pathogenesis of GDM, although the molecular and cellular mechanisms involved in the development of GDM are not yet fully understood. Increasing evidence from clinical and experimental studies indicates that adipose tissue chronic inflammation, characterised by abnormal production of adipokines, is an essential factor linked to insulin resistance and GDM. Adipokines production is driven by a highly coordinated transcriptional cascade. Although some studies have identified several microRNAs involved in this process, molecular events regard to long noncoding RNAs (lncRNAs) during adipokines production remain to be explored. Using methods of High-throughput sequencing and Bioinformatics, we has identified a novel human lncRNA—lnc-GAT1, whose expression is down-regulated while its potential target gene TNFSF12 is up-regulated in abdomen subcutaneous adipose tissue of GDM women. Our preliminary data suggests lnc-GAT1 influences adipose tissue chronic inflammation through TNFSF12, which is known to be essential for inflammation. The present investigation aims to characterize and determine the physiological significance of the lnc-GAT1 with respect to adipose tissue chronic inflammation in GDM women. In order to investigate the novel role and potental mechanism of lnc-GAT1, the methods of RT-qPCR, western blotting, RNA pull down, MS, RIP and ChIRP will be also used in SGBS cell and primary human preadipocytes with overexpression/interferece lnc-GAT1 or/and TNFSF12. The results and conclusions will increase the understanding of mechanisms regulating insulin resistance and provide new insights into the pathophysiology of GDM. This knowledge also provides a framework for future investigations into the role of lncRNA in adipose tissue dysfunction and may ultimately help to identify novel therapeutic strategies aimed at ameliorating GDM.