LncRNA Gm26870在脂肪组织胰岛素抵抗中的作用和机制研究

Obesity is a critical public health issue globally in developed and developing countries with numerous complications. Evidence for links between obesity and insulin resistance have existed for decades. Meanwhile, insulin resistance is a major determinant of chronic metabolic disorders, including cardiovascular disease and type 2 diabetes mellitus(T2DM). More recent studies have implied the potential involvement of transcriptional and epigenetic regulation in insulin resistance. We hypothesized that lncRNA may have an effect on the process of insulin resistance in adipose tissues. In previous studies, deep RNA sequencing identified the up-regulation of lncRNA Gm26870 in insulin resistant mouse epididymal adipose tissues. In 3T3-L1 adipocytes exposed to palmitic acid (PA), a cellular insulin resistance model, the expression of Gm26870 was significantly elevated. The silence of Gm26870 in insulin resistant adipocytes contributed to the recovery of glucose uptake, indicating that Gm26870 might have an influence on regulating insulin resistance. Therefore, this study will further investigate the effect and potential mechanisms for Gm26870 on insulin sensitivity in adipocytes and adipose tissues. A better understanding of the complex processes in insulin resistance will help to find a better therapeutic strategy for metabolic syndrome related disorders, such as Type 2 diabetes mellitus and cardiovascular diseases.

肥胖是全球性的公共卫生难题。胰岛素抵抗与肥胖密切相关，同时也是2型糖尿病和多种心血管疾病的共同发病机制。最近有新的研究发现转录调控和表观遗传学修饰在胰岛素抵抗的发生发展中也起着重要的作用。LncRNA可能也参与了胰岛素抵抗的调控。在预实验中，我们通过测序发现lncRNA Gm26870在胰岛素抵抗的附睾脂肪组织中表达显著升高。在3T3-L1诱导的成熟脂肪细胞中，棕榈酸刺激诱导细胞胰岛素抵抗模型后Gm26870表达也显著上调。我们发现在脂肪细胞中，敲低Gm26870能够改善胰岛素抵抗引起的葡萄糖摄取率下降。提示Gm26870可能具有调节胰岛素敏感性的作用。因此本研究将深入研究Gm26870对脂肪细胞胰岛素抵抗的影响，探索其可能的机制，并在小鼠体内验证Gm26870对胰岛素敏感性的影响。了解胰岛素抵抗发生和发展的机制有助于人们找到能更有效治疗2型糖尿病和心血管疾病等代谢相关疾病的策略。

肥胖是全球性的公共卫生难题。胰岛素抵抗与肥胖密切相关，同时也是2型糖尿病和多种心血管疾病的共同发病机制。通过测序发现lncRNA Gm26870在胰岛素抵抗的附睾脂肪组织中表达显著升高。在3T3-L1诱导的成熟脂肪细胞中，棕榈酸刺激诱导细胞胰岛素抵抗模型后Gm26879表达也显著上调。我们使用sh-Gm26870敲低小鼠Gm26870和沉默脂肪细胞Gm26870后发现胰岛素抵抗得到改善。在机制上，抑制Gm26870可缓解胰岛素抵抗造成的炎症反应。Gm26870吸附结合miR-30e-3p导致IL1β mRNA的调控作用减弱，因而产生改善胰岛素敏感性的作用。本研究对胰岛素抵抗发生和发展的机制研究有助于人们找到能更有效治疗2型糖尿病和心血管疾病等代谢相关疾病的策略。