脂肪细胞外泌体来源的miR-374b在骨骼肌胰岛素抵抗发生机制中的研究

The expression of miR-374b is significantly elevated in exosomes derived from adipocytes in obese. It is reported that skeletal muscle insulin resistance is a critical factor in pathogenesis of obesity related complication. Our previous study showed that exosomes derived from adipocytes in obese could lead to insulin resistance in skeletal muscles. The miR-374b is significantly higher in exosomes derived from adipocytes in obese. It was tested and confirmed that Pgc-1α is the target gene of miR-374b by bioinformatics and luciferase reporter gene analysis. Pgc-1α is reported to be a critical role in the development of insulin resistance in skeletal muscle. Our research is designed to evaluate the expression of miR-374b in exosomes derived from adipocytes in obese on obesity related complication. The molecular mechanisms of miR-374b, transported by exosomes derived from adipocytes in obese, on regulating Pgc-1α in skeletal muscle insulin resistance is investigated by inhibiting the formation of exosomes, overexpression and knock down the expression of miRNA-374b, and rescue experiment. To date, there is no report about the adipocytes transport miR-374b exerts its biological function via exosomes. Our research is expected to provide new targets for the prevention and treatment of obesity related complication.

miR-374b是我们采用miRNA测序技术筛选到的、显著高表达于肥胖患者脂肪细胞外泌体的miRNA。已证实骨骼肌胰岛素抵抗是肥胖相关并发症发生的重要环节。前期研究发现：肥胖患者脂肪细胞外泌体可导致骨骼肌胰岛素抵抗；miR-374b显著高表达于肥胖患者脂肪细胞外泌体；生物信息学预测及荧光素酶报告基因技术证实Pgc-1α为miR-374b靶基因；文献报道Pgc-1α在骨骼肌胰岛素抵抗的发生中发挥重要作用。本研究拟：检测肥胖患者脂肪细胞外泌体中miR-374b表达水平及胰岛素抵抗的相关指标，评估miR-374b与肥胖相关并发症之间的关系；通过抑制外泌体、过表达和沉默miR-374b以及挽救策略，系统评判外泌体中miR-374b通过调控Pgc-1α影响骨骼肌胰岛素抵抗的分子机制。目前尚未见有脂肪细胞通过外泌体转运miR-374b发挥功能的报道，本研究如获成功，有望为肥胖相关并发症防治提供新靶标。