LncRNARP11-34D15.2通过miR-223调控PGC-1a/Irisin通路参与儿童肥胖FFA升高及胰岛素抵抗的机制

肥胖儿童体内高游离脂肪酸（FFA）具有脂毒性，可以引起胰岛素抵抗，严重威胁儿童健康。阐明FFA升高的机制是防治胰岛素抵抗的关键。我们发现RP11-34D15.2可以调控Irisin表达并影响线粒体对FFA清除。在此基础上，提出RP11-34D15.2通过miR-223调控PGC-1a/Irisin通路参与儿童肥胖FFA升高及胰岛素抵抗的假说。本研究首先将明确肥胖儿童 RP11-34D15.2与Irisin的变化及Irisin与FFA及胰岛素抵抗指数间的关系；进而从功能上证实 RP11-34D15.2对靶向miR-223及PGC-1a/Irisin的影响及在FFA清除与胰岛素抵抗中的作用；最后，从机制上探讨RP11-34D15.2通过miR-223调控PGC-1a/Irisin通路，影响FFA清除，促使FFA升高而引起胰岛素抵抗的假说。本研究将为高FFA及胰岛素抵抗的治疗提供新的策略及靶点。

The high plasma FFA in obese children has lipotoxicity. Elevated FFA also has a significant role in contributing to insulin resistance and seriously threating children's health.To explore the mechanism of elevated FFA is the key to preventing insulin resistance. We found that RP11-34D15.2 can regulate Irisin expression and affect mitochondrial clearance of FFA. So we propose that LncRNA RP11-34D15.2 contributes to elevated FFA and insulin resistance in obese children through sponging miR-223 and regulating PGC-1a/Irisin pathway. Firstly, we want to clarify the changes of RP11-34D15.2 and Irisin and the relationship between Irisin, FFA and insulin resistance index in obese children. Secondly, we will study the effect of RP11-34D15.2 on miR-223/PGC-1a/Irisin signaling pathway and its role in FFA clearance and insulin resistance. Finally, our study will elucidate the molecular mechanism of RP11-34D15.2 involved in elevated FFA and insulin resistance in obese children through regulating the PGC-1a/Irisin pathway by targeting miR-223 . This study will provide new therapeutic strategies and molecular targets for elevated FFA and insulin resistance in obese children.