高果糖饲养仓鼠模型是研究胰岛素抵抗状态下VLDL合成机制的经典模型。我们与该动物模型的建立者Adeli教授合作，首次解析了高果糖喂养的仓鼠肝脏microRNA表达谱，以寻找调控VLDL合成相关的miRNA分子。结果发现均来自Ank1基因内含子的miR-486/3107在果糖饲养后出现显著下调。研究已证实，PTEN和Foxo1 为miR-486的靶基因，可以通过影响胰岛素信号通路及某些基因表达，调控VLDL合成。我们推测，在果糖喂养后，miR-486/3107表达下降，导致PTEN 和Foxo1 表达上升，进而促进VLDL的合成。这揭示了一种果糖饮食诱导VLDL合成增加的新机制，发现了可以调节VLDL合成的潜在miRNA，为在转录水平调节VLDL合成，治疗高脂血症提供了新思路。本课题将在细胞和动物模型深入研究miR-486/3107通过调节PTEN/Foxo1表达影响VLDL合成的分子机制。

Fructose-fed Syrian golden hamster model was a typical animal model employed to investigate the overproduction of very low density lipoprotein (VLDL) in the insulin resistant state. We collaborated with Dr. Adeli, who established the hamster model in the world, first analyzed the hepatic miRNA profiling from the Fructose-fed hamster in order to explore the miRNAs regulaing the assembly of VLDL. It was found that 2 miRNAs from the intron of Ank1 gene, miR-486/3107 were significantly down-regulated after fructose fed. The previous work has proved that PTEN and Foxo1, targeted by miR-486, played important role in the regualtion of VLDL via affecting the activity of insulin signal pathway and the expression of some certain genes. We hypothesized that the down-regulation of miR-486 resulted from the fructose feeding, led to the up-regulation of PTEN and Foxo1, which further promoted the increased VLDL production.It suggeted one novel mechanism of hepatic VLDL overproduction due to fructose diet, discovered the miRNAs potentially regualting VLDL assembly. It indicated a novel strategy in the therapy of hypertriglyceridemia via regulating VLDL at transcriptional levels. In this project, we will further investigate the molecular mechanism of VLDL production directed by miR-486/3107 via targeting PTEN/Foxo1.