Abstract：
Tissues release microRNAs (miRNAs) in small extracellular vesicles (sEVs) including exosomes, which can regulate gene expression in distal cells, thus acting as modulators of local and systemic metabolism. Here, we show that insulin regulates miRNA secretion into sEVs from 3T3-L1 adipocytes and that this process is differentially regulated from cellular expression. Thus, of the 53 miRNAs upregulated and 66 miRNAs downregulated by insulin in 3T3-L1 sEVs, only 12 were regulated in parallel in cells. Insulin regulated this process in part by phosphorylating hnRNPA1, causing it to bind to AU-rich motifs in miRNAs, mediating their secretion into sEVs. Importantly, 43% of insulin-regulated sEV-miRNAs are implicated in obesity and insulin resistance. These include let-7 and miR-103, which we show regulate insulin signaling in AML12 hepatocytes. Together, these findings demonstrate an important layer to insulin\'s regulation of adipose biology and provide a mechanism of tissue crosstalk in obesity and other hyperinsulinemic states.
摘要：
组织在小的细胞外囊泡（sEV）中释放微小RNA（miRNA），包括外泌体，可以调节远端细胞的基因表达，从而充当局部和全身代谢的调节剂。这里,我们显示胰岛素调节3T3-L1脂肪细胞分泌到sEV中的miRNA,并且该过程与细胞表达不同.因此，在3T3-L1sEV中，胰岛素上调的53个miRNA和下调的66个miRNA，在细胞中只有12个被平行调节。胰岛素部分通过磷酸化hnRNPA1调节这一过程，使其与miRNAs中富含AU的基序结合，将它们的分泌介导到sEV中。重要的是,43%的胰岛素调节sEV-miRNA与肥胖和胰岛素抵抗有关。这些包括let-7和miR-103，我们显示在AML12肝细胞中调节胰岛素信号。一起,这些发现证明了胰岛素调节脂肪生物学的一个重要层面，并提供了肥胖和其他高胰岛素血症状态的组织串扰机制。
