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Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity
来源: | 作者:pmo597dc1 | 时间 :2017-11-20 | 1067 次浏览 | 分享到:

Cell. 2017 Oct 5;171(2):372-384.e12.


ABSTRACT

MiRNAs are regulatory molecules that can be packaged into exosomes and secreted from cells. Here, we show that adipose tissue macrophages (ATMs) in obese mice secrete miRNA-containing exosomes (Exos), which cause glucose intolerance and insulin resistance when administered to lean mice. Conversely, ATM Exos obtained from lean mice improve glucose tolerance and insulin sensitivity when administered to obese recipients. miR-155 is one of the miRNAs overexpressed in obese ATM Exos, and earlier studies have shown that PPARγ?is a miR-155 target. Our results show that miR-155KO animals are insulin sensitive and glucose tolerant compared to controls. Furthermore, transplantation of WT bone marrow into miR-155KO mice mitigated this phenotype. Taken together, these studies show that ATMs secrete exosomes containing miRNA cargo. These miRNAs can be transferred to insulin target cell types through mechanisms of paracrine or endocrine regulation with robust effects on cellular insulin action, in vivo insulin sensitivity, and overall glucose homeostasis.

解读:

MiRNAs是一种调控分子,可以被包装进外泌体,并从细胞中分泌出来。我们发现肥胖小鼠体内的脂肪组织巨噬细胞(ATMs),分泌含miRNA的外泌体(Exos),它会引起痩小鼠的葡萄糖不耐受和胰岛素抵抗。相反地,从瘦小鼠获得的ATM Exos,可以改善肥胖个体的葡萄糖耐受性和胰岛素敏感性。mir - 155是在肥胖ATM Exos中被过度表达的miRNAs之一,早期的研究表明PPARγmir - 155的靶基因。我们的研究结果显示,与对照组相比,mir – 155敲除动物具有胰岛素敏感性和葡萄糖耐受能力。此外,将WT小鼠骨髓移植入mir – 155敲除小鼠减轻了该表型。综上所述,这些研究表明,ATMs可以分泌含有miRNA的外泌体被运输到胰岛素靶细胞再通过旁分泌或内分泌调节机制影响细胞的胰岛素作用,体内胰岛素敏感性和整体葡萄糖稳态。



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