Adipose-derived circulating miRNAs regulate gene expression in other tissues.
Adipose-derived circulating miRNAs regulate gene expression in other tissues.
复制标题
脂肪来源的循环 miRNA 调节其他组织中的基因表达。
DOI：
10.1038/nature21365
复制
发表时间：
2017-02-23
期刊：
影响因子：
64.8
通讯作者：
Kahn CR
中科院分区：
文献类型：
--
作者：
Thomou T;Mori MA;Dreyfuss JM;Konishi M;Sakaguchi M;Wolfrum C;Rao TN;Winnay JN;Garcia-Martin R;Grinspoon SK;Gorden P;Kahn CR
脂肪组织是能量储存的主要场所，并通过释放脂肪因子在代谢调节中起作用。在这里，我们发现，脂肪特异性敲除miRNA加工酶Dicer（ADicerKO）的小鼠以及患有脂肪营养不良的人类，循环外泌体miRNA的主要减少。将白色和特别是棕色脂肪组织（BAT）移植到ADicerKO小鼠中恢复了与葡萄糖耐量改善和肝FGF 21 mRNA和循环FGF 21减少相关的循环miRNA。这种基因调控可以通过施用正常血清外泌体而不是AdicerKO来模拟。一只小鼠体内BAT中的人类特异性miRNA表达也可以通过血清外泌体转移调节另一只小鼠肝脏中的3'UTR报告基因。因此，脂肪组织构成了循环外泌体miRNA的主要来源，并且这些miRNA可以调节远处组织中的基因表达，从而充当脂肪因子的新形式。
Adipose tissue is a major site of energy storage and plays a role in regulation of metabolism through release of adipokines. Here we show that mice with a fat-specific knockout of the miRNA-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, have major decreases in circulating exosomal miRNAs. Transplantation of white and especially brown adipose tissue (BAT) into ADicerKO mice restores circulating miRNAs associated with an improvement in glucose tolerance and a reduction of hepatic FGF21 mRNA and circulating FGF21. This gene regulation can be mimicked by administration of normal, but not AdicerKO, serum exosomes. Expression of a human-specific miRNA in BAT of one mouse in vivo can also regulate its 3’UTR-reporter in liver of another mouse through serum exosomal transfer. Thus, adipose tissue constitutes a major source of circulating exosomal miRNAs, and these miRNAs can regulate gene expression in distant tissues thereby serving as novel forms of adipokines.