Induction of miR-29a by saturated fatty acids impairs insulin signaling and glucose uptake through translational repression of IRS-1 in myocytes

被引:116
作者
Yang, Won-Mo [1 ]
Jeong, Hyo-Jin [1 ]
Park, Seung-Yoon [1 ]
Lee, Wan [1 ,2 ]
机构
[1] Dongguk Univ, Coll Med, Dept Biochem, Gyeongju 780714, South Korea
[2] Dongguk Univ, Coll Med, Channelopathy Res Ctr, Goyang 410773, South Korea
基金
新加坡国家研究基金会;
关键词
MicroRNA; miR-29a; Palmitate; Insulin resistance; IRS-1; Saturated fatty acid; PHOSPHATIDYLINOSITOL; 3-KINASE; RECEPTOR SUBSTRATE-1; TARGET RECOGNITION; DIABETES-MELLITUS; SKELETAL-MUSCLE; GENE-EXPRESSION; RESISTANCE; LIVER; PHOSPHORYLATION; ADIPOCYTES;
D O I
10.1016/j.febslet.2014.05.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
MicroRNAs have been shown to play an important role in insulin signaling but their biological function in insulin resistance induced by saturated fatty acids (SFA) remains largely unknown. Here, we report that SFA palmitate and high fat diet (HFD) significantly increase expression of miR-29a in myocytes. miR-29a targets IRS-1 3'UTR directly and represses IRS-1 expression at the translational level. Furthermore, the ectopic expression of miR-29a impairs insulin signaling and glucose uptake in myocytes through a substantial decrease in IRS-1. These findings suggest that the up-regulation of miR-29a by SFA is causally related to the development of insulin resistance in myocytes. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:2170 / 2176
页数:7
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