Aberrant expression of microRNA induced by high-fructose diet: implications in the pathogenesis of hyperlipidemia and hepatic insulin resistance.
Aberrant expression of microRNA induced by high-fructose diet: implications in the pathogenesis of hyperlipidemia and hepatic insulin resistance.
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DOI：
10.1016/j.jnutbio.2017.02.003
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Su Q
中科院分区：
文献类型：
--
作者：
Sud N;Zhang H;Pan K;Cheng X;Cui J;Su Q
果糖是一种高脂糖，可以改变能量代谢并引发代谢紊乱。本研究全面探讨了高果糖饮食改变的microRNAs (miRNAs)，以阐明其在慢性代谢性疾病发病机制中的意义。使用小非编码RNA测序的miRNA表达谱显示，与低食小鼠相比，高果糖喂养小鼠的肝脏中有19个miRNA显著上调，26个miRNA下调。计算预测和功能分析确定了10个mirna， miR-19b-3p、miR-101a-3p、miR-30a-5p、miR-223-3p、miR-378a-3p、miR-33-5p、miR-145a-3p、miR-128-3p、miR-125b-5p和miR-582-3p，它们组装成一个调控网络，可能在多个水平上靶向脂质和脂蛋白代谢和胰岛素信号传导的关键基因。对其潜在靶基因[IRS-1、FOXO1、SREBP-1c/2、ChREBP、胰岛素诱导基因1 (Insig-1)/基因2 （Insig-2）、微体甘油三酯转移蛋白（MTTP）和载脂蛋白B (apoB)]的qRT-PCR分析表明，果糖诱导的mirna改变也反映在其靶基因的mRNA表达谱中。此外，高果糖饮食诱导的miRNA谱与高脂肪饮食诱导的miRNA谱不同，表明miRNA在饮食诱导的代谢紊乱中介导不同的致病机制。本研究对高果糖饮食改变的一组新的肝脏mirna进行了全面分析，并为代谢综合征发展中mirna与其靶基因之间的相互作用提供了新的见解。
Fructose is a highly lipogenic sugar which can alter energy metabolism and trigger metabolic disorders. In the current study, microRNAs (miRNAs) altered by a high-fructose diet were comprehensively explored to elucidate their significance in the pathogenesis of chronic metabolic disorders. miRNA expression profiling using small non-coding RNA sequencing revealed that 19 miRNAs were significantly upregulated and 26 were downregulated in the livers of high-fructosefed mice compared to chow-fed mice. Computational prediction and functional analysis identified ten miRNAs, miR-19b-3p, miR-101a-3p, miR-30a-5p, miR-223-3p, miR-378a-3p, miR-33-5p, miR-145a-3p, miR-128-3p, miR-125b-5p and miR-582-3p, assembled as a regulatory network to potentially target key genes in lipid and lipoprotein metabolism and insulin signaling at multiple levels. qRT-PCR analysis of their potential target genes [IRS-1, FOXO1, SREBP-1c/2, ChREBP, insulin induced gene-1 (Insig-1)/gene-2 (Insig-2), microsomal triglyceride transfer protein (MTTP) and apolipoprotein B (apoB)] demonstrated that fructose induced alterations of miRNAs were also reflected in mRNA expression profiles of their target genes. Moreover, the miRNA profile induced by high-fructose diet differed from that induced by high-fat diet, indicating that miRNAs mediate distinct pathogenic mechanisms in dietary-induced metabolic disorders. This study presents a comprehensive analysis of a new set of hepatic miRNAs, which were altered by high-fructose diet and provides novel insights into the interaction between miRNAs and their target genes in the development of metabolic syndrome.