Comprehensive Transcriptome Analyses of the Fructose-Fed Syrian Golden Hamster Liver Provides Novel Insights into Lipid Metabolism.
Comprehensive Transcriptome Analyses of the Fructose-Fed Syrian Golden Hamster Liver Provides Novel Insights into Lipid Metabolism.
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果糖喂养的叙利亚金仓鼠肝脏的全面转录组分析为脂质代谢提供了新的见解
DOI：
10.1371/journal.pone.0162402
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Li Z;Xiong C;Mo S;Tian H;Yu M;Mao T;Chen Q;Luo H;Li Q;Lu J;Zhao Y;Li W
血脂异常已被广泛证明有助于心血管疾病和其他代谢紊乱，特别是在胰岛素抵抗和2型糖尿病中。VLDL的过量产生是血脂异常的一个重要特征，表明肝脏从甘油三酯合成到转运的脂质代谢功能障碍。果糖喂养的叙利亚金黄仓鼠是研究VLDL组装与胰岛素抵抗的既定动物模型，然而，由于缺乏完整的仓鼠基因组，VLDL的产生如何在转录水平上调节仍然未知。在此，我们进行了深度测序并构建了叙利亚金黄地鼠肝脏的mRNA-miRNA-lncRNA相互作用网络，以揭示整体转录谱并发现VLDL产生的潜在RNA分子调控。我们鉴定了4，450种新的多外显子仓鼠lncRNA和755种在肝脏中表达的miRNA。此外，146个差异表达的编码基因，27个差异表达的lncRNA基因，以及16个差异表达的miRNA。然后，我们构建了一个mRNA-miRNA-lncRNA相互作用网络，可能潜在地调节VLDL的产生，有趣的是，我们发现了几个以microRNA为中心的调控网络。为了验证我们的解释，选择miR-486进行进一步的实验。在果糖喂养的仓鼠中，miR-486的过表达或下调导致参与VLDL产生的蛋白质的肝脏表达改变，以及循环VLDL水平的调节。我们的研究结果表明，miR-486是循环VLDL水平的潜在调节剂。这些结果为进一步研究VLDL分泌的分子机制提供了新的见解和宝贵的资源。
Dyslipidemia has been widely proven to contribute to cardiovascular diseases and other metabolic disorders, especially in insulin resistance and type 2 diabetes. The overproduction of VLDL is a significant characteristic of dyslipidemia, indicating the dysfunction of hepatic lipid metabolism, from triglyceride synthesis to transport. The fructose-fed Syrian golden hamster is an established animal model for the study of VLDL assembly with insulin resistance, however, it remains unknown how VLDL production is regulated at the transcriptional level due to the absence of a complete hamster genome. Here, we performed deep sequencing and constructed an mRNA-miRNA-lncRNA interaction network of Syrian golden hamster liver in order to reveal the global transcription profile and find potential RNA molecular regulation of VLDL production. We identified 4,450 novel multi-exon hamster lncRNAs and 755 miRNAs expressed in liver. Additionally, 146 differentially expressed coding genes, 27 differentially expressed lncRNA genes, as well as 16 differentially expressed miRNAs were identified. We then constructed an mRNA-miRNA-lncRNA interaction network that may potentially regulate VLDL production, and interestingly found several microRNA-centered regulatory networks. In order to verify our interpretation, miR-486 was selected for further experiments. Overexpression or down-regulation of miR-486 in fructose-fed hamsters resulted in altered hepatic expression of proteins involved in VLDL production, and in modulated levels of circulating VLDL. Our findings implicated that miR-486 is a potential regulator of circulating VLDL levels. These results provide new insights and a valuable resource for further study of the molecular mechanisms of VLDL secretion.
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影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
DOI：
10.1161/01.atv.0000115638.27381.97
发表时间：
2004-03-01
影响因子：
8.7
作者：
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通讯作者：
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64.8
作者：
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通讯作者：
TILGHMAN, SM
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29
作者：
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通讯作者：
Osborne TF
X 染色体失活对 Xist 的要求
影响因子：
64.8
作者：
Penny, GD;Kay, GF;Brockdorff, N
通讯作者：
Brockdorff, N