Analysis of N6-Methyladenosine Methylation Modification in Fructose-Induced Non-Alcoholic Fatty Liver Disease.
Analysis of N6-Methyladenosine Methylation Modification in Fructose-Induced Non-Alcoholic Fatty Liver Disease.
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果糖诱导的非酒精性脂肪肝中 N6-甲基腺苷甲基化修饰分析
DOI：
10.3389/fendo.2021.780617
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发表时间：
2021
影响因子：
5.2
通讯作者：
Peng Y
中科院分区：
文献类型：
--
作者：
Luo Y;Zhang Z;Xiang L;Zhou B;Wang X;Lin Y;Ding X;Liu F;Lu Y;Peng Y
生活水平的提高导致了非酒精性脂肪性肝病(NAFLD)，这是全球最常见的慢性肝病之一。最近的研究表明，N6-甲基腺苷(M6A)是一种RNA修饰，与许多重要的生物学过程密切相关。然而，m6A甲基化修饰和NAFLD之间的关系仍然知之甚少。在本研究中，通过对高果糖饮食诱导的NAFLD小鼠的甲基化RNA免疫沉淀测序和RNA转录组测序，我们发现高甲基化编码基因主要在脂质代谢过程中富含。我们鉴定了266个重叠和差异表达基因(DEG)，这些基因在mRNA表达水平和M6A修饰水平都发生了变化。其中193个基因表达增加，m6A基因发生修饰，提示m6A RNA修饰与NAFLD呈正相关。我们进一步比较了高果糖饮食诱导的NAFLD小鼠模型和瘦素受体缺陷小鼠，发现在脂代谢途径中丰富的DEG在两组中都上调。相反，与免疫炎症反应相关的DEG在高果糖饮食组上调，但在瘦素受体缺陷小鼠下调。综上所述，我们的结果表明M6A甲基化修饰可能在NAFLD的发生发展中起重要作用。
Improvements in living standards have led to non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases worldwide. Recent studies have shown that N6-methyladenosine (m6A), a type of RNA modification, is strongly associated with many important biological processes. However, the relationship between m6A methylation modifications and NAFLD remains poorly understood. In the present study, through methylated RNA immunoprecipitation sequencing and RNA transcriptome sequencing in high fructose diet-induced NAFLD mice, we found that hypermethylation-encoding genes were mainly enriched in lipid metabolism processes. We identified 266 overlapping and differentially expressed genes (DEGs) that changed at both the mRNA expression level and m6A modification level. Among them, 193 genes displayed increased expression and m6A modification, indicating that m6A RNA modifications tend to be positively correlated with NAFLD. We further compared the high fructose diet-induced NAFLD mouse model with leptin receptor-deficient mice and found that DEGs enriched in the lipid metabolism pathway were up-regulated in both groups. In contrast, DEGs associated with the immune inflammatory response were up-regulated in the high fructose diet group, but down-regulated in leptin receptor-deficient mice. Taken together, our results demonstrate that m6A methylation modifications may play an important role in the development of NAFLD.
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影响因子：
20.8
作者：
De Jesus, Dario F.;Zhang, Zijie;Kulkarni, Rohit N.
通讯作者：
Kulkarni, Rohit N.
影响因子：
5.9
作者：
Van Herck MA;Vonghia L;Francque SM
通讯作者：
Francque SM
n（6） - 甲基腺苷依赖性RNA结构开关调节RNA蛋白质相互作用。
影响因子：
64.8
作者：
Liu, Nian;Dai, Qing;Zheng, Guanqun;He, Chuan;Parisien, Marc;Pan, Tao
通讯作者：
Pan, Tao
影响因子：
3.7
作者：
Shen L;Shao NY;Liu X;Maze I;Feng J;Nestler EJ
通讯作者：
Nestler EJ
影响因子：
25.7
作者：
Malhi, Harmeet;Kaufman, Randal J.
通讯作者：
Kaufman, Randal J.