A high-fat diet alters genome-wide DNA methylation and gene expression in SM/J mice
A high-fat diet alters genome-wide DNA methylation and gene expression in SM/J mice
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DOI：
10.1186/s12864-018-5327-0
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发表时间：
2018-12-07
期刊：
影响因子：
4.4
通讯作者：
Cheverud, James M.
中科院分区：
文献类型：
--
作者：
Keleher, Madeline Rose;Zaidi, Rabab;Cheverud, James M.
研究背景肥胖的遗传学已被很好地定义，但肥胖的表观遗传学却知之甚少。在这里，我们使用了全基因组的方法来确定基因的差异，在DNA甲基化和表达与高脂dietinmice.ResultsWe断奶遗传相同的小（SM/J）小鼠到高脂或低脂饮食，每周测量他们的体重，测试他们的葡萄糖和胰岛素耐受性，评估血清生物标志物，并在尸检时称他们的器官。我们用RNA-seq（使用21个总文库，每个文库与2只相同性别和饮食的小鼠合并）测量肝脏基因表达，并用MRE-seq和MeDIP-seq（使用8个总文库，每个文库与4只相同性别和饮食的小鼠合并）测量DNA甲基化。有4356个基因与饮食相关的表达差异，其中184个基因表现出性别与饮食的相互作用。膳食脂肪失调的几个途径，包括那些参与的精氨酸-细胞因子受体相互作用，趋化因子信号，氧化磷酸化。超过7000个基因的差异甲基化区域与饮食有关，这发生在调控区比预期的更频繁的机会。只有5-10%的差异甲基化区域发生在差异表达的基因中，然而这比预期的更常见（p=2.2x10（-8））。结论发现与高脂饮食相关的基因表达和甲基化变化有助于识别表观遗传治疗的新靶点，并为肥胖的生理变化提供信息。在这里，我们确定了许多基因的表达和甲基化改变，是有希望的候选人进行进一步研究。
BackgroundWhile the genetics of obesity has been well defined, the epigenetics of obesity is poorly understood. Here, we used a genome-wide approach to identify genes with differences in both DNA methylation and expression associated with a high-fat diet in mice.ResultsWe weaned genetically identical Small (SM/J) mice onto a high-fat or low-fat diet and measured their weights weekly, tested their glucose and insulin tolerance, assessed serum biomarkers, and weighed their organs at necropsy. We measured liver gene expression with RNA-seq (using 21 total libraries, each pooled with 2 mice of the same sex and diet) and DNA methylation with MRE-seq and MeDIP-seq (using 8 total libraries, each pooled with 4 mice of the same sex and diet). There were 4356 genes with expression differences associated with diet, with 184 genes exhibiting a sex-by-diet interaction. Dietary fat dysregulated several pathways, including those involved in cytokine-cytokine receptor interaction, chemokine signaling, and oxidative phosphorylation. Over 7000 genes had differentially methylated regions associated with diet, which occurred in regulatory regions more often than expected by chance. Only 5-10% of differentially methylated regions occurred in differentially expressed genes, however this was more often than expected by chance (p=2.2x10(-8)).ConclusionsDiscovering the gene expression and methylation changes associated with a high-fat diet can help to identify new targets for epigenetic therapies and inform about the physiological changes in obesity. Here, we identified numerous genes with altered expression and methylation that are promising candidates for further study.