Maternal Choline Supplementation and High-Fat Feeding Interact to Influence DNA Methylation in Offspring in a Time-Specific Manner.
Maternal Choline Supplementation and High-Fat Feeding Interact to Influence DNA Methylation in Offspring in a Time-Specific Manner.
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DOI：
10.3389/fnut.2022.841787
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发表时间：
2022
影响因子：
5
通讯作者：
Jiang X
中科院分区：
文献类型：
--
作者：
Korsmo HW;Dave B;Trasino S;Saxena A;Liu J;Caviglia JM;Edwards K;Dembitzer M;Sheeraz S;Khaldi S;Jiang X
母亲在怀孕期间补充甲基供体对后代DNA甲基化有持久的影响。然而，目前尚不清楚是否不利的出生后环境，如高脂肪（HF）喂养，覆盖产前甲基供体补充对后代表观基因组的影响。在这项研究中，我们研究了母亲补充胆碱（CS），甲基供体，是否与产前和产后HF喂养相互作用，以改变后代的整体和位点特异性DNA甲基化。我们在整个妊娠期给野生型C57 BL/6 J小鼠母鼠喂食含或不含CS的HF饮食。断奶后，后代暴露于HF喂养6周，类似于持续的致肥胖环境。我们的研究结果表明，母亲CS HF条件下（HFCS）增加全球DNA甲基化和DNA甲基转移酶1（Dnmt 1）在胎儿肝脏和大脑的表达。然而，在出生后期间，HFCS后代表现出较低的整体DNA甲基化和Dnmt 1表达在肝脏和内脏脂肪组织中没有改变。在胎儿和出生后的特定位点的DNA甲基化分析表明，HFCS后代有较高的甲基化的CpG在启动子的Srebf 1，从头脂肪生成的关键介质。总之，母体CS对后代DNA甲基化的影响是特定于产前和产后期间的HF喂养状态。没有持续CS在出生后期间，全球DNA甲基化增强产前CS在后代被推翻出生后HF喂养。
Maternal methyl donor supplementation during pregnancy has demonstrated lasting influence on offspring DNA methylation. However, it is unknown whether an adverse postnatal environment, such as high-fat (HF) feeding, overrides the influence of prenatal methyl donor supplementation on offspring epigenome. In this study, we examined whether maternal supplementation of choline (CS), a methyl donor, interacts with prenatal and postnatal HF feeding to alter global and site-specific DNA methylation in offspring. We fed wild-type C57BL/6J mouse dams a HF diet with or without CS throughout gestation. After weaning, the offspring were exposed to HF feeding for 6 weeks resembling a continued obesogenic environment. Our results suggest that maternal CS under the HF condition (HFCS) increased global DNA methylation and DNA methyltransferase 1 (Dnmt1) expression in both fetal liver and brain. However, during the postnatal period, HFCS offspring demonstrated lower global DNA methylation and Dnmt1 expression was unaltered in both the liver and visceral adipose tissue. Site-specific DNA methylation analysis during both fetal and postnatal periods demonstrated that HFCS offspring had higher methylation of CpGs in the promoter of Srebf1, a key mediator of de novo lipogenesis. In conclusion, the influence of maternal CS on offspring DNA methylation is specific to HF feeding status during prenatal and postnatal periods. Without continued CS during the postnatal period, global DNA methylation enhanced by prenatal CS in the offspring was overridden by postnatal HF feeding.
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