Abstract
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.
Highlights
Epigenetic marks are heritable modifications on the chromosomes that are pivotal in controlling gene expression during normal physiological development and in response to pathological conditions
We earlier described that maternal HF feeding led to higher fetal whole body adiposity and hepatic triglycerides while maternal Choline supplementation (CS) mitigated these adverse alterations at E17.5 [16]
In male offspring who received CS during prenatal HF feeding, there was no difference in weight gain yet improved blood glucose control compared to the control group after 6-week post-weaning HF feeding [17]
Summary
Epigenetic marks are heritable modifications on the chromosomes that are pivotal in controlling gene expression during normal physiological development and in response to pathological conditions. DNA methylation is one of the major mechanisms that direct organismic epigenome. A semi-essential nutrient, participates in phospholipid and one carbon metabolism (OCM). Epigenetic Programming by Choline [1]. When choline is oxidized to betaine, its labile methyl group can be used for homocysteine remethylation to methionine. Thereafter, methionine is converted to the universal methyl donor S-adenosylmethionine (SAM). Choline-derived methyl group is used for various methylation reactions, including those that affect epigenetic modifications
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