TitlePerinatal high fat diet and early life methyl donor supplementation alter one carbon metabolism and DNA methylation in the brain.
Publication TypeJournal Article
Year of Publication2018
AuthorsMcKee, SE, Zhang, S, Chen, L, Rabinowitz, JD, Reyes, TM
JournalJ Neurochem
Date Published2018 06
KeywordsAnimals, Brain, Carbon, Diet, High-Fat, Dietary Supplements, DNA Methylation, Female, Gene Expression, Male, Mice, Pregnancy, Prenatal Exposure Delayed Effects, Sex Characteristics

One carbon metabolism is regulated by the availability of nutrients known as methyl donors, and disruption of this pathway can affect multiple physiological systems. DNA methylation, critical for the regulation of gene expression, is linked to one carbon metabolism, and can be altered by perinatal diet. In this study, dams (n = 12/group) were fed HF or standard control (SC) diet through pregnancy and lactation, and male and female offspring were then fed either SC or methyl donor-supplemented diet (MDS) between 3 and 6 weeks of age (n = 20-26/group). Concentration of one carbon intermediates and other related metabolites were assessed within brain tissue (prefrontal cortex, PFC) through the use of mass spectrometry at 6 weeks of age. In addition, the expression of target genes and enzymes that participate in DNA methylation or are relevant to one carbon metabolism were measured. We found that MDS increases the concentration of folate intermediates in the PFC, and that this increase is blunted in male offspring from dams fed a HF diet. In addition, perinatal HF diet increased the concentration of cysteine in the PFC of both male and female offspring, consistent with oxidative stress. Furthermore, both maternal HF diet and postnatal MDS altered global DNA methylation in the PFC in males but not females. Collectively, these data demonstrate sex differences in changes in one carbon metabolites in the prefrontal cortex in response to early life high fat diet and methyl donor supplementation. Read the Editorial Highlight for this article on page 358.

Alternate JournalJ. Neurochem.
PubMed ID29423909
PubMed Central IDPMC6288810
Grant ListDP1 DK113643 / DK / NIDDK NIH HHS / United States
P30 ES013508 / ES / NIEHS NIH HHS / United States
T32 ES019851 / ES / NIEHS NIH HHS / United States
R01 MH106330 / MH / NIMH NIH HHS / United States
P30 DK019525 / DK / NIDDK NIH HHS / United States
R01 MH087978 / MH / NIMH NIH HHS / United States