Perinatal high fat diet and early life methyl donor supplementation alter one carbon metabolism and DNA methylation in the brain

Sarah E. McKee, Sisi Zhang, Li Chen, Joshua D. Rabinowitz, Teresa M. Reyes

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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. (Figure presented.). Read the Editorial Highlight for this article on page 358.

Original languageEnglish (US)
Pages (from-to)362-373
Number of pages12
JournalJournal of Neurochemistry
Volume145
Issue number5
DOIs
StatePublished - Jun 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Keywords

  • DNA methylation
  • developmental programming
  • high fat diet
  • methyl donors
  • one carbon metabolism

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