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Here, we characterized profiles of one\u2010carbon metabolism and related pathways and\u00a0patterns of DNA methylation in offspring exposed to excess or imbalanced micronutrients prenatally. Pregnant Wistar rats were fed either recommended 1\u00d7 vitamins (RV), high 10\u00d7 vitamins (HV), high 10\u00d7 folic acid with recommended choline (HFolRC), or high 10\u00d7 folic acid with no choline (HFolNC). Offspring were weaned to a high\u2010fat diet for 12\u2009weeks. Circulating metabolites were analyzed with a focus on the hypothalamus, an area known to be under epigenetic regulation. HV, HFolRC, and HFolNC males had higher body weight (BW) and lower plasma choline and methionine consistent with lower hypothalamic\n                    <jats:italic>S<\/jats:italic>\n                    \u2010adenosylmethionine (SAM):\n                    <jats:italic>S<\/jats:italic>\n                    \u2010adenosylhomocysteine (SAH) and global DNA methylation compared with RV. HV and HFolNC females had higher BW and lower plasma 5\u2010methyltetrahydrofolate and methionine consistent with lower hypothalamic global DNA methylation compared with RV. Plasma dimethylglycine (DMG) and methionine were higher as with hypothalamic SAM:SAH and global DNA methylation in HFolRC females without changes in BW compared with RV. Plasma trimethylamine and trimethylamine\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010oxide were higher in males but lower in females from HFolRC compared with RV. Network modeling revealed a link between the folate\u2010dependent pathway and SAH, with most connections through DMG. Final BW was negatively correlated with choline, DMG, and global DNA methylation. In conclusion, prenatal intake of excess or imbalanced micronutrients induces distinct metabolic and epigenetic perturbations in offspring that reflect long\u2010term nutritional programming of health.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401018rr","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T07:04:11Z","timestamp":1725001451000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Exposure to prenatal excess or imbalanced micronutrients leads to long\u2010term perturbations in one\u2010carbon metabolism, trimethylamine\u2010\n                    <i>N<\/i>\n                    \u2010oxide and DNA methylation in Wistar rat offspring"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3492-9529","authenticated-orcid":false,"given":"Gia V.","family":"Shelp","sequence":"first","affiliation":[{"name":"Department of Human Health and 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