Early gestational hepatic lipidomic profiles are modulated by one-carbon metabolite supplementation and nutrient restriction in beef heifers and fetuses

Authors: SAFAIN, KAZI - North Dakota State University; Crouse, Matthew; SYRING, JESSICA - North Dakota State University; ENTZIE, YSSI - North Dakota State University; KING, LAYLA - University Of Minnesota Crookston; WARD, ALISON - University Of Saskatchewan; REYNOLDS, LAWRENCE - North Dakota State University; BOROWICZ, PAWEL - North Dakota State University; DAHLEN, CARL - North Dakota State University; SWANSON, KENDALL - North Dakota State University; CATON, JOEL - North Dakota State University

Submitted to: Metabolites
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/30/2025
Publication Date: 5/1/2025
Citation: Safain, K.S., Crouse, M.S., Syring, J.G., Entzie, Y.L., King, L.E., Ward, A.K., Reynolds, L.P., Borowicz, P.P., Dahlen, C.R., Swanson, K.C., Caton, J.S. 2025. Early gestational hepatic lipidomic profiles are modulated by one-carbon metabolite supplementation and nutrient restriction in beef heifers and fetuses. Metabolites. 15(5). Article 302. https://doi.org/10.3390/metabo15050302.
DOI: https://doi.org/10.3390/metabo15050302

Interpretive Summary: Maternal nutrition during pregnancy significantly impacts offspring health and productivity. Inadequate nutrition can result in fetal growth restriction and impaired liver development, increasing susceptibility to metabolic disorders and compromised immune function. Specifically, optimal nutrition during early pregnancy in cattle is vital for reproductive efficiency and overall herd health. This critical developmental window involves epigenetic programming, whereby environmental and genetic factors induce heritable modifications. Maternal diet profoundly influences these epigenetic changes, particularly through the availability of essential one-carbon metabolites (OCM), such as methionine, choline, folate, and vitamin B12. Supplementing these nutrients early in gestation may mitigate adverse effects associated with nutritional deficiencies. This study examines how OCM supplementation and dietary restrictions influence maternal and fetal liver lipid metabolism in beef heifers during early gestation. The findings indicated substantial lipidomic changes in the maternal liver due to nutrient restriction, specifically increased levels of lipids linked to fatty acid oxidation, cellular membranes, and lipid signaling. Moreover, combining nutrient restriction with OCM supplementation significantly elevated metabolites related to enhanced lipid utilization efficiency. Conversely, fetal liver lipid profiles exhibited minimal changes, indicating a protective mechanism that maintains fetal lipid homeostasis during early pregnancy. Overall, these results highlight the critical role of maternal nutrition in determining hepatic lipid metabolism, revealing essential metabolic adaptations that support both maternal health and fetal development. This research provides valuable insights for formulating targeted nutritional interventions to improve livestock productivity and serves as a foundation for developing dietary guidelines aimed at optimizing pregnancy outcomes and enhancing long-term offspring health.

Technical Abstract: Background: Maternal nutrition during early gestation induces metabolic adaptations that support maternal health and fetal development. This study evaluated the effects of maternal one-carbon metabolite (OCM: methionine, choline, folate, and vitamin B12) supplementation and restricted rates of maternal gain on hepatic lipid profiles of dams and fetuses at day 63 of gestation. Methods: Thirty-one crossbred Angus heifers were inseminated and assigned to a 2 × 2 factorial design with two factors: maternal dietary intake (control [CON]; 0.60 kg/day average daily gain [ADG] vs. restricted [RES]; -0.23 kg/day ADG) and OCM supplementation (supplemented [+OCM] vs. not supplemented [-OCM]). The four resulting groups (CON-OCM, CON+OCM, RES-OCM, RES+OCM) were maintained for 63 days post-breeding. Maternal and fetal liver samples were collected, and lipidomic profiling was performed using ultra-performance liquid chromatography–tandem mass-spectrometry. Results: In maternal liver, 485 lipid metabolites were detected, with 243 differing significantly by maternal gain. RES heifers showed increased levels (P