Early Gestational Hepatic Lipidomic Profiles Are Modulated by One-Carbon Metabolite Supplementation and Nutrient Restriction in Beef Heifers and Fetuses

<b>Background:</b> 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 the hepatic lipid profiles of dams and fetuses at day 63 of gestation. <b>Methods:</b> 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. <b>Results:</b> In maternal liver, 485 lipid metabolites were detected, with 243 differing significantly in maternal gain. RES heifers showed increased levels (<i>p</i> ≤ 0.05) of acylcarnitines, plasmalogens, lysoplasmalogens, glycosphingolipids, and sphingomyelins. Additionally, RES combined with OCM supplementation led to the accumulation of secondary bile acids and a depletion of monoacylglycerols (<i>p</i> ≤ 0.05) in maternal liver. In fetal liver, 487 lipid metabolites were detected, but treatment effects were minimal. <b>Conclusions:</b> Maternal rate of gain significantly influenced hepatic lipid metabolism in the maternal liver, while fetal liver lipid profiles remained relatively unaffected. These findings underscore the significant role of dietary intake/rate of gain compared with OCM supplementation in modulating hepatic lipid metabolism and highlight the maternal liver’s metabolic adaptations during early pregnancy.