{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:20:59Z","timestamp":1790976059189,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000199","name":"USDA-NIFA","doi-asserted-by":"publisher","award":["2018-67011-31708"],"award-info":[{"award-number":["2018-67011-31708"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Herein, we evaluated the hepatic lipid metabolic profiles of bovine fetuses in response to maternal vitamin and mineral supplementation (VMSUP; supplemented (VTM) or not (NoVTM)) and two different rates of gain (GAIN; low gain (LG), 0.28 kg\/d, or moderate gain (MG), 0.79 kg\/d). Crossbred Angus heifers (n = 35; initial BW = 359.5 \u00b1 7.1 kg) were randomly assigned to a 2 \u00d7 2 factorial arrangement, resulting in the following treatment combinations: NoVTM-LG (n = 9), NoVTM-MG (n = 9), VTM-LG (n = 9), and VTM-MG (n = 8). Heifers received their treatments until d 83 of gestation, when they were ovariohysterectomized. Fetuses were harvested and liver samples were analyzed via ultrahigh-performance liquid chromatography\u2013tandem mass spectroscopy to characterize lipid profiles and abundances. We identified 374 biochemicals\/metabolites belonging to 57 sub-pathways of the lipid metabolism super-pathway. The majority of the biochemicals\/metabolites (n = 152) were significantly affected by the main effect of GAIN. Maternal moderate rates of gain resulted in greater abundances (p \u2264 0.0001) of \u03c9-3 fatty acids (eicosapentaenoate, docosapentaenoate, and docosahexaenoate) and lower abundances (p \u2264 0.0001) of \u03c9-6 fatty acids. Further, MG resulted in the accumulation of several diacylglycerols and depletion of the majority of the monoacylglycerols. Concentrations of nearly all acylcarnitines (p \u2264 0.03) were decreased in VTM-LG fetal livers compared to all other treatment combinations, indicating a greater rate of complete oxidation of fatty acids. Levels of secondary bile acids were impacted by VMSUP, being greater (p \u2264 0.0048) in NoVTM than in VTM fetal livers. Moreover, NoVTM combined with lower rate of gain resulted in greater concentrations of most secondary bile acid biochemicals\/metabolites. These data indicate that maternal diet influenced and altered fetal hepatic lipid composition in the first trimester of gestation. Maternal body weight gain exerted a greater influence on fetal lipid profiles than vitamin and mineral supplementation. Specifically, lower rate of gain (0.28 kg\/d) resulted in an increased abundance of the majority of the biochemicals\/metabolites identified in this study.<\/jats:p>","DOI":"10.3390\/metabo13020175","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T03:53:18Z","timestamp":1674618798000},"page":"175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Fetal Hepatic Lipidome Is More Greatly Affected by Maternal Rate of Gain Compared with Vitamin and Mineral Supplementation at day 83 of Gestation"],"prefix":"10.3390","volume":"13","author":[{"given":"Ana Clara B.","family":"Menezes","sequence":"first","affiliation":[{"name":"Department of Animal Science, South Dakota State University, Brookings, SD 57006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4556-4315","authenticated-orcid":false,"given":"Carl R.","family":"Dahlen","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8526-3891","authenticated-orcid":false,"given":"Kacie L.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, University of Nebraska-Lincoln, Lincoln, NE 68588, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cierrah J.","family":"Kassetas","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Baumgaertner","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Kirsch","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheri T.","family":"Dorsam","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6642-9449","authenticated-orcid":false,"given":"Tammi L.","family":"Neville","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-8677","authenticated-orcid":false,"given":"Alison K.","family":"Ward","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-393X","authenticated-orcid":false,"given":"Pawel P.","family":"Borowicz","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6838-7809","authenticated-orcid":false,"given":"Lawrence P.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3759-3861","authenticated-orcid":false,"given":"Kevin K.","family":"Sedivec","sequence":"additional","affiliation":[{"name":"Central Grasslands Research and Extension Center, North Dakota State University, Streeter, ND 58483, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Chris","family":"Forcherio","sequence":"additional","affiliation":[{"name":"Purina Animal Nutrition LLC, Gray Summit, MO 63039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Scott","sequence":"additional","affiliation":[{"name":"Purina Animal Nutrition LLC, Gray Summit, MO 63039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel S.","family":"Caton","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4579-2737","authenticated-orcid":false,"given":"Matthew S.","family":"Crouse","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture, Agriculture Research Service, U.S. Meat Animal Research Center, Clay Center, NE 68933, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.plefa.2015.04.007","article-title":"Maternal Omega-3 Fatty Acids and Micronutrients Modulate Fetal Lipid Metabolism: A Review","volume":"98","author":"Khaire","year":"2015","journal-title":"Prostaglandins Leukot. Essent."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13614","DOI":"10.1038\/s41598-018-31832-5","article-title":"Metabolic Profiling and Targeted Lipidomics Reveals a Disturbed Lipid Profile in Mothers and Fetuses with Intrauterine Growth Restriction","volume":"8","author":"Miranda","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s40104-020-00513-7","article-title":"Effects of Maternal Dietary Omega-3 Polyunsaturated Fatty Acids and Methionine during Late Gestation on Fetal Growth, DNA Methylation, and MRNA Relative Expression of Genes Associated with the Inflammatory Response, Lipid Metabolism and DNA Methylation in Placenta and Offspring\u2019s Liver in Sheep","volume":"11","author":"Batistel","year":"2020","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_4","unstructured":"Ridgway, N.D., and McLeod, R.S. (2021). Biochemistry of Lipids, Lipoproteins and Membranes, Elsevier. [7th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Roque-Jim\u00e9nez, J.A., Rosa-Vel\u00e1zquez, M., Pinos-Rodr\u00edguez, J.M., Vicente-Mart\u00ednez, J.G., Mendoza-Cervantes, G., Flores-Primo, A., Lee-Rangel, H.A., and Relling, A.E. (2021). Role of Long Chain Fatty Acids in Developmental Programming in Ruminants. Animals, 11.","DOI":"10.3390\/ani11030762"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1093\/ajcn\/71.5.1344s","article-title":"Fetal nutrition and adult disease","volume":"71","author":"Godfrey","year":"2000","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Menezes, A.C.B., McCarthy, K.L., Kassetas, C.J., Baumgaertner, F., Kirsch, J.D., Dorsam, S.T., Neville, T.L., Ward, A.K., Borowicz, P.P., and Reynolds, L.P. (2022). Vitamin and Mineral Supplementation and Rate of Gain in Beef Heifers I: Effects on Dam Hormonal and Metabolic Status, Fetal Tissue and Organ Mass, and Concentration of Glucose and Fructose in Fetal Fluids at d 83 of Gestation. Animals, 12.","DOI":"10.3390\/ani12141757"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Crouse, M.S., McCarthy, K.L., Menezes, A.C.B., Kassetas, C.J., Baumgaertner, F., Kirsch, J.D., Dorsam, S., Neville, T.L., Ward, A.K., and Borowicz, P.P. (2022). Vitamin and Mineral Supplementation and Rate of Weight Gain during the First Trimester of Gestation in Beef Heifers Alters the Fetal Liver Amino Acid, Carbohydrate, and Energy Profile at Day 83 of Gestation. Metabolites, 12.","DOI":"10.3390\/metabo12080696"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Diniz, W.J.S., Reynolds, L.P., Borowicz, P.P., Ward, A.K., Sedivec, K.K., McCarthy, K.L., Kassetas, C.J., Baumgaertner, F., Kirsch, J.D., and Dorsam, S.T. (2021). Maternal Vitamin and Mineral Supplementation and Rate of Maternal Weight Gain Affects Placental Expression of Energy Metabolism and Transport-Related Genes. Genes, 12.","DOI":"10.3390\/genes12030385"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/jas\/skab235.651","article-title":"PSVIII-22 Maternal Vitamin and Mineral Supplementation Affect Fetal Hepatic Expression of Genes Underlying Mineral Homeostasis and Lipid Metabolism in Early Pregnancy","volume":"99","author":"Diniz","year":"2021","journal-title":"J. Anim. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"McCarthy, K.L., Menezes, A.C.B., Kassetas, C.J., Baumgaertner, F., Kirsch, J.D., Dorsam, S.T., Neville, T.L., Ward, A.K., Borowicz, P.P., and Reynolds, L.P. (2022). Vitamin and Mineral Supplementation and Rate of Gain in Beef Heifers II: Effects on tConcentration of Trace Minerals in Maternal Liver and Fetal Liver, Muscle, Allantoic, and Amniotic Fluid at d 83 of gestation. Animals, 12.","DOI":"10.3390\/ani12151925"},{"key":"ref_12","unstructured":"National Academy of Sciences Engineering and Medicine (2016). Nutrient Requirements of Beef Cattle: Eighth Revised Edition, The National Academies Press."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.2527\/jas.2016-0761","article-title":"Technical note: A new surgical technique for ovariohysterectomy during early pregnancy in beef heifers","volume":"94","author":"McLean","year":"2016","journal-title":"J. Anim. Sci."},{"key":"ref_14","first-page":"672","article-title":"Biochemical Characterization of Progesterone-Induced Alterations in Bovine Uterine Fluid Amino Acid and Carbohydrate Composition during the Conceptus Elongation Window","volume":"100","author":"Simintiras","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.theriogenology.2008.04.002","article-title":"Effect of Level of Dietary N-3 Polyunsaturated Fatty Acid Supplementation on Systemic and Tissue Fatty Acid Concentrations and on Selected Reproductive Variables in Cattle","volume":"70","author":"Childs","year":"2008","journal-title":"Theriogenology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0005-2760(94)90043-4","article-title":"Plasma Membrane Fatty Acid-Binding Protein (FABP) of the Sheep Placenta","volume":"1214","author":"Campbell","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16153","DOI":"10.3390\/ijms150916153","article-title":"Maternal\u2013Fetal Nutrient Transport in Pregnancy Pathologies: The Role of the Placenta","volume":"15","author":"Brett","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_18","unstructured":"Waisundara, V.Y., and Jovandaric, M.Z. (2020). Apolipoproteins, Triglycerides, and Cholesterol, Intech Open."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"645","DOI":"10.3389\/fmicb.2019.00645","article-title":"Very Long Chain Polyunsaturated Fatty Acids Accumulated in Triacylglycerol Are Channeled from Phosphatidylcholine in Thraustochytrium","volume":"10","author":"Zhao","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1016\/j.bbamem.2012.01.011","article-title":"Fatty Acid Composition of Membrane Bilayers: Importance of Diet Polyunsaturated Fat Balance","volume":"1818","author":"Abbott","year":"2012","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0005-2760(92)90248-T","article-title":"Diacylglycerol Metabolism in Neonatal Rat Liver: Characterization of Cytosolic Diacylglycerol Lipase Activity and Its Activation by Monoalkylglycerols","volume":"1126","author":"Xia","year":"1992","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/0076-6879(92)09013-S","article-title":"Diacylglycerol Acyltransferase and Monoacylglycerol Acyltransferase from Liver and Intestine","volume":"Volume 209","author":"Dennis","year":"1992","journal-title":"Phospholipid Biosynthesis"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"McCann, M.R., de la Rosa, M.V.G., Rosania, G.R., and Stringer, K.A. (2021). L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine. Metabolites, 11.","DOI":"10.3390\/metabo11010051"},{"key":"ref_24","unstructured":"Menezes, A.C.B., Baumgaertner, F., Hurlbert, J.L., Bochantin, K.A., Kirsch, J.D., Dorsam, S., Sedivec, K.K., Swanson, K.C., and Dahlen, C.R. (2022, January 16\u201320). Feeding a Se-Containing Trace Mineral Supplement during Pregnancy: Effects on Mitochondrial Oxygen Consumption in Liver and Small Intestine of Neonatal Calves. Proceedings of the 12th International Symposium on Selenium in Biology and Medicine, Honolulu, HI, USA."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3748\/wjg.15.817","article-title":"Excretion of Biliary Compounds during Intrauterine Life","volume":"15","author":"Macias","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1113\/jphysiol.1980.sp013489","article-title":"Bile acid metabolism in fetal sheep; Perinatal changes in the bile acid pool","volume":"309","author":"Hardy","year":"1980","journal-title":"J. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"771832","DOI":"10.3389\/fmicb.2021.771832","article-title":"Characterization of the Microbiota Associated with 12-Week-Old Bovine Fetuses Exposed to Divergent in Utero Nutrition","volume":"12","author":"Amat","year":"2022","journal-title":"Front. Microbiol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/2\/175\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:15:04Z","timestamp":1760120104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/2\/175"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,25]]},"references-count":27,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["metabo13020175"],"URL":"https:\/\/doi.org\/10.3390\/metabo13020175","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,25]]}}}