Abstract To determine the effects of maternal nutrient restriction and re-alimentation on offspring metabolism, 48 pregnant ewes with singletons, were fed a control diet [100% National Research Council (NRC) requirements (CON)] starting at the beginning of gestation. On day 50 of gestation, ewes (n = 7) were euthanized and fetal liver, muscle, and blood samples were collected. The remaining animals were fed either CON or 60% NRC requirements (RES), a subset were euthanized at day 90 of gestation (n = 7/treatment), and fetal samples obtained. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to alternative diet (CON-RES, RES-CON; n = 7/treatment). On day 130 of gestation, remaining ewes were euthanized, and fetal samples collected. Fetal liver, longissimus dorsi, and blood metabolites were analyzed using LC-MS/MS at Metabolon Inc. Pathway enrichment analysis was conducted using MetaboAnalyst 4.0. In liver, muscle, and blood, 64, 44, and 34 pathways were enriched between treatments at day 130 gestation and 10, 6, and 11 pathways were enriched at day 90 gestation, respectively. Arginine and proline metabolism; primary bile acid biosynthesis; and valine, leucine, and isoleucine biosynthesis were the most highly enriched pathways in RES compared with CON in liver, muscle, and blood, respectively. Additionally, the pentose phosphate pathway; valine, leucine, and isoleucine metabolism; and phenylalanine metabolism were the most highly enriched pathways in RES-CON compared with CON-CON in liver, muscle, and blood, respectively. In liver, ribulose 5-phosphate, xylulose 5-phosphate, and ribose 5-phosphate were decreased 1.82-, 1.54-, and 2.38-fold, respectively in RES-CON compared with CON-CON (P ≤ 0.05). Total triacylglycerols were increased 3.04-fold in muscle and decreased 1.57-fold in blood in RES-CON and RES-RES compared with CON-CON and CON-RES (P ≤ 0.05). Mid-gestational nutrient restriction and subsequent re-alimentation altered distinct metabolic amino acid, carbohydrate, and lipid pathways, potentially altering postnatal growth. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.
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