Date of Completion
Sarah A. Reed, Kristen E. Govoni, Steven A. Zinn, Ji-Young Lee
Field of Study
Master of Science
Poor maternal nutrition during gestation alters offspring muscle composition, fiber number, postnatal growth, and stem cell function. Additionally, poor maternal nutrition impacts offspring whole body and stem cell metabolism. We hypothesized that over- or restricted-feeding during gestation would alter muscle myoblast metabolism as well as offspring Longissimus dorsi muscle (LD) metabolome. Pregnant Western White-faced ewes (n = 47) were individually fed 60% (RES), 100% (CON), or 140% (OVER) of NRC requirements starting at d 30.2 ± 0.2 of gestation. At d 90 and 135 of gestation, ewes were euthanized for fetal muscle collection. Another group of ewes were allowed to lamb and offspring were necropsied within 24 h of birth for offspring serum and muscle sample collection. C2C12 myoblasts were cultured in fetal serum to determine effects of poor maternal nutrition on cell proliferation, differentiation, and metabolism. Glycolytic function and mitochondrial respiration of C2C12 cells cultured in serum from CON, RES, and OVER lambs at birth were analyzed using the Seahorse Bioscience XF analyzer. Cell culture data were analyzed as a completely randomized design using PROC MIXED in SAS with main effects and interaction of gender and maternal diet. Mass spectrophotometry of LD samples (n = 8 fetuses per treatment per time point) identified 612 metabolites. Metabolome data were analyzed by ANOVA for main effects of treatment, time point, and their interaction. There was no observed effect (P ≤ 0.05) of maternal diet on C2C12 proliferation, fusion index, or glycolytic function. Proton leak was increased in C2C12 cells cultured in RES serum compared with CON (P = 0.04). For the metabolome analysis, compared with CON, maternal over-feeding altered metabolites in 63 pathways and maternal restricted-feeding altered metabolites in 56 pathways (P ≤ 0.05) in the offspring. Both maternal restricted- and over-feeding altered offspring metabolites in each of the 8 major metabolic pathways including amino acid, peptide, carbohydrate, energy, lipid, nucleotide, cofactors and vitamins, and xenobiotics. Maternal over-feeding decreased concentrations of 1 phosphatidylcholine (PC) metabolite at d 90, 2 PC metabolites at d 135, and 4 PC metabolites at birth compared with CON (P ≤ 0.05). Additionally, at d 135, maternal over-feeding increased 1 phosphatidylethanolamine (PE) metabolite while reducing 10 PE metabolites at birth compared with CON (P ≤ 0.05). Offspring from over-fed ewes had decreased concentrations of 12 lysolipids at birth compared with CON (P ≤ 0.05). Maternal restricted-feeding increased expression of reduced glutathione 3.07-fold at d 90 (P = 0.008), whereas at d 135, oxidized glutathione was decreased 21% compared with CON (P = 0.03). Overall, poor maternal nutrition during gestation alters offspring metabolism. Specifically, maternal over-feeding may promote increased lipid oxidation in offspring muscle, which may predispose offspring to altered lipid utilization and storage postnatally. Maternal restricted-feeding resulted in alterations in glutathione metabolism, potentially indicative of changes to redox status in these offspring.
Martin, Dominique, "The Effects of Poor Maternal Nutrition on Offspring Muscle Metabolism" (2018). Master's Theses. 1282.
Sarah A. Reed