PSIV-16 Maternal Nutrient Restriction Followed by Re-alimentation Alters Distinct Metabolic Pathways in Sheep Offspring

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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PSV-2 Maternal nutrient restriction and re-alimentation influences liver and muscle tissue development and gene expression

Journal of Animal Science ◽

10.1093/jas/skab235.563 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 307-307

Author(s):

Brandon I Smith ◽

Manuel A Vasquez-Hidalgo ◽

Kimberly A Vonnahme ◽

Anna T Grazul-Bilska ◽

Kendall C Swanson ◽

...

Keyword(s):

Gene Expression ◽

Lipid Content ◽

Muscle Development ◽

Glycogen Synthase ◽

Fetal Liver ◽

Control Diet ◽

National Research Council ◽

Pyruvate Dehydrogenase Kinase ◽

Nutrient Restriction ◽

Metabolic Factors

Abstract To determine the effects of maternal nutrient restriction and re-alimentation on fetal liver and muscle development, 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 and skeletal muscle 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 was analyzed for general tissue morphology, and fetal skeletal muscles were analyzed for lipid accumulation. mRNA expression of growth and metabolic factors were quantified in liver and muscle tissues. Hepatocellular vacuolation was increased in RES-CON and RES-RES compared with CON-CON and CON-RES (P < 0.01). In semitendinosus and triceps brachii, intramyocellular lipid content increased 19% and 15%, respectively, in RES-CON and RES-RES compared with CON-CON and CON-RES (P£0.02) and in longissimus dorsi, lipid content was decreased 7% in CON-RES and RES-RES compared with CON-CON and RES-CON (P=0.01). In liver, insulin-like growth factor binding protein-1, glycogen synthase 2, and pyruvate dehydrogenase kinase 1 expression increased 1.92-fold, 1.45-fold, and 1.47-fold, respectively (P£0.03) in CON-RES and RES-RES compared with RES-CON and CON-CON. In LD, IGF1-R expression increased 3.19-fold in CON-RES and RES-RES compared with RES-CON and CON-CON (P = 0.05). These results demonstrate that maternal nutrient restriction followed by re-alimentation restores liver and muscle gene expression of growth and metabolic factors while negatively impacting liver composition and muscle lipid content potentially leading to altered tissue function and metabolism later in life. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.

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PSII-20 Effects of maternal nutrient restriction during gestation on bovine serum microRNA abundance

Journal of Animal Science ◽

10.1093/jas/skz258.489 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 241-241

Author(s):

Keelee J McCarty ◽

Andrea DeCarlo ◽

Ralph Ricks ◽

Scott Pratt ◽

Nathan Long

Keyword(s):

Bovine Serum ◽

Target Genes ◽

Bos Taurus ◽

National Research Council ◽

Enrichment Analysis ◽

Long Term Potentiation ◽

Maternal Blood ◽

Nutrient Restriction ◽

Pathway Enrichment Analysis ◽

Serum Samples

Abstract The objective of this study was to determine the effects of maternal nutrient restriction during gestation on microRNA abundance in bovine serum. Primiparous Angus-cross cows (n = 22) were fed either control (CON; to gain 1 kg/wk) or nutrient restricted (NR; 0.55 % NEm) diets based on National Research Council requirements. On d 30 of gestation, cows were blocked by body condition and randomly assigned to one of three diets: CON fed from d 30 to 190 (n = 8), or NR/C (n = 7) or C/NR (n = 7) fed either the CON or NR diet from d 30 to 110 followed by CON or NR from d 110 to 190 of gestation. Maternal blood samples were collected the day before harvest on 190 d of gestation. RNA was isolated from serum samples using the mirVANA microRNA Isolation kit and analyzed using a previously validated miRNA microarray of known Bos Taurus sequences. MicroRNA abundance were analyzed via ANOVA using procedures correcting for false discovery rate of the microarray data. At d 190 of gestation, 26 miRNAs observed differential (P < 0.05) abundance between treatments, in which 11 miRNAs were downregulated and 15 miRNAs were upregulated in both NR/CON and CON/NR compared to CON cows. Additionally, a set of miRNAs (bta-miR-2487_L-2R-3_1ss15CT, bta-miR-215, and bta-miR-760-5p) were differentially abundant (P < 0.04) between NR/CON and CON/NR cows. Top KEGG pathway enrichment analysis of target genes included pathways in cancer, cAMP signaling pathway, axon guidance, long term potentiation, and insulin signaling. In summary, maternal nutrient restriction observed altered miRNA abundance irrespective of the time at which the nutritional insult was induced.

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Placental Transcriptome Adaptations to Maternal Nutrient Restriction in Sheep

International Journal of Molecular Sciences ◽

10.3390/ijms22147654 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7654

Author(s):

Chelsie B. Steinhauser ◽

Colleen A. Lambo ◽

Katharine Askelson ◽

Gregory W. Burns ◽

Susanta K. Behura ◽

...

Keyword(s):

Mhc Class Ii ◽

Killer Cell ◽

National Research Council ◽

Enrichment Analysis ◽

Nutrient Utilization ◽

Gene Set Enrichment Analysis ◽

Nutrient Restriction ◽

Placental Development ◽

Gene Set Enrichment ◽

Pregnant Sheep

Placental development is modified in response to maternal nutrient restriction (NR), resulting in a spectrum of fetal growth rates. Pregnant sheep carrying singleton fetuses and fed either 100% (n = 8) or 50% (NR; n = 28) of their National Research Council (NRC) recommended intake from days 35–135 of pregnancy were used to elucidate placentome transcriptome alterations at both day 70 and day 135. NR fetuses were further designated into upper (NR NonSGA; n = 7) and lower quartiles (NR SGA; n = 7) based on day 135 fetal weight. At day 70 of pregnancy, there were 22 genes dysregulated between NR SGA and 100% NRC placentomes, 27 genes between NR NonSGA and 100% NRC placentomes, and 22 genes between NR SGA and NR NonSGA placentomes. These genes mediated molecular functions such as MHC class II protein binding, signaling receptor binding, and cytokine activity. Gene set enrichment analysis (GSEA) revealed significant overrepresentation of genes for natural-killer-cell-mediated cytotoxicity in NR SGA compared to 100% NRC placentomes, and alterations in nutrient utilization pathways between NR SGA and NR NonSGA placentomes at day 70. Results identify novel factors associated with impaired function in SGA placentomes and potential for placentomes from NR NonSGA pregnancies to adapt to nutritional hardship.

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Tissue-based metabolomics profiling reveals metabolic signatures and major metabolic pathways of gastric cancer

10.21203/rs.3.rs-326163/v1 ◽

2021 ◽

Author(s):

Yaqin Wang ◽

Wenchao Chen ◽

Kun Li ◽

Gang Wu ◽

Wei Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Predictive Ability ◽

Principal Component ◽

Enrichment Analysis ◽

Pentose Phosphate ◽

P Value ◽

Pathway Enrichment Analysis ◽

Dodecanoic Acid ◽

Orthogonal Projections ◽

Latent Structures

Abstract Purpose This study was aimed to screen differential metabolites between gastric cancer (GC) and paracancerous (PC) tissues and find new biomarkers of GC. Methods GC (n = 28) and matched PC (n = 28) tissues were collected and LC-MS/MS analyses were performed to detect metabolites of GC and PC tissues in positive and negative models. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminate analysis (OPLS-DA) were conducted to describe distribution of origin data and general separation and estimate the robustness and the predictive ability of our mode. Differential metabolites were screened based on criterion of variables with p value < 0.05 and VIP (variable importance in the projection) > 1.0. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic power of differential metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to search for metabolite pathways and MetaboAnalyst was used for pathway enrichment analysis. Results Several metabolites were significantly changed in GC group compared with PC group. Thirteen metabolites with high VIP were chose and among which 1-methylnicotinamide, dodecanoic acid and sphinganine possessed high AUC values (AUC > 0.8) indicating an excellent discriminatory ability on GC. Pathways such as pentose phosphate pathway and histidine metabolism were focused based on differential metabolites demonstrating their effects on progress of GC. Conclusions In conclusion, we investigated the tissue-based metabolomics profile of GC and several differential metabolites and signaling pathways were focused. Further study is needed to verify those results.

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PSX-A-16 Late-Breaking: Maternal nutrient restriction and re-alimentation influences liver protein expression in fetal sheep

Journal of Animal Science ◽

10.1093/jas/skab235.689 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 376-377

Author(s):

Brandon I Smith ◽

Manuel A Vasquez-Hidalgo ◽

Kendall C Swanson ◽

Kimberly A Vonnahme ◽

Anna T Grazul-Bilska ◽

...

Keyword(s):

Glycogen Synthase ◽

Fetal Liver ◽

National Research Council ◽

Trna Synthetase ◽

Differentially Expressed ◽

Mass Spectrometry Analysis ◽

Nutrient Restriction ◽

Liver Protein ◽

Fetal Sheep ◽

Migration Pathways

Abstract To determine the effects of maternal nutrient restriction and re-alimentation on the fetal liver proteome, 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, a subset of ewes were fed either CON or 60% NRC requirements (RES). A subset of ewes were euthanized at day 90 of gestation (n = 7/treatment), and fetal liver samples collected. 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 proteins were extracted, digested by trypsin and subjected to multiplexed, label-based quantitative mass spectrometry analysis integrating Tandem Mass Tags. Proteins were identified and quantified using Proteome Discoverer (v2.5, Thermo Scientific) and differential abundance analysis was performed using ANOVA and post hoc Tukey’s HSD test. Hierarchal clustering analysis showed clustering of treatments by day of gestation. However, differences were also observed between treatments. At day 90 of gestation, 23 proteins were differentially expressed in RES compared with CON among which glycyl tRNA synthetase and pyruvate carboxylase were increased 12% and 10%, respectively (P < 0.03). At day 130 of gestation, 24, 5, and 71 proteins were differentially expressed in CON-RES, RES-CON, and RES-RES, respectively, compared with CON-CON. Carnosine dipeptidase 2 was decreased 7% in CON-RES and rho associated protein kinase and glycogen synthase 2 were increased 20% and 26% in RES-CON and RES-RES, respectively, compared with CON-CON (P < 0.04). These results indicate that nutrient restriction during mid- and late-gestation impacts expression of proteins involved in gluconeogenesis, glycogenesis, and the formation of carnosine, an integral molecule in beta-oxidation, and that re-alimentation alters proteins involved in cell migration pathways. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.

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345 The effects of maternal nutrient restriction followed by re-alimentation on offspring growth and metabolism in sheep

Journal of Animal Science ◽

10.1093/jas/skz258.202 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 98-98

Author(s):

Brandon I Smith ◽

Manuel A Vásquez-Hidalgo ◽

Kimberly A Vonnahme ◽

Kendall C Swanson ◽

Anna T Grazul-Bilska ◽

...

Keyword(s):

Maternal Nutrition ◽

Management Practice ◽

Fetal Liver ◽

Control Diet ◽

Liver Lipid ◽

Nutrient Restriction ◽

Triceps Brachii ◽

Liver Growth ◽

Offspring Growth ◽

Negative Impacts

Abstract The duration and timing of inadequate maternal nutrition can have detrimental effects on metabolism and organogenesis in the offspring. Re-alimentation, a common management practice that involves feeding full nutrient requirements following a period of nutrient restriction, may reduce the negative impacts of maternal nutrient restriction. To determine the effects of maternal nutrient restriction and re-alimentation on offspring growth,48 primiparous ewes, confirmed pregnant with singletons, were fed a control diet consisting of100% NRC requirements (CON) starting on day25 of gestation. On day50 of gestation, ewes (n = 7) were euthanized and fetal liver, muscle, and blood samples were collected. The remaining animals were fed either CON or60% NRC requirements (RES). On day90 of gestation, a portion of ewes were euthanized (n = 7 per treatment) and fetal samples and weights were collected. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to the alternative diet (CON-RES, RES-CON; n = 7/treatment). On day130 of gestation, all remaining ewes were euthanized. All fetal BW, liver, longissimus muscle, semitendinosus, and triceps brachii weights were determined for each day of gestation. Fetal BW’s were not different between treatment groups (P = 0.29; P = 0.83). Fetal liver weights decreased12.89% in RES-RES compared with CON-CON at day130 (P = 0.049), but were not different at day90 (P = 0.69). There was a tendency for decreased semitendinosus weight in RES group compared with CON at day90 (P = 0.055). Liver lipid droplet accumulation was analyzed for day90 and130 using histochemistry and an effect of maternal nutrition was not observed (P = 0.562). In summary, maternal nutrient restriction reduces offspring muscle and liver growth. To gain insight into the effects of maternal nutrient restriction and re-alimentation on liver development and metabolism, analysis of liver morphology, gene expression, and global metabolomics are needed. Supported by USDA-AFRI grant2016-67016-24884

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Quantitative proteomics suggests changes in the carbohydrate metabolism of maize in response to larvae of the belowground herbivore Holotrichia parallela

PeerJ ◽

10.7717/peerj.9819 ◽

2020 ◽

Vol 8 ◽

pp. e9819

Author(s):

Yu Pan ◽

Shiwen Zhao ◽

Zhun Wang ◽

Xiao Wang ◽

Xinxin Zhang ◽

...

Keyword(s):

Carbohydrate Metabolism ◽

Pentose Phosphate Pathway ◽

Quantitative Proteomics ◽

Enrichment Analysis ◽

Pentose Phosphate ◽

Pathway Enrichment Analysis ◽

Holotrichia Parallela ◽

Functional Studies ◽

Tandem Mass Tag ◽

Mannose Metabolism

The larvae of Holotrichia parallela, a destructive belowground herbivore, may cause yield losses of up to 20% in maize in a typical year. To understand the protein-level mechanisms governing the response of maize to this herbivore, tandem mass tag (TMT) quantitative proteomics was used for the comparative analysis of protein abundance in the maize roots after H. parallela larval attack. A total of 351 upregulated proteins and 303 downregulated proteins were identified. Pathway enrichment analysis revealed that the differentially abundant proteins (DAPs) were most strongly associated with carbohydrate and energy metabolism pathways, such as glycolysis, pentose phosphate pathway and fructose and mannose metabolism. Most glycolysis-related proteins were significantly induced. In addition, H. parallela larval attack decreased the glucose concentrations in the roots. This study demonstrates that maize can manipulate carbohydrate metabolism by modifying glycolysis and pentose phosphate pathway response to root-feeding herbivorous attackers. The results of this study may help to establish a foundation for further functional studies of key protein-mediated responses to H. parallela larvae in maize.

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Hyperphosphorylation of fetal liver IGFBP-1 precedes slowing of fetal growth in nutrient-restricted baboons and may be a mechanism underlying IUGR

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00220.2020 ◽

2020 ◽

Vol 319 (3) ◽

pp. E614-E628

Author(s):

Jenica H. Kakadia ◽

Bhawani B. Jain ◽

Kyle Biggar ◽

Austen Sutherland ◽

Karen Nygard ◽

...

Keyword(s):

Amino Acid ◽

Fetal Liver ◽

Control Diet ◽

Nutrient Restriction ◽

Mtor Inhibition ◽

Group 13 ◽

Umbilical Blood ◽

Parallel Reaction Monitoring ◽

Igf Binding ◽

Igf Binding Protein

In cultured fetal liver cells, insulin-like growth factor (IGF) binding protein (IGFBP)-1 hyperphosphorylation in response to hypoxia and amino acid deprivation is mediated by inhibition of mechanistic target of rapamycin (mTOR) and activation of amino acid response (AAR) signaling and casein kinase (CK)2. We hypothesized that fetal liver mTOR inhibition, activation of AAR and CK2, and IGFBP-1 hyperphosphorylation occur before development of intrauterine growth restriction (IUGR). Pregnant baboons were fed a control (C) or a maternal nutrient restriction (MNR; 70% calories of control) diet starting at gestational day (GD) 30 (term GD 185). Umbilical blood and fetal liver tissue were obtained at GD 120 (C, n = 7; MNR, n = 10) and 165 (C, n = 7; MNR, n = 8). Fetal weights were unchanged at GD 120 but decreased at GD 165 in the MNR group (−13%, P = 0.03). IGFBP-1 phosphorylation, as determined by parallel reaction monitoring mass spectrometry (PRM-MS), immunohistochemistry, and/or Western blot, was enhanced in MNR fetal liver and umbilical plasma at GD 120 and 165. IGF-I receptor autophosphorylationTyr1135 (−64%, P = 0.05) was reduced in MNR fetal liver at GD 120. Furthermore, fetal liver CK2 (α/α′/β) expression, CK2β colocalization, proximity with IGFBP-1, and CK2 autophosphorylationTyr182 were greater at GD 120 and 165 in MNR vs. C. Additionally, mTOR complex (mTORC)1 (p-P70S6KThr389, −52%, P = 0.05) and mTORC2 (p-AktSer473, −56%, P < 0.001) activity were decreased and AAR was activated (p-GCN2Thr898, +117%, P = 0.02; p-eIF2αSer51, +294%, P = 0.002; p-ERKThr202, +111%, P = 0.03) in MNR liver at GD 120. Our data suggest that fetal liver IGFBP-1 hyperphosphorylation, mediated by mTOR inhibition and both AAR and CK2 activation, is a key link between restricted nutrient and oxygen availability and the development of IUGR.

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