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Hepatic Metabolic Profile Reveals the Adaptive Mechanisms of Ewes to Severe Undernutrition during Late Gestation.

ABSTRACT: The mechanisms underlying the adaption of liver metabolism to the undernutrition in ewes during late gestation remain unclear. This research aimed to explore the adaptive mechanisms of liver metabolism by hepatic metabolome analysis in pregnant ewes to the negative energy balance induced by severe feed restriction. Twenty ewes carrying multiple fetuses and gestating for 115 days were fed normally or restricted to a 30% feed level (10 ewes in each group) for 15 days. All ewes were sacrificed and hepatic samples were collected and analyzed by liquid chromatography-mass spectrometry. Both the principal components analysis and partial least squares of discriminant analysis of hepatic metabolites showed the clear separation between ewes in the control and severely feed-restricted groups. The metabolic profile demonstrated that the proportions of differential metabolites between the two groups in fatty acids and lipids, organic acids, and amino acids and derivatives were 61.11%, 16.67%, and 11.11%, respectively. Enriched pathways of differential metabolites were mainly involved in fatty acids and amino acids metabolism and biosynthesis. Correlation networks of differential metabolites revealed that general metabolic pattern was changed apparently and mainly based on fatty acids and lipids in the livers of feed-restricted ewes. The accumulation and oxidation of long-chain fatty acids were intensified in the livers of feed-restricted ewes, while those of medium-chain fatty acids were the opposite. In general, severe feed restriction significantly affected the levels of hepatic metabolites and altered the overall metabolic pattern. Furthermore, fatty acids oxidation as well as the utilization of amino acids and organic acids were intensified to adapt to the negative energy balance during late gestation.

SUBMITTER: Xue Y

PROVIDER: S-EPMC6316483 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Hepatic Metabolic Profile Reveals the Adaptive Mechanisms of Ewes to Severe Undernutrition during Late Gestation.

Xue Yanfeng Y Guo Changzheng C Hu Fan F Liu Junhua J Mao Shengyong S

Metabolites 20181127 4

The mechanisms underlying the adaption of liver metabolism to the undernutrition in ewes during late gestation remain unclear. This research aimed to explore the adaptive mechanisms of liver metabolism by hepatic metabolome analysis in pregnant ewes to the negative energy balance induced by severe feed restriction. Twenty ewes carrying multiple fetuses and gestating for 115 days were fed normally or restricted to a 30% feed level (10 ewes in each group) for 15 days. All ewes were sacrificed and ...[more]

PMID: 30486444

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Project description:Pregnant Suffolk ewes (n = 19; 81.2kg ± 7.7) estimated to be carrying twins were assigned to endophyte-infected tall fescue seed (E+; 4.14 µg ergovaline + ergovalinine/g seed) or a control diet (CON; 0 µg ergovaline + ergovalinine) and evaluated at different stages of gestation (gd85 [pre-treatment, n = 3], gd110 [n = 4/treatment] or gd133 [n = 4/treatment). Ewes were individually fed a basal diet with (E+) or without (CON) endophyte-infected tall fescue seed from gd86 to gd110 or gd133. A terminal necropsy was performed, and uterine components were evaluated for size, weight, and type. Data were analyzed using a priori contrasts to test effects of stage of gestation (gd85 vs. gd110 or gd110 vs. gd133) and adaptive responses to feeding E+ fescue seed versus CON at gd110 and gd133. Serum prolactin concentrations were greater (P < 0.05) at gd110 than gd85, and then remained constant to gd133. Feeding E+ tall fescue seed reduced (P < 0.05) serum prolactin concentrations compared to CON at both gd110 and gd133. From gd85 to gd110, placentome type and number changed from type A to type B (P < 0.05) but did not change (P > 0.05) after gd110. Total fetal weight per ewe increased 2977 g from gd85 to gd110 (P = 0.011) and then 3151 g from gd110 to 133 (P = 0.012). Brain weight as a percentage of fetal body weight was higher (P = 0.029) for E+ fetuses on gd110 compared to CON, which demonstrates asymmetrical growth and intrauterine growth restriction (IUGR). In total, 15,961 genes were identified in the cotyledon through mapping to the ovine genome across all samples. There were 136 genes differentially expressed (FDR < 0.05; log2foldchange < -1 and > 1) from gd85 to gd110 with ovarian steroidogenesis and steroid biosynthesis pathways enriched and 469 genes differentially expressed from gd110 to gd133 with ribosome and oxidative phosphorylation pathways enriched. Exposure to E+ fescue resulted in differential expression of 22 genes at gd110 but only one gene at gd133 compared to CON. These results show that there are major changes in fetal growth and placental remodeling during the late gestation period that are influenced by exposure to ergot alkaloids from endophyte-infected tall fescue seed; however, major changes in the transcriptome of the cotyledon tissue in response to E+ fescue were not observed and other factors must be involved in the reduction of placental efficiency and fetal growth observed with E+ fescue exposure.

Project description:IntroductionMaternal periconceptional undernutrition (PCUN) alters fetal hypothalamic-pituitary-adrenal axis (HPAA) function and placental glucocorticoid metabolism in sheep. The effects of PCUN on HPAA function in adult life are not known. We investigated the effects of PCUN on fetal adrenal development across gestation and on cortisol regulation in adult offspring.MethodsEwes were undernourished from 61 days before to 30 days after conception ('PCUN') or fed ad libitum ('N'). mRNA expression in the fetal adrenal gland of ACTH receptor (ACTHR), steroidogenic acute regulatory protein (STAR), cytochrome P450 17A1 (CYP17A1), 11beta-hydroxysteroid-dehydrogenase type 2 (11βHSD2), insulin-like growth factor-2 (IGF2), and in the fetal hippocampus of 11βHSD1, 11βHSD2, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) was determined at 50 (adrenal only), 85, 120 and 131 days of gestation (term=148 days). In adult offspring (≥ 3 years, N; 10 female, 5 male, PCUN; 10 female, 10 male) a combined arginine vasopressin (AVP, 0.1 μg/kg) and corticotropin-releasing hormone (CRH, 0.5 μg/kg) challenge and a metyrapone (40 mg/kg) challenge were undertaken. mRNA expression of ACTHR, STAR and CYP17A1 were determined in adult adrenals.ResultsFetal adrenal STAR, CYP17A1 and IGF2 mRNA expression were not different between groups in early gestation but were higher in PCUN than N at 131 days' gestation (all p<0.01). PCUN reduced fetal hippocampal MR and GR mRNA expression by 50% at 85 day, but not in later gestation. Adult offspring plasma cortisol responses to AVP+CRH or metyrapone were not different between groups. Plasma ACTH response to AVP+CRH was lower in PCUN males but ACTH response to metyrapone was not different between groups. Adult adrenal ACTHR, STAR, and CYP17A1 mRNA expression were not affected by PCUN.ConclusionsWe conclude that the effects of PCUN on fetal HPAA function that became apparent in late gestation, are not reflected in adrenal cortisol secretion in mid-adulthood.

Project description:Background:Heat stress (HS) jeopardizes intestinal barrier functions and augments intestinal permeability in pigs. However, whether HS-induced maternal microbial and metabolic changes in primiparous sows during late gestation remains elusive. We present here, a study investigating the fecal microbial and metabolic responses in late gestational primiparous sows when exposed to HS. Methods:Twelve first-parity Landrace × Large White F1 sows were randomly assigned into two environmental treatments including the thermoneutral (TN) (18-22?°C; n?=?6) and HS (28-32?°C; n?=?6) conditions. Both treatments were applied from 85 d of gestation to farrowing. The serum and feces samples were collected on d 107 of gestation, for analyses including intestinal integrity biomarkers, high-throughput sequencing metagenomics, short-chain fatty acid (SCFA) profiles and nontargeted metabolomics. Results:Our results show that HS group has higher serum Heat shock protein 70 (HSP70), lipopolysaccharide (LPS) and lipopolysaccharide-binding protein (LBP) levels. The gut microbial community can be altered upon HS by using ?-diversity and taxon-based analysis. In particular, the relative abundance of genera and operational taxonomic units (OTUs) related to Clostridiales and Halomonas are higher in HS group, the relative abundance of genera and OTUs related to Bacteroidales and Streptococcus, however, are lower in HS group. Results of metabolic analysis reveal that HS lowers the concentrations of propionate, butyrate, total SCFA, succinate, fumarate, malate, lactate, aspartate, ethanolamine, ?-alanine and niacin, whereas that of fructose and azelaic acid are higher in HS group. These metabolites mainly affect propanoate metabolism, alanine, aspartate and glutamate metabolism, phenylalanine metabolism, ?-alanine metabolism, pantothenate and CoA biosynthesis, tricarboxylic acid cycle (TCA) and nicotinate and nicotinamide metabolism. Additionally, correlation analysis between significant microbes and metabolites indicated that the HS-induced microbiota shift is likely the cause of changes of intestinal metabolism. Conclusions:Taken together, we reveal characteristic structural and metabolic changes in maternal gut microbiota as a result of late gestational HS, which could potentially provide the basis for further study on offspring gut microbiota and immune programming.

Project description:Tall fescue (Schedonorus arundinaceus) is a cool-season perennial grass that is widely used as a forage for many livestock species including sheep. An endophyte (Neotyphodium coenophialum) in tall fescue produces ergot alkaloids that enhance plant survival but produce toxicosis in animals. The objective of this study was to investigate the rumen microbiota from gestation and lactation in ewes grazing tall fescue pastures with high (HA) or moderate (MA) levels of endophyte infection, and their relationship with serum parameters. Data were collected at the beginning of the study (d1), the week before initiation of lambing (d51), and at the end of the trial (d115). The rumen microbiota was evaluated using 16S rRNA gene sequencing. Ewes grazing HA had greater serum non-esterified fatty acid (NEFA) (P = 0.024) levels compared with ewes in MA pasture at d115. Both the number of observed OTUs and Shannon diversity index tended (P = 0.08, P = 0.06) to be greater for HA than for MA on d115. At the genus level, Prevotella relative abundance increased with time in both MA and HA (on d1, d51, and d115: 15.17, 25.59, and 24.78% in MA; 14.17, 18.10, and 19.41% in HA). Taxa unclassified at the genus level including (unclassified) Lachnospiraceae, Coriobacteriaceae, and Veillonellaceae exhibited higher abundances in HA at d51 (3.72, 2.07, and 11.22%) compared with MA (2.06, 1.28, and 7.42%). The predictor microbiota for HA and MA were identified by a random forest classification model. The HA predictors included bacteria associated with unclassified Coriobacteriaceae and Ruminococcaceae. Other OTUs classified as Prevotella and Clostridiales could be microbial predictors for MA. The OTUs classified as Prevotella and Lachnospiraceae were negatively correlated with serum concentration of prolactin. Negative correlations with NEFA were observed in the microbiota such as species affiliated to unclassified Clostridiales and Prevotella. OTUs classified as Bacteroidetes and Coriobacteriaceae exhibited a positive correlation with NEFA. Our study confirmed that the rumen microbiota populations were affected by high levels of toxins in endophyte-infected tall fescue and were associated with host hormone and energy metabolism.

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Hepatic Metabolic Profile Reveals the Adaptive Mechanisms of Ewes to Severe Undernutrition during Late Gestation.

Publications

Hepatic Metabolic Profile Reveals the Adaptive Mechanisms of Ewes to Severe Undernutrition during Late Gestation.

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