PSVIII-22 Maternal vitamin and mineral supplementation affect fetal hepatic expression of genes underlying mineral homeostasis and lipid metabolism in early pregnancy

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 354-355
Author(s):  
Wellison Jarles da Silva Diniz ◽  
Alison K K Ward ◽  
Lawrence P P Reynolds ◽  
Pawel P P Borowicz ◽  
Kevin K K Sedivec ◽  
...  

Abstract Vitamins and minerals play critical roles in functions such as hormone production, DNA synthesis, regulation of gene expression, and lipid metabolism. However, the impact of vitamin and mineral supplementation on fetal programming and the interplay with gene expression of fetal organs remains unclear. We used a differential gene expression analysis to determine effects of maternal vitamin and mineral supplementation (from pre-breeding to d 83 post-breeding) on fetal hepatic gene expression and the pathways underlying liver function and metabolism at 83 d of gestation. Crossbred Angus beef heifers were supplemented (VTM, n = 7) or not (CON, n = 8) with 113 g•heifer-1•d-1 of mineral premix (Purina® Wind & Rain Storm All-Season 7.5 Complete) from a minimum d 71 before breeding through d 83 of gestation. After breeding, heifers were fed to gain 0.79 kg/d. All heifers were surgically ovariohysterectomized on d 83 and fetal liver collected. Total RNA was isolated from the fetal liver (n = 15) and gene expression measured with RNA-Seq. After library quality control and read mapping, differential expression was performed using edgeR. We identified 53 genes upregulated and 37 downregulated in the VTM group (adj.Pval < 0.1). Genes involved with mineral homeostasis, such as MT1A, MT1E, and MT2A, were among those differentially expressed underlying the mineral absorption pathway. ABCA1 and ABCA6, which are involved in cholesterol and metal ion transport across the plasma membrane, and PPARG and SDR16C5, that act on lipoprotein transport and metabolism, were upregulated in the VTM group. Also upregulated in the VTM group, the CUBN gene plays a role in vitamin and iron metabolism. In summary, maternal vitamin and mineral supplementation from pre-breeding to d 83 of gestation leads to upregulation of fetal hepatic genes acting on mineral homeostasis, lipid transport, and metabolism.

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 385
Author(s):  
Wellison J. S. Diniz ◽  
Lawrence P. Reynolds ◽  
Pawel P. Borowicz ◽  
Alison K. Ward ◽  
Kevin K. Sedivec ◽  
...  

Maternal nutrients are essential for proper fetal and placental development and function. However, the effects of vitamin and mineral supplementation under two rates of maternal weight gain on placental genome-wide gene expression have not been investigated so far. Furthermore, biological processes and pathways in the placenta that act in response to early maternal nutrition are yet to be elucidated. Herein, we examined the impact of maternal vitamin and mineral supplementation (from pre-breeding to day 83 post-breeding) and two rates of gain during the first 83 days of pregnancy on the gene expression of placental caruncles (CAR; maternal placenta) and cotyledons (COT; fetal placenta) of crossbred Angus beef heifers. We identified 267 unique differentially expressed genes (DEG). Among the DEGs from CAR, we identified ACAT2, SREBF2, and HMGCCS1 that underlie the cholesterol biosynthesis pathway. Furthermore, the transcription factors PAX2 and PAX8 were over-represented in biological processes related to kidney organogenesis. The DEGs from COT included SLC2A1, SLC2A3, SLC27A4, and INSIG1. Our over-representation analysis retrieved biological processes related to nutrient transport and ion homeostasis, whereas the pathways included insulin secretion, PPAR signaling, and biosynthesis of amino acids. Vitamin and mineral supplementation and rate of gain were associated with changes in gene expression, biological processes, and KEGG pathways in beef cattle placental tissues.


2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 157-158
Author(s):  
Wellison Jarles Da Silva Diniz ◽  
Lawrence P Reynolds ◽  
Alison K Ward ◽  
Pawel P Borowicz ◽  
Kevin K K Sedivec ◽  
...  

Abstract Vitamins and minerals are essential for proper fetal and placental development and function. However, the impact of micronutrient supplementation on placental function and gene expression remains unclear. Herein, we performed a transcriptomic analysis to determine the impact of pre-breeding maternal micronutrient supplementation on the gene expression of placental caruncles (CAR; maternal placenta). Crossbred Angus beef heifers were supplemented (VTM, n = 7) or not (CON, n = 7) with 113 g•heifer-1•d-1 of mineral premix (Purina® Wind & Rain® Storm® All-Season 7.5 Complete) from d 71 to 148 before breeding and until d 83 of gestation. After breeding, heifers were fed a diet to gain 0.79 kg/d. Uteroplacental tissues were collected at d 83. The largest placentome closest to the fetus was collected, and CAR was manually dissected from the cotyledon. Total RNA was isolated from CAR, and gene expression was measured with RNA-Seq. After data quality control and read mapping, differential expression was performed using DESeq2. We identified 46 upregulated and 19 downregulated genes in the VTM group (adj.Pval < 0.1). ShinyGO pathway analysis software was used to identify genes in the Ca and CGMP-PKG signaling pathways, including CALM2 and CAMK2G, which were down and upregulated, respectively. Calcium-mediated systems may activate steroidogenic activity in bovine placentomes, while the cGMP-PKG pathway plays a key role in vascular homeostasis mediated by nitric oxide and decreased Ca concentrations. Furthermore, biological processes underlying blood circulation were among those over-represented. Previous studies report that maternal nutrition may impact placental vascularity and uterine blood flow. ATP2B, that is upregulated in the VTM group, is a calcium/calmodulin-regulated, magnesium-dependent protein involved in intracellular Ca homeostasis. In summary, pre-breeding and early gestation maternal micronutrient supplementation leads to differential expression of genes involved in Ca homeostasis and has a putative effect on placenta vascular function.


2019 ◽  
Vol 20 (7) ◽  
pp. 1581 ◽  
Author(s):  
Lucie Janeckova ◽  
Klara Kostovcikova ◽  
Jiri Svec ◽  
Monika Stastna ◽  
Hynek Strnad ◽  
...  

Commensal microbiota contribute to gut homeostasis by inducing transcription of mucosal genes. Analysis of the impact of various microbiota on intestinal tissue provides an important insight into the function of this organ. We used cDNA microarrays to determine the gene expression signature of mucosa isolated from the small intestine and colon of germ-free (GF) mice and animals monoassociated with two E. coli strains. The results were compared to the expression data obtained in conventionally reared (CR) mice. In addition, we analyzed gene expression in colon organoids derived from CR, GF, and monoassociated animals. The analysis revealed that the complete absence of intestinal microbiota mainly affected the mucosal immune system, which was not restored upon monoassociation. The most important expression changes observed in the colon mucosa indicated alterations in adipose tissue and lipid metabolism. In the comparison of differentially expressed genes in the mucosa or organoids obtained from GF and CR mice, only six genes were common for both types of samples. The results show that the increased expression of the angiopoietin-like 4 (Angptl4) gene encoding a secreted regulator of lipid metabolism indicates the GF status.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kieran Finney ◽  
Anthony Oxley ◽  
Catherine Winder ◽  
Andrew Southam ◽  
Andris Jankevics ◽  
...  

Abstract Objectives The objective of this study was to assess the impact of high-dose vitamin A (VA) on lipid metabolism. Previously, VA has been shown to enhance fat mobilisation, leading to a reduction in body fat. We hypothesise that hypervitaminosis A will increase expression of genes associated with lipid catabolism. Methods To induce chronic hypervitaminosis A, two groups of pigs (n = 8) were fed a commercial diet. The treatment group was additionally dosed, daily, with an oral supplement of retinyl propionate of 10,000 µg/KgBW for 17 weeks. To assess the impact of VA on lipid metabolism, a microarray analysis was performed to identify gene expression in adipose tissue. Differentially expressed transcripts and pathways were identified using Genespring and mapped to human orthologues for Ingenuity Pathway Analysis (IPA); gene fold changes were confirmed using qRT-PCR. Additionally, an untargeted UPLC-MS lipidomic analysis was carried out in serum samples to identify changes in lipd classes and their metabolites. Results In dosed animals, significant increases in plasma retinol (0.66 μmol/L) and liver retinyl ester concentrations (11.98 μmol/g both P < 0.001), as well as an increase in serum NEFA of 92.84 μmol/L (P = 0.001) were observed. Gene expression fold changes in subcutaneous adipose tissue were related to mitochondrial dysfunction and lipid metabolism, including increased expression of MT-CYTB (↑4.78x, P < 0.05) and ATP5A1 (↑3.13x, P < 0.05). Metabolomics confirmed changes in lipids and their metabolites relevant to adipose tissue in blood (P = 0.05), namely a decrease in triacylglyceride concentration and increases in acyl carnitine and cardiolipin concentrations. Conclusions An integrated pathway is suggested to explain the role of vitamin A in leading to increased lipolysis, β-oxidation and oxidative phosphorylation, but when in excess, markers of mitochondrial dysfunction were observed. Funding Sources Funded by the Bill and Melinda Gates foundation.


2011 ◽  
Vol 107 (8) ◽  
pp. 1147-1159 ◽  
Author(s):  
L. Bernard ◽  
C. Leroux ◽  
J. Rouel ◽  
M. Bonnet ◽  
Y. Chilliard

The potential benefits on human health have prompted an interest in developing nutritional strategies for reducing saturated and increasing specific unsaturated fatty acids (FA) in ruminant milk. The impact of the level and type of starchy concentrate added to diets supplemented with sunflower-seed oil on caprine milk FA composition and on mammary, omental and perirenal adipose, and liver lipid metabolism was examined in fourteen Alpine goats in a replicated 3 × 3 Latin square with 21 d experimental periods. Treatments were a grass hay-based diet with a high level of forage (F) or a high level of concentrate with either maize grain (CM) or flattened wheat (CW) as source of starch and supplemented with 130 g/d sunflower-seed oil. Milk yield was enhanced (P < 0·01) and milk fat content was decreased on the CM and CW diets compared with the F diet, resulting in similar milk fat secretion. Both high-concentrate diets increased (P < 0·05) milk yield of 10 : 0-16 : 0 and decreased trans-9,11-18 : 1 and cis-9, trans-11-18 : 2. The CW diet decreased (P < 0·05) the output of Σ C18 and Σ cis-18 : 1 and increased (P < 0·05) the output of trans-10-18 : 1 in milk. The expression and/or activity of fourteen proteins involved in the major lipogenic pathways in mammary tissues and of lipogenic genes in adipose and liver tissues were similar among treatments. In conclusion, high starch concentrates alter milk FA yield via mechanisms independent of changes in mammary, liver or adipose tissue lipogenic gene expression. Furthermore, data provided indications that mammary lipogenic responses to starch-rich diets differ between caprine and bovine ruminants.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 164-165
Author(s):  
Ana Clara B Menezes ◽  
Kacie L L McCarthy ◽  
Cierrah Kassetas ◽  
Friederike Baumgaertner ◽  
James D Kirsch ◽  
...  

Abstract Thirty-five crossbred Angus heifers (body weight = 359.5 &gt;± 7.1 kg) were randomly assigned to a 2 × 2 factorial design to evaluate the effects of vitamin and mineral supplementation [VMSUP; supplemented (VTM) vs. unsupplemented (NoVTM)] and rate of gain [GAIN; low gain (LG), 0.28 kg/d vs. moderate gain (MG), 0.79 kg/d] during the first 83 d of gestation on trace mineral concentrations in fetal liver, muscle, and allantoic (ALF) and amniotic (AMF) fluids. The VTM treatment (113 g supplement•heifer-1•d-1) was initiated a minimum 71 d before breeding. At breeding, heifers were either maintained on the basal diet (LG) or received the MG diet by adding a protein/energy supplement to the basal diet. On d 83 of gestation, samples of fetal liver, muscle, ALF, and AMF were collected and analyzed for trace mineral concentrations. In fetal liver, Se, Cu, Mn, and Co concentrations were greater (P ≤ 0.04) for VTM than NoVTM, while Mo and Co greater (P ≤ 0.04) for LG than MG. In fetal muscle, VTM increased (P ≤ 0.02) concentrations of Se and Zn, whereas LG increased (P &lt; 0.01) Zn. In ALF, Mo concentrations were affected (P = 0.03) by a VMSUP × GAIN interaction, with VTM-MG greater than NoVTM-MG; while VTM increased (P &lt; 0.01) concentrations of Se and Co. Trace mineral concentrations were not affected (P ≥ 0.13) in AMF. In conclusion, VTM increased fetal liver Se, Cu, Mn, and Co concentrations; fetal muscle Se and Zn; and ALF Se and Co; while LG increased fetal liver Mo and Co concentrations and fetal muscle Zn. Our results confirm that managerial decisions associated with vitamin and mineral supplementation and rate of gain can alter fetal reserves of trace elements during early pregnancy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrea Costa ◽  
Bàrbara Reynés ◽  
Jadwiga Konieczna ◽  
Marian Martín ◽  
Miquel Fiol ◽  
...  

AbstractPeripheral blood mononuclear cells (PBMC) are widely used as a biomarker source in nutrition/obesity studies because they reflect gene expression profiles of internal tissues. In this pilot proof-of-concept study we analysed in humans if, as we previously suggested in rodents, PBMC could be a surrogate tissue to study overweight/obesity impact on lipid metabolism. Pre-selected key lipid metabolism genes based in our previous preclinical studies were analysed in PBMC of normoglycemic normal-weight (NW), and overweight-obese (OW-OB) subjects before and after a 6-month weight-loss plan. PBMC mRNA levels of CPT1A, FASN and SREBP-1c increased in the OW-OB group, according with what described in liver and adipose tissue of humans with obesity. This altered expression pattern was related to increased adiposity and early signs of metabolic impairment. Greater weight loss and/or metabolic improvement as result of the intervention was related to lower CPT1A, FASN and SREBP-1c gene expression in an adjusted linear mixed-effects regression analysis, although no gene expression recovery was observed when considering mean comparisons. Thus, human PBMC reflect lipid metabolism expression profile of energy homeostatic tissues, and early obesity-related alterations in metabolic at-risk subjects. Further studies are needed to understand PBMC usefulness for analysis of metabolic recovery in weigh management programs.


2018 ◽  
Vol 237 (3) ◽  
pp. 301-310 ◽  
Author(s):  
K M Jeckel ◽  
A C Boyarko ◽  
G J Bouma ◽  
Q A Winger ◽  
R V Anthony

Several developmental windows, including placentation, must be negotiated to establish and maintain pregnancy. Impaired placental function can lead to preeclampsia and/or intrauterine growth restriction (IUGR), resulting in increased infant mortality and morbidity. It has been hypothesized that chorionic somatomammotropin (CSH) plays a significant role in fetal development, potentially by modifying maternal and fetal metabolism. Recently, using lentiviral-mediated in vivo RNA interference in sheep, we demonstrated significant reductions in near-term (135 days of gestation; dGA) fetal and placental size, and altered fetal liver gene expression, resulting from CSH deficiency. We sought to examine the impact of CSH deficiency on fetal and placental size earlier in gestation (50 dGA), and to examine placental gene expression at 50 and 135 dGA. At 50 dGA, CSH-deficient pregnancies exhibited a 41% reduction (P ≤ 0.05) in uterine vein concentrations of CSH, and significant (P ≤ 0.05) reductions (≈21%) in both fetal body and liver weights. Placentae harvested at 50 and 135 dGA exhibited reductions in IGF1 and IGF2 mRNA concentrations, along with reductions in SLC2A1 and SLC2A3 mRNA. By contrast, mRNA concentrations for various members of the System A, System L and System y+ amino acid transporter families were not significantly impacted. The IUGR observed at the end of the first-third of gestation indicates that the near-term IUGR reported previously, began early in gestation, and may have in part resulted from deficits in the paracrine action of CSH within the placenta. These results provide further compelling evidence for the importance of CSH in the progression and outcome of pregnancy.


Sign in / Sign up

Export Citation Format

Share Document