scholarly journals Fetal expression of genes related to metabolic function is impacted by supplementation of ground beef and sucrose during gestation in a swine model

2020 ◽  
Vol 98 (8) ◽  
Author(s):  
Ashley S Hoyle ◽  
Ana Clara B Menezes ◽  
Megan A Nelson ◽  
Kendall C Swanson ◽  
Kimberly A Vonnahme ◽  
...  

Abstract To determine the effects of maternal supplementation on the mRNA abundance of genes associated with metabolic function in fetal muscle and liver, pregnant sows (Landrace × Yorkshire; initial body weight (BW) 221.58 ± 33.26 kg; n = 21) fed a complete gestation diet (corn–soybean meal based diet, CSM) were randomly assigned to 1 of 4 isocaloric supplementation treatments: control (CON, 378 g/d CSM, n = 5), sucrose (SUGAR, 255 g/d crystalized sugar, n = 5), cooked ground beef (BEEF, 330 g/d n = 6), or BEEF + SUGAR (B+S, 165 g/d cooked ground beef and 129 g/d crystalized sugar, n = 5), from days 40 to 110 of gestation. Sows were euthanized on day 111 of gestation. Two male and 2 female fetuses of median BW were selected from each litter, and samples of the longissimus dorsi muscle and liver were collected. Relative transcript level was quantified via qPCR with HPRT1 as the reference gene for both muscle and liver samples. The following genes were selected and analyzed in the muscle: IGF1R, IGF2, IGF2R, GYS-1, IRS-1, INSR, SREBP-1C, and LEPR; while the following were analyzed in the liver: IGF2, IGF2R, FBFase, G6PC, PC, PCK1, FGF21, and LIPC. No effect of fetal sex by maternal treatment interaction was observed in mRNA abundance of any of the genes evaluated (P > 0.11). In muscle, the maternal nutritional treatment influenced (P = 0.02) IGF2 mRNA abundance, with B+S and SUGAR fetuses having lower abundance than CON, which was not different from BEEF. Additionally, SREBP-1 mRNA abundance was greater (P < 0.01) for B+S compared with CON, BEEF, or SUGAR fetuses; and females tended (P = 0.06) to have an increased abundance of SREBP-1 than males. In fetal liver, IGF2R mRNA abundance was greater (P = 0.01) for CON and BEEF than SUGAR and B+S; while FBPase mRNA abundance was greater (P = 0.03) for B+S compared with the other groups. In addition, maternal nutritional tended (P = 0.06) to influence LIPC mRNA abundance, with increased abundance in CON compared with SUGAR and B+S. These data indicate limited changes in transcript abundance due to substitution of supplemental sugar by ground beef during mid to late gestation. However, the differential expression of FBPase and SREBP-1c in response to the simultaneous supplementation of sucrose and ground beef warrants further investigations, since these genes may play important roles in determining the offspring susceptibility to metabolic diseases.

2015 ◽  
Vol 308 (4) ◽  
pp. E306-E314 ◽  
Author(s):  
Satya S. Houin ◽  
Paul J. Rozance ◽  
Laura D. Brown ◽  
William W. Hay ◽  
Randall B. Wilkening ◽  
...  

Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 ( P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-13C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 ( P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia ( P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia.


Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 695-705 ◽  
Author(s):  
Lingyun Zhu ◽  
Samir B. Kahwash ◽  
Long-Sheng Chang

Abstract Erythrocyte protein 4.2 (P4.2) is an important component of the erythrocyte membrane skeletal network with an undefined biologic function. Presently, very little is known about the expression of the P4.2 gene during mouse embryonic development and in adult animals. By using the Northern blot and in situ hybridization techniques, we have examined the spatial and temporal expression of the P4.2 gene during mouse development. We show that expression of the mouse P4.2 gene is temporally regulated during embryogenesis and that the P4.2 mRNA expression pattern coincides with the timing of erythropoietic activity in hematopoietic organs. P4.2 transcripts are first detected in embryos on day 7.5 of gestation and are localized exclusively in primitive erythroid cells of yolk sac origin. These erythroid cells remain to be the only source for P4.2 expression until the switch of the hematopoietic producing site to fetal liver. In mid- and late-gestation periods, P4.2 mRNA expression is restricted to the erythroid cells in fetal liver and to circulating erythrocytes. Around and after birth, the site for P4.2 expression is switched from liver to spleen and bone marrow, and P4.2 transcripts are only detected in cells of the erythroid lineage. These results provide the evidence for specific P4.2 expression in erythroid cells. In addition, the timing and pattern of expression of the P4.2 gene suggest the specific regulation of the P4.2 gene.


Reproduction ◽  
2007 ◽  
Vol 133 (4) ◽  
pp. 785-796 ◽  
Author(s):  
Richard G Lea ◽  
Peter Wooding ◽  
Ian Stewart ◽  
Lisa T Hannah ◽  
Stephen Morton ◽  
...  

Overnourishing pregnant adolescent sheep promotes maternal growth but reduces placental mass, lamb birth weight and circulating progesterone. This study aimed to determine whether altered progesterone reflected transcript abundance forStAR(cholesterol transporter) and the steroidogenic enzymes (Cyp11A1,Hsd3bandCyp17). Circulating and placental expression of ovine placental lactogen (oPL) was also investigated. Adolescent ewes with singleton pregnancies were fed high (H) or moderate (M) nutrient intake diets to restrict or support placental growth. Experiment 1: peripheral progesterone and oPL concentrations were measured in H (n=7) and M (n=6) animals across gestation (days 7–140). Experiment 2: progesterone was measured to mid- (day 81; M:n=11, H:n=13) or late gestation (day 130; M:n=21, H:n=22), placental oPL,StARand steroidogenic enzymes were measured by qPCR and oPL protein by immunohistochemistry. Experiment 1: in H vs M animals, term placental (P<0.05), total cotyledon (P<0.01) and foetal size (P<0.05) were reduced. Circulating oPL and progesterone were reduced at mid- (P<0.001,P<0.01) and late gestation (P<0.01,P<0.05) and oPL detection was delayed (P<0.01). Experiment 2: placental oPL was not altered by nutrition. In day 81 H animals, progesterone levels were reduced (P<0.001) but not related to placental or foetal size. Moreover, placental steroidogenic enzymes were unaffected. Day 130 progesterone (P<0.001) andCyp11A1(P<0.05) were reduced in H animals with intrauterine growth restriction (H+IUGR). Reduced mid-gestation peripheral oPL and progesterone may reflect altered placental differentiation and/or increased hepatic clearance respectively. Restricted placental growth and reduced biosynthesis may account for reduced progesterone in day 130 H+IUGR ewes.


1992 ◽  
Vol 263 (3) ◽  
pp. R619-R623
Author(s):  
I. Vatnick ◽  
A. W. Bell

Ontogeny of fetal hepatic and placental growth and in vitro oxygen consumption (VO2) was investigated in fetal lambs at 75, 100, and 136 days postconception. Fetal hepatic relative weight and placental absolute and relative weights declined during this period. Oxygen consumption per gram dry weight of fetal liver and maternal placenta declined between mid and late gestation while fetal placental VO2 was unchanged. Estimated VO2 of the whole placenta did not change while the estimated total hepatic VO2 increased more than threefold between 75 and 136 days. Total hepatic VO2 was highly correlated with total placental VO2 at 136 days (r = 0.84). The results suggest that the placenta reaches its maximum growth and metabolic capacity before 100 days and possibly at or before midgestation. Changes in hepatic weight-specific total VO2, in addition to the declining relative size of the fetal liver, must contribute to the progressive decline in metabolic rate of the whole fetus during the second half of pregnancy. Correlations between placental and fetal liver weights and metabolic rates suggest the possibility of placental regulation of fetal hepatic growth and metabolism.


2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 139-139
Author(s):  
Jose Alejandro Roque ◽  
Mario Francisco Oviedo ◽  
Hector Aaron Lee ◽  
Alejandro E Relling

Abstract Polyunsaturated fatty acids supplementation in late gestation change offspring metabolism; however, their effect is not well known on early gestation in ewes. The objectives of this study were to determine the effect of dietary supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in pregnant ewes on the concentration of EPA and DHA on fetal liver (FL) and fetal central nervous system (FCNS), and to evaluate the effect of the supplementation with EPA+ DHA on mRNA expression of genes associated with transport and metabolism of fatty acids (FA) in FL and placenta (caruncles and cotyledons). Twelve ewes (4 pens, three per pen) were blocked by pregnancy day. The ewes were assigned during the first 45 d of gestation to diet with an addition of 1.5% (dry matter bases) monounsaturated FA (MUFA) or EPA+DHA. A C-section was conducted at d 45 of gestation to collect FL, FCNS, caruncle and cotyledon. Data were analyzed using a mixed procedure (SAS). For the placenta mRNA concentration, a 2x2 factorial was used considering caruncle and cotyledon as the second main factor. Isomers of C18:1 (t6,8 and t12) increase (P < 0.05) in FL and FCNS with MUFA supplementation, fatty acids C20:3 (n-6), C20:3 (n-3), C22:1, C22:5 and C22:6 increase (P < 0.05) in FL and FCNS with EPA+DHA supplementation. In FL there was a tendency to increase for mRNA expression of FATP-1 (P = 0.10) with EPA+DHA supplementation, while mRNA concentration for LPL was greater (P = 0.02) for MUFA supplementation. In placenta DNMT3b and FFAR-4 showed a significant FA x tissue interaction (P < 0.05). These results suggest that FA supplementation during early gestation alters the FA profile in FL and FCNS and changed mRNA concentration of genes involved in the transport of FA and cell metabolism.


2019 ◽  
Vol 20 (S24) ◽  
Author(s):  
Hongfei Cui ◽  
Hailin Hu ◽  
Jianyang Zeng ◽  
Ting Chen

Abstract Background Ribosome profiling brings insight to the process of translation. A basic step in profile construction at transcript level is to map Ribo-seq data to transcripts, and then assign a huge number of multiple-mapped reads to similar isoforms. Existing methods either discard the multiple mapped-reads, or allocate them randomly, or assign them proportionally according to transcript abundance estimated from RNA-seq data. Results Here we present DeepShape, an RNA-seq free computational method to estimate ribosome abundance of isoforms, and simultaneously compute their ribosome profiles using a deep learning model. Our simulation results demonstrate that DeepShape can provide more accurate estimations on both ribosome abundance and profiles when compared to state-of-the-art methods. We applied DeepShape to a set of Ribo-seq data from PC3 human prostate cancer cells with and without PP242 treatment. In the four cell invasion/metastasis genes that are translationally regulated by PP242 treatment, different isoforms show very different characteristics of translational efficiency and regulation patterns. Transcript level ribosome distributions were analyzed by “Codon Residence Index (CRI)” proposed in this study to investigate the relative speed that a ribosome moves on a codon compared to its synonymous codons. We observe consistent CRI patterns in PC3 cells. We found that the translation of several codons could be regulated by PP242 treatment. Conclusion In summary, we demonstrate that DeepShape can serve as a powerful tool for Ribo-seq data analysis.


Author(s):  
Sidharth P Mishra ◽  
Shalini Jain ◽  
Subhash Taraphder ◽  
Hariom Yadav

Abstract Decade-old studies have demonstrated that microbes living in our gut (microbiota) contribute to both maintaining normal metabolic function and to the pathology of metabolic diseases, such as obesity and diabetes. Emerging evidence suggests that gut microbiota influences the personalized effects of diets and drugs and impact the gut–brain axis and leaky gut inflammation to control metabolic function/diseases. Gut microbiota can be an ideal source of prognostic markers and therapies for metabolic diseases. Here we discuss the emerging concepts in the area of microbiota and metabolic interactions in personalized nutrition, drug response, and disease prognosis.


2018 ◽  
Vol 315 (2) ◽  
pp. R312-R322 ◽  
Author(s):  
Dennis Kolosov ◽  
Scott P. Kelly

Molecular physiology of the tricellular tight junction (tTJ)-associated proteins lipolysis-stimulated lipoprotein receptor ( lsr, = angulin-1) and an immunoglobulin-like domain-containing receptor ( ildr2, ≈angulin-3) was examined in model trout gill epithelia. Transcripts encoding lsr and ildr2 are broadly expressed in trout organs. A reduction in lsr and ildr2 mRNA abundance was observed during and after confluence in flask-cultured gill cells. In contrast, as high-resistance and low-permeability characteristics developed in a model gill epithelium cultured on permeable polyethylene terephthalate membrane inserts, lsr and ildr2 transcript abundance increased. However, as epithelia entered the developmental plateau phase, lsr abundance returned to initial values, while ildr2 transcript abundance remained elevated. When mitochondrion-rich cells were introduced to model preparations, lsr mRNA abundance was unaltered and ildr2 mRNA abundance significantly increased. Transcript abundance of ildr2 was not altered in association with corticosteroid-induced tightening of the gill epithelium, while lsr mRNA abundance decreased. Transcriptional knockdown of the tTJ protein tricelluin (Tric) reduced Tric abundance, increased gill epithelium permeability, and increased lsr without significantly altering ildr2 transcript abundance. Data suggest that angulins contribute to fish gill epithelium barrier properties but that Lsr and Ildr2 seem likely to play different roles. This is because ildr2 typically exhibited increased abundance in association with decreased model permeability, while lsr abundance changed in a manner that suggested a role in Tric recruitment to the tTJ.


1998 ◽  
Vol 10 (5) ◽  
pp. 399 ◽  
Author(s):  
David Y. Zhang ◽  
Eugenie R. Lumbers ◽  
June J. Wu

The aim of the study was to determine the amount of angiotensinogen expression and its protein product in fetal sheep liver and kidney in the last third of gestation. Angiotensinogen mRNA was measured by RNase protection assay and its protein levels were measured by radioimmunoassay. Levels were measured at 80, 95, 111, 125 and 139 days. Angiotensinogen mRNA was present in all fetal liver and kidney samples tested. The ratio of hepatic angiotensinogen mRNA/18 S rRNA increased by 100% (P<0.001) and angiotensinogen levels increased by 33% (P<0.001) in fetal sheep from 80 to 139 d. Over the same period the ratio of renal angiotensinogen mRNA/18 S rRNA increased by 170% (P<0.001) and renal angiotensinogen protein increased by 41% (P<0.001). The levels of angiotensinogen mRNA and its protein in the adult kidney were less than in kidneys of 139 d old fetuses (P<0.01). There was a direct relationship between levels of angiotensinogen mRNA and its protein in the liver (r = 0.53, P<0.01, n = 25) and in the kidney (r = 0.75, P<0.0001, n = 24). These findings demonstrate that there is a significant increase in both hepatic and renal angiotensinogen gene expression in the last third of gestation in the fetal sheep and that this increase is associated with an increase of angiotensinogen levels in both tissues. This increase in angiotensinogen in late gestation could influence the activity of both the intrarenal and circulating renin angiotensin systems.


1986 ◽  
Vol 251 (3) ◽  
pp. E328-E333 ◽  
Author(s):  
M. Freemark ◽  
M. Comer ◽  
S. Handwerger

To determine whether changes in the relative biological potencies of ovine placental lactogen (oPL) and ovine growth hormone (oGH) during development derive from ontogenetic changes in the binding of these hormones to hepatic receptors, we have compared the binding of 125I-oPL and 125I-oGH to hepatic membranes from fetal lambs and pregnant sheep at mid- and late gestation and from postnatal sheep at 1 day to 7 mo of age. Specific high-affinity 125I-oPL binding sites in ovine fetal liver were detected as early as day 70 of gestation (term = 145 days), and the number of fetal 125I-oPL binding sites increased progressively throughout the latter half of gestation, reaching a maximum (11.2 fmol/mg protein) at 3-7 days before parturition. The potency of oPL (Kd 0.27 nM) in competing for 125I-oPL binding sites was 90 and 1,300 times greater than that of oGH and ovine prolactin, respectively. Although the number of fetal 125I-oPL binding sites increased throughout pregnancy, there was little or no specific binding of 125I-oGH noted in the fetus. Treatment of fetal liver membranes with 4 M MgCl2 did not enhance the subsequent specific binding of 125I-oGH, suggesting that the low specific binding of oGH did not result from occupation of hepatic receptors by endogenous circulating oPL or oGH. In contrast, MgCL2 treatment markedly increased the apparent number of fetal 125I-oPL binding sites, suggesting that oPL receptors in fetal liver are partly saturated in vivo by oPL.(ABSTRACT TRUNCATED AT 250 WORDS)


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