PSX-A-3 Late-Breaking: Analysis of serum chemistry for metabolic function in GnRH-II receptor knockdown and littermate control boars

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 377-377
Author(s):  
Caitlin E Ross ◽  
Amy T Desaulniers ◽  
Rebecca A Cederberg ◽  
Ginger A Mills ◽  
Clay A Lents ◽  
...  
Keyword(s):  
Equal Opportunity ◽  
Physiological Role ◽  
Lactic Dehydrogenase ◽  
High Density Lipoproteins ◽  
Mrna Levels ◽  
Gamma Glutamyl Transpeptidase ◽  
Littermate Control ◽  
Elevated Creatinine ◽  
Metabolic Disruption ◽  
And Control

Abstract Pigs are the only livestock species encoding functional proteins for both the second form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II), which are uniquely expressed in reproductive and non-reproductive tissues. To examine the physiological role of the GnRH-II/GnRHR-II system, we produced a swine line with reduced endogenous levels of GnRHR-II (GnRHR-II KD); males exhibit 70% diminished testicular GnRHR-II mRNA levels and 82% reduced circulating testosterone concentrations. Given that testosterone impacts metabolism, blood was collected from GnRHR-II KD (n = 5) and littermate control (n = 5) boars via indwelling jugular catheters, with serum isolated and subjected to veterinary diagnostic panels for metabolic analyte examination (PhysLab, Lincoln, NE). Statistical analyses utilized the MIXED procedure of SAS; the model included line as fixed and litter as random effects. Creatine kinase and blood urea nitrogen (BUN):creatinine ratios were elevated, creatinine was reduced (P < 0.01), and thyroxine tended to be decreased (P < 0.10) in GnRHR-II KD compared with control boars. Glucose, BUN, amylase, and lipase levels were not different. Liver products differed in transgenic versus control boars; levels of lactic dehydrogenase, aspartate and alanine aminotransferases (AST; ALT), and gamma-glutamyl transpeptidase were higher, whereas AST:ALT ratios, total protein, albumin, and globulin levels were lower (P < 0.05) in GnRHR-II KD boars. Albumin:globulin ratios and bilirubin (total and direct) did not differ. Additionally, serum cholesterol was decreased (P < 0.05), non-high density lipoproteins (HDLs) and low density lipoproteins (LDLs) tended to be decreased (P < 0.10), and triglycerides, HDLs, and cholesterol:HDL ratios did not differ between GnRHR-II KD and control males. These data suggest metabolic disruption in GnRHR-II KD boars, which may be due to suppressed gonadal steroidogenesis or ubiquitous knockdown of GnRHR-II expression. Supported by USDA/NIFA AFRI (2017-67015-26508) and Hatch Multistate (NEB-26–244) funds. USDA is an equal opportunity provider and employer.

scholarly journals A Role for the Calcitonin Receptor to Limit Bone Loss During Lactation in Female Mice by Inhibiting Osteocytic Osteolysis

Endocrinology ◽  
2015 ◽  
Vol 156 (9) ◽  
pp. 3203-3214 ◽  
Author(s):  
Michele V. Clarke ◽  
Patricia K. Russell ◽  
David M. Findlay ◽  
Stephen Sastra ◽  
Paul H. Anderson ◽  
...  
Keyword(s):  
Cortical Bone ◽  
Direct Action ◽  
Bone Matrix ◽  
Physiological Role ◽  
Mrna Levels ◽  
Calcitonin Receptor ◽  
Micro Computed Tomography ◽  
Littermate Control ◽  
Osteocytic Osteolysis ◽  
Osteocyte Lacunar

During lactation, the large transfer of calcium from the mother to the milk is primarily sourced from the maternal skeleton. To determine whether the calcitonin receptor (CTR) plays a physiological role to protect the skeleton from excessive resorption during lactation, we assessed the maternal skeleton of global CTR knockout (CTRKO) and littermate control mice at the end of lactation (postnatal day 21). Micro-computed tomography analyses showed no effect on trabecular or cortical bone in the distal femur and L1 vertebra of maternal global CTR deletion at the end of lactation in global CTRKO mice compared with that in control mice. Bone resorption, as assessed by osteoclast number and activity at the end of lactation, was unaffected by maternal CTR deletion. Cathepsin K, carbonic anhydrase 2, matrix metalloproteinase 13, and receptor activator of nuclear factor-κB ligand mRNA levels, however, were markedly elevated by 3- to 6.5-fold in whole bone of lactating global CTRKO females. Because these genes have been shown to be up-regulated in osteocytes during lactation when osteocytes resorb their surrounding bone matrix, together with their reported expression of the CTR, we determined the osteocyte lacunar area in cortical bone. After lactation, the top 20% of osteocyte lacunar area in global CTRKO mice was 10% larger than the top 20% in control mice. These data are consistent with an increased osteocytic osteolysis in global CTRKO mice during lactation, which is further supported by the increased serum calcium observed in global CTRKO mice after lactation. These results provide evidence for a physiological role for the CTR to protect the maternal skeleton during lactation by a direct action on osteocytes to inhibit osteolysis.

scholarly journals The deletion of glucagon-like peptide-1 receptors expressing neurons in the dorsomedial hypothalamic nucleus disrupts the diurnal feeding pattern and induces hyperphagia and obesity

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuko Maejima ◽  
Shoko Yokota ◽  
Masaru Shimizu ◽  
Shoichiro Horita ◽  
Daisuke Kobayashi ◽  
...  
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Physiological Role ◽  
Feeding Pattern ◽  
Hypothalamic Nucleus ◽  
Acid Decarboxylase ◽  
Mrna Levels ◽  
Dorsomedial Hypothalamic Nucleus ◽  
Fos Expression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background Feeding rhythm disruption contributes to the development of obesity. The receptors of glucagon-like peptide-1 (GLP-1) are distributed in the wide regions of the brain. Among these regions, GLP-1 receptors (GLP-1R) are expressed in the dorsomedial hypothalamic nucleus (DMH) which are known to be associated with thermogenesis and circadian rhythm development. However, the physiological roles of GLP-1R expressing neurons in the DMH remain elusive. Methods To examine the physiological role of GLP-1R expressing neurons in the DMH, saporin-conjugated exenatide4 was injected into rat brain DMH to delete GLP-1R-positive neurons. Subsequently, locomotor activity, diurnal feeding pattern, amount of food intake and body weight were measured. Results This deletion of GLP-1R-positive neurons in the DMH induced hyperphagia, the disruption of diurnal feeding pattern, and obesity. The deletion of GLP-1R expressing neurons also reduced glutamic acid decarboxylase 67 and cholecystokinin A receptor mRNA levels in the DMH. Also, it reduced the c-fos expression after refeeding in the suprachiasmatic nucleus (SCN). Thirty percent of DMH neurons projecting to the SCN expressed GLP-1R. Functionally, refeeding after fasting induced c-fos expression in the SCN projecting neurons in the DMH. As for the projection to the DMH, neurons in the nucleus tractus solitarius (NTS) were found to be projecting to the DMH, with 33% of those neurons being GLP-1-positive. Refeeding induced c-fos expression in the DMH projecting neurons in the NTS. Conclusion These findings suggest that GLP-1R expressing neurons in the DMH may mediate feeding termination. In addition, this meal signal may be transmitted to SCN neurons and change the neural activities.

Abstract 3426: Myostatin Deletion Preserves Cardiac Function in Senescent Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Michael R Morissette ◽  
Janelle C Stricker ◽  
Anthony Rosenzweig
Keyword(s):  
Cardiac Function ◽  
Rhode Island ◽  
Cardiac Fibrosis ◽  
Physiological Role ◽  
Heart Association ◽  
Negative Regulator ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Mrna Levels ◽  
Age Related

Myostatin (MSTN) is a well-known negative regulator of skeletal muscle mass, and MSTN inhibition is being considered as therapy for multiple conditions associated with muscle wasting, including sarcopenia of aging. We have previously shown that MSTN inhibits phenylephrine-induced cardiomyocyte hypertrophy, however whether MSTN has a physiological role in regulating cardiac hypertrophy or function at baseline or with aging remains unclear. To determine if MSTN is dynamically regulated with aging, we performed QRT-PCR on hearts from male wild-type (WT) senescent mice (24 months old (mos)) and rats (32 mos). MSTN mRNA levels were increased in old versus young (4 mos) hearts (2.5- and 4-fold respectively, p<0.05). To study the functional significance of MSTN in aging, we maintained germline MSTN-knockout mice (MSTN −/− ) and their WT littermates for 24 –27 months. We found no difference in heart weight of aged male MSTN −/− compared to WT mice (162.5±17.0 (n=4) vs 153.2±4.2 (n=4) mg, p=0.51), which would argue against an inhibitory role for MSTN in age-related increases in cardiac mass. We also performed echocardiography on unanesthetized senescent MSTN −/− and WT mice. MSTN −/− mice had better fractional shortening (58.1±2.0 (n=7) vs 49.4±1.2 (n=8) %, p=0.002) and smaller LV end-diastolic diameter (3.41±0.19 vs 2.71±0.14 mm, p=0.012) compared to WT. The decreased cardiac function seen in aged WT mice was associated with increased cardiac fibrosis on Masson-Trichrome stained sections. Western blot analysis also demonstrated a 3.3-fold increase in phospholamban phosphorylation in MSTN −/− hearts (p<0.05), compared to WT, while no differences in SERCA2a or calsequestrin protein levels were seen. We conclude that MSTN increases in the heart with aging, and that genetic deletion of MSTN results in improved cardiac function without a difference in heart mass in senescent mice. Decreased cardiac fibrosis and increased inhibition (phosphorylation) of phospholamban likely contribute to the better cardiac function seen in senescent MSTN −/− mice. These results suggest that inhibiting MSTN for sarcopenia in the elderly may also benefit cardiac function and could represent a novel therapeutic approach for ameliorating cardiac dysfunction and/or fibrosis. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).

scholarly journals Whole Blood Transcriptome Analysis in Children with Sickle Cell Anemia

2022 ◽  
Vol 12 ◽  
Author(s):  
Beatrice E. Gee ◽  
Andrea Pearson ◽  
Iris Buchanan-Perry ◽  
Roger P. Simon ◽  
David R. Archer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Whole Blood ◽  
Differentially Expressed ◽  
Mrna Levels ◽  
Control Subjects ◽  
Non Coding Rna ◽  
And Control

Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)—based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol. Data were aligned to the hg19 reference genome and analyzed in the Partek Genomics studio package (v7.0). 223 genes were differentially expressed between SCA and controls (± 1.5 fold change FDR p &lt; 0.001) and 441 genes show differential transcript expression (± 1.5 fold FDR p &lt; 0.001). Differentially expressed RNA are enriched for hemoglobin associated genes and ubiquitin-proteasome pathway genes. Further analysis shows higher gamma globin gene expression in SCA (33-fold HBG1 and 49-fold HBG2, both FDR p &lt; 0.05), which did not correlate with hemoglobin F protein levels. eQTL analysis identified SNPs in novel non-coding RNA RYR2 gene as having a potential regulatory role in HBG1 and HBG2 expression levels. Gene expression correlation identified JHDM1D-AS1(KDM7A-DT), a non-coding RNA associated with angiogenesis, enhanced GATA1 and decreased JAK-STAT signaling to correlate with HBG1 and HBG2 mRNA levels. These data suggest novel regulatory mechanisms for fetal hemoglobin regulation, which may offer innovative therapeutic approaches for SCA.

scholarly journals Effect of Various Feed Phosphates on Biochemical Indices of Blood and Mineral Composition of Bones in Finishing Pigs

2010 ◽  
Vol 79 (3) ◽  
pp. 355-361 ◽  
Author(s):  
Zbigniew Dobrzański ◽  
Krystyna Pogoda-Sewerniak ◽  
Szymon Dragan ◽  
Daniel Korniewicz ◽  
Krystyna Hoffmann ◽  
...  
Keyword(s):  
Lactic Dehydrogenase ◽  
Low Density Lipoproteins ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Finishing Pigs ◽  
Biochemical Indicators ◽  
Blood Biochemical ◽  
Mineral Components ◽  
Blood Biochemical Indicators ◽  
Biochemical Indices

The aim of this study was to evaluate the effect of three different chemical feed phosphates on the blood biochemical indicators and the content of main minerals of bones in finishing pigs. Over a period of 85 days of fattening, monocalcium (MCP, Finnish product), dicalcium (DCP, Polish product) and calcium-sodium (CSP, Russian product) phosphates were used in fattener feeding. The feeding was based on standard mixtures of starter, grower and finisher type. Dicalcium phosphate was produced according to the new, pro-ecological technology based on phosphoric acid. The content of Ca, Na, P, solubility of P in citric acid, and the concentration of undesirable substances (As, Cd, F, Hg and Pb) were determined in feed phosphates. At the end of the fattening period, blood was collected from 36 finishing pigs (12 from each group) and the following biochemical indicators were determined in the serum: enzymatic activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), creatine kinase (CK), lactic dehydrogenase (LDH), lactic acid (LA); the concentration of total protein, albumins, glucose, urea, creatinine, content of triglycerides, cholesterol and its high density lipoproteins (HDL) and low density lipoproteins (LDL) fractions, and mineral components concentration (Ca, Cl, Cu, Fe, K, Mg, Na, P, Zn). Basic macroelement content (Ca, Mg, P) was determined in the thigh bones from 30 pigs (10 from each group). Significant differences (p < 0.05) between groups were observed only in some biochemical indicators, i.e. CK, LDH and LA. The highest content of Ca, Mg and P was found in the bones of pigs fed mixtures supplemented with DCP which indicates improved bioavailability of main macroelements from that phosphate.

scholarly journals Expression patterns of endothelial and inducible nitric oxide synthase isoforms in corpora lutea of pseudopregnant rabbits at different luteal stages

2002 ◽  
Vol 173 (2) ◽  
pp. 285-296 ◽  
Author(s):  
C Boiti ◽  
D Zampini ◽  
G Guelfi ◽  
F Paolocci ◽  
M Zerani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Expression Patterns ◽  
Physiological Role ◽  
Total Activity ◽  
Pcr Analysis ◽  
Inos Mrna ◽  
Corpora Lutea ◽  
Mrna Levels ◽  
Isolated Cells ◽  
Protein Levels

Total activity of nitric oxide (NO) synthase (NOS) and expression of both endothelial (eNOS) and inducible (iNOS) isoforms were examined in corpora lutea (CL) of rabbits across pseudopregnancy by quantitative RT-PCR analysis, Western blot and immunohistochemistry. CL were collected at early- (day 4), mid- (day 9) and late- (day 13) luteal phases of pseudopregnancy. The PCR product of rabbit luteal eNOS was cloned and its direct sequence exhibited 90% homology with those of other species. The steady-state mRNA levels encoding eNOS remained fairly constant throughout both early- and mid-luteal stages of pseudopregnancy but dropped almost to half (P</=0.05) by day 13. By contrast, luteal eNOS proteins increased 2-fold (P</=0.05) from the early- to late-luteal phase. Independently of CL age, iNOS mRNA was very poorly expressed while protein levels gradually declined from the early- to late-luteal stage. Intense eNOS-like immunoreactivity was detected in large luteal cells, while iNOS staining was targeted to a few, isolated cells, probably macrophages. Basal NOS activity was greater in day 4 CL than in both day 9 and day 13 CL. These data are the first to characterize in rabbit CL the temporal expression patterns of NOS isoforms across different luteal stages of pseudopregnancy and, collectively, suggest the existence of an expressional control for this constitutive isoform, which might have a physiological role in regulating CL function during development.

Increased NOX1 and DOUX2 Expression in the Colonic Mucosa of Patients with Chronic Functional Constipation

2021 ◽  
Author(s):  
Xiuqin Wei ◽  
Chunbo Kang ◽  
Lei Gao ◽  
Mengqiao Zhang ◽  
Mei Xue ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Healthy Subjects ◽  
Mrna Level ◽  
Functional Constipation ◽  
Inflammatory Cells ◽  
Histological Structure ◽  
Mrna Levels ◽  
Significant Difference ◽  
And Control ◽  
Colonic Biopsies

Abstract Aim To determine whether oxidative stress and inflammation are associated with constipation by examining the expression of the main producers of reactive oxygen species, NADPH oxidases, and pro-inflammatory cytokines in the colon of patients with chronic functional constipation. Methods The colonic biopsies were collected from 32 patients with chronic functional constipation and 30 healthy subjects who underwent colonoscopy. Colonic mucosal histology was observed. IL-1β, IL-6, IL-8 mRNA, and four members of NADPH oxidase (NOX1, NOX2, DOUX2 and NOX4) protein and mRNA were assessed by immunohistochemistry, western blotting and RT-PCR. Results The tissues from both patients and healthy subjects showed normal histological structure without increase of inflammatory cells. NOX1 protein and mRNA levels were significantly increased compared to controls (P<0.05). DOUX2 protein, but not mRNA, was increased by twofold compared to controls (P<0.05). The levels of NOX2 and NOX4 protein and mRNA demonstrated no significant difference between patients and control subjects. The levels of IL-1β and IL-6 mRNA were significantly higher in constipation patients (P<0.05), while IL-8 mRNA level was no different between the two groups. Conclusion NADPH oxidase and pro-inflammatory cytokine might be involved in the pathogeneses of chronic functional constipation.

Abstract 450: Modification of HDL by Reactive Aldehydes Impairs HDL's Athero-protective Functions

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Rebecca L Holme ◽  
Alexandra C Chadwick ◽  
Sarah C Proudfoot ◽  
Yiliang Chen ◽  
Devi Prasadh Ramakrishnan ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Oxidative Modification ◽  
High Density Lipoproteins ◽  
Foam Cell Formation ◽  
Macrophage Migration ◽  
Mrna Levels ◽  
Protective Effects ◽  
Impaired Ability ◽  
Reactive Aldehydes

High density lipoproteins (HDL) are athero-protective particles that promote the removal of excess cholesterol from lipid-loaded macrophages and stimulate their migration in order to protect against foam cell formation, a precursor to atherosclerotic plaque build-up. Recently, studies have shown that oxidative modification of HDL prevents HDL from protecting against atherosclerosis; however, the exact mechanisms by which this occurs are not well defined. We hypothesize that oxidative modification of HDL by reactive aldehydes such as acrolein (a major component of cigarette smoke) and 4-hydroxynonenal (HNE; a product of lipid peroxidation) impairs HDL’s athero-protective effects in macrophages. We tested our hypothesis using three different assays. First, we determined that modified forms of HDL upregulate mRNA levels of pro-atherogenic scavenger receptors such as cluster of differentiation 36 (CD36), a known oxidized LDL receptor. Incubation of macrophages with native HDL did not exert similar effects. Second, we tested the ability of oxidized HDL to prevent foam cell formation. Peritoneal macrophages isolated from WT C57Bl/J mice were cholesterol-loaded and incubated with native HDL, acrolein-modified HDL (acro-HDL), or HNE-modified HDL (HNE-HDL). Oil Red-O staining demonstrated that 24% of macrophages had foam cell formation upon incubation with native HDL, whereas 61% and 49% foam cell formation was observed for acro- and HNE-HDL, respectively. Preliminary data suggests this may be CD36-dependent. Finally, using a Boyden chamber assay, we demonstrated that both acro- and HNE-HDL, but not native HDL, had an impaired ability to promote macrophage migration (43% and 72% of HDL cell migration levels, respectively). We determined that the inability of acro- and/or HNE-HDL to stimulate macrophage migration may be due to an impaired ability of these modified lipoproteins to activate the PI3K pathway, as shown by decreased levels of phosphorylated protein kinase B (Akt). In conclusion, we have identified three independent mechanisms by which modification of HDL with acrolein or HNE impairs HDL’s cardio-protective effects and, instead, generates a particle that promotes pathways that lead to atherosclerosis.

scholarly journals Role of ghrelin in fertilization, early embryo development, and implantation periods

Reproduction ◽  
2014 ◽  
Vol 148 (2) ◽  
pp. 159-167 ◽  
Author(s):  
Eugenia Mercedes Luque ◽  
Pedro Javier Torres ◽  
Nicolás de Loredo ◽  
Laura María Vincenti ◽  
Graciela Stutz ◽  
...  
Keyword(s):  
Embryo Development ◽  
Ovulation Induction ◽  
Physiological Role ◽  
Fertilization Rate ◽  
Early Embryo ◽  
Corpora Lutea ◽  
Negative Effects ◽  
Early Embryo Development ◽  
And Control

In order to clarify the physiological role of ghrelin in gestation, we evaluated the effects of administration of exogenous ghrelin (2 or 4 nmol/animal per day) or its antagonist (6 nmol/animal per day of (d-Lys3)GHRP6) on fertilization, early embryo development, and implantation periods in mice. Three experiments were performed, treating female mice with ghrelin or its antagonist: i) starting from 1 week before copulation to 12 h after copulation, mice were killed at day 18 of gestation; ii) since ovulation induction until 80 h later, when we retrieved the embryos from oviducts/uterus, and iii) starting from days 3 to 7 of gestation (peri-implantation), mice were killed at day 18. In experiments 1 and 3, the antagonist and/or the highest dose of ghrelin significantly increased the percentage of atrophied fetuses and that of females exhibiting this finding or a higher amount of corpora lutea compared with fetuses (nCL/nF) (experiment 3: higher nCL/nF-atrophied fetuses: ghrelin 4, 71.4–71.4% and antagonist, 75.0–62.5% vs ghrelin 2, 46.2−15.4% and control, 10–0.0%;n=7–13 females/group;P<0.01). In experiment 2, the antagonist diminished the fertilization rate, and both, ghrelin and the antagonist, delayed embryo development (blastocysts: ghrelin 2, 62.5%; ghrelin 4, 50.6%; and antagonist, 61.0% vs control 78.4%;n=82–102 embryos/treatment;P<0.0001). In experiment 3, additionally, ghrelin (4 nmol/day) and the antagonist significantly diminished the weight gain of fetuses and dams during pregnancy. Our results indicate that not only hyperghrelinemia but also the inhibition of the endogenous ghrelin effects exerts negative effects on the fertilization, implantation, and embryo/fetal development periods, supporting the hypothesis that ghrelin (in ‘adequate’ concentrations) has a physiological role in early gestational events.

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