scholarly journals PO-153 The metabolic changes in the hippocampus of an atherosclerotic rat model and the regulation of exercise

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Beibei Liu ◽  
Shujie Lou
Keyword(s):  
Arachidonic Acid ◽  
Rat Model ◽  
Methyl Stearate ◽  
Tca Cycle ◽  
Pentose Phosphate ◽  
Metabolic Changes ◽  
Nonanoic Acid ◽  
Control Group ◽  
Acid Oxidation ◽  
Running Exercise

Objective atherosclerosis has been associated with the progression of cognitive impairment and dementia. Several features, such as high oxygen consumption, a large content of peroxidation-sensitive polyunsaturated fatty acids (PUFAs) and a strong dependency on the supply of glucose make the brain vulnerable to even small metabolic changes. The hippocampus is closely related to memory and learning function, and prone to ischemic injury. However, using metabolomics technology to explore metabolites of hippocampus from atherosclerosis animals is rarely reported. We aim to reveal the metabolic changes during atherosclerosis, and clarify the possible role of exercise in regulating hippocampus metabolism. Methods we established a rat model of atherosclerosis(n=18) along with control group (n=10). The model group was assigned into the AS group (n=8) and the TAS group (n=8), which was intervened by running exercise for 4 weeks. A Y maze test was performed to evaluate initial memory. Metabolomics based on GC-MS was applied to detect small molecules metabolites in rat hippocampus. Results we found that the AS and TAS group both showed elevation in HDL, meanwhile decrement in TC and LDL after 4 weeks’ intervention. The behavioral test showed rats from AS group entered less frequently into and spent less time in the novel arm than rats from C group (P<0.01), while other indexes showed no difference. Compared to the C group, metabolites including xylulose 5-phosphate, threonine, succinate and nonanoic acid were markedly elevated, whereas methyl arachidonic acid and methyl stearate decreased in the AS group. Meanwhile, the levels of succinic acid, branched chain amino acids, nonanoic acid and desmosterol decreased, whereas methyl arachidonic acid, methyl stearate, and glyceraldehyde-3-phosphate elevated in the hippocampus of the TAS group in comparison with the AS group. Conclusions A series of metabolic changes implicated in the hippocampus of atherosclerotic rats, including a decrease in anaerobic glycolysis and TCA cycle, an activation of pentose phosphate pathway, and a disturbance in fatty acid oxidation and cholesterol synthesis, which could lead to insufficient ATP in the hippocampus and related to the behavioral changes of atherosclerotic rats, while running exercise may take part in regulating metabolism to normal state in the hippocampus of atherosclerotic rats.

Physiology of sporeforming bacteria associated with insects. I. Glucose catabolism in vegetative cells

1970 ◽  
Vol 16 (4) ◽  
pp. 243-248 ◽  
Author(s):  
L. A. Bulla ◽  
G. St. Julian ◽  
R. A. Rhodes ◽  
C. W. Hesseltine
Keyword(s):  
Carbon Dioxide ◽  
Bacillus Thuringiensis ◽  
Glutamic Acid ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Acid Oxidation ◽  
Glucose Medium ◽  
Vegetative Cells ◽  
Tentative Evidence

The catabolic pathways for use of glucose in proliferating vegetative cells of Bacillus thuringiensis, B. alvei, B. lentimorbus, and B. popilliae were studied by radiorespirometry. These organisms dissimilate glucose predominately via the Embden–Meyerhof–Parnas pathway and to a lesser extent by the pentose phosphate pathway. Extent of participation of concurrent pathways varied with each organism. Tentative evidence suggests that B. popilliae and B. lentimorbus, grown in a yeast extract – glucose medium, lack a fully operational tricarboxylic acid (TCA) cycle. Dilution of this medium slightly enhanced TCA cycle activity in B. popilliae but had no effect with B. lentimorbus. Radiorespirometric data regarding glutamic acid oxidation also were obtained for each bacterium. All organisms studied except B. lentimorbus were capable of oxidizing glutamic acid to carbon dioxide.

scholarly journals Absence of retbindin blocks glycolytic flux, disrupts metabolic homeostasis, and leads to photoreceptor degeneration

2021 ◽  
Vol 118 (6) ◽  
pp. e2018956118
Author(s):  
Tirthankar Sinha ◽  
Jianhai Du ◽  
Mustafa S. Makia ◽  
James B. Hurley ◽  
Muna I. Naash ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Tca Cycle ◽  
Underlying Mechanism ◽  
Neural Retina ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Glycolytic Flux ◽  
Acid Oxidation ◽  
Atp Production ◽  
Almost All

We previously reported a model of progressive retinal degeneration resulting from the knockout of the retina-specific riboflavin binding protein, retbindin (Rtbdn−/−). We also demonstrated a reduction in neural retinal flavins as a result of the elimination of RTBDN. Given the role of flavins in metabolism, herein we investigated the underlying mechanism of this retinal degeneration by performing metabolomic analyses on predegeneration at postnatal day (P) 45 and at the onset of functional degeneration in the P120 retinas. Metabolomics of hydrophilic metabolites revealed that individual glycolytic products accumulated in the P45 Rtbdn−/− neural retinas along with the elevation of pentose phosphate pathway, while TCA cycle intermediates remained unchanged. This was confirmed by using 13C-labeled flux measurements and immunoblotting, revealing that the key regulatory step of phosphoenolpyruvate to pyruvate was inhibited via down-regulation of the tetrameric pyruvate kinase M2 (PKM2). Separate metabolite assessments revealed that almost all intermediates of acylcarnitine fatty acid oxidation, ceramides, sphingomyelins, and multiple toxic metabolites were significantly elevated in the predegeneration Rtbdn−/− neural retina. Our data show that lack of RTBDN, and hence reduction in flavins, forced the neural retina into repurposing glucose for free-radical mitigation over ATP production. However, such sustained metabolic reprogramming resulted in an eventual metabolic collapse leading to neurodegeneration.

scholarly journals Metabolic Mitigation of Staphylococcus aureus Vancomycin Intermediate-Level Susceptibility

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Stewart G. Gardner ◽  
Darrell D. Marshall ◽  
Robert S. Daum ◽  
Robert Powers ◽  
Greg A. Somerville
Keyword(s):  
Staphylococcus Aureus ◽  
Teichoic Acid ◽  
Tca Cycle ◽  
Amino Sugar ◽  
Pentose Phosphate ◽  
Metabolic Changes ◽  
Purine Biosynthesis ◽  
Wall Teichoic Acid ◽  
Content Type ◽  
Adaptive Resistance

ABSTRACTStaphylococcus aureusis a major human pathogen whose infections are increasingly difficult to treat due to increased antibiotic resistance, including resistance to vancomycin. Vancomycin-intermediateS. aureus(VISA) strains develop resistance to vancomycin through adaptive changes that are incompletely understood. Central to this adaptation are metabolic changes that permit growth in the presence of vancomycin. To define the metabolic changes associated with adaptive resistance to vancomycin inS. aureus, the metabolomes of a vancomycin-sensitive and VISA strain pair isolated from the same patient shortly after vancomycin therapy began and following vancomycin treatment failure were analyzed. The metabolic adaptations included increases in acetogenesis, carbon flow through the pentose phosphate pathway, wall teichoic acid and peptidoglycan precursor biosynthesis, purine biosynthesis, and decreased tricarboxylic acid (TCA) cycle activity. The significance of these metabolic pathways for vancomycin-intermediate susceptibility was determined by assessing the synergistic potential of human-use-approved inhibitors of these pathways in combination with vancomycin against VISA strains. Importantly, inhibitors of amino sugar and purine biosynthesis acted synergistically with vancomycin to kill a diverse set of VISA strains, suggesting that combinatorial therapy could augment the efficacy of vancomycin even in patients infected with VISA strains.

scholarly journals Assessment of metabolic changes in the striatum of a rat model of parkinsonism: an in vivo 1 H MRS study

2009 ◽  
Vol 22 (2) ◽  
pp. 207-212 ◽  
Author(s):  
N. Kickler ◽  
E. Lacombe ◽  
C. Chassain ◽  
F. Durif ◽  
A. Krainik ◽  
...  
Keyword(s):  
Rat Model ◽  
Metabolic Changes

scholarly journals Systemic Administration of G-CSF Accelerates Bone Regeneration and Modulates Mobilization of Progenitor Cells in a Rat Model of Distraction Osteogenesis

2021 ◽  
Vol 22 (7) ◽  
pp. 3505
Author(s):  
Flavy Roseren ◽  
Martine Pithioux ◽  
Stéphane Robert ◽  
Laure Balasse ◽  
Benjamin Guillet ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Progenitor Cells ◽  
Distraction Osteogenesis ◽  
Rat Model ◽  
Late Phase ◽  
Control Group ◽  
Bone Lengthening ◽  
Hematopoietic Stem ◽  
Osteoblast Activity ◽  
Positron Emission

Granulocyte colony-stimulating factor (G-CSF) was shown to promote bone regeneration and mobilization of vascular and osteogenic progenitor cells. In this study, we investigated the effects of a systemic low dose of G-CSF on both bone consolidation and mobilization of hematopoietic stem/progenitor cells (HSPCs), endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs) in a rat model of distraction osteogenesis (DO). Neovascularization and mineralization were longitudinally monitored using positron emission tomography and planar scintigraphy. Histological analysis was performed and the number of circulating HSPCs, EPCs and MSCs was studied by flow cytometry. Contrary to control group, in the early phase of consolidation, a bony bridge with lower osteoclast activity and a trend of an increase in osteoblast activity were observed in the distracted callus in the G-CSF group, whereas, at the late phase of consolidation, a significantly lower neovascularization was observed. While no difference was observed in the number of circulating EPCs between control and G-CSF groups, the number of MSCs was significantly lower at the end of the latency phase and that of HSPCs was significantly higher 4 days after the bone lengthening. Our results indicate that G-CSF accelerates bone regeneration and modulates mobilization of progenitor cells during DO.

scholarly journals Metabolic changes following transcatheter bariatric embolotherapy for weight loss in obesity: secondary outcomes from a prospective RCT

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fried ◽  
V.Y Reddy ◽  
P Neuzil ◽  
R Rosen ◽  
P Sramkova ◽  
...  
Keyword(s):  
Weight Loss ◽  
Metabolic Changes ◽  
Exclusion Criterion ◽  
Control Group ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Funding Source ◽  
Post Intervention ◽  
Private Company ◽  
C Peptide

Abstract Background/Introduction Obesity and its comorbid conditions (i.e. type II diabetes mellitus, atrial fibrillation, coronary artery disease, hypertension, etc...) is a growing burden globally, however, the current treatments (i.e. bariatric surgery, intragasrtic balloons and/or pharmaceutical therapy) pose substantial risks or are contraindicated for various populations. Transcatheter bariatric embolotherapy of left gastric artery by reducing “hunger” hormones from the gastric fundus is a procedure for weight loss that has been growing in prominence over the last several years, however, to date no randomized-controlled trial has been conducted until our study. We studied TBE in a double-blind, sham procedure, first in human RCT of patients (pts) with obesity. Purpose The purpose of this study was to assess the safety and efficacy of TBE for weight loss in obese patients as well as to evaluate metabolic changes. Methods After IV propofol, eligible pts (age 21–60; BMI 35–50 kg/m2) were randomized 1:1 to Sham (skin nick & 1 hr wait) or TBE. All pts received Lifestyle Therapy (behavioral and diet education). Study staff following the pts were also blinded to treatment. Blood samples for gastrointestinal hormones were collected in EDTA tubes containing a protease inhibitor cocktail and frozen per local laboratory standards. All collected samples were assessed together in two batches at the end of the study. The hormones analyzed included ghrelin, GIP, GLP-1, Visfatin, resistin, PAI-1 (total), Leptin, and C-Peptide. An Oral Glucose Tolerance Test (OGTT) and a diabetes assay was performed at baseline and at 6- and 12-months post-intervention. Note, while diabetes was an exclusion criterion for this study, pre-diabetes was not. Results 44 pts were enrolled, of which 40 pts were randomized equally to the groups, with no major complications in either group. TBE demonstrated superior weight loss over the control group at 6- and 12-months post-intervention in both intention-to-treat and per-protocol analyses. At 6 and 12 months, the TBE group demonstrated a clinically meaningful decrease in glucose 1-hour post-fasting by OGTT. GIP levels in the TBE group increased at a mean of 21%, indicative of an improvement in pre-diabetic milieu. Circulating plasma visfatin levels decreased 20% at 6 months and 26% at 12 months in the TBE group indicating a decrease in body fat. C-Peptide levels were noticeably increased in the TBE group at 6 months possibly indicating improvements in insulin sensitivity and beta-cell function. Conclusion(s) TBE is safe and results in clinically significant weight loss and demonstrated a positive effect on glucose homeostasis in pre-diabetic patients. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Endobar Solutions, LLC

Construction and Evaluation of a Rat Model of Postpartum Fatigue

2021 ◽  
pp. 1-9
Author(s):  
Ting Bai ◽  
Fan Wu ◽  
Shuhan Yan ◽  
Feng Zhang ◽  
Xujuan Xu
Keyword(s):  
Lactic Acid ◽  
Rat Model ◽  
Water Maze ◽  
Acid Level ◽  
Model Building ◽  
Small Sample ◽  
Control Group ◽  
Lactic Acid Level ◽  
Physical Fatigue ◽  
Postpartum Fatigue

<b><i>Objectives:</i></b> The aim of the study was to construct and evaluate a rat model of postpartum fatigue. <b><i>Design:</i></b> This is an article about animal model building. <b><i>Methods:</i></b> Sprague-Dawley rats on the 1st day after delivery were randomized into control group and fatigue group. The deep sleep of rats was interfered with by forcing them to stand in water, to make the rats experience mental and physical fatigue. To maintain galactosis and lactation, rats and pups were caged for 90 min after every 3 h of separation. The control group was separated routinely without any stimulus. The model was evaluated from mental and physical fatigue on the 8th day and 15th day. The mental fatigue was evaluated by a water maze test and the rat’s 5-hydroxytryptamine (5-HT) level in hippocampus, while the physical fatigue was evaluated using lactic acid level in serum and duration of weight-loaded forced swimming. <b><i>Results:</i></b> Among the 7-day and 14-day modeling groups, compared with the control group, the success rate of water maze landing was significantly decreased, the time for water maze landing was significantly prolonged and 5-HT level in hippocampus significantly decreased in the fatigue group. With respect to physical fatigue, among the 7-day and 14-day modeling groups, the lactic acid level in serum in the fatigue group was significantly increased, and the duration of exhaustive swimming of rats was significantly shortened. <b><i>Limitations:</i></b> A small sample size was the main limitation of this study. <b><i>Conclusions:</i></b> We have successfully constructed a rat model of postpartum fatigue by forcing postpartum rats to stand in water, which was similar to a level of stress that contributes to the development of postpartum fatigue. Our model opens the door for future studies evaluating the effectiveness of pharmacological and behavioral therapies.

Abstract 100: Integrated Cardiac Metabolism In End-Stage Human Heart Failure

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Emily Flam ◽  
Cholsoon Jang ◽  
Ken Bedi ◽  
Danielle Murashige ◽  
Yifan Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Human Heart ◽  
Glycogen Synthesis ◽  
Cardiac Metabolism ◽  
Pentose Phosphate ◽  
Metabolic Changes ◽  
Phospholipid Content ◽  
Human Heart Failure ◽  
Nucleotide Synthesis ◽  
End Stage

Heart failure affects millions of people worldwide with mortality near 50% within five years. This disease is characterized by widespread cardiac and systemic metabolic changes, but a comprehensive evaluation of metabolism in failing human hearts is lacking. Here, we provide a comprehensive depiction of cardiac and systemic metabolic changes in 89 explanted failing and non-failing human hearts through integration of plasma and cardiac tissue metabolomics, genome-wide RNAseq, and proteomic data. The data confirm a profound bioenergetic defect in end-stage human heart failure and demonstrate extensive changes in metabolic homeostasis. The data indicate a substantial defect in fatty acid (FA) use in failing hearts, in particular unsaturated FAs. Reduction of FAs and acyl-carnitines in failing tissue in contrast to concomitant elevations in plasma suggest a defect in import of FAs into the cell, rather than a defect in FA oxidation. Intermediates of glycolysis, the pentose phosphate pathway, and glycogen synthesis are all similarly reduced, as is expression of GLUT1, indicating diminished glucose uptake. However, there was no significant change in tissue pyruvate content, suggesting an increase in lactate utilization. The data suggest increased flux of pyruvate into mitochondria, likely promoting pyruvate oxidation but not pyruvate carboxylation. Blunted anabolic pyruvate flux, in turn, likely leads to insufficient TCA cycle intermediates. Ketone levels were increased in both failing tissue and plasma, as previously reported. The phospholipid content of failing human hearts is greatly increased in both failing tissue and plasma. Nucleotide synthesis pathways also appear to be reprogrammed, with a notable decrease in adenosine metabolism, specifically. Together, these data indicate widespread change in the local cardiac and greater systemic metabolic landscape in severe human heart failure.

Abstract 320: End-Tidal Carbon Dioxide Can Guide Fluid Resuscitation in a Cecal Ligation and Puncture Induced Rat Model of Sepsis

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Liangliang Wu ◽  
Xiangshao Fang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Survival Time ◽  
Fluid Resuscitation ◽  
Rat Model ◽  
Cecal Ligation ◽  
Control Group ◽  
Cecal Ligation And Puncture ◽  
End Tidal Carbon Dioxide ◽  
Lactate Levels ◽  
End Tidal

Introduction: Abnormal levels of end-tidal carbon dioxide (ETCO 2 ) may reflect a derangement in perfusion, metabolism, or gas exchange. It is unclear if ETCO 2 can be used for fluid resuscitation (FR) compared with traditional mean arterial pressure (MAP) as an outcome predictor in sepsis. Hypothesis: Use of ETCO2 is better than MAP in guiding fluid resuscitation to improve lactate levels and microcirculatory blood flow in sepsis. Methods: Thirty-five male Sprague-Dawley rats weighing 350-400g were randomized to: 1) SHAM, n=5; 2) cecal ligation and puncture (CLP) Control group (with CLP, without FR, n=10); 3) ETCO 2 group (with CLP, FR began when ETCO 2 ≤25 mmHg, n=10) and 4) MAP group (with CLP, FR began when MAP≤100 mmHg, n=10). Lactate level, cardiac output (CO), perfused small vessel density (PSVD) and sublingual microvascular flow index (MFI) was assessed at baseline, 2 h, 4 h, 8 h, 10 h and 12 h post-CLP. Survival duration was recorded. Results: After FR,CO in the ETCO 2 group increased compared with the MAP group 12h after CLP while lactate levels decreased compared with the Control and MAP groups (p<0.05) (Figure-1). Both sublingual PSVD and MFI decreased after CLP in the control group and MAP group but significantly improved in the ETCO 2 group 8h post-CLP. The average survival time in the ETCO 2 group was significantly greater than MAP group (Figure-2). Conclusions: ETCO 2 guided FR was associated with improved CO, lactate, microcirculatory flow, and survival time compared to MAP guided FR in a CLP-induced rat model of sepsis.

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