Summary of Study ST002544

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001639. The data can be accessed directly via it's Project DOI: 10.21228/M8V41D This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002544
Study TitleMetabolomic study on the chronic Toxoplasma gondii infection in mice.
Study SummaryCachexia is a life-threatening disease characterized by chronic, inflammatory muscle wasting and systemic metabolic impairment. Despite its high prevalence, there are no efficacious therapies for cachexia. Mice chronically infected with the protozoan parasite Toxoplasma gondii represent a novel animal model recapitulating the chronic kinetics of cachexia. To understand how perturbations to metabolic tissue homeostasis influence circulating metabolite availability we used mass spectrometry analysis. Despite the significant reduction in circulating triacylglycerides, nonesterified fatty acids, and glycerol, sphingolipid long-chain bases and a subset of phosphatidylcholines (PCs) were significantly increased in the sera of mice with T. gondii infection-induced cachexia. In addition, the TCA cycle intermediates -ketoglutarate, 2- hydroxyglutarate, succinate, fumarate, and malate were highly depleted in cachectic mouse sera. Sphingolipids and their de novo synthesis precursors PCs are the major components of the mitochondrial membrane and regulate mitochondrial function consistent with a causal relationship in the energy imbalance driving T. gondii-induced chronic cachexia.
Institute
University of Virginia
Last NameFeng
First NameTzu-Yu
Address345 Crispell DR.
Emailttf4ye@virginia.edu
Phone70221744554
Submit Date2023-04-05
Raw Data AvailableYes
Raw Data File Type(s)cdf
Analysis Type DetailGC-MS
Release Date2023-04-20
Release Version1
Tzu-Yu Feng Tzu-Yu Feng
https://dx.doi.org/10.21228/M8V41D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001639
Project DOI:doi: 10.21228/M8V41D
Project Title:Metabolomic study on the chronic Toxoplasma gondii infection in mice.
Project Type:Untargeted MS
Project Summary:Cachexia is a life-threatening disease characterized by chronic, inflammatory muscle wasting and systemic metabolic impairment. Despite its high prevalence, there are no efficacious therapies for cachexia. Mice chronically infected with the protozoan parasite Toxoplasma gondii represent a novel animal model recapitulating the chronic kinetics of cachexia. To understand how perturbations to metabolic tissue homeostasis influence circulating metabolite availability we used mass spectrometry analysis. Despite the significant reduction in circulating triacylglycerides, nonesterified fatty acids, and glycerol, sphingolipid long-chain bases and a subset of phosphatidylcholines (PCs) were significantly increased in the sera of mice with T. gondii infection-induced cachexia. In addition, the TCA cycle intermediates alpha-ketoglutarate, 2- hydroxyglutarate, succinate, fumarate, and malate were highly depleted in cachectic mouse sera. Sphingolipids and their de novo synthesis precursors PCs are the major components of the mitochondrial membrane and regulate mitochondrial function consistent with a causal relationship in the energy imbalance driving T. gondii-induced chronic cachexia.
Institute:University of Virginia
Last Name:Feng
First Name:Tzu-Yu
Address:345 Crispell Dr.
Email:ttf4ye@virginia.edu
Phone:702-217-4454

Subject:

Subject ID:SU002644
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Factor
SA255626Toxoplasma infected-7Infection
SA255627Toxoplasma infected-2Infection
SA255628Toxoplasma infected-1Infection
SA255629Toxoplasma infected-5Infection
SA255630Toxoplasma infected-4Infection
SA255631Toxoplasma infected-8Infection
SA255632Toxoplasma infected-6Infection
SA255633Toxoplasma infected-3Infection
SA255634Uninfected-8Uninfection
SA255635Uninfected-6Uninfection
SA255636Uninfected-1Uninfection
SA255637Uninfected-7Uninfection
SA255638Uninfected-3Uninfection
SA255639Uninfected-4Uninfection
SA255640Uninfected-5Uninfection
SA255641Uninfected-2Uninfection
Showing results 1 to 16 of 16

Collection:

Collection ID:CO002637
Collection Summary:To generate cysts for infection, 8-10 week female CBA/J mice were infected with 10 Me49 bradyzoite cysts by intraperitoneal injection. 4–8 weeks following infection, mice were euthanized by CO2 inhalation and cysts were harvest from brains homogenate passed through a 70 μm filter. Homegenate was washed 3 times in PBS, stained with dolichos biflorus agglutinin conjugated to FITC (Vector labs) at a 1:500 dilution. The number of cysts were determined by counting FITCpositive cysts at 20x magnification using an EVOS FL imaging system (Thermo Fisher). For experimental infections 10–14-week-old male C57BL/6 mice were infected with 10 Me49 bradyzoite cysts by intraperitoneal infection resuspended in 200 Μl PBS per mouse using a 5G 5/8” tuberculin syringe. Prior to infection, mice were cross-housed on dirty, wood chip bedding for two weeks to normalize commensal microbiota and limit the effect of eating corn husk bedding on dietary metabolites. At experimental endpoints, mice were fasted for 4 hours and isoflurane anaesthetized to isolate sera via retro-orbital bleed and/or euthanized by CO2 asphyxiation to harvest tissues for weighing and histological analysis.
Sample Type:Blood (serum)
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002656
Treatment Summary:10–14-week-old male C57BL/6 mice were infected with 10 Me49 bradyzoite cysts by intraperitoneal infection resuspended in 200 Μl PBS per mouse using a 5G 5/8” tuberculin syringe. Uninfected B6 mice were included as controls.

Sample Preparation:

Sampleprep ID:SP002650
Sampleprep Summary:At 7 weeks post-infection, isoflurane-anesthetized mice were retro-orbitally bled and sera was flash frozen and sent to the National Institute of Health (NIH) West Coast Metabolomics Center (UC Davis) for untargeted mass spectrometry analysisusing the primary metabolism assay (ALEXCIS GCTOF-MS) or the complex lipids (CSH-QTOF MS) assay. Detected meatbolites were identified based on retention time and mass spectra from MassBank of North America, curated by the NIH West Coast Metabolomics Center , and reported as raw peak heights. The raw peak heights from each analytical platform were normalized to the average peak heights of the identified metabolites in uninfected group. The resulting data were analyzed for fold-change and multiple unpaired t-test and visualized using volcano plots to identify the differential expression of metabolites in response to T. gondii-induced cachexia

Combined analysis:

Analysis ID AN004191
Analysis type MS
Chromatography type GC
Chromatography system Leco Pegasus III GC TOF
Column Restek Rtx-5Sil MS (30m x 0.25mm, 0.25um)
MS Type EI
MS instrument type GC-TOF
MS instrument name Leco Pegasus III GC TOF
Ion Mode POSITIVE
Units intensity

Chromatography:

Chromatography ID:CH003105
Instrument Name:Leco Pegasus III GC TOF
Column Name:Restek Rtx-5Sil MS (30m x 0.25mm, 0.25um)
Column Temperature:50
Flow Gradient:none
Flow Rate:1 ml/min
Solvent A:none
Solvent B:none
Chromatography Type:GC

MS:

MS ID:MS003938
Analysis ID:AN004191
Instrument Name:Leco Pegasus III GC TOF
Instrument Type:GC-TOF
MS Type:EI
MS Comments:-
Ion Mode:POSITIVE
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