Summary of Study ST002545

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.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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.

Study ID	ST002545
Study Title	Lipidomic profile of Toxoplasma gondii-infected mice (Positive mode MS)
Study 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 -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
Submit Date	2023-04-06
Raw Data Available	Yes
Raw Data File Type(s)	d
Analysis Type Detail	LC-MS
Release Date	2023-04-20
Release Version	1

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Treatment:

Treatment ID:	TR002657
Treatment 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.

Treatment ID:

TR002657

Treatment 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.