Summary of Study ST002424

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 PR001560. The data can be accessed directly via it's Project DOI: 10.21228/M8242N 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.

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Study IDST002424
Study TitleIntegrated gut microbiome and lipidomic analyses in animal models of Wilson disease reveal a role of intestine ATP7B in copper-related metabolic dysregulation (Part 2)
Study SummaryAlthough the main pathogenic mechanism of Wilson disease (WD) is related to copper accumulation in the liver and brain, there is limited knowledge about the role of ATP7B copper transporter in extra-hepatic organs, including the intestine, and how it could affect metabolic manifestations of the disease. The aims of the present study were to profile and correlate the gut microbiota and lipidome in mouse models of WD, and to study the metabolic effects of intestine-specific ATP7B deficiency in a newly generated mouse model. Animal models of WD presented reduced gut microbiota diversity compared to mice with normal copper metabolism. Comparative prediction analysis of the functional metagenome showed the involvement of several pathways including amino acid, carbohydrate, and lipid metabolisms. Lipidomic profiles showed dysregulated tri- and diglyceride, phospholipid, and sphingolipid metabolism. When challenged with a high-fat diet, Atp7bΔIEC mice confirmed profound deregulation of fatty acid desaturation and sphingolipid metabolism pathways as well as altered APOB48 distribution in intestinal epithelial cells. Gut microbiome and lipidomic analyses reveal integrated metabolic changes underlying the systemic manifestations of WD. Intestine-specific ATP7B deficit affects both intestine and systemic response to high-fat challenge. WD is as systemic disease and organ-specific ATP7B variants can explain the varied phenotypic presentations.
Institute
University of California, Davis
DepartmentInternal Medicine
LaboratoryMedici's Lab
Last NameSarode
First NameGaurav Vilas
Address451 E. Health Sciences Dr. Genome and Biomedical Sciences Facility Room 6404A Davis, CA 95616
Emailgsarode@ucdavis.edu
Phone5307526715
Submit Date2022-12-22
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2023-06-20
Release Version1
Gaurav Vilas Sarode Gaurav Vilas Sarode
https://dx.doi.org/10.21228/M8242N
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001560
Project DOI:doi: 10.21228/M8242N
Project Title:Integrated gut microbiome and lipidomic analyses in animal models of Wilson disease reveal a role of intestine ATP7B in copper-related metabolic dysregulation
Project Summary:Although the main pathogenic mechanism of Wilson disease (WD) is related to copper accumulation in the liver and brain, there is limited knowledge about the role of ATP7B copper transporter in extra-hepatic organs, including the intestine, and how it could affect metabolic manifestations of the disease. The aims of the present study were to profile and correlate the gut microbiota and lipidome in mouse models of WD, and to study the metabolic effects of intestine-specific ATP7B deficiency in a newly generated mouse model. Animal models of WD presented reduced gut microbiota diversity compared to mice with normal copper metabolism. Comparative prediction analysis of the functional metagenome showed the involvement of several pathways including amino acid, carbohydrate, and lipid metabolisms. Lipidomic profiles showed dysregulated tri- and diglyceride, phospholipid, and sphingolipid metabolism. When challenged with a high-fat diet, Atp7bΔIEC mice confirmed profound deregulation of fatty acid desaturation and sphingolipid metabolism pathways as well as altered APOB48 distribution in intestinal epithelial cells. Gut microbiome and lipidomic analyses reveal integrated metabolic changes underlying the systemic manifestations of WD. Intestine-specific ATP7B deficit affects both intestine and systemic response to high-fat challenge. WD is as systemic disease and organ-specific ATP7B variants can explain the varied phenotypic presentations.
Institute:University of California, Davis
Department:Department of Internal Medicine, Division of Hepatology/Gastroenterology
Last Name:Sarode
First Name:Gaurav Vilas
Address:451 E. Health Sciences Dr. Genome and Biomedical Sciences Facility Room 6404A Davis, CA 95616
Email:gsarode@ucdavis.edu
Phone:5307526715
Funding Source:National Institutes of Health grants R01DK104770 (V.M.)

Subject:

Subject ID:SU002513
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 Treatment
SA242625BiorecPlasma005_MX562952_posCSH_postShibataPlasma033.d-
SA242626MtdBlank001_MX562952_posCSH_preShibataLiver001.d-
SA242627BiorecPlasma002_MX562952_posCSH_postShibataPlasma010.d-
SA242628MtdBlank004_MX562952_posCSH_postShibataLiver030.d-
SA242629MtdBlank004_MX562952_posCSH_postShibataPlasma030.d-
SA242630MtdBlank005_MX562952_posCSH_postShibataPlasma033.d-
SA242631MtdBlank005_MX562952_posCSH_postShibataLiver033.d-
SA242632MtdBlank001_MX562952_posCSH_preShibataPlasma001.d-
SA242633BiorecLiver003_MX562952_posCSH_postShibataLiver020.d-
SA242634MtdBlank003_MX562952_posCSH_postShibataPlasma020.d-
SA242635BiorecLiver005_MX562952_posCSH_postShibataLiver033.d-
SA242636BiorecLiver002_MX562952_posCSH_postShibataLiver010.d-
SA242637MtdBlank003_MX562952_posCSH_postShibataLiver020.d-
SA242638MtdBlank002_MX562952_posCSH_postShibataLiver010.d-
SA242639MtdBlank002_MX562952_posCSH_postShibataPlasma010.d-
SA242640BiorecLiver004_MX562952_posCSH_postShibataLiver030.d-
SA242641PoolQC001_MX562952_posCSH_preShibataLiver001.d-
SA242642PoolQC001_MX562952_posCSH_preShibataPlasma001.d-
SA242643PoolQC005_MX562952_posCSH_postShibataPlasma033.d-
SA242644BiorecPlasma004_MX562952_posCSH_postShibataPlasma030.d-
SA242645BiorecPlasma003_MX562952_posCSH_postShibataPlasma020.d-
SA242646BiorecLiver001_MX562952_posCSH_preShibataLiver001.d-
SA242647PoolQC005_MX562952_posCSH_postShibataLiver033.d-
SA242648BiorecPlasma001_MX562952_posCSH_preShibataPlasma001.d-
SA242649PoolQC004_MX562952_posCSH_postShibataPlasma030.d-
SA242650PoolQC002_MX562952_posCSH_postShibataLiver010.d-
SA242651PoolQC002_MX562952_posCSH_postShibataPlasma010.d-
SA242652PoolQC003_MX562952_posCSH_postShibataLiver020.d-
SA242653PoolQC004_MX562952_posCSH_postShibataLiver030.d-
SA242654PoolQC003_MX562952_posCSH_postShibataPlasma020.d-
SA242675ShibataPlasma024_MX562952_posCSH_iKO-IEC9-1-034.diKO 5001
SA242676ShibataLiver028_MX562952_posCSH_iKO-IEC9-6-006.diKO 5001
SA242677ShibataLiver012_MX562952_posCSH_iKO-IEC9-7-007.diKO 5001
SA242678ShibataLiver006_MX562952_posCSH_iKO-IEC9-5-005.diKO 5001
SA242679ShibataLiver005_MX562952_posCSH_iKO-IEC9-4-004.diKO 5001
SA242680ShibataLiver010_MX562952_posCSH_iKO-IEC9-2-002.diKO 5001
SA242681ShibataLiver026_MX562952_posCSH_iKO-IEC9-3-003.diKO 5001
SA242682ShibataLiver016_MX562952_posCSH_iKO-IEC9-8-008.diKO 5001
SA242683ShibataPlasma010_MX562952_posCSH_iKO-IEC9-2-035.diKO 5001
SA242684ShibataPlasma012_MX562952_posCSH_iKO-IEC9-7-040.diKO 5001
SA242685ShibataPlasma016_MX562952_posCSH_iKO-IEC9-8-041.diKO 5001
SA242686ShibataPlasma028_MX562952_posCSH_iKO-IEC9-6-039.diKO 5001
SA242687ShibataPlasma006_MX562952_posCSH_iKO-IEC9-5-038_2.diKO 5001
SA242688ShibataPlasma026_MX562952_posCSH_iKO-IEC9-3-036.diKO 5001
SA242689ShibataPlasma005_MX562952_posCSH_iKO-IEC9-4-037.diKO 5001
SA242690ShibataLiver024_MX562952_posCSH_iKO-IEC9-1-001.diKO 5001
SA242691ShibataPlasma002_MX562952_posCSH_iKO-IEChf9-1-049.diKO 60% kcal fat
SA242692ShibataLiver004_MX562952_posCSH_iKO-IEChf9-5-020.diKO 60% kcal fat
SA242693ShibataLiver021_MX562952_posCSH_iKO-IEChf9-6-021.diKO 60% kcal fat
SA242694ShibataLiver031_MX562952_posCSH_iKO-IEChf9-7-022.diKO 60% kcal fat
SA242695ShibataLiver023_MX562952_posCSH_iKO-IEChf9-4-019.diKO 60% kcal fat
SA242696ShibataLiver001_MX562952_posCSH_iKO-IEChf9-3-018.diKO 60% kcal fat
SA242697ShibataLiver002_MX562952_posCSH_iKO-IEChf9-1-016.diKO 60% kcal fat
SA242698ShibataLiver020_MX562952_posCSH_iKO-IEChf9-2-017.diKO 60% kcal fat
SA242699ShibataPlasma017_MX562952_posCSH_iKO-IEChf9-8-056.diKO 60% kcal fat
SA242700ShibataLiver017_MX562952_posCSH_iKO-IEChf9-8-023.diKO 60% kcal fat
SA242701ShibataPlasma001_MX562952_posCSH_iKO-IEChf9-3-051.diKO 60% kcal fat
SA242702ShibataPlasma004_MX562952_posCSH_iKO-IEChf9-5-053.diKO 60% kcal fat
SA242703ShibataPlasma021_MX562952_posCSH_iKO-IEChf9-6-054.diKO 60% kcal fat
SA242704ShibataPlasma031_MX562952_posCSH_iKO-IEChf9-7-055.diKO 60% kcal fat
SA242705ShibataPlasma020_MX562952_posCSH_iKO-IEChf9-2-050.diKO 60% kcal fat
SA242706ShibataPlasma023_MX562952_posCSH_iKO-IEChf9-4-052.diKO 60% kcal fat
SA242707ShibataLiver011_MX562952_posCSH_iWT-IEC9-5-013.diWT 5001
SA242708ShibataLiver029_MX562952_posCSH_iWT-IEC9-6-014.diWT 5001
SA242709ShibataLiver033_MX562952_posCSH_iWT-IEC9-4-012.diWT 5001
SA242710ShibataLiver013_MX562952_posCSH_iWT-IEC9-3-011.diWT 5001
SA242711ShibataLiver018_MX562952_posCSH_iWT-IEC9-1-009.diWT 5001
SA242712ShibataLiver022_MX562952_posCSH_iWT-IEC9-2-010.diWT 5001
SA242713ShibataLiver032_MX562952_posCSH_iWT-IEC9-7-015.diWT 5001
SA242714ShibataPlasma033_MX562952_posCSH_iWT-IEC9-4-045.diWT 5001
SA242715ShibataPlasma018_MX562952_posCSH_iWT-IEC9-1-042.diWT 5001
SA242716ShibataPlasma029_MX562952_posCSH_iWT-IEC9-6-047.diWT 5001
SA242717ShibataPlasma011_MX562952_posCSH_iWT-IEC9-5-046.diWT 5001
SA242718ShibataPlasma022_MX562952_posCSH_iWT-IEC9-2-043.diWT 5001
SA242719ShibataPlasma013_MX562952_posCSH_iWT-IEC9-3-044.diWT 5001
SA242720ShibataPlasma032_MX562952_posCSH_iWT-IEC9-7-048.diWT 5001
SA242655ShibataPlasma008_MX562952_posCSH_KO-IEC9-3-066.dKO 5001
SA242656ShibataPlasma003_MX562952_posCSH_KO-IEC9-2-065.dKO 5001
SA242657ShibataLiver009_MX562952_posCSH_KO-IEC9-1-031.dKO 5001
SA242658ShibataLiver003_MX562952_posCSH_KO-IEC9-2-032.dKO 5001
SA242659ShibataLiver008_MX562952_posCSH_KO-IEC9-3-033.dKO 5001
SA242660ShibataPlasma009_MX562952_posCSH_KO-IEC9-1-064.dKO 5001
SA242661ShibataLiver025_MX562952_posCSH_KO-IEChf9-3-026.dKO 60% kcal fat
SA242662ShibataLiver030_MX562952_posCSH_KO-IEChf9-2-025.dKO 60% kcal fat
SA242663ShibataPlasma007_MX562952_posCSH_KO-IEChf9-1-057.dKO 60% kcal fat
SA242664ShibataLiver007_MX562952_posCSH_KO-IEChf9-1-024.dKO 60% kcal fat
SA242665ShibataPlasma015_MX562952_posCSH_KO-IEChf9-4-060.dKO 60% kcal fat
SA242666ShibataPlasma030_MX562952_posCSH_KO-IEChf9-2-058.dKO 60% kcal fat
SA242667ShibataPlasma025_MX562952_posCSH_KO-IEChf9-3-059.dKO 60% kcal fat
SA242668ShibataLiver015_MX562952_posCSH_KO-IEChf9-4-027.dKO 60% kcal fat
SA242669ShibataPlasma019_MX562952_posCSH_WT-IEChf9-3-063.dWT 60% kcal fat
SA242670ShibataPlasma027_MX562952_posCSH_WT-IEChf9-1-061.dWT 60% kcal fat
SA242671ShibataPlasma014_MX562952_posCSH_WT-IEChf9-2-062.dWT 60% kcal fat
SA242672ShibataLiver027_MX562952_posCSH_WT-IEChf9-1-028.dWT 60% kcal fat
SA242673ShibataLiver019_MX562952_posCSH_WT-IEChf9-3-030.dWT 60% kcal fat
SA242674ShibataLiver014_MX562952_posCSH_WT-IEChf9-2-029.dWT 60% kcal fat
Showing results 1 to 96 of 96

Collection:

Collection ID:CO002506
Collection Summary:The liver was isolated. Blood samples were centrifuged at 8,000 rpm for 10 minutes and the plasma was aliquoted. All samples were stored at -80°C until further analysis.
Sample Type:Liver
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002525
Treatment Summary:From 8 weeks of age, tx-j, KO, and Atp7bΔIEC mice, and their respective controls, were either continued on LabDiet 5001 diet or switched to a 60% kcal fat diet (D12492, Research Diets, Inc., New Brunswick, NJ). After 8 days, mice had body weights measured then were anesthetized with isoflurane, bled retro-orbitally into K3EDTA collection tubes, euthanized by cervical dislocation, and the liver weighed and flash-frozen in liquid nitrogen

Sample Preparation:

Sampleprep ID:SP002519
Sampleprep Summary:Combine 120 mL of chilled MeOH/QC mix with 400 mL of chilled MTBE/Cholesterol Ester 22:1 in a clean 500 mL stock bottle. Mix thoroughly by swirling or stirring the plate and store at -20°C until use.

Combined analysis:

Analysis ID AN003947
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 6530
Column Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6530 QTOF
Ion Mode POSITIVE
Units Peak Height

Chromatography:

Chromatography ID:CH002922
Instrument Name:Agilent 6530
Column Name:Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um)
Column Temperature:65°C
Flow Gradient:0 min 15% (B), 0–2 min 30% (B), 2–2.5 min 48% (B), 2.5–11 min 82% (B), 11–11.5 min 99% (B), 11.5–12 min 99% (B), 12–12.1 min 15% (B), 12.1–15 min 15% (B)
Flow Rate:0.6 mL/min
Solvent A:60% acetonitrile/40% water; 0.1% formic acid; 10 mM ammonium formate
Solvent B:90% isopropanol/10% acetonitrile; 0.1% formic acid; 10 mM ammonium formate
Chromatography Type:Reversed phase

MS:

MS ID:MS003683
Analysis ID:AN003947
Instrument Name:Agilent 6530 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:Data are analyzed in a four-stage process.First, raw data are processed in an untargeted (qualitative) manner by Agilent’s software MassHunterQual to find peaks in up to 300 chromatograms. Peak features are then imported intoMassProfilerProfessional for peak alignments to seek which peaks are present in multiplechromatograms, using exclusion criteria by the minimumpercentage of chromatograms in which these peaks arepositively detected. We usually use 30% as minimumcriterion. In a tedious manual process, these peaks arethen collated and constrained into a MassHunterquantification method on the accurate mass precursorion level, using the MS/MS information and theLipidBlast library to identify lipids with manualconfirmation of adduct ions and spectral scoringaccuracy. MassHunter enables back-filling ofquantifications for peaks that were missed in theprimary peak finding process, hence yielding data setswithout missing values. The procedure is given in thepanel to the left as workflow diagram
Ion Mode:POSITIVE
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