Summary of Study ST002423

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 IDST002423
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 1)
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 Date2022-12-20
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:SU002512
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
SA242415MtdBlank004_MX491966_posCSH_postMaziPlasma030.d-
SA242416MtdBlank004_MX475710_posCSH_postMaziPlasma030.d-
SA242417MtdBlank005_MX475710_posCSH_postMaziPlasma040.d-
SA242418PoolQC001_MX491966_posCSH_preMaziLiver001.d-
SA242419PoolQC001_MX491966_posCSH_preMaziPlasma001_2.d-
SA242420MtdBlank003_MX491966_posCSH_postMaziPlasma020.d-
SA242421PoolQC001_MX475710_posCSH_preMaziPlasma001.d-
SA242422MtdBlank003_MX475710_posCSH_postMaziPlasma020.d-
SA242423MtdBlank001_MX475710_posCSH_preMaziPlasma001.d-
SA242424MtdBlank005_MX475710_posCSH_postMaziLiver040.d-
SA242425MtdBlank001_MX491966_posCSH_preMaziPlasma001_2.d-
SA242426MtdBlank002_MX475710_posCSH_postMaziPlasma010.d-
SA242427MtdBlank002_MX491966_posCSH_postMaziPlasma010_2.d-
SA242428PoolQC002_MX475710_posCSH_postMaziLiver010.d-
SA242429PoolQC002_MX491966_posCSH_postMaziLiver010.d-
SA242430PoolQC004_MX491966_posCSH_postMaziLiver030.d-
SA242431PoolQC004_MX475710_posCSH_postMaziPlasma030.d-
SA242432PoolQC004_MX491966_posCSH_postMaziPlasma030.d-
SA242433PoolQC005_MX475710_posCSH_postMaziLiver040.d-
SA242434MtdBlank001_MX491966_posCSH_preMaziLiver001.d-
SA242435PoolQC005_MX475710_posCSH_postMaziPlasma040_2.d-
SA242436PoolQC004_MX475710_posCSH_postMaziLiver030.d-
SA242437PoolQC003_MX491966_posCSH_postMaziPlasma020.d-
SA242438PoolQC002_MX491966_posCSH_postMaziPlasma010_2.d-
SA242439MtdBlank004_MX491966_posCSH_postMaziLiver030.d-
SA242440PoolQC003_MX475710_posCSH_postMaziLiver020.d-
SA242441PoolQC003_MX475710_posCSH_postMaziPlasma020.d-
SA242442PoolQC003_MX491966_posCSH_postMaziLiver020.d-
SA242443PoolQC002_MX475710_posCSH_postMaziPlasma010.d-
SA242444PoolQC001_MX475710_posCSH_preMaziLiver001.d-
SA242445Biorec002_MX491966_posCSH_postMaziPlasma010_2.d-
SA242446Biorec003_MX475710_posCSH_postMaziLiver020.d-
SA242447Biorec003_MX475710_posCSH_postMaziPlasma020.d-
SA242448Biorec002_MX491966_posCSH_postMaziLiver010.d-
SA242449Biorec002_MX475710_posCSH_postMaziPlasma010.d-
SA242450MtdBlank004_MX475710_posCSH_postMaziLiver030.d-
SA242451Biorec001_MX491966_posCSH_preMaziPlasma001_2.d-
SA242452Biorec002_MX475710_posCSH_postMaziLiver010.d-
SA242453Biorec003_MX491966_posCSH_postMaziLiver020.d-
SA242454Biorec003_MX491966_posCSH_postMaziPlasma020.d-
SA242455Biorec005_MX475710_posCSH_postMaziLiver040.d-
SA242456Biorec005_MX475710_posCSH_postMaziPlasma040_2.d-
SA242457MtdBlank001_MX475710_posCSH_preMaziLiver001.d-
SA242458Biorec004_MX491966_posCSH_postMaziPlasma030.d-
SA242459Biorec004_MX491966_posCSH_postMaziLiver030.d-
SA242460Biorec004_MX475710_posCSH_postMaziLiver030.d-
SA242461Biorec004_MX475710_posCSH_postMaziPlasma030.d-
SA242462Biorec001_MX475710_posCSH_preMaziPlasma001.d-
SA242463Biorec001_MX491966_posCSH_preMaziLiver001.d-
SA242464Biorec001_MX475710_posCSH_preMaziLiver001.d-
SA242465MtdBlank002_MX491966_posCSH_postMaziLiver010.d-
SA242466MtdBlank003_MX475710_posCSH_postMaziLiver020.d-
SA242467MtdBlank003_MX491966_posCSH_postMaziLiver020.d-
SA242468MtdBlank002_MX475710_posCSH_postMaziLiver010.d-
SA242469MaziLiver029_MX491966_posCSH_926-056.dC3H 5001
SA242470MaziLiver019_MX491966_posCSH_927-057.dC3H 5001
SA242471MaziPlasma011_MX491966_posCSH_906-007.dC3H 5001
SA242472MaziPlasma017_MX491966_posCSH_905-006.dC3H 5001
SA242473MaziPlasma006_MX491966_posCSH_901-002_2.dC3H 5001
SA242474MaziPlasma014_MX491966_posCSH_900-001.dC3H 5001
SA242475MaziPlasma008_MX491966_posCSH_902-003_2.dC3H 5001
SA242476MaziPlasma022_MX491966_posCSH_903-004.dC3H 5001
SA242477MaziPlasma002_MX491966_posCSH_904-005_2.dC3H 5001
SA242478MaziPlasma001_MX491966_posCSH_930-030_2.dC3H 5001
SA242479MaziLiver023_MX491966_posCSH_928-058.dC3H 5001
SA242480MaziLiver014_MX491966_posCSH_900-031.dC3H 5001
SA242481MaziLiver021_MX491966_posCSH_929-059.dC3H 5001
SA242482MaziPlasma029_MX491966_posCSH_926-026.dC3H 5001
SA242483MaziPlasma019_MX491966_posCSH_927-027.dC3H 5001
SA242484MaziPlasma021_MX491966_posCSH_929-029.dC3H 5001
SA242485MaziPlasma023_MX491966_posCSH_928-028.dC3H 5001
SA242486MaziLiver008_MX491966_posCSH_902-033.dC3H 5001
SA242487MaziLiver006_MX491966_posCSH_901-032.dC3H 5001
SA242488MaziLiver022_MX491966_posCSH_903-034.dC3H 5001
SA242489MaziLiver011_MX491966_posCSH_906-037.dC3H 5001
SA242490MaziLiver017_MX491966_posCSH_905-036.dC3H 5001
SA242491MaziLiver001_MX491966_posCSH_930-060.dC3H 5001
SA242492MaziLiver002_MX491966_posCSH_904-035.dC3H 5001
SA242493MaziLiver021_MX475710_posCSH_KO39-087.dKO
SA242494MaziLiver046_MX475710_posCSH_KO37-085.dKO
SA242495MaziLiver004_MX475710_posCSH_KO44-092.dKO
SA242496MaziLiver042_MX475710_posCSH_KO42-090.dKO
SA242497MaziLiver022_MX475710_posCSH_KO40-088.dKO
SA242498MaziLiver044_MX475710_posCSH_KO9-057.dKO
SA242499MaziLiver009_MX475710_posCSH_KO11-059.dKO
SA242500MaziLiver038_MX475710_posCSH_KO5-053.dKO
SA242501MaziLiver035_MX475710_posCSH_KO4-052.dKO
SA242502MaziLiver048_MX475710_posCSH_KO3-051.dKO
SA242503MaziPlasma032_MX475710_posCSH_KO20-020.dKO
SA242504MaziPlasma034_MX475710_posCSH_KO19-019.dKO
SA242505MaziLiver043_MX475710_posCSH_KO18-066.dKO
SA242506MaziLiver039_MX475710_posCSH_KO17-065.dKO
SA242507MaziPlasma002_MX475710_posCSH_KO34-034.dKO
SA242508MaziPlasma043_MX475710_posCSH_KO18-018_2.dKO
SA242509MaziPlasma026_MX475710_posCSH_KO26-026.dKO
SA242510MaziPlasma018_MX475710_posCSH_KO28-028.dKO
SA242511MaziPlasma006_MX475710_posCSH_KO33-033.dKO
SA242512MaziPlasma021_MX475710_posCSH_KO39-039.dKO
SA242513MaziPlasma046_MX475710_posCSH_KO37-037_2.dKO
SA242514MaziPlasma030_MX475710_posCSH_KO36-036.dKO
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Collection:

Collection ID:CO002505
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.
Collection Protocol Filename:Isolation_protocol.docx
Sample Type:Liver; Plasma
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002524
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:SP002518
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 AN003946
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:CH002921
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:60:40 acetonitrile:water + 10 mM ammonium formiate + 0.1% formic acid
Solvent B:90:10 v/v isopropanol:acetonitrile + 10 mM ammonium formiate + 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS003682
Analysis ID:AN003946
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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