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.
| Study ID | ST002424 |
| Study Title | Integrated 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 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 | Internal Medicine |
| Laboratory | Medici's Lab |
| Last Name | Sarode |
| First Name | Gaurav Vilas |
| Address | 451 E. Health Sciences Dr. Genome and Biomedical Sciences Facility Room 6404A Davis, CA 95616 |
| gsarode@ucdavis.edu | |
| Phone | 5307526715 |
| Submit Date | 2022-12-22 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-06-20 |
| Release Version | 1 |
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 |
|---|---|---|
| SA242625 | BiorecPlasma005_MX562952_posCSH_postShibataPlasma033.d | - |
| SA242626 | MtdBlank001_MX562952_posCSH_preShibataLiver001.d | - |
| SA242627 | BiorecPlasma002_MX562952_posCSH_postShibataPlasma010.d | - |
| SA242628 | MtdBlank004_MX562952_posCSH_postShibataLiver030.d | - |
| SA242629 | MtdBlank004_MX562952_posCSH_postShibataPlasma030.d | - |
| SA242630 | MtdBlank005_MX562952_posCSH_postShibataPlasma033.d | - |
| SA242631 | MtdBlank005_MX562952_posCSH_postShibataLiver033.d | - |
| SA242632 | MtdBlank001_MX562952_posCSH_preShibataPlasma001.d | - |
| SA242633 | BiorecLiver003_MX562952_posCSH_postShibataLiver020.d | - |
| SA242634 | MtdBlank003_MX562952_posCSH_postShibataPlasma020.d | - |
| SA242635 | BiorecLiver005_MX562952_posCSH_postShibataLiver033.d | - |
| SA242636 | BiorecLiver002_MX562952_posCSH_postShibataLiver010.d | - |
| SA242637 | MtdBlank003_MX562952_posCSH_postShibataLiver020.d | - |
| SA242638 | MtdBlank002_MX562952_posCSH_postShibataLiver010.d | - |
| SA242639 | MtdBlank002_MX562952_posCSH_postShibataPlasma010.d | - |
| SA242640 | BiorecLiver004_MX562952_posCSH_postShibataLiver030.d | - |
| SA242641 | PoolQC001_MX562952_posCSH_preShibataLiver001.d | - |
| SA242642 | PoolQC001_MX562952_posCSH_preShibataPlasma001.d | - |
| SA242643 | PoolQC005_MX562952_posCSH_postShibataPlasma033.d | - |
| SA242644 | BiorecPlasma004_MX562952_posCSH_postShibataPlasma030.d | - |
| SA242645 | BiorecPlasma003_MX562952_posCSH_postShibataPlasma020.d | - |
| SA242646 | BiorecLiver001_MX562952_posCSH_preShibataLiver001.d | - |
| SA242647 | PoolQC005_MX562952_posCSH_postShibataLiver033.d | - |
| SA242648 | BiorecPlasma001_MX562952_posCSH_preShibataPlasma001.d | - |
| SA242649 | PoolQC004_MX562952_posCSH_postShibataPlasma030.d | - |
| SA242650 | PoolQC002_MX562952_posCSH_postShibataLiver010.d | - |
| SA242651 | PoolQC002_MX562952_posCSH_postShibataPlasma010.d | - |
| SA242652 | PoolQC003_MX562952_posCSH_postShibataLiver020.d | - |
| SA242653 | PoolQC004_MX562952_posCSH_postShibataLiver030.d | - |
| SA242654 | PoolQC003_MX562952_posCSH_postShibataPlasma020.d | - |
| SA242675 | ShibataPlasma024_MX562952_posCSH_iKO-IEC9-1-034.d | iKO 5001 |
| SA242676 | ShibataLiver028_MX562952_posCSH_iKO-IEC9-6-006.d | iKO 5001 |
| SA242677 | ShibataLiver012_MX562952_posCSH_iKO-IEC9-7-007.d | iKO 5001 |
| SA242678 | ShibataLiver006_MX562952_posCSH_iKO-IEC9-5-005.d | iKO 5001 |
| SA242679 | ShibataLiver005_MX562952_posCSH_iKO-IEC9-4-004.d | iKO 5001 |
| SA242680 | ShibataLiver010_MX562952_posCSH_iKO-IEC9-2-002.d | iKO 5001 |
| SA242681 | ShibataLiver026_MX562952_posCSH_iKO-IEC9-3-003.d | iKO 5001 |
| SA242682 | ShibataLiver016_MX562952_posCSH_iKO-IEC9-8-008.d | iKO 5001 |
| SA242683 | ShibataPlasma010_MX562952_posCSH_iKO-IEC9-2-035.d | iKO 5001 |
| SA242684 | ShibataPlasma012_MX562952_posCSH_iKO-IEC9-7-040.d | iKO 5001 |
| SA242685 | ShibataPlasma016_MX562952_posCSH_iKO-IEC9-8-041.d | iKO 5001 |
| SA242686 | ShibataPlasma028_MX562952_posCSH_iKO-IEC9-6-039.d | iKO 5001 |
| SA242687 | ShibataPlasma006_MX562952_posCSH_iKO-IEC9-5-038_2.d | iKO 5001 |
| SA242688 | ShibataPlasma026_MX562952_posCSH_iKO-IEC9-3-036.d | iKO 5001 |
| SA242689 | ShibataPlasma005_MX562952_posCSH_iKO-IEC9-4-037.d | iKO 5001 |
| SA242690 | ShibataLiver024_MX562952_posCSH_iKO-IEC9-1-001.d | iKO 5001 |
| SA242691 | ShibataPlasma002_MX562952_posCSH_iKO-IEChf9-1-049.d | iKO 60% kcal fat |
| SA242692 | ShibataLiver004_MX562952_posCSH_iKO-IEChf9-5-020.d | iKO 60% kcal fat |
| SA242693 | ShibataLiver021_MX562952_posCSH_iKO-IEChf9-6-021.d | iKO 60% kcal fat |
| SA242694 | ShibataLiver031_MX562952_posCSH_iKO-IEChf9-7-022.d | iKO 60% kcal fat |
| SA242695 | ShibataLiver023_MX562952_posCSH_iKO-IEChf9-4-019.d | iKO 60% kcal fat |
| SA242696 | ShibataLiver001_MX562952_posCSH_iKO-IEChf9-3-018.d | iKO 60% kcal fat |
| SA242697 | ShibataLiver002_MX562952_posCSH_iKO-IEChf9-1-016.d | iKO 60% kcal fat |
| SA242698 | ShibataLiver020_MX562952_posCSH_iKO-IEChf9-2-017.d | iKO 60% kcal fat |
| SA242699 | ShibataPlasma017_MX562952_posCSH_iKO-IEChf9-8-056.d | iKO 60% kcal fat |
| SA242700 | ShibataLiver017_MX562952_posCSH_iKO-IEChf9-8-023.d | iKO 60% kcal fat |
| SA242701 | ShibataPlasma001_MX562952_posCSH_iKO-IEChf9-3-051.d | iKO 60% kcal fat |
| SA242702 | ShibataPlasma004_MX562952_posCSH_iKO-IEChf9-5-053.d | iKO 60% kcal fat |
| SA242703 | ShibataPlasma021_MX562952_posCSH_iKO-IEChf9-6-054.d | iKO 60% kcal fat |
| SA242704 | ShibataPlasma031_MX562952_posCSH_iKO-IEChf9-7-055.d | iKO 60% kcal fat |
| SA242705 | ShibataPlasma020_MX562952_posCSH_iKO-IEChf9-2-050.d | iKO 60% kcal fat |
| SA242706 | ShibataPlasma023_MX562952_posCSH_iKO-IEChf9-4-052.d | iKO 60% kcal fat |
| SA242707 | ShibataLiver011_MX562952_posCSH_iWT-IEC9-5-013.d | iWT 5001 |
| SA242708 | ShibataLiver029_MX562952_posCSH_iWT-IEC9-6-014.d | iWT 5001 |
| SA242709 | ShibataLiver033_MX562952_posCSH_iWT-IEC9-4-012.d | iWT 5001 |
| SA242710 | ShibataLiver013_MX562952_posCSH_iWT-IEC9-3-011.d | iWT 5001 |
| SA242711 | ShibataLiver018_MX562952_posCSH_iWT-IEC9-1-009.d | iWT 5001 |
| SA242712 | ShibataLiver022_MX562952_posCSH_iWT-IEC9-2-010.d | iWT 5001 |
| SA242713 | ShibataLiver032_MX562952_posCSH_iWT-IEC9-7-015.d | iWT 5001 |
| SA242714 | ShibataPlasma033_MX562952_posCSH_iWT-IEC9-4-045.d | iWT 5001 |
| SA242715 | ShibataPlasma018_MX562952_posCSH_iWT-IEC9-1-042.d | iWT 5001 |
| SA242716 | ShibataPlasma029_MX562952_posCSH_iWT-IEC9-6-047.d | iWT 5001 |
| SA242717 | ShibataPlasma011_MX562952_posCSH_iWT-IEC9-5-046.d | iWT 5001 |
| SA242718 | ShibataPlasma022_MX562952_posCSH_iWT-IEC9-2-043.d | iWT 5001 |
| SA242719 | ShibataPlasma013_MX562952_posCSH_iWT-IEC9-3-044.d | iWT 5001 |
| SA242720 | ShibataPlasma032_MX562952_posCSH_iWT-IEC9-7-048.d | iWT 5001 |
| SA242655 | ShibataPlasma008_MX562952_posCSH_KO-IEC9-3-066.d | KO 5001 |
| SA242656 | ShibataPlasma003_MX562952_posCSH_KO-IEC9-2-065.d | KO 5001 |
| SA242657 | ShibataLiver009_MX562952_posCSH_KO-IEC9-1-031.d | KO 5001 |
| SA242658 | ShibataLiver003_MX562952_posCSH_KO-IEC9-2-032.d | KO 5001 |
| SA242659 | ShibataLiver008_MX562952_posCSH_KO-IEC9-3-033.d | KO 5001 |
| SA242660 | ShibataPlasma009_MX562952_posCSH_KO-IEC9-1-064.d | KO 5001 |
| SA242661 | ShibataLiver025_MX562952_posCSH_KO-IEChf9-3-026.d | KO 60% kcal fat |
| SA242662 | ShibataLiver030_MX562952_posCSH_KO-IEChf9-2-025.d | KO 60% kcal fat |
| SA242663 | ShibataPlasma007_MX562952_posCSH_KO-IEChf9-1-057.d | KO 60% kcal fat |
| SA242664 | ShibataLiver007_MX562952_posCSH_KO-IEChf9-1-024.d | KO 60% kcal fat |
| SA242665 | ShibataPlasma015_MX562952_posCSH_KO-IEChf9-4-060.d | KO 60% kcal fat |
| SA242666 | ShibataPlasma030_MX562952_posCSH_KO-IEChf9-2-058.d | KO 60% kcal fat |
| SA242667 | ShibataPlasma025_MX562952_posCSH_KO-IEChf9-3-059.d | KO 60% kcal fat |
| SA242668 | ShibataLiver015_MX562952_posCSH_KO-IEChf9-4-027.d | KO 60% kcal fat |
| SA242669 | ShibataPlasma019_MX562952_posCSH_WT-IEChf9-3-063.d | WT 60% kcal fat |
| SA242670 | ShibataPlasma027_MX562952_posCSH_WT-IEChf9-1-061.d | WT 60% kcal fat |
| SA242671 | ShibataPlasma014_MX562952_posCSH_WT-IEChf9-2-062.d | WT 60% kcal fat |
| SA242672 | ShibataLiver027_MX562952_posCSH_WT-IEChf9-1-028.d | WT 60% kcal fat |
| SA242673 | ShibataLiver019_MX562952_posCSH_WT-IEChf9-3-030.d | WT 60% kcal fat |
| SA242674 | ShibataLiver014_MX562952_posCSH_WT-IEChf9-2-029.d | WT 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 |
