Summary of Study ST002696

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 PR001668. The data can be accessed directly via it's Project DOI: 10.21228/M83H7N 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 IDST002696
Study TitleDeficiency of the lipid flippase ATP10A causes diet-induced dyslipidemia in female mice
Study TypeMS Untargeted Lipidomics
Study SummaryGenetic association studies have linked ATP10A and closely related type IV P-type ATPases (P4-ATPases) to insulin resistance and vascular complications, such as atherosclerosis. In addition, prior studies of mice harboring large, overlapping chromosomal deletions implicated Atp10A in the development of diet-induced obesity and insulin resistance. Here, we generated gene-specific Atp10A knockout mice and show that Atp10A-/- mice fed a high-fat diet did not gain excess weight relative to wild-type littermates. However, Atp10A-/- mice displayed female-specific dyslipidemia characterized by elevated plasma triglycerides, free fatty acids and cholesterol, as well as altered VLDL and HDL properties. We also observed increased circulating levels of several sphingolipid species along with reduced levels of eicosanoids and bile acids. The Atp10A-/- mice also displayed hepatic insulin resistance without perturbations to whole-body glucose homeostasis. Thus, ATP10A has a sex-specific role in regulating plasma lipid composition and maintaining hepatic liver insulin sensitivity in mice.
Institute
Vanderbilt University
DepartmentChemistry
LaboratoryCenter for Innovative Technology
Last NameMay
First NameJody
Address2301 Vanderbilt Place, Nashville, TN, 37235, USA
Emailjody.c.may@vanderbilt.edu
Phone615-875-8438
Submit Date2023-04-20
Num Groups2
Total Subjects10
Publicationssubmitted
Raw Data AvailableYes
Raw Data File Type(s)d, mzML
Analysis Type DetailLC-MS
Release Date2023-05-24
Release Version1
Jody May Jody May
https://dx.doi.org/10.21228/M83H7N
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001668
Project DOI:doi: 10.21228/M83H7N
Project Title:Deficiency of the lipid flippase ATP10A causes diet-induced dyslipidemia in female mice
Project Type:MS Untargeted Lipidomics
Project Summary:Genetic association studies have linked ATP10A and closely related type IV P-type ATPases (P4-ATPases) to insulin resistance and vascular complications, such as atherosclerosis. In addition, prior studies of mice harboring large, overlapping chromosomal deletions implicated Atp10A in the development of diet-induced obesity and insulin resistance. Here, we generated gene-specific Atp10A knockout mice and show that Atp10A-/- mice fed a high-fat diet did not gain excess weight relative to wild-type littermates. However, Atp10A-/- mice displayed female-specific dyslipidemia characterized by elevated plasma triglycerides, free fatty acids and cholesterol, as well as altered VLDL and HDL properties. We also observed increased circulating levels of several sphingolipid species along with reduced levels of eicosanoids and bile acids. The Atp10A-/- mice also displayed hepatic insulin resistance without perturbations to whole-body glucose homeostasis. Thus, ATP10A has a sex-specific role in regulating plasma lipid composition and maintaining hepatic liver insulin sensitivity in mice.
Institute:Vanderbilt University
Department:Biological Sciences
Laboratory:Graham
Last Name:Graham
First Name:Todd
Address:5260 Medical Research Building III BSB
Email:tr.graham@Vanderbilt.Edu
Phone:615-343-1835
Publications:TBA

Subject:

Subject ID:SU002798
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:Wild-type and ATP10A knockouts
Age Or Age Range:16-20 weeks
Weight Or Weight Range:23-28 grams
Animal Housing:temperature and humidity-controlled facilities
Animal Light Cycle:12 h light/dark cycles
Animal Feed:standard chow or 60% HFD (D12492, Research Diets) ad libitum,
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Genotype
SA267002ko1-2pATP10A-knockout
SA267003ko3-1nATP10A-knockout
SA267004ko2-1nATP10A-knockout
SA267005ko2-2pATP10A-knockout
SA267006ko1-1nATP10A-knockout
SA267007ko3-2pATP10A-knockout
SA267008ko4-1nATP10A-knockout
SA267009ko5-2pATP10A-knockout
SA267010ko4-2pATP10A-knockout
SA267011ko1-2nATP10A-knockout
SA267012ko2-2nATP10A-knockout
SA267013ko3-2nATP10A-knockout
SA267014ko4-2nATP10A-knockout
SA267015ko5-2nATP10A-knockout
SA267016ko1-1pATP10A-knockout
SA267017ko2-1pATP10A-knockout
SA267018ko5-1pATP10A-knockout
SA267019ko4-1pATP10A-knockout
SA267020ko3-1pATP10A-knockout
SA267021ko5-1nATP10A-knockout
SA267022wt5-2nWild-type
SA267023wt4-2nWild-type
SA267024wt3-2nWild-type
SA267025wt2-2nWild-type
SA267026wt1-2nWild-type
SA267027wt1-1nWild-type
SA267028wt1-2pWild-type
SA267029wt2-2pWild-type
SA267030wt5-1pWild-type
SA267031wt4-1pWild-type
SA267032wt2-1pWild-type
SA267033wt3-1pWild-type
SA267034wt3-2pWild-type
SA267035wt4-2pWild-type
SA267036wt3-1nWild-type
SA267037wt4-1nWild-type
SA267038wt2-1nWild-type
SA267039wt1-1pWild-type
SA267040wt5-2pWild-type
SA267041wt5-1nWild-type
Showing results 1 to 40 of 40

Collection:

Collection ID:CO002791
Collection Summary:Plasma was collected, via a retroorbital bleed or cardiac puncture, from 5-hr fasted mice and 5-hr fasted mice that had undergone an OGTT.
Sample Type:Blood (plasma)
Collection Method:retroorbital bleed or cardiac puncture
Storage Conditions:-20℃

Treatment:

Treatment ID:TR002807
Treatment Summary:Mice were fasted for 5 hours (7AM-12PM). No additional treatments were administered.
Treatment:WT vs KO
Treatment Compound:n/a
Treatment Route:n/a
Treatment Dose:n/a
Treatment Dosevolume:n/a
Treatment Doseduration:n/a
Treatment Vehicle:n/a
Animal Vet Treatments:n/a
Animal Anesthesia:n/a
Animal Acclimation Duration:n/a
Animal Fasting:5 hour
Animal Endp Euthanasia:n/a
Animal Endp Tissue Coll List:Plasma was collected, via a retroorbital bleed or cardiac puncture
Animal Endp Clinical Signs:n/a

Sample Preparation:

Sampleprep ID:SP002804
Sampleprep Summary:100 uL of plasma was collected from each mouse. An isotopically labeled lipid mixture (SPLASH LIPIDOMIX, Avanti) was added as an internal standard to each plasma sample. A liquid-liquid extraction was performed by adding 1 mL methyl tert-butyl ether (MTBE), vortexing, and subsequently centrifuging for 10 minutes at 10,000 rpm and 4˚C. The nonpolar, MTBE fraction (top liquid layer) containing the lipophilic components was removed and dried under vacuum centrifugation. Dried samples were stored at -80˚C until the day of MS analysis. For LC-IM-MS analysis, dried samples were resuspended in 100 µL IPA containing 40 µg/mL heptadecanoic acid and nonadecanoic acid, as well as 10 µg/mL glucosyl(β) sphingosine and N-heptadecanoyl-D-erythrosphingosine.
Processing Storage Conditions:4℃
Extraction Method:MTBE
Extract Enrichment:vacuum centrifuge
Extract Storage:-80℃
Sample Resuspension:100 uL IPA
Sample Derivatization:n/a
Sample Spiking:14 heavy-labeled lipids prior to extraction; 4 odd-chain lipids during reconstitution
Subcellular Location:n/a

Combined analysis:

Analysis ID AN004369 AN004370
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Agilent 6560 Agilent 6560
Column Agilent ZORBAX RRHD Extend-C18 (50 x 2.1mm,1.8um) Agilent ZORBAX RRHD Extend-C18 (50 x 2.1mm,1.8um)
MS Type ESI ESI
MS instrument type QTOF QTOF
MS instrument name Agilent 6560 Ion Mobility Agilent 6560 Ion Mobility
Ion Mode POSITIVE NEGATIVE
Units Ion Abundances Ion Abundances

Chromatography:

Chromatography ID:CH003275
Chromatography Summary:HPLC-IM-MS/MS on an Agilent 6560 mass spectrometer using a ZORBAX Extend-C18 RPLC column (Phase A: 0.1% formic acid and 10 mM NH4CHOO in water, Phase B: 0.1% formic acid and 10 mM NH4CHOO in 60:36:4 isopropanol:acetonitrile:water).
Instrument Name:Agilent 6560
Column Name:Agilent ZORBAX RRHD Extend-C18 (50 x 2.1mm,1.8um)
Column Temperature:40
Flow Gradient:70% B for 1 min, 70-86% B in 2.5 min, 86% B for 6.5 min, 86-100% B in 1 min, 100% B for 6 min, 100-70% B in 0.1 min, and 70% B for 1.9 min.
Flow Rate:300 ul/min
Solvent A:Water (10mM Amm. Formate) 0.1% formic acid
Solvent B:60:36:4 IPA:ACN:H2O (10mM Amm. Formate) 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS004116
Analysis ID:AN004369
Instrument Name:Agilent 6560 Ion Mobility
Instrument Type:QTOF
MS Type:ESI
MS Comments:Data alignment and biostatical analysis was performed using Progenesis QI (Waters).
Ion Mode:POSITIVE
  
MS ID:MS004117
Analysis ID:AN004370
Instrument Name:Agilent 6560 Ion Mobility
Instrument Type:QTOF
MS Type:ESI
MS Comments:Data alignment and biostatical analysis was performed using Progenesis QI (Waters).
Ion Mode:NEGATIVE
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