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

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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
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