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 TitleATP10A promotes endothelial cell insulin sensitivity and protects against female-specific dyslipidemia
Study TypeMS Untargeted Lipidomics
Study SummaryEndothelial dysfunction is strongly associated with metabolic and cardiovascular disease but how genetic and environmental factors intersect to promote disease progression remains elusive. 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. Here, we generated Atp10A knockout mice and show that Atp10A deficiency results in female-specific dyslipidemia, independent of diet-induced obesity, characterized by elevated plasma triglycerides, free fatty acids and cholesterol, and altered HDL properties. We also observed increased circulating levels of several sphingolipid species and reduced levels of eicosanoids and bile acids. The Atp10A-/- mice also display hepatic insulin resistance without perturbations to whole-body glucose homeostasis. ATP10A is expressed in vascular and lymphatic endothelial cells, where reduced expression causes hyperactive insulin receptor signaling at basal insulin levels and an inability to properly respond to added insulin. This unique form of insulin resistance suggests that ATP10A promotes insulin receptor desensitization to maintain endothelial cell insulin sensitivity. These findings are clinically relevant because therapeutics that enhance ATP10A expression could improve vascular health and lipid metabolic profiles.
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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Project:

Project ID:PR001668
Project DOI:doi: 10.21228/M83H7N
Project Title:ATP10A promotes endothelial cell insulin sensitivity and protects against female-specific dyslipidemia
Project Type:MS Untargeted Lipidomics
Project Summary:The role of ATP10A in endothelial dysfunction
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:Norris, A.C., Yazlovitskaya, E., Zhu, L., Rose, B., Yu, S., McLean, J.A., Stafford, J. and Graham, T.R., 2022. ATP10A has a protective and sex‚Äźspecific role in lipid metabolism. The FASEB Journal, 36.
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