Summary of Study ST000659

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 PR000463. The data can be accessed directly via it's Project DOI: 10.21228/M86P5J This work is supported by NIH grant, U2C- DK119886.

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Study IDST000659
Study TitleChanges in metabolites and lipid mediators associated with supervised exercise training for peripheral
Study TypeTimecourse
Study SummaryPeripheral artery disease (PAD) is a leading cause of cardiovascular related morbidity and mortality, affecting over 8.5 million men and women in the United States and greater than 200 million individuals worldwide. The mainstay of treatment to improve lower limb symptoms is supervised walking therapy, which does not affect plaque morphology or alter conduit artery blood flow, but rather ameliorates endothelial dysfunction, enhances skeletal muscle metabolism and mitochondrial function, and suppresses inflammatory activation. In this pilot feasibility project we will employ metabolic and lipidomic techniques to measure the effects of supervised exercise therapy on primary metabolism, complex lipids, and lipid mediators, and correlate these effects with individual, subject-level measures of the response to exercise therapy among subjects with PAD. The overarching theme of this work is to identify metabolites, complex lipids, and lipid mediators that are associated with the inter-individual variability in the response of subjects with PAD to supervised exercise therapy. This knowledge will significantly enhance our understanding of the pathophysiology of lower extremity symptoms in PAD, as well as the manner in which supervised exercise therapy improves walking intolerance. It will identify novel therapeutic targets and pathways for pharmacologic manipulation in the treatment of PAD. Aside from having the potential to generate multiple high-impact publications, it will serve as the basis for a planned NIH R01 submission by the PI at the conclusion of the award period.
Institute
University of California, Davis
DepartmentUSDA Western Human Nutrition Research Center
Last NameNewman
First NameJohn
Address430 West Health Sciences Dr. Davis, Ca, 95616
Emailjohn.newman@ars.usda.gov
Phone(530) 752-1009
Submit Date2017-06-28
Study CommentsFatty acids measured but not against a calibration curve. Therefore values are expressed as a relative abundance of the entire samples set such that the sum of all subjects eguals 100%.
Raw Data AvailableYes
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2017-10-03
Release Version1
John Newman John Newman
https://dx.doi.org/10.21228/M86P5J
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Sample Preparation:

Sampleprep ID:SP000689
Sampleprep Summary:Lipid mediator extraction and quantification: Oxylipins, endocannabinoids, and fatty acids were isolated from plasma using Ostro Sample Preparation Plates (Waters; Milford, MA) in the presence of BHT/EDTA and quantified by UPLC-MS/MS using internal standard methods. Briefly, in the Ostro Plate well, 100µl plasma aliquots were mixed with 5µl of BHT/EDTA (1:1 v/v MeOH/water) and 5µl methanol containing a suite of deuterated surrogates. The samples were then mixed with 300µL of acetonitrile with 1% formic acid and eluted with 15 mmHg vacuum for 10 min into 200µL glass inserts containing 10µl of 20% glycerol in methanol. Solvent was removed by vacuum centrifugation and the glycerol plug was stored at -80Co until analysis. Prior acquisition, samples were reconstituted in 100µl of 1:1 methanol:acetonitrile containing 100nM of 1-cyclohexyl ureido, 3-dodecanoic acid (CUDA) and 1-phenyl ureido, 3-hexadecanoic acid (PUHA). Residues within extracts were separated on a 2.1 x 150mm 0.17µm BEH column (Waters) and detected by electrospray ionization with multi reaction monitoring on a API 6500 QTRAP (Sciex; Redwood City, CA) and quantified against 7-9 point calibration curves of authentic standards using modifications of previously reported methods (Grapov, D., et al. 2012. PLoS One 7: e48852.; doi: 10.1371/journal.pone.0048852).
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