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Screening phosphatidylcholine biomarkers in mouse liver extracts from a hypercholesterolemia study using ESI-MS and chemometrics

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Abstract

When fed a high-fat, high-cholesterol diet (HFD), homozygous LDL receptor knockout mice exhibit extremely high levels of plasma cholesterol that are expected to influence liver metabolism. One step in the investigation of potential hepatic alterations was the analysis of organic extracts of livers from these and control mice by electrospray mass spectrometry (ESI-MS). Chemometrics (bioinformatics) analysis shows that the sample spectra cluster into two groups: one from mice with plasma cholesterol levels in excess of 900 mg dL−1 and one from animals with cholesterol levels of 60–250 mg dL−1. The loadings plot of the first PC in the principal-components analysis (PCA) reveals the chemical basis for clustering, i.e., biomarkers present at different concentrations in the different groups. The exact masses of the key peaks in this loadings plot indicate these species are phosphatidylcholines (PtdChos). This assignment is confirmed by tandem MS. Partial least-squares (PLS) with variable selection shows that the spectra are well correlated with plasma total cholesterol, HDL cholesterol, and triglyceride (TG) levels.

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Acknowledgements

The authors wish to thank Virginia “Jill” Patch and William Kang for technical assistance. They also wish to thank Brigham Young University (BYU) for Mentoring Environment Grants, and the Department of Chemistry and Biochemistry, and the College of Physical and Mathematical Sciences at BYU for their support of this work.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA

    Li Yang, Richard Bennett, John Strum, Benjamin B. Ellsworth, David Hamilton, Matthew Tomlinson, Rudolf W. Wolf, Michael Housley, Brad A. Roberts, Jesse Welsh, Bruce J. Jackson, Steven G. Wood & Matthew R. Linford

  2. La Jolla Institute for Molecular Medicine, San Diego, CA, USA

    Carole L. Banka

  3. Department of Chemistry, Utah Valley University, Orem, UT, 84058, USA

    Craig D. Thulin

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  1. Li Yang
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  2. Richard Bennett
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Correspondence to Matthew R. Linford.

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Yang, L., Bennett, R., Strum, J. et al. Screening phosphatidylcholine biomarkers in mouse liver extracts from a hypercholesterolemia study using ESI-MS and chemometrics. Anal Bioanal Chem 393, 643–654 (2009). https://doi.org/10.1007/s00216-008-2504-z

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  • DOI: https://doi.org/10.1007/s00216-008-2504-z

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