title: Screening phosphatidylcholine biomarkers in mouse liver extracts from a hypercholesterolemia study using ESI-MS and chemometrics.
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.
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Richard
authors.initials: R
authors.lastname: Bennett
authors.forename: John
authors.initials: J
authors.lastname: Strum
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Ellsworth
authors.forename: David
authors.initials: D
authors.lastname: Hamilton
authors.forename: Matthew
authors.initials: M
authors.lastname: Tomlinson
authors.forename: Rudolf W
authors.initials: RW
authors.lastname: Wolf
authors.forename: Michael
authors.initials: M
authors.lastname: Housley
authors.forename: Brad A
authors.initials: BA
authors.lastname: Roberts
authors.forename: Jesse
authors.initials: J
authors.lastname: Welsh
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Jackson
authors.forename: Steven G
authors.initials: SG
authors.lastname: Wood
authors.forename: Carole L
authors.initials: CL
authors.lastname: Banka
authors.forename: Craig D
authors.initials: CD
authors.lastname: Thulin
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Linford
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D016000:Cluster Analysis; D019295:Computational Biology; D006937:Hypercholesterolemia / Q000097:blood*; D008099:Liver / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D010713:Phosphatidylcholines / Q000032:analysis*; D011973:Receptors, LDL / Q000172:deficiency; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D015415:Biomarkers; D010713:Phosphatidylcholines; D011973:Receptors, LDL