INTRODUCTION: The absolute quantitation of lipids at the lipidome-wide scale is a challenge but plays an important role in the comprehensive study of lipid metabolism. OBJECTIVES: We aim to develop a high-throughput quantitative lipidomics approach to enable the simultaneous identification and absolute quantification of hundreds of lipids in a single experiment. Then, we will systematically characterize lipidome-wide changes in the aging mouse brain and provide a link between aging and disordered lipid homeostasis. METHODS: We created an in-house lipid spectral library, containing 76,361 lipids and 181,300 MS/MS spectra in total, to support accurate lipid identification. Then, we developed a response factor-based approach for the large-scale absolute quantifications of lipids. RESULTS: Using the lipidomics approach, we absolutely quantified 1212 and 864 lipids in human cells and mouse brains, respectively. The quantification accuracy was validated using the traditional approach with a median relative error of 12.6%. We further characterized the lipidome-wide changes in aging mouse brains, and dramatic changes were observed in both glycerophospholipids and sphingolipids. Sphingolipids with longer acyl chains tend to accumulate in aging brains. Membrane-esterified fatty acids demonstrated diverse changes with aging, while most polyunsaturated fatty acids consistently decreased. CONCLUSION: We developed a high-throughput quantitative lipidomics approach and systematically characterized the lipidome-wide changes in aging mouse brains. The results proved a link between aging and disordered lipid homeostasis. Mouse brain NEG UPLC-MS assay data is reported in the current study MTBLS495. Mouse brain POS UPLC-MS assay data associated to this study is reported in MTBLS562.
Linked Studies: MTBLS562
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: GNPS Metabolomics MetaboLights
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Zhu Zheng-Jiang, Chinese Academy of Sciences, 26 Qiuyue Road, Pudong New Area, Shanghai, China |
Submitting User: | caceves |
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