Analytical and computational workflow for in-depth analysis of oxidized complex lipids in blood plasma

Angela Criscuolo, Palina Nepachalovich, Diego Fernando Garcia-del Rio, Mike Lange, Zhixu Ni, Massimo Baroni, Gabriele Cruciani, Laura Goracci, Matthias Blüher and Maria Fedorova ()
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Angela Criscuolo: University of Leipzig
Palina Nepachalovich: Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine Carl Gustav Carus of TU Dresden
Diego Fernando Garcia-del Rio: University of Leipzig
Mike Lange: University of Leipzig
Zhixu Ni: Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine Carl Gustav Carus of TU Dresden
Massimo Baroni: Molecular Discovery, Kinetic Business Centre
Gabriele Cruciani: University of Perugia
Laura Goracci: University of Perugia
Matthias Blüher: University of Leipzig
Maria Fedorova: Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine Carl Gustav Carus of TU Dresden

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Lipids are a structurally diverse class of biomolecules which can undergo a variety of chemical modifications. Among them, lipid (per)oxidation attracts most of the attention due to its significance in the regulation of inflammation, cell proliferation and death programs. Despite their apparent regulatory significance, the molecular repertoire of oxidized lipids remains largely elusive as accurate annotation of lipid modifications is complicated by their low abundance and often unknown, biological context-dependent structural diversity. Here, we provide a workflow based on the combination of bioinformatics and LC-MS/MS technologies to support identification and relative quantification of oxidized complex lipids in a modification type- and position-specific manner. The developed methodology is used to identify epilipidomics signatures of lean and obese individuals with and without type 2 diabetes. The characteristic signature of lipid modifications in lean individuals, dominated by the presence of modified octadecanoid acyl chains in phospho- and neutral lipids, is drastically shifted towards lipid peroxidation-driven accumulation of oxidized eicosanoids, suggesting significant alteration of endocrine signalling by oxidized lipids in metabolic disorders.

Date: 2022
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DOI: 10.1038/s41467-022-33225-9

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