Epilipidomics platform for holistic profiling of oxidized complex lipids in blood plasma of obese individuals

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 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 challenged by their low abundance and largely unknown, biological context-dependent structural diversity. Here we provide a holistic 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 was used to identify epilipidomics signatures of lean and obese individuals with and without type II diabetes. Characteristic signature of lipid modifications in lean individuals, dominated by the presence of modified octadecanoid acyl chains in phospho- and neutral lipids, was drastically shifted towards lipid peroxidation-driven accumulation of oxidized eicosanoids, suggesting significant alteration of endocrine signalling by oxidized lipids in metabolic disorders.

Reorganization of innate immune cell lipid profiles by bioinspired meroterpenoids to limit inflammation

“…The epilipidome comprises structurally and functionally diverse lipids, including oxidized species, whose physiological functions on a global scale we are only beginning to understand. [55] Lipid mediators such as prostanoids, LTs, or EETs have been recognized early on to play a fundamental role in inflammatory diseases but also beyond, [2b, 4e, 4h, 4i] and great efforts have been made to develop antiinflammatory drug candidates against key enzymes in their biosynthesis or degradation, such as COX, 5-LOX, FLAP, microsomal prostaglandin E2 synthase, or soluble epoxide hydrolase, [2b, 16b, 21c, 56] and also polypharmacological ligands have been successfully…”

Software and Computational Tools for LC-MS-Based Epilipidomics: Challenges and Solutions

“…The number and type of generated adducts do not depend only on the chemical structure and characteristics of the individual molecule, but also on experimental variables difficult to control (e.g., solvent purity). Moreover, certain structural modifications can change the ionization behavior and efficiency with respect to the native species (e.g., a different adduct distribution can be favored). , For instance, the majority of oxidized phosphatidylcholines (oxPCs, e.g., LMGP20010003 and LMGP20010005) are generally detected as formate or acetate adducts, while truncated oxPCs with terminal carboxylic moieties (e.g, LMGP20010006 and LMGP20010007) tend to form [M–H] − adducts . Algorithms for the automatic grouping of multiple ion species produced by the same chemical entity can address this problem.…”