Lipidomic Analysis by Mass Spectrometry

Lipidomic analysis by mass spectrometry entails the comprehensive characterisation and quantification of the diverse lipid species within biological samples. Central to this endeavour are high-resolution instruments that combine separation techniques, such as liquid chromatography, with mass analysers capable of distinguishing lipid classes by exact mass and fragmentation patterns. Shotgun lipidomics permits direct infusion of total lipid extracts into the mass spectrometer, offering rapid coverage of hundreds of molecular species, while LC–MS approaches introduce chromatographic separation to resolve isomeric and isobaric lipids prior to detection. Tandem MS (MS/MS) further fragments selected precursor ions, yielding structural information on fatty acyl chains, double‐bond positions and head-group composition. Recent advances in ion mobility and gas-phase chemistries, such as ozonolysis, have enhanced discrimination of double-bond isomers and improved structural elucidation. Quantitative accuracy is achieved through stable-isotope internal standards and rigorous calibration, enabling dynamic range spanning several orders of magnitude. Coupled with bioinformatic pipelines for peak annotation and standardised nomenclature, MS-based lipidomics has become indispensable for investigating lipid metabolism, identifying disease biomarkers and mapping lipid-mediated signalling pathways across health, ageing and environmental responses.

Research from Nature Portfolio

Recent studies have introduced an integrated liquid chromatography–mass spectrometry workflow incorporating gas-phase ozonolysis to cleave carbon–carbon double bonds, thereby enabling de novo identification of unsaturated fatty acids in complex media. This approach doubled the number of identified plasma fatty acids, revealed non-canonical double-bond positions and quantified isomer abundances across a dynamic range of five orders of magnitude. Another landmark investigation employed longitudinal deep lipidome profiling of over 1,500 plasma samples collected from individuals over several years. More than 800 lipid species were tracked, uncovering dynamic alterations in large and small triacylglycerols, ether-linked phosphatidylethanolamines, lysophospholipids, cholesterol esters and ceramides during respiratory viral infection, insulin resistance and ageing. The work illuminated cytokine–lipidome networks and suggested lipid subclasses as potential indicators of immune homeostasis and personalised metabolic trajectories.

Lipidomic Analysis by Mass Spectrometry publication trend

The graph below shows the total number of articles in lipidomic analysis by mass spectrometry across all publications each year (not limited to Nature Index journals).

Technical terms

Lipidome: The complete collection of lipid molecular species within a cell, tissue or organism.

Liquid chromatography–mass spectrometry (LC–MS): A technique combining chromatographic separation with mass analysis for identification and quantification of lipids.

Tandem mass spectrometry (MS/MS): A two-stage mass analyser process that selects and fragments ions to reveal detailed structural information.

Ozonolysis: A gas-phase reaction used in MS workflows to cleave carbon–carbon double bonds, generating diagnostic fragments for locating unsaturations.

References

1. Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome. Nature Communications (2023).
2. LIPID MAPS: update to databases and tools for the lipidomics community. Nucleic Acids Research (2023).
3. Dynamic lipidome alterations associated with human health, disease and ageing. Nature Metabolism (2023).
4. Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures. Journal of Lipid Research (2020).
5. MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines 1. Journal of Lipid Research (2018).