Aleš Kvasnička,a, Sander Johannes Thorbjørnsen Guttorma,b, and Katja Benedikte Prestø Elgstøen,a,
a Section for Metabolomics and Lipidomics, Department of Medical Biochemistry,
Oslo University Hospital, Oslo, Norway
b Faculty of Health Sciences, Department of Life Sciences and Health,
Oslo Metropolitan University, Oslo, Norway
Email: alkvas@ous-hf.no
Lipidomics emerged as an independent branch of metabolomics over two decades ago. Given the complexity of lipid structures, comprising dozens of lipid classes, the process of their description and discovery has pushed the boundaries of analytical chemistry itself. On one hand, advanced chromatographic columns and systems are now capable of separating over a thousand individual lipid species robustly and quantitatively. The most popular and developed methods utilize liquid chromatography combined with reversed-phase and HILIC columns. The most effective columns combine extended or modified alkyl chains with advanced packing material with sub 2 µm sizes, which allows for a high degree of chromatographic separation between lipid isomers. Additionally, highly sensitive and high-resolution mass spectrometry, in combination with ion mobility, offers the resolution of many lipid isomers. Although the advancements in separation technologies have boosted the identification and quantification rate of lipids, there are still some tasks that only the mass spectrometer can handle. It is now possible to elucidate the complete structure of lipids, including the sn-1/sn-2/sn-3 positions of their acyl chains and even the position and stereochemistry of their double bonds. Such structural insight has been achieved through innovative fragmentation techniques, including electron-activated dissociation (EAD), ozone-induced dissociation (OzID), ultraviolet photodissociation (UVPD), and oxygen-attachment dissociation (OAD). This demonstrates how lipidomics has advanced analytical chemistry, and vice versa. Beyond methodological innovation, lipidomic profiling of clinical cohorts has identified numerous diagnostically and biologically relevant lipid species across a wide range of medical disciplines. In this presentation, we highlight key analytical advances in lipidomics and illustrate their clinical relevance through real-world examples from lipidomics-driven research conducted at Oslo University Hospital.