Over the last two decades we have witnessed the emergence and advancement of lipidomics, a new omics approach, which is a field of research that investigates pathways and networks of cellular lipids in biological systems. Lipids are characterized by an extremely high structural diversity, reflecting the wide range of physicochemical properties, enabling them to perform various functions, including the organization of cell and organelle membranes, the regulation of membrane fluidity and curvature, the control of energy metabolism of cells and organisms, as well as mediation in several signalling pathways. According to their different functionalities, it is increasingly evident that specific lipids can serve as biomarkers of disease and could be a potential target for pharmaceutical interventions. It is therefore not surprising that more human diseases are being associated with significant lipidome alterations and, for many, changes in lipid metabolism have been identified as a major risk factor. Indeed, most metabolic disorders, including obesity, cardiovascular diseases and diabetes, are closely associated with the reconfiguration of lipid metabolism. In addition, a close association between lipidome changes and the onset and course of the disease has been demonstrated in the treatment of cancer and neurodegenerative disorders.
Recent studies have shown that lipidomics, as a large-scale study of diverse molecular lipid species, aims to address the identification, cell and tissue distribution of lipids, as well as associated signalling and metabolic pathways, has a very high potential in clinical research. Reliable lipid markers can accelerate clinical developments in several ways. To provide reliable coverage of different natural lipidomes the development, optimization and standardization of preliminary and analytical workflows, data analysis and reporting solutions for high throughput lipidomics is needed. The combination of modern separation techniques and mass spectrometry instruments capable of high resolution, mass accuracy, sensitivity, and speed has significantly improved accuracy and dynamic range in lipidomics analysis. This offers the possibility of identifying hundreds of lipid species from natural lipidomes using LC-MS/MS analysis. The reliable identification of lipids forms using LC-MS/MS datasets remains one of the main bottlenecks of high-throughput lipidomics, so software tools to support MS data processing must be further developed and applied.
The lipidome is also subject to various enzymatic and non-enzymatic modifications. Modifications of lipids via enzymatic and non-enzymatic modifications including oxidation, nitration, sulfation and halogenation constitute a new level of complexity of the lipidomes (epilipidome) necessary for the regulation of complex biological functions. There are clear examples illustrating the regulatory role of the epilipidome and lipid modifications in directing cell fate and signalling events. Enzymatically oxidized phospholipids are as important regulators of innate immune responses, while non-enzymatic lipid peroxidation could be associated with the induction of ferroptotic cell death as well as the activation of immune responses via pattern recognition and scavenger receptors. However, because of the largely unknown structural diversity and low natural abundance of modified lipids, high-throughput epilipidomics analysis of biological samples remains challenging. Thus (epi)-lipidomics is a fast-developing discipline with a constantly growing number of users, applications and methods, needing a platform for open discussion to ensure community-based standardization, harmonization and integration of available methodological and knowledge base resources.
The overreaching goal of EpiLipidNET is to establish a pan-European expert centre for integrative lipidomics, to facilitate multidisciplinary networking, knowledge building and technology development with a focus on the following areas:
- Community-based survey of lipidomics workflows for the identification and quantification of lipids from a variety of natural lipidomes from various species (human, mammalian, invertebrates, algae, plants and bacteria).
- Establishing a roadmap for clinical translation of MS-based lipidomics through a network-wide and community-wide assessment of strategies for implementing lipid-derived markers in clinical workflows, by taking into account the analytical and clinical performance, cost-effectiveness, and impact.
- Exploring the significance of epilipidomics in the regulation of biological systems in health and diseases by providing a harmonized solution for MS-based analysis of modified lipids, as well as the integration of available information into lipid-centric signalling pathways via the networking of researchers working on redox and other types of lipid modifications using different model systems and clinical samples (e.g. atherosclerosis, cardiovascular diseases, cancer, aging).
- Integration of the current knowledge on lipid signalling and modes of action with the focus on developing the expertise hub on lipid signalling mechanisms, mainly related to the role of native and modified lipids as well as their protein interactions in a variety of model systems, including cell culture and animal models.