Current state-of-the-art of separation methods used in LC-MS based metabolomics and lipidomics.

Metabolomics deals with the large-scale analysis of metabolites, belonging to numerous compound classes and showing an extremely high chemical diversity and complexity. Lipidomics, being a subcategory of metabolomics, analyzes the cellular lipid species. Both require state-of-the-art analytical methods capable of accessing the underlying chemical complexity. One of the major techniques used for the analysis of metabolites and lipids is Liquid Chromatography-Mass Spectrometry (LC-MS), offering both different selectivities in LC separation and high sensitivity in MS detection. Chromatography can be divided into different modes, based on the properties of the employed separation system. The most popular ones are Reversed-Phase (RP) separation for non- to mid-polar molecules and Hydrophilic Interaction Liquid Chromatography (HILIC) for polar molecules. So far, no single analysis method exists that can cover the entire range of metabolites or lipids, due to the huge chemical diversity. Consequently, different separation methods have been used for different applications and research questions. In this review, we explore the current use of LC-MS in metabolomics and lipidomics. As a proxy, we examined the use of chromatographic methods in the public repositories EBI MetaboLights and NIH Metabolomics Workbench. We extracted 1484 method descriptions, collected separation metadata and generated an overview on the current use of columns, eluents, etc. Based on this overview, we reviewed current practices and identified potential future trends as well as required improvements that may allow us to increase metabolite coverage, throughput or both simultaneously.

Systems biology approaches to study lipidomes in health and disease.

Lipids have many important biological roles, such as energy storage sources, structural components of plasma membranes and as intermediates in metabolic and signaling pathways. Lipid metabolism is under tight homeostatic control, exhibiting spatial and dynamic complexity at multiple levels. Consequently, lipid-related disturbances play important roles in the pathogenesis of most of the common diseases. Lipidomics, defined as the study of lipidomes in biological systems, has emerged as a rapidly-growing field. Due to the chemical and functional diversity of lipids, the application of a systems biology approach is essential if one is to address lipid functionality at different physiological levels. In parallel with analytical advances to measure lipids in biological matrices, the field of computational lipidomics has been rapidly advancing, enabling modeling of lipidomes in their pathway, spatial and dynamic contexts. This review focuses on recent progress in systems biology approaches to study lipids in health and disease, with specific emphasis on methodological advances and biomedical applications.

Metabolomic and lipidomic approaches to identify biomarkers for bladder cancer and interstitial cystitis (Review).

The discovery, introduction and clinical use of prognostic and diagnostic biomarkers has significantly improved outcomes for patients with various illnesses, including bladder cancer (BC) and other bladder­related diseases, such as benign bladder dysfunction and interstitial cystitis (IC). Several sensitive and noninvasive clinically relevant biomarkers for BC and IC have been identified. Metabolomic­ and lipidomic­based biomarkers have notable clinical potential in improving treatment outcomes for patients with cancer; however, there are also some noted limitations. This review article provides a short and concise summary of the literature on metabolomic and lipidomic biomarkers for BC and IC, focusing on the possible clinical utility of profiling metabolic alterations in BC and IC.

Changes in the blood plasma lipidome associated with effective or poor response to atypical antipsychotic treatments in schizophrenia patients.

Atypical antipsychotics are widely used to manage schizophrenia symptoms. However, these drugs can induce deleterious side effects, such as MetS, which are associated with an increased cardiovascular risk to patients. Lipids play a central role in this context, and changes in lipid metabolism have been implicated in schizophrenia's pathobiology. Furthermore, recent evidence suggests that lipidome changes may be related to antipsychotic treatment response. The aim of this study was to evaluate the lipidome changes in blood plasma samples of schizophrenia patients before and after 6 weeks of treatment with either risperidone, olanzapine, or quetiapine. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis showed changes in the levels of ceramides (Cer), glycerophosphatidic acids (PA), glycerophosphocholines (PC), phosphatidylethanolamines (PE), phosphatidylinositols (PI), glycerophosphoglycerols (PG), and phosphatidylserines (PS) for all treatments. However, the treatment with risperidone also affected diacylglycerides (DG), ceramide 1-phosphates (CerP), triglycerides (TG), sphingomyelins (SM), and ceramide phosphoinositols (PI-Cer). Moreover, specific lipid profiles were observed that could be used to distinguish poor and good responders to the different antipsychotics. As such, further work in this area may lead to lipid-based biomarkers that could be used to improve the clinical management of schizophrenia patients.

[Research progress on biomarkers for endometriosis based on lipidomics].

The pathogenesis of endometriosis is not well understood at the moment, and the lack of effective biomarkers often leads to delayed diagnosis of the disease. Lipidomics provides a new approach for the diagnosis and prediction of endometriosis. Sphingomyelin, phosphatidylcholine and phosphatidylserine in peripheral blood, endometrial fluid, peritoneal fluid and follicular fluid have good diagnostic value for endometriosis and disease classification; the lipid metabolites in the eutopic endometrium tissue are expected to be biomarkers of early endometriosis; and the lipid metabolites in peripheral blood are also of great value for predicting endometriosis-related infertility. The development of lipidomics technique will further advance the progress on the pathogenesis, prediction, diagnosis and treatment of endometriosis.

Research progress on biomarkers for endometriosis based on lipidomics / 浙江大学学报·医学版

The pathogenesis of endometriosis is not well understood at the moment, and the lack of effective biomarkers often leads to delayed diagnosis of the disease. Lipidomics provides a new approach for the diagnosis and prediction of endometriosis. Sphingomyelin, phosphatidylcholine and phosphatidylserine in peripheral blood, endometrial fluid, peritoneal fluid and follicular fluid have good diagnostic value for endometriosis and disease classification; the lipid metabolites in the eutopic endometrium tissue are expected to be biomarkers of early endometriosis; and the lipid metabolites in peripheral blood are also of great value for predicting endometriosis-related infertility. The development of lipidomics technique will further advance the progress on the pathogenesis, prediction, diagnosis and treatment of endometriosis.

The impact of recent advances in lipidomics and redox lipidomics on dermatological research.

Dermatological research is a major beneficiary of the rapidly developing advances in lipid analytic technology and of bioinformatic tools which help to decipher and interpret the accumulating big lipid data. At its interface with the environment, the epidermis develops a blend of lipids that constitutes the epidermal lipid barrier, essential for the protection from water loss and entry of dangerous noxae. Apart from their structural role in the barrier, novel intra- and inter-cellular signaling functions of lipids and their oxidation products have been uncovered in most cutaneous cell types over the last decades, and the discovery rate has been boosted by the advent of high resolution and -throughput mass spectrometric techniques. Our understanding of epidermal development has benefited from studies on fetal surface lipids, which appear to signal for adaptation to desiccation post partum, and from studies on the dynamics of epidermal lipids during adjustment to the atmosphere in the first months of life. At birth, external insults begin to challenge the skin and its lipids, and recent years have yielded ample insights into the dynamics of lipid synthesis and -oxdiation after UV exposure, and upon contact with sensitizers and irritants. Psoriasis and atopic dermatitis are the most common chronic inflammatory skin diseases, affecting at least 3% and 7% of the global population, respectively. Consequently, novel (redox-) lipidomic techniques have been applied to study systemic and topical lipid abnormalities in patient cohorts. These studies have refined the knowledge on eicosanoid signaling in both diseases, and have identified novel biomarkers and potential disease mediators, such as lipid antigens recognized by psoriatic T cells, as well as ceramide species, which specifically correlate with atopic dermatitis severity. Both biomarkers have yielded novel mechanistic insights. Finally, the technological progress has enabled studies to be performed that have monitored the consequences of diet, lifestyle, therapy and cosmetic intervention on the skin lipidome, highlighting the translational potential of (redox-) lipidomics in dermatology.

Computational solutions in redox lipidomics - Current strategies and future perspectives.

The high chemical diversity of lipids allows them to perform multiple biological functions ranging from serving as structural building blocks of biological membranes to regulation of metabolism and signal transduction. In addition to the native lipidome, lipid species derived from enzymatic and non-enzymatic modifications (the epilipidome) make the overall picture even more complex, as their functions are still largely unknown. Oxidized lipids represent the fraction of epilipidome which has attracted high scientific attention due to their apparent involvement in the onset and development of numerous human disorders. Development of high-throughput analytical methods such as liquid chromatography coupled on-line to mass spectrometry provides the possibility to address epilipidome diversity in complex biological samples. However, the main bottleneck of redox lipidomics, the branch of lipidomics dealing with the characterization of oxidized lipids, remains the lack of optimal computational tools for robust, accurate and specific identification of already discovered and yet unknown modified lipids. Here we discuss the main principles of high-throughput identification of lipids and their modified forms and review the main software tools currently available in redox lipidomics. Different levels of confidence for software assisted identification of redox lipidome are defined and necessary steps toward optimal computational solutions are proposed.