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Cell Oct 2023The CD1 system binds lipid antigens for display to T cells. Here, we solved lipidomes for the four human CD1 antigen-presenting molecules, providing a map of self-lipid...
The CD1 system binds lipid antigens for display to T cells. Here, we solved lipidomes for the four human CD1 antigen-presenting molecules, providing a map of self-lipid display. Answering a basic question, the detection of >2,000 CD1-lipid complexes demonstrates broad presentation of self-sphingolipids and phospholipids. Whereas peptide antigens are chemically processed, many lipids are presented in an unaltered form. However, each type of CD1 protein differentially edits the self-lipidome to show distinct capture motifs based on lipid length and chemical composition, suggesting general antigen display mechanisms. For CD1a and CD1d, lipid size matches the CD1 cleft volume. CD1c cleft size is more variable, and CD1b is the outlier, where ligands and clefts show an extreme size mismatch that is explained by uniformly seating two small lipids in one cleft. Furthermore, the list of compounds that comprise the integrated CD1 lipidome supports the ongoing discovery of lipid blockers and antigens for T cells.
Topics: Humans; Antigen Presentation; Antigens, CD1; Lipidomics; Lipids; T-Lymphocytes; Amino Acid Motifs
PubMed: 37725977
DOI: 10.1016/j.cell.2023.08.022 -
Journal of Lipid Research Feb 2022Oxysterols, the oxidized forms of cholesterol or of its precursors, are formed in the first steps of cholesterol metabolism. Oxysterols have interested chemists,... (Review)
Review
Oxysterols, the oxidized forms of cholesterol or of its precursors, are formed in the first steps of cholesterol metabolism. Oxysterols have interested chemists, biologists, and physicians for many decades, but their exact biological relevance in vivo, other than as intermediates in bile acid biosynthesis, has long been debated. However, in the first quarter of this century, a role for side-chain oxysterols and their C-7 oxidized metabolites has been convincingly established in the immune system. 25-Hydroxycholesterol has been shown to be synthesized by macrophages in response to the activation of Toll-like receptors and to offer protection against microbial pathogens, whereas 7α,25-dihydroxycholesterol has been shown to act as a chemoattractant to lymphocytes expressing the G protein-coupled receptor Epstein-Barr virus-induced gene 2 and to be important in coordinating the action of B cells, T cells, and dendritic cells in secondary lymphoid tissue. There is a growing body of evidence that not only these two oxysterols but also many of their isomers are of importance to the proper function of the immune system. Here, we review recent findings related to the roles of oxysterols in immunology.
Topics: Lipidomics
PubMed: 34953867
DOI: 10.1016/j.jlr.2021.100165 -
Nature Metabolism Sep 2023Lipids can be of endogenous or exogenous origin and affect diverse biological functions, including cell membrane maintenance, energy management and cellular signalling....
Lipids can be of endogenous or exogenous origin and affect diverse biological functions, including cell membrane maintenance, energy management and cellular signalling. Here, we report >800 lipid species, many of which are associated with health-to-disease transitions in diabetes, ageing and inflammation, as well as cytokine-lipidome networks. We performed comprehensive longitudinal lipidomic profiling and analysed >1,500 plasma samples from 112 participants followed for up to 9 years (average 3.2 years) to define the distinct physiological roles of complex lipid subclasses, including large and small triacylglycerols, ester- and ether-linked phosphatidylethanolamines, lysophosphatidylcholines, lysophosphatidylethanolamines, cholesterol esters and ceramides. Our findings reveal dynamic changes in the plasma lipidome during respiratory viral infection, insulin resistance and ageing, suggesting that lipids may have roles in immune homoeostasis and inflammation regulation. Individuals with insulin resistance exhibit disturbed immune homoeostasis, altered associations between lipids and clinical markers, and accelerated changes in specific lipid subclasses during ageing. Our dataset based on longitudinal deep lipidome profiling offers insights into personalized ageing, metabolic health and inflammation, potentially guiding future monitoring and intervention strategies.
Topics: Humans; Insulin Resistance; Lipidomics; Aging; Ceramides; Inflammation
PubMed: 37697054
DOI: 10.1038/s42255-023-00880-1 -
Analytical and Bioanalytical Chemistry Oct 2021Metabolomics and lipidomics are new drivers of the omics era as molecular signatures and selected analytes allow phenotypic characterization and serve as biomarkers,... (Review)
Review
Metabolomics and lipidomics are new drivers of the omics era as molecular signatures and selected analytes allow phenotypic characterization and serve as biomarkers, respectively. The growing capabilities of untargeted and targeted workflows, which primarily rely on mass spectrometric platforms, enable extensive charting or identification of bioactive metabolites and lipids. Structural annotation of these compounds is key in order to link specific molecular entities to defined biochemical functions or phenotypes. Tandem mass spectrometry (MS), first and foremost collision-induced dissociation (CID), is the method of choice to unveil structural details of metabolites and lipids. But CID fragment ions are often not sufficient to fully characterize analytes. Therefore, recent years have seen a surge in alternative tandem MS methodologies that aim to offer full structural characterization of metabolites and lipids. In this article, principles, capabilities, drawbacks, and first applications of these "advanced tandem mass spectrometry" strategies will be critically reviewed. This includes tandem MS methods that are based on electrons, photons, and ion/molecule, as well as ion/ion reactions, combining tandem MS with concepts from optical spectroscopy and making use of derivatization strategies. In the final sections of this review, the first applications of these methodologies in combination with liquid chromatography or mass spectrometry imaging are highlighted and future perspectives for research in metabolomics and lipidomics are discussed.
Topics: Lipidomics; Metabolomics; Photons; Tandem Mass Spectrometry
PubMed: 34142202
DOI: 10.1007/s00216-021-03425-1 -
Molecules (Basel, Switzerland) Aug 2021Metabolomics and lipidomics have demonstrated increasing importance in underlying biochemical mechanisms involved in the pathogenesis of diseases to identify novel drug... (Review)
Review
Metabolomics and lipidomics have demonstrated increasing importance in underlying biochemical mechanisms involved in the pathogenesis of diseases to identify novel drug targets and/or biomarkers for establishing therapeutic approaches for human health. Particularly, bioactive metabolites and lipids have biological activity and have been implicated in various biological processes in physiological conditions. Thus, comprehensive metabolites, and lipids profiling are required to obtain further advances in understanding pathophysiological changes that occur in cells and tissues. Chirality is one of the most important phenomena in living organisms and has attracted long-term interest in medical and natural science. Enantioselective separation plays a pivotal role in understanding the distribution and physiological function of a diversity of chiral bioactive molecules. In this context, it has been the goal of method development for targeted and untargeted metabolomics and lipidomic assays. Herein we will highlight the benefits and challenges involved in these stereoselective analyses for clinical samples.
Topics: Amino Acids; Animals; Biomarkers; Chromatography, Liquid; Humans; Lipidomics; Mass Spectrometry; Metabolomics; Stereoisomerism
PubMed: 34500665
DOI: 10.3390/molecules26175231 -
Mass Spectrometry Reviews Jan 2022Lipid research is attracting more and more attention as various key roles and novel biological functions of lipids have been demonstrated and discovered in the organism.... (Review)
Review
Lipid research is attracting more and more attention as various key roles and novel biological functions of lipids have been demonstrated and discovered in the organism. Mass spectrometry (MS)-based lipidomics approaches are the most powerful and effective tools for analysis of cellular lipidomes with very high sensitivity and specificity. However, the artifacts generated from in-source fragmentation are always present in all kinds of ion sources, even soft ionization techniques (i.e., electrospray ionization and matrix-assisted laser desorption/ionization [MALDI]). These artifacts can cause many problems for lipidomics, especially when the fragment ions correspond to/are isomeric species of other endogenous lipid species in complex biological samples. These commonly observed artifacts could lead to misannotation, false identification, and consequently, incorrect attribution of phenotypes, and will have negative impact on any MS-based lipidomics research including but not limited to biomarker discovery, drug development, etc. Liquid chromatography-MS, shotgun lipidomics, and MALDI-MS imaging are three representative lipidomics approaches in which ion source-generated artifacts are all manifested and are comprehensively summarized in this article. The strategies on how to avoid/reduce the artifacts of in-source fragmentation on lipidomics analysis are also discussed in detail. We believe that with the recognition and avoidance of ion source-generated artifacts, MS-based lipidomics approaches will provide better accuracy on comprehensive analysis of biological samples and will make greater contribution to the research on metabolism and translational/precision medicine (collectively termed functional lipidomics). © 2020 John Wiley & Sons Ltd. Mass Spec Rev.
Topics: Artifacts; Chromatography, Liquid; Ions; Lipidomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 32997818
DOI: 10.1002/mas.21659 -
Cellular and Molecular Life Sciences :... Mar 2021Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide leading to 31% of all global deaths. Early prediction and prevention could... (Review)
Review
Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide leading to 31% of all global deaths. Early prediction and prevention could greatly reduce the enormous socio-economic burden posed by CVDs. Plasma lipids have been at the center stage of the prediction and prevention strategies for CVDs that have mostly relied on traditional lipids (total cholesterol, total triglycerides, HDL-C and LDL-C). The tremendous advancement in the field of lipidomics in last two decades has facilitated the research efforts to unravel the metabolic dysregulation in CVDs and their genetic determinants, enabling the understanding of pathophysiological mechanisms and identification of predictive biomarkers, beyond traditional lipids. This review presents an overview of the application of lipidomics in epidemiological and genetic studies and their contributions to the current understanding of the field. We review findings of these studies and discuss examples that demonstrates the potential of lipidomics in revealing new biology not captured by traditional lipids and lipoprotein measurements. The promising findings from these studies have raised new opportunities in the fields of personalized and predictive medicine for CVDs. The review further discusses prospects of integrating emerging genomics tools with the high-dimensional lipidome to move forward from the statistical associations towards biological understanding, therapeutic target development and risk prediction. We believe that integrating genomics with lipidome holds a great potential but further advancements in statistical and computational tools are needed to handle the high-dimensional and correlated lipidome.
Topics: Cardiovascular Diseases; Ceramides; Fatty Acid Desaturases; Genomics; Humans; Life Style; Lipid Metabolism; Lipidomics; Lipids; Risk Factors
PubMed: 33449144
DOI: 10.1007/s00018-020-03715-4 -
Current Osteoporosis Reports Apr 2021The goal of this review is to highlight the need for new biomarkers for the diagnosis and treatment of musculoskeletal disorders, especially osteoporosis and sarcopenia.... (Review)
Review
PURPOSE OF REVIEW
The goal of this review is to highlight the need for new biomarkers for the diagnosis and treatment of musculoskeletal disorders, especially osteoporosis and sarcopenia. These conditions are characterized by loss of bone and muscle mass, respectively, leading to functional deterioration and the development of disabilities. Advances in high-resolution lipidomics platforms are being used to help identify new lipid biomarkers for these diseases.
RECENT FINDINGS
It is now well established that bone and muscle have important endocrine functions, including the release of bioactive factors in response to mechanical and biochemical stimuli. Bioactive lipids are a prominent set of these factors and some of these lipids are directly related to the mass and function of bone and muscle. Recent lipidomics studies have shown significant dysregulation of lipids in aged muscle and bone, including alterations in diacylglycerols and ceramides. Studies have shown that alterations in some types of plasma lipids are associated with aging including reduced bone mineral density and the occurrence of osteoporosis. Musculoskeletal disorders are a major burden in our society, especially for older adults. The development and application of new lipidomics methods is making significant advances in identifying new biomarkers for these diseases. These studies will not only lead to improved detection, but new mechanistic insights that could lead to new therapeutic targets and interventions.
Topics: Biomarkers; Humans; Lipid Metabolism; Lipidomics; Musculoskeletal Diseases
PubMed: 33591486
DOI: 10.1007/s11914-021-00656-0 -
Mitochondrial Fatty Acid β-Oxidation Disorders: From Disease to Lipidomic Studies-A Critical Review.International Journal of Molecular... Nov 2022Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial β-oxidation. The most common FAODs... (Review)
Review
Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial β-oxidation. The most common FAODs are characterized by the accumulation of medium-chain FAs and long-chain (3-hydroxy) FAs (and their carnitine derivatives), respectively. These deregulations are associated with lipotoxicity which affects several organs and potentially leads to life-threatening complications and comorbidities. Changes in the lipidome have been associated with several diseases, including some IEMs. In FAODs, the alteration of acylcarnitines (CARs) and FA profiles have been reported in patients and animal models, but changes in polar and neutral lipid profile are still scarcely studied. In this review, we present the main findings on FA and CAR profile changes associated with FAOD pathogenesis, their correlation with oxidative damage, and the consequent disturbance of mitochondrial homeostasis. Moreover, alterations in polar and neutral lipid classes and lipid species identified so far and their possible role in FAODs are discussed. We highlight the need of mass-spectrometry-based lipidomic studies to understand (epi)lipidome remodelling in FAODs, thus allowing to elucidate the pathophysiology and the identification of possible biomarkers for disease prognosis and an evaluation of therapeutic efficacy.
Topics: Animals; Lipidomics; Mitochondrial Diseases; Lipid Metabolism, Inborn Errors; Muscular Diseases; Fatty Acids; Lipids
PubMed: 36430419
DOI: 10.3390/ijms232213933 -
Journal of Lipid Research 2021In the last 2 decades, lipidomics has become one of the fastest expanding scientific disciplines in biomedical research. With an increasing number of new research groups... (Review)
Review
In the last 2 decades, lipidomics has become one of the fastest expanding scientific disciplines in biomedical research. With an increasing number of new research groups to the field, it is even more important to design guidelines for assuring high standards of data quality. The Lipidomics Standards Initiative is a community-based endeavor for the coordination of development of these best practice guidelines in lipidomics and is embedded within the International Lipidomics Society. It is the intention of this review to highlight the most quality-relevant aspects of the lipidomics workflow, including preanalytics, sample preparation, MS, and lipid species identification and quantitation. Furthermore, this review just does not only highlights examples of best practice but also sheds light on strengths, drawbacks, and pitfalls in the lipidomic analysis workflow. While this review is neither designed to be a step-by-step protocol by itself nor dedicated to a specific application of lipidomics, it should nevertheless provide the interested reader with links and original publications to obtain a comprehensive overview concerning the state-of-the-art practices in the field.
Topics: Humans; Lipidomics; Lipids; Mass Spectrometry
PubMed: 34662536
DOI: 10.1016/j.jlr.2021.100138