Special Issue "Mass Spectrometry-Based Lipidomics"

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Frontiers in Metabolomics".

Deadline for manuscript submissions: closed (28 February 2021).

Special Issue Editors

Dr. Amaury Cazenave Gassiot
E-Mail Website
Guest Editor
Department of Biochemistry, Yong Loo Lin School of Medicine, and Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore
Interests: lipidomics; chromatography; mass spectrometry; lipid biochemistry; harmonisation
Dr. Federico Tesio Torta
E-Mail Website
Guest Editor
Department of Biochemistry, Yong Loo Lin School of Medicine, and Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore
Interests: lipidomics; protein and lipid biochemistry; metabolic diseases; harmonisation
Dr. Bo Johannes Burla
E-Mail Website
Guest Editor
Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore
Interests: lipidomics; MS data processing; glycosphingolipids; platelets; reproducible data analysis

Special Issue Information

Dear Colleagues,

In the last few years, it has become increasingly apparent that explaining complex biochemical pathways cannot rely solely on the study of genetic background and genetic variation. A better understanding of proteins, peptides, metabolites, and lipids at the molecular level is required. However, these components and their natural variations are still poorly characterized, be it in model organisms or human populations.

Of particular interest, the implication of lipids in many biological processes, such as plant growth, viral infection mechanisms, neuronal pathologies, autoimmune diseases, diabetes, obesity, or cancer, has only recently emerged. These developments have been made possible by advances in mass-spectrometry-based lipidomics and associated techniques, which have made it easier to grasp the lipidome’s complexity.

Mass-spectrometry-based lipidomic workflows have considerably improved over the years, yielding ever more comprehensive coverage, structural resolution, and better quantification of the lipidome and its variations. The field has now reached a point where translation to clinical applications is within reach. In this context, the lipidomics community must work towards developing ever-better analytics and establishing widely accepted guidelines for validation and reproducibility.

In this Special Issue, we would like to invite manuscripts on all aspects of mass-spectrometry-based lipidomic workflows: sample preparation, chromatographic separation, MS and MS/MS, quality control, data processing and statistical analysis, harmonization efforts, and clinical translation. Both review articles and original studies are welcome.

Dr. Amaury Cazenave Gassiot
Dr. Federico Tesio Torta
Dr. Bo Johannes Burla
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Lipidomics
  • Mass spectrometry
  • Targeted and untargeted lipidomics
  • Workflows

Published Papers (8 papers)

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Research

Open AccessArticle
Untargeted Lipidomic Profiling of Dry Blood Spots Using SFC-HRMS
by , , , , , , , , and
Metabolites 2021, 11(5), 305; https://doi.org/10.3390/metabo11050305 (registering DOI) - 11 May 2021
Abstract
Lipids are essential cellular constituents that have many critical roles in physiological functions. They are notably involved in energy storage and cell signaling as second messengers, and they are major constituents of cell membranes, including lipid rafts. As a consequence, they are implicated [...] Read more.
Lipids are essential cellular constituents that have many critical roles in physiological functions. They are notably involved in energy storage and cell signaling as second messengers, and they are major constituents of cell membranes, including lipid rafts. As a consequence, they are implicated in a large number of heterogeneous diseases, such as cancer, diabetes, neurological disorders, and inherited metabolic diseases. Due to the high structural diversity and complexity of lipid species, the presence of isomeric and isobaric lipid species, and their occurrence at a large concentration scale, a complete lipidomic profiling of biological matrices remains challenging, especially in clinical contexts. Using supercritical fluid chromatography coupled with high-resolution mass spectrometry, we have developed and validated an untargeted lipidomic approach to the profiling of plasma and blood. Moreover, we have tested the technique using the Dry Blood Spot (DBS) method and found that it allows for the easy collection of blood for analysis. To develop the method, we performed the optimization of the separation and detection of lipid species on pure standards, reference human plasma (SRM1950), whole blood, and DBS. These analyses allowed an in-house lipid data bank to be built. Using the MS-Dial software, we developed an automatic process for the relative quantification of around 500 lipids species belonging to the 6 main classes of lipids (including phospholipids, sphingolipids, free fatty acids, sterols, and fatty acyl-carnitines). Then, we compared the method using the published data for SRM 1950 and a mouse blood sample, along with another sample of the same blood collected using the DBS method. In this study, we provided a method for blood lipidomic profiling that can be used for the easy sampling of dry blood spots. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Lipidomics)
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Open AccessArticle
A Novel Solid Phase Extraction Sample Preparation Method for Lipidomic Analysis of Human Plasma Using Liquid Chromatography/Mass Spectrometry
Metabolites 2021, 11(5), 294; https://doi.org/10.3390/metabo11050294 - 04 May 2021
Viewed by 248
Abstract
Lipidomic approaches are widely used to investigate the relationship between lipids, human health, and disease. Conventional sample preparation techniques for the extraction of lipids from biological matrices like human plasma are based on liquid-liquid extraction (LLE). However, these methods are labor-intensive, time-consuming, and [...] Read more.
Lipidomic approaches are widely used to investigate the relationship between lipids, human health, and disease. Conventional sample preparation techniques for the extraction of lipids from biological matrices like human plasma are based on liquid-liquid extraction (LLE). However, these methods are labor-intensive, time-consuming, and can show poor reproducibility and selectivity on lipid extraction. A novel, solid-phase extraction (SPE) approach was demonstrated to extract lipids from human plasma using a lipid extraction SPE in both cartridge and 96-well-plate formats, followed by analysis using a combination of targeted and untargeted liquid chromatography/mass spectrometry. The Lipid Extraction SPE method was compared to traditional LLE methods for lipid class recovery, lipidome coverage, and reproducibility. The novel SPE method used a simplified protocol with significant time and labor savings and provided equivalent or better qualitative and quantitative results than traditional LLE methods with respect to several critical performance metrics; recovery, reproducibility, and lipidome coverage. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Lipidomics)
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Open AccessArticle
Control of n-Butanol Induced Lipidome Adaptations in E. coli
Metabolites 2021, 11(5), 286; https://doi.org/10.3390/metabo11050286 - 29 Apr 2021
Viewed by 326
Abstract
The versatile compound n-butanol is one of the most promising biofuels for use in existing internal combustion engines, contributing to a smooth transition towards a clean energy society. Furthermore, n-butanol is a valuable resource to produce more complex molecules such as [...] Read more.
The versatile compound n-butanol is one of the most promising biofuels for use in existing internal combustion engines, contributing to a smooth transition towards a clean energy society. Furthermore, n-butanol is a valuable resource to produce more complex molecules such as bioplastics. Microbial production of n-butanol from waste materials is hampered by the biotoxicity of n-butanol as it interferes with the proper functioning of lipid membranes. In this study we perform a large-scale investigation of the complete lipid-related enzyme machinery and its response to exposure to a sublethal concentration of n-butanol. We profiled, in triplicate, the growth characteristics and phospholipidomes of 116 different genetic constructs of E. coli, both in the presence and absence of 0.5% n-butanol (v/v). This led to the identification of 230 lipid species and subsequently to the reconstruction of the network of metabolites, enzymes and lipid properties driving the homeostasis of the E. coli lipidome. We were able to identify key lipids and biochemical pathways leading to altered n-butanol tolerance. The data led to new conceptual insights into the bacterial lipid metabolism which are discussed. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Lipidomics)
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Open AccessArticle
Application of Lipid Class Ratios for Sample Stability Monitoring—Evaluation of Murine Tissue Homogenates and SDS as a Stabilizer
Metabolites 2021, 11(5), 277; https://doi.org/10.3390/metabo11050277 - 27 Apr 2021
Viewed by 432
Abstract
Lipids are a ubiquitous class of structurally complex molecules involved in various biological processes. In the fast-growing field of lipidomics, preanalytical issues are frequently neglected. Here, we investigated the stability of lipid profiles of murine liver, brain, lung, heart, and spleen homogenates by [...] Read more.
Lipids are a ubiquitous class of structurally complex molecules involved in various biological processes. In the fast-growing field of lipidomics, preanalytical issues are frequently neglected. Here, we investigated the stability of lipid profiles of murine liver, brain, lung, heart, and spleen homogenates by quantitative flow injection analysis using tandem mass spectrometry and high-resolution mass spectrometry. Storage of tissue homogenates at room temperature showed substantial alterations of the lipid profiles reflecting lipolytic action. Therefore, ratios of ceramide to sphingomyelin, lysophosphatidylethanolamine to phosphatidylethanolamine, lysophosphatidylcholine to phosphatidylcholine, and diglyceride to triglyceride were applied to monitor sample stability and the effect of sodium dodecyl sulfate (SDS) as a potential stabilizing agent. The addition of SDS led to a concentration-dependent stabilization of lipid profiles in liver, brain, and heart homogenates, while in lung and spleen homogenates, in particular, the lysophosphatidylethanolamine to phosphatidylethanolamine ratio increased upon addition of SDS. In conclusion, we demonstrated that lipid class ratios reflecting lipolytic activity could be applied to evaluate both the stability of samples and the influence of stabilizers. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Lipidomics)
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Open AccessArticle
Plasma Metabolome and Lipidome Associations with Type 2 Diabetes and Diabetic Nephropathy
Metabolites 2021, 11(4), 228; https://doi.org/10.3390/metabo11040228 - 08 Apr 2021
Viewed by 420
Abstract
We conducted untargeted metabolomics analysis of plasma samples from a cross-sectional case–control study with 30 healthy controls, 30 patients with diabetes mellitus and normal renal function (DM-N), and 30 early diabetic nephropathy (DKD) patients using liquid chromatography-mass spectrometry (LC-MS). We employed two different [...] Read more.
We conducted untargeted metabolomics analysis of plasma samples from a cross-sectional case–control study with 30 healthy controls, 30 patients with diabetes mellitus and normal renal function (DM-N), and 30 early diabetic nephropathy (DKD) patients using liquid chromatography-mass spectrometry (LC-MS). We employed two different modes of MS acquisition on a high-resolution MS instrument for identification and semi-quantification, and analyzed data using an advanced multivariate method for prioritizing differentially abundant metabolites. We obtained semi-quantification data for 1088 unique compounds (~55% lipids), excluding compounds that may be either exogenous compounds or treated as medication. Supervised classification analysis over a confounding-free partial correlation network shows that prostaglandins, phospholipids, nucleotides, sugars, and glycans are elevated in the DM-N and DKD patients, whereas glutamine, phenylacetylglutamine, 3-indoxyl sulfate, acetylphenylalanine, xanthine, dimethyluric acid, and asymmetric dimethylarginine are increased in DKD compared to DM-N. The data recapitulate the well-established plasma metabolome changes associated with DM-N and suggest uremic solutes and oxidative stress markers as the compounds indicating early renal function decline in DM patients. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Lipidomics)
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Open AccessArticle
Analyses of Lipid A Diversity in Gram-Negative Intestinal Bacteria Using Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry
Metabolites 2021, 11(4), 197; https://doi.org/10.3390/metabo11040197 - 26 Mar 2021
Viewed by 382
Abstract
Lipid A is a characteristic molecule of Gram-negative bacteria that elicits an immune response in mammalian cells. The presence of structurally diverse lipid A types in the human gut bacteria has been suggested before, and this appears associated with the immune response. However, [...] Read more.
Lipid A is a characteristic molecule of Gram-negative bacteria that elicits an immune response in mammalian cells. The presence of structurally diverse lipid A types in the human gut bacteria has been suggested before, and this appears associated with the immune response. However, lipid A structures and their quantitative heterogeneity have not been well characterized. In this study, a method of analysis for lipid A using liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) was developed and applied to the analyses of Escherichia coli and Bacteroidetes strains. In general, phosphate compounds adsorb on stainless-steel piping and cause peak tailing, but the use of an ammonia-containing alkaline solvent produced sharp lipid A peaks with high sensitivity. The method was applied to E. coli strains, and revealed the accumulation of lipid A with abnormal acyl side chains in knockout strains as well as known diphosphoryl hexa-acylated lipid A in a wild-type strain. The analysis of nine representative strains of Bacteroidetes showed the presence of monophosphoryl penta-acylated lipid A characterized by a highly heterogeneous main acyl chain length. Comparison of the structures and amounts of lipid A among the strains suggested a relationship between lipid A profiles and the phylogenetic classification of the strains. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Lipidomics)
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Open AccessArticle
Comprehensive Identification of Glycosphingolipids in Human Plasma Using Hydrophilic Interaction Liquid Chromatography—Electrospray Ionization Mass Spectrometry
Metabolites 2021, 11(3), 140; https://doi.org/10.3390/metabo11030140 - 26 Feb 2021
Viewed by 693
Abstract
Glycosphingolipids (GSL) represent a highly heterogeneous class of lipids with many cellular functions, implicated in a wide spectrum of human diseases. Their isolation, detection, and comprehensive structural analysis is a challenging task due to the structural diversity of GSL molecules. In this work, [...] Read more.
Glycosphingolipids (GSL) represent a highly heterogeneous class of lipids with many cellular functions, implicated in a wide spectrum of human diseases. Their isolation, detection, and comprehensive structural analysis is a challenging task due to the structural diversity of GSL molecules. In this work, GSL subclasses are isolated from human plasma using an optimized monophasic ethanol–water solvent system capable to recover a broad range of GSL species. Obtained deproteinized plasma is subsequently purified and concentrated by C18-based solid-phase extraction (SPE). The hydrophilic interaction liquid chromatography coupled to electrospray ionization linear ion trap tandem mass spectrometry (HILIC-ESI-LIT-MS/MS) is used for GSL analysis in the human plasma extract. Our results provide an in-depth profiling and structural characterization of glycosphingolipid and some phospholipid subclasses identified in the human plasma based on their retention times and the interpretation of tandem mass spectra. The structural composition of particular lipid species is readily characterized based on the detailed interpretation of mass spectrometry (MS) and tandem mass spectrometry (MS/MS) spectra and further confirmed by specific fragmentation behavior following predictable patterns, which yields to the unambiguous identification of 154 GSL species within 7 lipid subclasses and 77 phospholipids representing the highest number of GSL species ever reported in the human plasma. The developed HILIC-ESI-MS/MS method can be used for further clinical and biological research of GSL in the human blood or other biological samples. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Lipidomics)
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Open AccessArticle
Free Saturated Oxo Fatty Acids (SOFAs) and Ricinoleic Acid in Milk Determined by a Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS) Method
Metabolites 2021, 11(1), 46; https://doi.org/10.3390/metabo11010046 - 11 Jan 2021
Viewed by 760
Abstract
Oxidized saturated fatty acids, containing a hydroxyl or an oxo functionality, have attracted little attention so far. Recent studies have shown that saturated hydroxy fatty acids, which exhibit cancer cell growth inhibition and may suppress β-cell apoptosis, are present in milk. Herein, we [...] Read more.
Oxidized saturated fatty acids, containing a hydroxyl or an oxo functionality, have attracted little attention so far. Recent studies have shown that saturated hydroxy fatty acids, which exhibit cancer cell growth inhibition and may suppress β-cell apoptosis, are present in milk. Herein, we present the application of a liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method for the detection and quantification of various saturated oxo fatty acids (SOFAs) previously unrecognized in milk. This robust and rapid analytical method, which involves simple sample preparation and a single 10-min run, revealed the presence of families of oxostearic acids (OSAs) and oxopalmitic acids (OPAs) in milk. 8OSA, 9OSA, 7OSA, 10OSA and 10OPA were found to be the most abundant SOFAs in both cow and goat milk. Higher contents of SOFAs were found in cow milk in comparison to goat milk. Together with SOFAs, ricinoleic acid, which is isobaric to OSA, was detected and quantified in all milk samples, following a “suspect” HRMS analysis approach. This unique natural fatty acid, which is the main component (>90%) of castor oil triglycerides, was estimated at mean content values of 534.3 ± 6.0 μg/mL and 460 ± 8.1 μg/mL in cow and goat milk samples, respectively. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Lipidomics)
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