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Biochimica Et Biophysica Acta.... Jun 2019Phospholipase A (PLA) enzymes are the upstream regulators of the eicosanoid pathway liberating free arachidonic acid from the sn-2 position of membrane phospholipids.... (Review)
Review
Phospholipase A (PLA) enzymes are the upstream regulators of the eicosanoid pathway liberating free arachidonic acid from the sn-2 position of membrane phospholipids. Free intracellular arachidonic acid serves as a substrate for the eicosanoid biosynthetic enzymes including cyclooxygenases, lipoxygenases, and cytochrome P450s that lead to inflammation. The Group IVA cytosolic (cPLA), Group VIA calcium-independent (iPLA), and Group V secreted (sPLA) are three well-characterized human enzymes that have been implicated in eicosanoid formation. In this review, we will introduce and summarize the regulation of catalytic activity and cellular localization, structural characteristics, interfacial activation and kinetics, substrate specificity, inhibitor binding and interactions, and the downstream implications for eicosanoid biosynthesis of these three important PLA enzymes.
Topics: Arachidonic Acid; Catalysis; Humans; Lipid Metabolism; Lipidomics; Phospholipases A2; Substrate Specificity
PubMed: 30905345
DOI: 10.1016/j.bbalip.2018.08.010 -
Advanced Science (Weinheim,... Apr 2024Lipid metabolism and signaling play pivotal functions in biology and disease development. Despite this, currently available optical techniques are limited in their...
Lipid metabolism and signaling play pivotal functions in biology and disease development. Despite this, currently available optical techniques are limited in their ability to directly visualize the lipidome in tissues. In this study, opto-lipidomics, a new approach to optical molecular tissue imaging is introduced. The capability of vibrational Raman spectroscopy is expanded to identify individual lipids in complex tissue matrices through correlation with desorption electrospray ionization (DESI) - mass spectrometry (MS) imaging in an integrated instrument. A computational pipeline of inter-modality analysis is established to infer lipidomic information from optical vibrational spectra. Opto-lipidomic imaging of transient cerebral ischemia-reperfusion injury in a murine model of ischemic stroke demonstrates the visualization and identification of lipids in disease with high molecular specificity using Raman scattered light. Furthermore, opto-lipidomics in a handheld fiber-optic Raman probe is deployed and demonstrates real-time classification of bulk brain tissues based on specific lipid abundances. Opto-lipidomics opens a host of new opportunities to study lipid biomarkers for diagnostics, prognostics, and novel therapeutic targets.
Topics: Animals; Mice; Lipidomics; Lipids; Spectrometry, Mass, Electrospray Ionization; Biomarkers; Lipid Metabolism
PubMed: 38145965
DOI: 10.1002/advs.202302962 -
Current Opinion in Chemical Biology Feb 2023Despite being a relatively new addition to the Omics' landscape, lipidomics is increasingly being recognized as an important tool for the identification of druggable... (Review)
Review
Despite being a relatively new addition to the Omics' landscape, lipidomics is increasingly being recognized as an important tool for the identification of druggable targets and biochemical markers. In this review we present recent advances of lipid analysis in drug discovery and development. We cover current state of the art technologies which are constantly evolving to meet demands in terms of sensitivity and selectivity. A careful selection of important examples is then provided, illustrating the versatility of lipidomics analysis in the drug discovery and development process. Integration of lipidomics with other omics', stem-cell technologies, and metabolic flux analysis will open new avenues for deciphering pathophysiological mechanisms and the discovery of novel targets and biomarkers.
Topics: Lipidomics; Lipid Metabolism; Lipids; Biomarkers; Drug Discovery
PubMed: 36586190
DOI: 10.1016/j.cbpa.2022.102256 -
Biochimica Et Biophysica Acta.... Mar 2022Microbial lipids provide signals that are responsible for maintaining host health and controlling disease. The differences in the structures of microbial lipids have... (Review)
Review
Microbial lipids provide signals that are responsible for maintaining host health and controlling disease. The differences in the structures of microbial lipids have been shown to alter receptor selectivity and agonist/antagonist activity. Advanced lipidomics is an emerging field that helps to elucidate the complex bacterial lipid diversity. The use of cutting-edge technologies is expected to lead to the discovery of new functional metabolites involved in host homeostasis. This review aims to describe recent updates on functional lipid metabolites derived from gut microbiota, their structure-activity relationships, and advanced lipidomics technologies.
Topics: Lipidomics
PubMed: 34995792
DOI: 10.1016/j.bbalip.2021.159110 -
The Journal of Investigative Dermatology Jan 2022Although lipids are crucial molecules for cell structure, metabolism, and signaling in most organs, they have additional specific functions in the skin. Lipids are... (Review)
Review
Although lipids are crucial molecules for cell structure, metabolism, and signaling in most organs, they have additional specific functions in the skin. Lipids are required for the maintenance and regulation of the epidermal barrier, physical properties of the skin, and defense against microbes. Analysis of the lipidome-the totality of lipids-is of similar complexity to those of proteomics or other omics, with lipid structures ranging from simple, linear, to highly complex structures. In addition, the ordering and chemical modifications of lipids have consequences on their biological function, especially in the skin. Recent advances in analytic capability (usually with mass spectrometry), bioinformatic processing, and integration with other dermatological big data have allowed researchers to increasingly understand the roles of specific lipid species in skin biology. In this paper, we review the techniques used to analyze skin lipidomics and epilipidomics.
Topics: Animals; Big Data; Biomedical Research; Computational Biology; Epigenesis, Genetic; Humans; Lipid Metabolism; Lipidomics; Mass Spectrometry; Skin
PubMed: 34924150
DOI: 10.1016/j.jid.2021.09.017 -
Advanced Drug Delivery Reviews 2020Lipids are ubiquitous in the human organism and play essential roles as components of cell membranes and hormones, for energy storage or as mediators of cell signaling... (Review)
Review
Lipids are ubiquitous in the human organism and play essential roles as components of cell membranes and hormones, for energy storage or as mediators of cell signaling pathways. As crucial mediators of the human metabolism, lipids are also involved in metabolic diseases, cardiovascular and renal diseases, cancer and/or hepatological and neurological disorders. With rapidly growing evidence supporting the impact of lipids on both the genesis and progression of these diseases as well as patient wellbeing, the characterization of the human lipidome has gained high interest and importance in life sciences and clinical diagnostics within the last 15 years. This is mostly due to technically advanced molecular identification and quantification methods, mainly based on mass spectrometry. Mass spectrometry has become one of the most powerful tools for the identification of lipids. New lipidic mediators or biomarkers of diseases can be analysed by state-of-the art mass spectrometry techniques supported by sophisticated bioinformatics and biostatistics. The lipidomic approach has developed dramatically in the realm of life sciences and clinical diagnostics due to the available mass spectrometric methods and in particular due to the adaptation of biostatistical methods in recent years. Therefore, the current knowledge of lipid extraction methods, mass-spectrometric approaches, biostatistical data analysis, including workflows for the interpretation of lipidomic high-throughput data, are reviewed in this manuscript.
Topics: Humans; Lipidomics; Lipids; Mass Spectrometry
PubMed: 32553782
DOI: 10.1016/j.addr.2020.06.009 -
Current Opinion in Chemical Biology Oct 2023The objective of this review is to provide a comprehensive summary of the latest methodological advancements and emerging patterns in utilizing lipidomics in clinical... (Review)
Review
The objective of this review is to provide a comprehensive summary of the latest methodological advancements and emerging patterns in utilizing lipidomics in clinical research.In this review, we assess the recent advancements in lipidomics methodologies that exhibit high levels of selectivity and sensitivity, capable of generating numerous molecular lipid species from limited quantities of biological matrices. The reviewed studies demonstrate that molecular lipid signatures offer new opportunities for precision medicine by providing sensitive diagnostic tools for disease prediction and monitoring. Moreover, the latest innovations in microsampling techniques have the potential to make a substantial contribution to clinical lipidomics. The review also shows that more work is needed to harmonize results across diverse lipidomics platforms and avoid significant errors in analysis and reporting. The increased implementation of internal standards and standard reference materials in analytical workflows will aid in this direction.
Topics: Lipids; Lipidomics; Lipid Metabolism; Mass Spectrometry; Workflow
PubMed: 37473482
DOI: 10.1016/j.cbpa.2023.102370 -
Disease Models & Mechanisms Apr 2021Comprehensive metabolomic and lipidomic mass spectrometry methods are in increasing demand; for instance, in research related to nutrition and aging. The nematode...
Comprehensive metabolomic and lipidomic mass spectrometry methods are in increasing demand; for instance, in research related to nutrition and aging. The nematode Caenorhabditis elegans is a key model organism in these fields, owing to the large repository of available C. elegans mutants and their convenient natural lifespan. Here, we describe a robust and sensitive analytical method for the semi-quantitative analysis of >100 polar (metabolomics) and >1000 apolar (lipidomics) metabolites in C. elegans, using a single-sample preparation. Our method is capable of reliably detecting a wide variety of biologically relevant metabolic aberrations in, for example, glycolysis and the tricarboxylic acid cycle, pyrimidine metabolism and complex lipid biosynthesis. In conclusion, we provide a powerful analytical tool that maximizes metabolic data yield from a single sample. This article has an associated First Person interview with the joint first authors of the paper.
Topics: Animals; Caenorhabditis elegans; Gene Knockdown Techniques; Inbreeding; Lipidomics; Metabolome; Metabolomics; Phospholipids; RNA Interference; Reproducibility of Results
PubMed: 33653825
DOI: 10.1242/dmm.047746 -
Advances in Experimental Medicine and... 2021Lipids are the critical components of cellular and plasma membrane, which constitute an impermeable barrier of cellular compartments, and play important roles on...
Lipids are the critical components of cellular and plasma membrane, which constitute an impermeable barrier of cellular compartments, and play important roles on numerous cellular processes including cell growth, proliferation, differentiation, and signaling. Alterations in lipid metabolism have been implicated in the development and progression of cancers. However, unlike other biomolecules, the diversity in the structures and characteristics of lipid species results in the limited understanding of their metabolic alterations in cancers. Lipidomics is an emerging discipline that studies lipids in a large scale based on analytical chemistry principles and technological tools. Multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) uses direct infusion to avoid difficulties from alterations in concentration, chromatographic anomalies, and ion-pairing alterations to improve resolution and achieve rapid and accurate qualitative and quantitative analysis. In this chapter, lipids and lipid metabolism relevant to cancer research are introduced, followed by a brief description of MDMS-SL and other shotgun lipidomics techniques and some applications for cancer research.
Topics: Lipid Metabolism; Lipidomics; Lipids; Mass Spectrometry; Metabolomics; Neoplasms
PubMed: 33740240
DOI: 10.1007/978-981-33-6785-2_1 -
EBioMedicine Mar 2021
Topics: Brain; Humans; Lipidomics; Lipids
PubMed: 33639400
DOI: 10.1016/j.ebiom.2021.103256