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Bioactive Lipids and Lipidomics 2018
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Bioactive Lipids and Lipidomics 2018

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 January 2019) | Viewed by 71380

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Mario Ollero

E-Mail Website
Guest Editor
UPEC, Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil Val de Marne—Université Paris 12, U955 Créteil, France
Interests: lipid signaling; membrane microdomains; protein-lipid interactions
Special Issues, Collections and Topics in MDPI journals
Dr. David Touboul

E-Mail Website
Guest Editor
CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, UPR 2301, 91198 Gif-sur-Yvette, France
Interests: antimicrobial compounds; fatty acid; lkaloids; phytochemicals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advances in technologies for lipid analysis have contributed to the consolidation of lipidomics as a particular discipline in metabolomics. This technological development has paralleled the discovery of a broad range of cellular functions associated with lipids, from cell signaling and membrane dynamics, to intercellular communication and the regulation of gene expression. Lipid molecules have been identified as therapeutic targets, therapeutic agents, nutraceuticals and disease biomarkers.

The scope of this Special Issue is to provide the readers from the disciplines of chemistry, biology, as well as connected disciplines with the state-of-the-art of lipid science with regard to the progress in the discovery of bioactive lipid and technical advances in lipidomics.

Authors are invited to submit original research and review articles. Topics include, but are not limited to:

  • Bioactive lipids in cell biology
  • Lipid molecules as therapeutic agents, nutraceuticals
  • Lipids as diagnostic and prognostic biomarkers of disease
  • Lipids in systems biology and metabolic networks
  • New advances in lipid analysis and lipidomics

Prof. Dr. Mario Ollero
Dr. David Touboul
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • Bioactive lipids
  • Biomarkers
  • Nutraceuticals
  • Metabolomics
  • Membrane dynamics
  • Imaging

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Published Papers (17 papers)

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Editorial

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4 pages, 304 KiB  
Editorial
Lipidomics Conquers a Niche, Consolidates Growth
by David Touboul and Mario Ollero
Int. J. Mol. Sci. 2019, 20(13), 3188; https://doi.org/10.3390/ijms20133188 - 29 Jun 2019
Cited by 2 | Viewed by 2068
Abstract
Sixteen years after the first published article in which the term “lipidomics” was stated [...] Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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Research

Jump to: Editorial, Review

18 pages, 3841 KiB  
Article
Multi-Staged Regulation of Lipid Signaling Mediators during Myogenesis by COX-1/2 Pathways
by Chenglin Mo, Zhiying Wang, Lynda Bonewald and Marco Brotto
Int. J. Mol. Sci. 2019, 20(18), 4326; https://doi.org/10.3390/ijms20184326 - 04 Sep 2019
Cited by 10 | Viewed by 4003
Abstract
Cyclooxygenases (COXs), including COX-1 and -2, are enzymes essential for lipid mediator (LMs) syntheses from arachidonic acid (AA), such as prostaglandins (PGs). Furthermore, COXs could interplay with other enzymes such as lipoxygenases (LOXs) and cytochrome P450s (CYPs) to regulate the signaling of LMs. [...] Read more.
Cyclooxygenases (COXs), including COX-1 and -2, are enzymes essential for lipid mediator (LMs) syntheses from arachidonic acid (AA), such as prostaglandins (PGs). Furthermore, COXs could interplay with other enzymes such as lipoxygenases (LOXs) and cytochrome P450s (CYPs) to regulate the signaling of LMs. In this study, to comprehensively analyze the function of COX-1 and -2 in regulating the signaling of bioactive LMs in skeletal muscle, mouse primary myoblasts and C2C12 cells were transfected with specific COX-1 and -2 siRNAs, followed by targeted lipidomic analysis and customized quantitative PCR gene array analysis. Knocking down COXs, particularly COX-1, significantly reduced the release of PGs from muscle cells, especially PGE2 and PGF2α, as well as oleoylethanolamide (OEA) and arachidonoylethanolamine (AEA). Moreover, COXs could interplay with LOXs to regulate the signaling of hydroxyeicosatetraenoic acids (HETEs). The changes in LMs are associated with the expression of genes, such as Itrp1 (calcium signaling) and Myh7 (myogenic differentiation), in skeletal muscle. In conclusion, both COX-1 and -2 contribute to LMs production during myogenesis in vitro, and COXs could interact with LOXs during this process. These interactions and the fine-tuning of the levels of these LMs are most likely important for skeletal muscle myogenesis, and potentially, muscle repair and regeneration. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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13 pages, 2533 KiB  
Article
Structural Identification of Antibacterial Lipids from Amazonian Palm Tree Endophytes through the Molecular Network Approach
by Morgane Barthélemy, Nicolas Elie, Léonie Pellissier, Jean-Luc Wolfender, Didier Stien, David Touboul and Véronique Eparvier
Int. J. Mol. Sci. 2019, 20(8), 2006; https://doi.org/10.3390/ijms20082006 - 24 Apr 2019
Cited by 19 | Viewed by 3646
Abstract
A library of 197 endophytic fungi and bacteria isolated from the Amazonian palm tree Astrocaryum sciophilum was extracted and screened for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Four out of five antibacterial ethyl acetate extracts were also cytotoxic for the MRC-5 cells [...] Read more.
A library of 197 endophytic fungi and bacteria isolated from the Amazonian palm tree Astrocaryum sciophilum was extracted and screened for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Four out of five antibacterial ethyl acetate extracts were also cytotoxic for the MRC-5 cells line. Liquid chromatography coupled to tandem mass spectrometry (UPHLC-HRMS/MS) analyses combined with molecular networking data processing were carried out to allow the identification of depsipeptides and cyclopeptides responsible for the cytotoxicity in the dataset. Specific ion clusters from the active Luteibacter sp. extract were also highlighted using an MRSA activity filter. A chemical study of Luteibacter sp. was conducted leading to the structural characterization of eight fatty acid exhibiting antimicrobial activity against MRSA in the tens of µg/mL range. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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20 pages, 2357 KiB  
Article
Molecular Characterization of Microtubule Affinity-Regulating Kinase4 from Sus scrofa and Promotion of Lipogenesis in Primary Porcine Placental Trophoblasts
by Liang Tian, Aiyou Wen, Shusheng Dong and Peishi Yan
Int. J. Mol. Sci. 2019, 20(5), 1206; https://doi.org/10.3390/ijms20051206 - 09 Mar 2019
Cited by 16 | Viewed by 3107
Abstract
This study aimed to characterize the full-length cDNA of MARK4 in Sus scrofa, and evaluated its potential role in the regulation of lipid accumulation in pig placental trophoblasts and analyzed signaling pathways involved, thereby providing insights into mechanisms for placental lipotoxicity induced [...] Read more.
This study aimed to characterize the full-length cDNA of MARK4 in Sus scrofa, and evaluated its potential role in the regulation of lipid accumulation in pig placental trophoblasts and analyzed signaling pathways involved, thereby providing insights into mechanisms for placental lipotoxicity induced by excessive back-fat during pregnancy of sows. The cDNA obtained with 5′ and 3′ RACE amplification covered 3216 bp with an open reading frame of 2259 bp encoding 752 amino acids. Multiple alignments and phylogenetic analysis revealed MARK4 protein of Sus scrofa had a high homology (95%–99%) to that of other higher vertebrates. After transfection, enhanced MARK4 significantly promoted lipogenesis in pig trophoblasts, as evidenced by accelerated lipid accumulation and consistently increased mRNA expressions of lipogenic genes DGAT1, LPIN1, LPIN3, LPL, PPARδ and SREBP-1c. Meanwhile, PPARγ remarkably inhibited the stimulating effect of MARK4 on non-receptor-mediated lipid accumulation in trophoblasts. Further analyses revealed WNT signaling enhanced lipid accumulation and activation of MARK4 in pig trophoblast cells. Finally, we demonstrated that WNT/β-catenin signal pathway is involved in MARK4 activated lipogenesis. These results suggest that MARK4 promotes lipid accumulation in porcine placental trophoblasts and can be considered as a potential regulator of lipotoxicity associated with maternal obesity in the pig placenta. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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16 pages, 4653 KiB  
Article
Characterization, Diversity, and Structure-Activity Relationship Study of Lipoamino Acids from Pantoea sp. and Synthetic Analogues
by Seindé Touré, Sandy Desrat, Léonie Pellissier, Pierre-Marie Allard, Jean-Luc Wolfender, Isabelle Dusfour, Didier Stien and Véronique Eparvier
Int. J. Mol. Sci. 2019, 20(5), 1083; https://doi.org/10.3390/ijms20051083 - 02 Mar 2019
Cited by 7 | Viewed by 3142
Abstract
A biological evaluation of a library of extracts from entomopathogen strains showed that Pantoea sp. extract has significant antimicrobial and insecticidal activities. Three hydroxyacyl-phenylalanine derivatives were isolated from this strain. Their structures were elucidated by a comprehensive analysis of their NMR and MS [...] Read more.
A biological evaluation of a library of extracts from entomopathogen strains showed that Pantoea sp. extract has significant antimicrobial and insecticidal activities. Three hydroxyacyl-phenylalanine derivatives were isolated from this strain. Their structures were elucidated by a comprehensive analysis of their NMR and MS spectroscopic data. The antimicrobial and insecticidal potencies of these compounds were evaluated, and compound 3 showed 67% mortality against Aedes aegypti larvae at a concentration of 100 ppm, and a minimum inhibitory concentration (MIC) of 16 µg/mL against methicillin-resistant Staphylococcus aureus. Subsequently, hydroxyacyl-phenylalanine analogues were synthesized to better understand the structure-activity relationships within this class of compounds. Bioassays highlighted the antimicrobial potential of analogues containing saturated medium-chain fatty acids (12 or 14 carbons), whereas an unsaturated long-chain fatty acid (16 carbons) imparted larvicidal activity. Finally, using a molecular networking-based approach, several close analogues of the isolated and newly synthesized lipoamino acids were discovered in the Pantoea sp. extract. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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26 pages, 7500 KiB  
Article
Lipomatrix: A Novel Ascorbyl Palmitate-Based Lipid Matrix to Enhancing Enteric Absorption of Serenoa Repens Oil
by Andrea Fratter, Vera Mason, Marzia Pellizzato, Stefano Valier, Arrigo Francesco Giuseppe Cicero, Erik Tedesco, Elisa Meneghetti and Federico Benetti
Int. J. Mol. Sci. 2019, 20(3), 669; https://doi.org/10.3390/ijms20030669 - 04 Feb 2019
Cited by 6 | Viewed by 3899
Abstract
The class of lipophilic compounds coming from vegetal source represents a perspective in the adjuvant treatment of several human diseases, despite their poor bioavailability in humans. These compounds are generally soluble in fats and poorly soluble in water. The major reason for the [...] Read more.
The class of lipophilic compounds coming from vegetal source represents a perspective in the adjuvant treatment of several human diseases, despite their poor bioavailability in humans. These compounds are generally soluble in fats and poorly soluble in water. The major reason for the poor bioavailability of lipophilic natural compounds after oral uptake in humans is related to their reduced solubility in enteric water-based fluids, leading to an ineffective contact with absorbing epithelium. The main goal to ensure efficacy of such compounds is then creating technological conditions to deliver them into the first enteric tract as hydro-dispersible forms to maximize epithelial absorption. The present work describes and characterizes a new technological matrix (Lipomatrix, Labomar Research, Istrana, TV, Italy) based on a molten fats core in which Ascorbyl Palmitate is embedded, able to deliver lipophilic compounds in a well-dispersed and emulsified form once exposed to duodenal fluids. Authors describe and quantify Lipomatrix delivery of Serenoa repens oil through an innovative in vitro model of human gastro-enteric digestion, reporting results of its improved bioaccessibility, enteric absorption and efficacy compared with not formulated Serenoa repens oil-containing commercial products using in vitro models of human intestine and prostatic tissue. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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13 pages, 13626 KiB  
Article
Oncogenic H-Ras Expression Induces Fatty Acid Profile Changes in Human Fibroblasts and Extracellular Vesicles
by Krizia Sagini, Lorena Urbanelli, Eva Costanzi, Nico Mitro, Donatella Caruso, Carla Emiliani and Sandra Buratta
Int. J. Mol. Sci. 2018, 19(11), 3515; https://doi.org/10.3390/ijms19113515 - 08 Nov 2018
Cited by 18 | Viewed by 2736
Abstract
Extracellular vesicles (EVs) are lipid bilayer surrounded particles that are considered an additional way to transmit signals outside the cell. Lipids have not only a structural role in the organization of EVs membrane bilayer, but they also represent a source of lipid mediators [...] Read more.
Extracellular vesicles (EVs) are lipid bilayer surrounded particles that are considered an additional way to transmit signals outside the cell. Lipids have not only a structural role in the organization of EVs membrane bilayer, but they also represent a source of lipid mediators that may act on target cells. Senescent cells are characterized by a permanent arrest of cell proliferation, but they are still metabolically active and influence nearby tissue secreting specific signaling mediators, including those carried by EVs. Notably, cellular senescence is associated with increased EVs release. Here, we used gas chromatography coupled to mass spectrometry to investigate the total fatty acid content of EVs released by fibroblasts undergoing H-RasV12-induced senescence and their parental cells. We find that H-RasV12 fibroblasts show increased level of monounsaturated and decreased level of saturated fatty acids, as compared to control cells. These changes are associated with transcriptional up-regulation of specific fatty acid-metabolizing enzymes. The EVs released by both controls and senescent fibroblasts show a higher level of saturated and polyunsaturated species, as compared to parental cells. Considering that fibroblasts undergoing H-RasV12-induced senescence release a higher number of EVs, these findings indicate that senescent cells release via EVs a higher amount of fatty acids, and in particular of polyunsaturated and saturated fatty acids, as compared to control cells. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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18 pages, 1635 KiB  
Article
Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia
by Lucille Stuani, Fabien Riols, Pierre Millard, Marie Sabatier, Aurélie Batut, Estelle Saland, Fanny Viars, Laure Tonini, Sonia Zaghdoudi, Laetitia K. Linares, Jean-Charles Portais, Jean-Emmanuel Sarry and Justine Bertrand-Michel
Int. J. Mol. Sci. 2018, 19(11), 3325; https://doi.org/10.3390/ijms19113325 - 25 Oct 2018
Cited by 45 | Viewed by 6141
Abstract
Background: In Acute Myeloid Leukemia (AML), a complete response to chemotherapy is usually obtained after conventional chemotherapy but overall patient survival is poor due to highly frequent relapses. As opposed to chronic myeloid leukemia, B lymphoma or multiple myeloma, AML is one [...] Read more.
Background: In Acute Myeloid Leukemia (AML), a complete response to chemotherapy is usually obtained after conventional chemotherapy but overall patient survival is poor due to highly frequent relapses. As opposed to chronic myeloid leukemia, B lymphoma or multiple myeloma, AML is one of the rare malignant hemopathies the therapy of which has not significantly improved during the past 30 years despite intense research efforts. One promising approach is to determine metabolic dependencies in AML cells. Moreover, two key metabolic enzymes, isocitrate dehydrogenases (IDH1/2), are mutated in more than 15% of AML patient, reinforcing the interest in studying metabolic reprogramming, in particular in this subgroup of patients. Methods: Using a multi-omics approach combining proteomics, lipidomics, and isotopic profiling of [U-13C] glucose and [U-13C] glutamine cultures with more classical biochemical analyses, we studied the impact of the IDH1 R132H mutation in AML cells on lipid biosynthesis. Results: Global proteomic and lipidomic approaches showed a dysregulation of lipid metabolism, especially an increase of phosphatidylinositol, sphingolipids (especially few species of ceramide, sphingosine, and sphinganine), free cholesterol and monounsaturated fatty acids in IDH1 mutant cells. Isotopic profiling of fatty acids revealed that higher lipid anabolism in IDH1 mutant cells corroborated with an increase in lipogenesis fluxes. Conclusions: This integrative approach was efficient to gain insight into metabolism and dynamics of lipid species in leukemic cells. Therefore, we have determined that lipid anabolism is strongly reprogrammed in IDH1 mutant AML cells with a crucial dysregulation of fatty acid metabolism and fluxes, both being mediated by 2-HG (2-Hydroxyglutarate) production. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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15 pages, 13534 KiB  
Article
Bivalent Ligand UDCA-LPE Inhibits Pro-Fibrogenic Integrin Signalling by Inducing Lipid Raft-Mediated Internalization
by Jie Su, Hongying Gan-Schreier, Benjamin Goeppert, Walee Chamulitrat, Wolfgang Stremmel and Anita Pathil
Int. J. Mol. Sci. 2018, 19(10), 3254; https://doi.org/10.3390/ijms19103254 - 20 Oct 2018
Cited by 5 | Viewed by 3476
Abstract
Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a synthetic bile acid-phospholipid conjugate with profound hepatoprotective and anti-fibrogenic functions in vitro and in vivo. Herein, we aimed to demonstrate the inhibitory effects of UDCA-LPE on pro-fibrogenic integrin signalling. UDCA-LPE treatment of human embryonic liver cell line CL48 [...] Read more.
Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a synthetic bile acid-phospholipid conjugate with profound hepatoprotective and anti-fibrogenic functions in vitro and in vivo. Herein, we aimed to demonstrate the inhibitory effects of UDCA-LPE on pro-fibrogenic integrin signalling. UDCA-LPE treatment of human embryonic liver cell line CL48 and primary human hepatic stellate cells induced a non-classical internalization of integrin β1 resulting in dephosphorylation and inhibition of SRC and focal adhesion kinase (FAK). Signalling analyses suggested that UDCA-LPE may act as a heterobivalent ligand for integrins and lysophospholipid receptor1 (LPAR1) and co-immunoprecipitation demonstrated the bridging effect of UDCA-LPE on integrin β1 and LPAR1. The disruption of either the UDCA-moiety binding to integrins by RGD-containing peptide GRGDSP or the LPE-moiety binding to LPAR1 by LPAR1 antagonist Ki16425 reversed inhibitory functions of UDCA-LPE. The lack of inhibitory functions of UDCA-PE and UDCA-LPE derivatives (14:0 and 12:0, LPE-moiety containing shorter fatty acid chain) as well as the consistency of the translocation of UDCA-LPE and integrins, which co-fractionated with LPE but not UDCA, suggested that the observed UDCA-LPE-induced translocation of integrins was mediated by LPE endocytic transport pathway. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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12 pages, 1314 KiB  
Article
Biochemical Characterization of the GBA2 c.1780G>C Missense Mutation in Lymphoblastoid Cells from Patients with Spastic Ataxia
by Anna Malekkou, Maura Samarani, Anthi Drousiotou, Christina Votsi, Sandro Sonnino, Marios Pantzaris, Elena Chiricozzi, Eleni Zamba-Papanicolaou, Massimo Aureli, Nicoletta Loberto and Kyproula Christodoulou
Int. J. Mol. Sci. 2018, 19(10), 3099; https://doi.org/10.3390/ijms19103099 - 10 Oct 2018
Cited by 11 | Viewed by 3554
Abstract
The GBA2 gene encodes the non-lysosomal glucosylceramidase (NLGase), an enzyme that catalyzes the conversion of glucosylceramide (GlcCer) to ceramide and glucose. Mutations in GBA2 have been associated with the development of neurological disorders such as autosomal recessive cerebellar ataxia, hereditary spastic paraplegia, and [...] Read more.
The GBA2 gene encodes the non-lysosomal glucosylceramidase (NLGase), an enzyme that catalyzes the conversion of glucosylceramide (GlcCer) to ceramide and glucose. Mutations in GBA2 have been associated with the development of neurological disorders such as autosomal recessive cerebellar ataxia, hereditary spastic paraplegia, and Marinesco-Sjogren-Like Syndrome. Our group has previously identified the GBA2 c.1780G>C [p.Asp594His] missense mutation, in a Cypriot consanguineous family with spastic ataxia. In this study, we carried out a biochemical characterization of lymphoblastoid cell lines (LCLs) derived from three patients of this family. We found that the mutation strongly reduce NLGase activity both intracellularly and at the plasma membrane level. Additionally, we observed a two-fold increase of GlcCer content in LCLs derived from patients compared to controls, with the C16 lipid being the most abundant GlcCer species. Moreover, we showed that there is an apparent compensatory effect between NLGase and the lysosomal glucosylceramidase (GCase), since we found that the activity of GCase was three-fold higher in LCLs derived from patients compared to controls. We conclude that the c.1780G>C mutation results in NLGase loss of function with abolishment of the enzymatic activity and accumulation of GlcCer accompanied by a compensatory increase in GCase. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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13 pages, 4015 KiB  
Article
Lipidomic Analysis of the Outer Membrane Vesicles from Paired Polymyxin-Susceptible and -Resistant Klebsiella pneumoniae Clinical Isolates
by Raad Jasim, Mei-Ling Han, Yan Zhu, Xiaohan Hu, Maytham H. Hussein, Yu-Wei Lin, Qi (Tony) Zhou, Charlie Yao Da Dong, Jian Li and Tony Velkov
Int. J. Mol. Sci. 2018, 19(8), 2356; https://doi.org/10.3390/ijms19082356 - 10 Aug 2018
Cited by 22 | Viewed by 5506
Abstract
Gram-negative bacteria produce outer membrane vesicles (OMVs) as delivery vehicles for nefarious bacterial cargo such as virulence factors, which are antibiotic resistance determinants. This study aimed to investigate the impact of polymyxin B treatment on the OMV lipidome from paired polymyxin-susceptible and -resistant [...] Read more.
Gram-negative bacteria produce outer membrane vesicles (OMVs) as delivery vehicles for nefarious bacterial cargo such as virulence factors, which are antibiotic resistance determinants. This study aimed to investigate the impact of polymyxin B treatment on the OMV lipidome from paired polymyxin-susceptible and -resistant Klebsiella pneumoniae isolates. K. pneumoniae ATCC 700721 was employed as a reference strain in addition to two clinical strains, K. pneumoniae FADDI-KP069 and K. pneumoniae BM3. Polymyxin B treatment of the polymyxin-susceptible strains resulted in a marked reduction in the glycerophospholipid, fatty acid, lysoglycerophosphate and sphingolipid content of their OMVs. Conversely, the polymyxin-resistant strains expressed OMVs richer in all of these lipid species, both intrinsically and increasingly under polymyxin treatment. The average diameter of the OMVs derived from the K. pneumoniae ATCC 700721 polymyxin-susceptible isolate, measured by dynamic light scattering measurements, was ~90.6 nm, whereas the average diameter of the OMVs isolated from the paired polymyxin-resistant isolate was ~141 nm. Polymyxin B treatment (2 mg/L) of the K. pneumoniae ATCC 700721 cells resulted in the production of OMVs with a larger average particle size in both the susceptible (average diameter ~124 nm) and resistant (average diameter ~154 nm) strains. In light of the above, we hypothesize that outer membrane remodelling associated with polymyxin resistance in K. pneumoniae may involve fortifying the membrane structure with increased glycerophospholipids, fatty acids, lysoglycerophosphates and sphingolipids. Putatively, these changes serve to make the outer membrane and OMVs more impervious to polymyxin attack. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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Review

Jump to: Editorial, Research

17 pages, 946 KiB  
Review
A Role for Lipid Mediators in Acute Myeloid Leukemia
by Andreas Loew, Thomas Köhnke, Emma Rehbeil, Anne Pietzner and Karsten-H. Weylandt
Int. J. Mol. Sci. 2019, 20(10), 2425; https://doi.org/10.3390/ijms20102425 - 16 May 2019
Cited by 15 | Viewed by 4542
Abstract
In spite of therapeutic improvements in the treatment of different hematologic malignancies, the prognosis of acute myeloid leukemia (AML) treated solely with conventional induction and consolidation chemotherapy remains poor, especially in association with high risk chromosomal or molecular aberrations. Recent discoveries describe the [...] Read more.
In spite of therapeutic improvements in the treatment of different hematologic malignancies, the prognosis of acute myeloid leukemia (AML) treated solely with conventional induction and consolidation chemotherapy remains poor, especially in association with high risk chromosomal or molecular aberrations. Recent discoveries describe the complex interaction of immune effector cells, as well as the role of the bone marrow microenvironment in the development, maintenance and progression of AML. Lipids, and in particular omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) have been shown to play a vital role as signaling molecules of immune processes in numerous benign and malignant conditions. While the majority of research in cancer has been focused on the role of lipid mediators in solid tumors, some data are showing their involvement also in hematologic malignancies. There is a considerable amount of evidence that AML cells are targetable by innate and adaptive immune mechanisms, paving the way for immune therapy approaches in AML. In this article we review the current data showing the lipid mediator and lipidome patterns in AML and their potential links to immune mechanisms. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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15 pages, 1639 KiB  
Review
Kidney Lipidomics by Mass Spectrometry Imaging: A Focus on the Glomerulus
by Imane Abbas, Manale Noun, David Touboul, Dil Sahali, Alain Brunelle and Mario Ollero
Int. J. Mol. Sci. 2019, 20(7), 1623; https://doi.org/10.3390/ijms20071623 - 01 Apr 2019
Cited by 19 | Viewed by 3791
Abstract
Lipid disorders have been associated with glomerulopathies, a distinct type of renal pathologies, such as nephrotic syndrome. Global analyses targeting kidney lipids in this pathophysiologic context have been extensively performed, but most often regardless of the architectural and functional complexity of the kidney. [...] Read more.
Lipid disorders have been associated with glomerulopathies, a distinct type of renal pathologies, such as nephrotic syndrome. Global analyses targeting kidney lipids in this pathophysiologic context have been extensively performed, but most often regardless of the architectural and functional complexity of the kidney. The new developments in mass spectrometry imaging technologies have opened a promising field in localized lipidomic studies focused on this organ. In this article, we revisit the main works having employed the Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) technology, and the few reports on the use of TOF-Secondary Ion Mass Spectrometry (TOF-SIMS). We also present a first analysis of mouse kidney cortex sections by cluster TOF-SIMS. The latter represents a good option for high resolution lipid imaging when frozen unfixed histological samples are available. The advantages and drawbacks of this developing field are discussed. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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16 pages, 783 KiB  
Review
Lipidomics of Bioactive Lipids in Acute Coronary Syndromes
by Zahra Solati and Amir Ravandi
Int. J. Mol. Sci. 2019, 20(5), 1051; https://doi.org/10.3390/ijms20051051 - 28 Feb 2019
Cited by 21 | Viewed by 4657
Abstract
Acute coronary syndrome (ACS) refers to ischemic conditions that occur as a result of atherosclerotic plaque rupture and thrombus formation. It has been shown that lipid peroxidation may cause plaque instability by inducing inflammation, apoptosis, and neovascularization. There is some evidence showing that [...] Read more.
Acute coronary syndrome (ACS) refers to ischemic conditions that occur as a result of atherosclerotic plaque rupture and thrombus formation. It has been shown that lipid peroxidation may cause plaque instability by inducing inflammation, apoptosis, and neovascularization. There is some evidence showing that these oxidized lipids may have a prognostic value in ACS. For instance, higher levels of oxidized phospholipids on apo B-100 lipoproteins (OxPL/apoB) predicted cardiovascular events independent of traditional risk factors, C-reactive protein (hsCRP), and the Framingham Risk Score (FRS). A recent cross-sectional study showed that levels of oxylipins, namely 8,9-DiHETrE and 16-HETE, were significantly associated with cardiovascular and cerebrovascular events, respectively. They found that with every 1 nmol/L increase in the concentrations of 8,9-DiHETrE, the odds of ACS increased by 454-fold. As lipid peroxidation makes heterogonous pools of secondary products, therefore, rapid multi-analyte quantification methods are needed for their assessment. Conventional lipid assessment methods such as chemical reagents or immunoassays lack specificity and sensitivity. Lipidomics may provide another layer of a detailed molecular level to lipid assessment, which may eventually lead to exploring novel biomarkers and/or new treatment options. Here, we will briefly review the lipidomics of bioactive lipids in ACS. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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25 pages, 2251 KiB  
Review
Cholesterol and the Safety Factor for Neuromuscular Transmission
by Igor I. Krivoi and Alexey M. Petrov
Int. J. Mol. Sci. 2019, 20(5), 1046; https://doi.org/10.3390/ijms20051046 - 28 Feb 2019
Cited by 42 | Viewed by 6466
Abstract
A present review is devoted to the analysis of literature data and results of own research. Skeletal muscle neuromuscular junction is specialized to trigger the striated muscle fiber contraction in response to motor neuron activity. The safety factor at the neuromuscular junction strongly [...] Read more.
A present review is devoted to the analysis of literature data and results of own research. Skeletal muscle neuromuscular junction is specialized to trigger the striated muscle fiber contraction in response to motor neuron activity. The safety factor at the neuromuscular junction strongly depends on a variety of pre- and postsynaptic factors. The review focuses on the crucial role of membrane cholesterol to maintain a high efficiency of neuromuscular transmission. Cholesterol metabolism in the neuromuscular junction, its role in the synaptic vesicle cycle and neurotransmitter release, endplate electrogenesis, as well as contribution of cholesterol to the synaptogenesis, synaptic integrity, and motor disorders are discussed. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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26 pages, 2308 KiB  
Review
Curbing Lipids: Impacts ON Cancer and Viral Infection
by Anika Dutta and Neelam Sharma-Walia
Int. J. Mol. Sci. 2019, 20(3), 644; https://doi.org/10.3390/ijms20030644 - 02 Feb 2019
Cited by 15 | Viewed by 4651
Abstract
Lipids play a fundamental role in maintaining normal function in healthy cells. Their functions include signaling, storing energy, and acting as the central structural component of cell membranes. Alteration of lipid metabolism is a prominent feature of cancer, as cancer cells must modify [...] Read more.
Lipids play a fundamental role in maintaining normal function in healthy cells. Their functions include signaling, storing energy, and acting as the central structural component of cell membranes. Alteration of lipid metabolism is a prominent feature of cancer, as cancer cells must modify their metabolism to fulfill the demands of their accelerated proliferation rate. This aberrant lipid metabolism can affect cellular processes such as cell growth, survival, and migration. Besides the gene mutations, environmental factors, and inheritance, several infectious pathogens are also linked with human cancers worldwide. Tumor viruses are top on the list of infectious pathogens to cause human cancers. These viruses insert their own DNA (or RNA) into that of the host cell and affect host cellular processes such as cell growth, survival, and migration. Several of these cancer-causing viruses are reported to be reprogramming host cell lipid metabolism. The reliance of cancer cells and viruses on lipid metabolism suggests enzymes that can be used as therapeutic targets to exploit the addiction of infected diseased cells on lipids and abrogate tumor growth. This review focuses on normal lipid metabolism, lipid metabolic pathways and their reprogramming in human cancers and viral infection linked cancers and the potential anticancer drugs that target specific lipid metabolic enzymes. Here, we discuss statins and fibrates as drugs to intervene in disordered lipid pathways in cancer cells. Further insight into the dysregulated pathways in lipid metabolism can help create more effective anticancer therapies. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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11 pages, 1444 KiB  
Review
Specialized Pro-Resolving Lipid Mediators in Cystic Fibrosis
by Réginald Philippe and Valerie Urbach
Int. J. Mol. Sci. 2018, 19(10), 2865; https://doi.org/10.3390/ijms19102865 - 21 Sep 2018
Cited by 21 | Viewed by 5054
Abstract
In cystic fibrosis (CF), impaired airway surface hydration (ASL) and mucociliary clearance that promote chronic bacterial colonization, persistent inflammation, and progressive structural damage to the airway wall architecture are typically explained by ion transport abnormalities related to the mutation of the gene coding [...] Read more.
In cystic fibrosis (CF), impaired airway surface hydration (ASL) and mucociliary clearance that promote chronic bacterial colonization, persistent inflammation, and progressive structural damage to the airway wall architecture are typically explained by ion transport abnormalities related to the mutation of the gene coding for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. However, the progressive and unrelenting inflammation of the CF airway begins early in life, becomes persistent, and is excessive relative to the bacterial burden. Intrinsic abnormalities of the inflammatory response in cystic fibrosis have been suggested but the mechanisms involved remain poorly understood. This review aims to give an overview of the recent advances in the understanding of the defective resolution of inflammation in CF including the abnormal production of specialized pro-resolving lipid mediators (lipoxin and resolvin) and their impact on the pathogenesis of the CF airway disease. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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