Featured
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Article
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Imputation of plasma lipid species to facilitate integration of lipidomic datasets
Advancements in plasma lipidomic profiling increase specificity of measurements but pose challenges in aligning datasets created at different times or platforms. Here the authors present a predictive framework for harmonising such datasets with different levels of granularity in their lipid measurements.
- Aleksandar Dakic
- , Jingqin Wu
- & Peter J. Meikle
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Article
| Open Access
Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease
Specialized pro-resolving mediators (SPM) are involved in the reprogramming of immune responses. Here the authors show that resolvin (RvT) 4 limits the progression of vascular disease in mouse models of arthritis exacerbated atherosclerotic inflammation.
- Mary E. Walker
- , Roberta De Matteis
- & Jesmond Dalli
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Matters Arising
| Open Access
Failure to apply standard limit-of-detection or limit-of-quantitation criteria to specialized pro-resolving mediator analysis incorrectly characterizes their presence in biological samples
- Valerie B. O’Donnell
- , Nils H. Schebb
- & Garret A. FitzGerald
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Article
| Open Access
A transcriptional network governing ceramide homeostasis establishes a cytokine-dependent developmental process
Bioactive small molecules mediate transcription factor functions to control cellular processes. Here, Liao et al. discover that a GATA1-regulated metabolic enzyme controls ceramide homeostasis to commission vital cytokine signaling for erythropoiesis.
- Ruiqi Liao
- , Abiola Babatunde
- & Emery H. Bresnick
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Article
| Open Access
The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism
Ferroptosis is an iron-dependent cell death mechanism that is emerging as a target for cancer therapy. Here, the authors find that lipoprotein-associated phospholipase A2 modulates ferroptosis resistance by controlling phospholipid metabolism.
- Mihee Oh
- , Seo Young Jang
- & Eun-Woo Lee
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Article
| Open Access
Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging
Single-cell analysis provides unique insight into individual cell dynamics and cell-to-cell heterogeneity. Here, the authors utilize trapped ion mobility separation coupled with dual-polarity ionization mass spectrometry imaging to enable high-throughput in situ profiling of single-cell lipidome.
- Hua Zhang
- , Yuan Liu
- & Lingjun Li
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Article
| Open Access
Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome
Fatty acids are fundamental biomolecular building blocks that are characterized by extraordinary structural diversity and present a formidable analytical challenge. Here the authors introduce a discovery workflow for de novo identification that adds more than 100 fatty acids to the human lipidome.
- Jan Philipp Menzel
- , Reuben S. E. Young
- & Stephen J. Blanksby
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Article
| Open Access
Four-dimensional trapped ion mobility spectrometry lipidomics for high throughput clinical profiling of human blood samples
The circulatory lipidome is a valuable source for disease markers, but reliable marker discovery requires continuous development of lipidomic methods for large-scale clinical profiling. Here, the authors present a 4-dimensional lipidomics solution for confident and reproducible blood lipidome profiling.
- Raissa Lerner
- , Dhanwin Baker
- & Laura Bindila
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Article
| Open Access
A Mycobacterium tuberculosis fingerprint in human breath allows tuberculosis detection
Most conventional tuberculosis diagnostic tests rely on difficult to obtain sputum samples. In this proof-of-concept study, authors analyse whether pulmonary tuberculosis can be detected using exhaled breath condensate samples.
- Sergio Fabián Mosquera-Restrepo
- , Sophie Zuberogoïtia
- & Jérôme Nigou
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Article
| Open Access
Analytical and computational workflow for in-depth analysis of oxidized complex lipids in blood plasma
Oxidized lipids are prominent bioactive agents, and yet their molecular repertoire remains largely unknown. Here, the authors apply bioinformatics and LC-MS/MS to uncover the diversity and specificity of modified lipids in human blood plasma of lean and obese individuals.
- Angela Criscuolo
- , Palina Nepachalovich
- & Maria Fedorova
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Article
| Open Access
Inhibition of the Niemann-Pick C1 protein is a conserved feature of multiple strains of pathogenic mycobacteria
Lipids shed by pathogenic mycobacteria have been shown to inhibit NPC1, a lysosomal membrane protein deficient in most cases of a rate inherited lysosomal storage disorder Niemann-Pick disease type C (NPC). Here, authors utilise lipid extracts from clinical Mycobacterium tuberculosis strains, and non-tubercular mycobacteria to investigate their ability to inhibit the NPC pathway.
- Yuzhe Weng
- , Dawn Shepherd
- & Frances M. Platt
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Article
| Open Access
A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants
Here, Farley et al. perform untargeted lipidomics to assess how SARS-CoV-2 rewires host lipid metabolism. SARS-CoV-2 viral proteins specifically induce lipid droplet formation and dramatically change lipid metabolism to support infection; interfering with lipid metabolism using small molecule inhibitors decreases virus production.
- Scotland E. Farley
- , Jennifer E. Kyle
- & Fikadu G. Tafesse
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Article
| Open Access
Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease
Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD.
- Gemma Cadby
- , Corey Giles
- & Eric K. Moses
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Article
| Open Access
PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling
Fatty acid unsaturation by stearoyl-CoA desaturase 1 (SCD1) protects against cellular stress through unclear mechanisms. Here the authors show 1,2-dioleoyl-sn-glycero-3-phospho-(1’-myo-inositol) is an SCD1-derived signaling lipid that regulates stress-adaption, protects against cell death and promotes proliferation.
- Maria Thürmer
- , André Gollowitzer
- & Andreas Koeberle
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Article
| Open Access
Dual-resolving of positional and geometric isomers of C=C bonds via bifunctional photocycloaddition-photoisomerization reaction system
The simultaneous identification of position and configuration of double bonds in unsaturated lipids is challenging. Here, the authors develop a workflow for deep structural lipidomics to address this issue using a bifunctional reaction system combined with liquid chromatography-mass spectrometry, revealing double bond patterns in bacteria and in mouse brain ischemia.
- Guifang Feng
- , Ming Gao
- & Suming Chen
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Article
| Open Access
Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle
Endoplasmic Reticulum stress induces cell non-autonomous Unfolded Protein Response (UPR) activation. Here the authors show that long-chain ceramides are secreted from muscle cells in extracellular vesicles and induce cell non-autonomous UPR activation in muscle cells in response to lipotoxcity.
- Ben D. McNally
- , Dean F. Ashley
- & Lee D. Roberts
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Article
| Open Access
Mechanism of action and therapeutic route for a muscular dystrophy caused by a genetic defect in lipid metabolism
Mutations in the CHKB gene cause muscular dystrophy. Here, the authors show that in mouse models of the disease changes in lipid metabolism are associated with decreased PPAR signaling, and show PPAR agonists can rescue expression of injury markers in myocytes in vitro.
- Mahtab Tavasoli
- , Sarah Lahire
- & Christopher R. McMaster
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Article
| Open Access
A mass spectrometric method for in-depth profiling of phosphoinositide regioisomers and their disease-associated regulation
Different phosphoinositide isomers are involved in a variety of physiological and pathological processes. Here, the authors combine chiral column chromatography and mass spectrometry to measure phosphoinositide regioisomers, revealing their dynamic changes in intra- and extracellular cancer cell milieus.
- Shin Morioka
- , Hiroki Nakanishi
- & Takehiko Sasaki
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Article
| Open Access
Structural library and visualization of endogenously oxidized phosphatidylcholines using mass spectrometry-based techniques
Oxidized phosphatidylcholines (oxPCs) are a structurally diverse class of lipids associated with various diseases. Here, the authors use mass spectrometry to construct a spectral library of 465 oxPCs and subsequently profile oxPCs formed during acetaminophen-induced acute liver failure in mice.
- Yuta Matsuoka
- , Masatomo Takahashi
- & Ken-ichi Yamada
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Article
| Open Access
Patched regulates lipid homeostasis by controlling cellular cholesterol levels
Cellular cholesterol levels are tightly regulated. Here, the authors show that the hedgehog signalling receptor PTCH is a cholesterol transporter. Reduction in PTCH activity leads to cellular cholesterol accumulation, changes in nuclear hormone receptor activity and fatty acid metabolism.
- Carla E. Cadena del Castillo
- , J. Thomas Hannich
- & Anne Spang
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Matters Arising
| Open Access
Quality control requirements for the correct annotation of lipidomics data
- Harald C. Köfeler
- , Thomas O. Eichmann
- & Kim Ekroos
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Matters Arising
| Open Access
Reply to “Quality control requirements for the correct annotation of lipidomics data”
- Catherine G. Vasilopoulou
- , Karolina Sulek
- & Florian Meier
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Article
| Open Access
UbiB proteins regulate cellular CoQ distribution in Saccharomyces cerevisiae
Coenzyme Q (CoQ) is a lipid made in the inner mitochondrial membrane with antioxidant roles throughout the cell, but regulation of its cellular distribution is unclear. Here the authors identify two proteins that have reciprocal CoQ trafficking functions to help coordinate CoQ localization in yeast.
- Zachary A. Kemmerer
- , Kyle P. Robinson
- & David J. Pagliarini
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Article
| Open Access
Ion mobility-based sterolomics reveals spatially and temporally distinctive sterol lipids in the mouse brain
Sterol lipids are crucial for maintaining proper brain function. Here, the authors combine ion mobility-mass spectrometry and machine learning to assemble a sterol lipid library and characterize differences in sterol lipids across ten brain regions and two age groups in mice.
- Tongzhou Li
- , Yandong Yin
- & Zheng-Jiang Zhu
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Article
| Open Access
Saturated free fatty acids and association with memory formation
Changes in poly-unsaturated free fatty acids (FFAs) have been associated with LTP. Here, using lipidomics analysis the authors characterise FFA changes in the rat brain associated with fear conditioning, and demonstrate that increases in saturated FFAs represent the major change.
- Tristan P. Wallis
- , Bharat G. Venkatesh
- & Frédéric A. Meunier
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Article
| Open Access
Single-cell lipidomics with high structural specificity by mass spectrometry
Analyzing the lipidomes of single cells remains a challenge. Here, the authors present a strategy to identify class, fatty acyl-chain, C=C locations and sn-positions of lipids in single cells, and use their method to identify individual gefitinib-resistant cells in a wild-type lung cancer cell population.
- Zishuai Li
- , Simin Cheng
- & Zheng Ouyang
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Article
| Open Access
Toxoplasma LIPIN is essential in channeling host lipid fluxes through membrane biogenesis and lipid storage
Apicomplexa generate essential lipids as combination of host fatty acids and de novo synthesized within the apicoplast. Here, the authors identify a phosphatidic acid phosphatase in Toxoplasma gondii, TgLIPIN, as central for controlled lipid synthesis and define the host-scavenged lipidome.
- Sheena Dass
- , Serena Shunmugam
- & Cyrille Y. Botté
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Article
| Open Access
Inositol triphosphate-triggered calcium release blocks lipid exchange at endoplasmic reticulum-Golgi contact sites
The interplay between non-vesicular lipid transport, calcium signaling, and membrane dynamics is unclear. Here, the authors report a function for inositol triphosphate hydrolysis by the inositol 5-phosphatase INPP5A in controlling lipid exchange at interorganelle membrane contact sites between the endoplasmic reticulum and Golgi.
- Mouhannad Malek
- , Anna M. Wawrzyniak
- & Volker Haucke
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Article
| Open Access
Prostaglandin in the ventromedial hypothalamus regulates peripheral glucose metabolism
The ventromedial hypothalamus regulates systemic glucose metabolism. Here the authors show that cytosolic phospholipase A2 mediated phospholipid metabolism contributes to this regulation in healthy animals but exert deteriorating effects on glucose homeostasis under high-fat-diet feeding.
- Ming-Liang Lee
- , Hirokazu Matsunaga
- & Chitoku Toda
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Article
| Open Access
Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1
Inhibition of the lipid peroxidase GPX4 promotes ferroptotic cell death. Here, the authors identify a complementary approach using conjugated linolenic fatty acids that trigger lipid peroxidation and ferroptosis via ACSL1, DGAT1/2, and neutral lipids.
- Alexander Beatty
- , Tanu Singh
- & Jeffrey R. Peterson
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Article
| Open Access
High-dimensional super-resolution imaging reveals heterogeneity and dynamics of subcellular lipid membranes
Lipid membranes are heterogeneous and dynamically regulated in cells. Here the authors report a Spectrum and Polarisation Optical Tomography (SPOT) method where they use Nile Red dye to resolve membrane morphology, polarity and phase in cells.
- Karl Zhanghao
- , Wenhui Liu
- & Dayong Jin
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Article
| Open Access
Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease
The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.
- Kevin Huynh
- , Wei Ling Florence Lim
- & Peter J. Meikle
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Article
| Open Access
FABP3-mediated membrane lipid saturation alters fluidity and induces ER stress in skeletal muscle with aging
Ageing leads to a loss of muscle mass and strength, called sarcopenia. Here, the authors show that fatty acid binding protein 3 (FABP3), a lipid chaperone, drives age-dependent lipidome remodeling in skeletal muscle and deteriorates muscle mass and contractility by modulating membrane fluidity and ER stress signaling.
- Seung-Min Lee
- , Seol Hee Lee
- & Ki-Sun Kwon
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Article
| Open Access
The lysophospholipase D enzyme Gdpd3 is required to maintain chronic myelogenous leukaemia stem cells
How lipid metabolism can affect cancer recurrence is still unclear. Here, the authors show that the lysophospholipase D Gdpd3 maintains self-renewal capacity of CML stem cells by regulating the quiescence, and AKT/mTORC1 and Foxo3a/β-catenin signalling in an oncogene-independent manner.
- Kazuhito Naka
- , Ryosuke Ochiai
- & Seong-Jin Kim
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Article
| Open Access
A global lipid map defines a network essential for Zika virus replication
Zika virus (ZIKV) remodels intracellular membranes for replication, but the role of different lipid types for infection and disease is unclear. Here, the authors perform lipidomics, show perturbation of the lipid network during ZIKV infection and show that ceramides are important for ZIKV infection.
- Hans C. Leier
- , Jules B. Weinstein
- & Fikadu G. Tafesse
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Article
| Open Access
Fast and sensitive flow-injection mass spectrometry metabolomics by analyzing sample-specific ion distributions
Flow-injection mass spectrometry (FI-MS) enables high-throughput metabolomic profiling, but ion overload typically limits its sensitivity. Here, the authors show rapid and highly sensitive FI-MS overcoming an overload of the Orbitrap by analyzing sample-specific ion distributions.
- Boris Sarvin
- , Shoval Lagziel
- & Tomer Shlomi
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Article
| Open Access
Metabolic reprogramming by Zika virus provokes inflammation in human placenta
Zika virus (ZIKV) infection of pregnant women is associated with pregnancy loss and birth defects, but molecular insights for the aetiology are scarce. Here the authors show that ZIKV reprograms the host lipidome to facilitate viral replication, induce mitochondria dysfunction, and cause immune imbalance, thereby identifying a potential target for ZIKV therapy.
- Qian Chen
- , Jordi Gouilly
- & Nabila Jabrane-Ferrat
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Article
| Open Access
2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer
Androgen receptor (AR) signalling regulates cellular metabolism in prostate cancer. Here, the authors perform a proteomics and metabolomics characterisation of prostate cancer cells adapted to long-term resistance to AR inhibition and show rewiring of glucose and lipid metabolism, and further identify a signature associated with resistance to AR inhibition.
- Arnaud Blomme
- , Catriona A. Ford
- & Hing Y. Leung
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Article
| Open Access
LipidCreator workbench to probe the lipidomic landscape
Targeted mass spectrometry enables reproducible and accurate lipid quantification but dedicated software tools to develop targeted lipidomics assays are lacking. Here, the authors develop a targeted lipidomics workbench and lipid knowledgebase for the streamlined generation of targeted assays.
- Bing Peng
- , Dominik Kopczynski
- & Robert Ahrends
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Article
| Open Access
Different regions of synaptic vesicle membrane regulate VAMP2 conformation for the SNARE assembly
Vesicle associated membrane protein 2 (VAMP2) contains a conserved SNARE motif that interacts with syntaxin-1 and SNAP25 for SNARE complex assembly. Here authors use in-cell NMR spectroscopy to describe the dynamic membrane association of VAMP2 SNARE motif in mammalian cells at the atomic resolution.
- Chuchu Wang
- , Jia Tu
- & Cong Liu
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Article
| Open Access
Lipidomic and biophysical homeostasis of mammalian membranes counteracts dietary lipid perturbations to maintain cellular fitness
Proper membrane physiology requires maintenance of a narrow range of physicochemical properties, which must be buffered from external perturbations. Here, authors report lipidomic remodeling to preserve membrane physical properties upon exogenous polyunsaturated fatty acids exposure.
- Kandice R. Levental
- , Eric Malmberg
- & Ilya Levental
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Article
| Open Access
Large-scale lipid analysis with C=C location and sn-position isomer resolving power
Coupling photochemical derivatization with tandem mass spectrometry enables C=C-isomer resolved lipidomics. Here, the authors further develop this approach into a shotgun lipidomics workflow that allows simultaneous characterization of lipid C=C locations and sn-positions in complex biological samples.
- Wenbo Cao
- , Simin Cheng
- & Xiaoxiao Ma
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Article
| Open Access
Trapped ion mobility spectrometry and PASEF enable in-depth lipidomics from minimal sample amounts
Trapped ion mobility (TIMS)-mass spectrometry with parallel accumulation-serial fragmentation (PASEF) facilitates high-sensitivity proteomics experiments. Here, the authors expand TIMS and PASEF to small molecules and demonstrate fast and comprehensive lipidomics of low biological sample amounts.
- Catherine G. Vasilopoulou
- , Karolina Sulek
- & Florian Meier
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Article
| Open Access
Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
Blood metabolite levels are under the influence of environmental and genetic factors. Here, Hagenbeek et al. perform heritability estimations for metabolite measures and determine the contribution of known metabolite loci to metabolite levels using data from 40 genome-wide association studies.
- Fiona A. Hagenbeek
- , René Pool
- & Dorret I. Boomsma
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Article
| Open Access
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
Cardiovascular diseases (CVD) are associated with plasma lipid levels. Here, Tabassum et al. perform genome-wide association studies for lipidomic profiles with 141 (non-standard) lipid species which highlights shared genetic loci with CVD and that traditional lipids have low genetic correlation with other lipids.
- Rubina Tabassum
- , Joel T. Rämö
- & Samuli Ripatti
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Article
| Open Access
A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis
Clear-cell carcinomas are aggressive tumours characterised by high accumulation of lipids and glycogen. Here, the authors report that these cancers have a common vulnerability to GPX4 inhibition-induced ferroptosis and using CRISPR screen and lipodomic profiling, they identify HIF-2α- HILPDA axis promotes ferroptosis via enrichment of PUFA lipids.
- Yilong Zou
- , Michael J. Palte
- & Stuart L. Schreiber
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Article
| Open Access
Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins
The Ups/PRELI family mediates intramitochondrial lipid distribution and synthesis by shuttling phospholipids between both mitochondrial membranes. Here the authors combine X-ray crystallography, MD simulations and yeast genetic screens and identify residues that are important for Ups/PRELI lipid specificity and reveal a dual lipid recognition mechanism in Ups/PRELI family members.
- Xeni Miliara
- , Takashi Tatsuta
- & Thomas Langer
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Article
| Open Access
Ion mobility conformational lipid atlas for high confidence lipidomics
The biological functions of lipids critically depend on their highly diverse molecular structures. Here, the authors determine the mass-resolved collision cross sections of 456 sphingolipid and glycerophospholipid species, providing a reference for future structural lipidomics studies.
- Katrina L. Leaptrot
- , Jody C. May
- & John A. McLean
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Article
| Open Access
SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target
Viruses rely on host cell metabolism for replication, making these pathways potential therapeutic targets. Here, the authors show that AM580, a retinoid derivative and RAR-α agonist, affects replication of several RNA viruses by interfering with the activity of SREBP.
- Shuofeng Yuan
- , Hin Chu
- & Kwok-Yung Yuen
Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans