Lipidomic analysis of adipose-derived extracellular vesicles reveals their potential as lipid mediators of obesity-associated metabolic complications

Adipose extracellular vesicles (AdEV) transport lipids that could participate to the development of obesity-related metabolic dysfunctions. This study aimed to define mice AdEV lipid signature in either healthy or obesity context by a targeted LC-MS/MS approach. Distinct clustering of AdEV and visceral adipose tissue (VAT) lipidomes by principal component analysis reveals specific lipid composition of AdEV compared to source VAT. Comprehensive analysis identifies enrichment of ceramides and phosphatidylglycerols in AdEV compared to VAT in lean conditions. Lipid subspecies commonly enriched in AdEV highlight specific AdEV-lipid sorting. Obesity impacts AdEV lipidome, driving triacylglycerols and sphingomyelins enrichment in obese versus lean conditions. Obese mice AdEV also display elevated phosphatidylglycerols and acid arachidonic subspecies contents highlighting novel biomarkers and/or mediators of metabolic dysfunctions. Our study identifies specific lipid-fingerprints for plasma, VAT and AdEV that are informative of the metabolic status and underline the signaling capacity of lipids transported by AdEV in obesity-associated complications.

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Lipidomic Analysis of Adipose-Derived Extracellular Vesicles Reveals Their Potential as Lipid Mediators of Obesity-Associated Metabolic Complications

SSRN Electronic Journal ◽

10.2139/ssrn.3924604 ◽

2021 ◽

Author(s):

Alexia Blandin ◽

Grégory Hilairet ◽

Maharajah Ponnaiah ◽

Simon Ducheix ◽

Isabelle Dugail ◽

...

Keyword(s):

Extracellular Vesicles ◽

Lipid Mediators ◽

Metabolic Complications ◽

Lipidomic Analysis

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Topical Application of Capsaicin Reduces Visceral Adipose Fat by Affecting Adipokine Levels in High-Fat Diet-Induced Obese Mice

Obesity ◽

10.1038/oby.2012.166 ◽

2012 ◽

Cited By ~ 2

Author(s):

Gong-Rak Lee ◽

Mi Kyung Shin ◽

Dong-Joon Yoon ◽

Ah-Ram Kim ◽

Rina Yu ◽

...

Keyword(s):

Topical Application ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Visceral Adipose

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Systems-wide effects of short-term feed deprivation in obese mice

Scientific Reports ◽

10.1038/s41598-021-85020-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daniel Andersen ◽

Henrik Munch Roager ◽

Li Zhang ◽

Janne Marie Moll ◽

Henrik Lauritz Frandsen ◽

...

Keyword(s):

Adipose Tissue ◽

Butyric Acid ◽

Visceral Adipose Tissue ◽

Animal Studies ◽

Uncoupling Protein ◽

Metabolic Changes ◽

Obese Mice ◽

Short Term ◽

Feed Deprivation ◽

Visceral Adipose

AbstractWhile prolonged fasting induces significant metabolic changes in humans and mice, less is known about systems-wide metabolic changes in response to short-term feed deprivation, which is used in experimental animal studies prior to metabolic challenge tests. We here performed a systems biology-based investigation of connections between gut bacterial composition and function, inflammatory and metabolic parameters in the intestine, liver, visceral adipose tissue, blood and urine in high-fat fed, obese mice that were feed deprived up to 12 h. The systems-wide analysis revealed that feed deprivation linked to enhanced intestinal butyric acid production and expression of the gene encoding the pro-thermogenic uncoupling protein UCP1 in visceral adipose tissue of obese mice. Ucp1 expression was also positively associated with Il33 expression in ileum, colon and adipose tissue as well as with the abundance of colonic Porphyromonadaceae, the latter also correlating to cecal butyric acid levels. Collectively, the data highlighted presence of a multi-tiered system of inter-tissue communication involving intestinal, immune and metabolic functions which is affected by feed deprivation in obese mice, thus pointing to careful use of short-feed deprivation in metabolic studies using obese mice.

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Detection of Prostate Cancer via IR Spectroscopic Analysis of Urinary Extracellular Vesicles: A Pilot Study

Membranes ◽

10.3390/membranes11080591 ◽

2021 ◽

Vol 11 (8) ◽

pp. 591

Author(s):

Xin-Le Yap ◽

Bayden Wood ◽

Teng-Aik Ong ◽

Jasmine Lim ◽

Bey-Hing Goh ◽

...

Keyword(s):

Prostate Cancer ◽

Extracellular Vesicles ◽

Cancer Progression ◽

Prostate Cancer Screening ◽

Principal Component ◽

Urine Samples ◽

Cancer Type ◽

Marker Proteins ◽

Novel Strategy ◽

Ir Spectroscopic

Extracellular vesicles (EVs) are membranous nanoparticles naturally released from living cells which can be found in all types of body fluids. Recent studies found that cancer cells secreted EVs containing the unique set of biomolecules, which give rise to a distinctive absorbance spectrum representing its cancer type. In this study, we aimed to detect the medium EVs (200–300 nm) from the urine of prostate cancer patients using Fourier transform infrared (FTIR) spectroscopy and determine their association with cancer progression. EVs extracted from 53 urine samples from patients suspected of prostate cancer were analyzed and their FTIR spectra were preprocessed for analysis. Characterization of morphology, particle size and marker proteins confirmed that EVs were successfully isolated from urine samples. Principal component analysis (PCA) of the EV’s spectra showed the model could discriminate prostate cancer with a sensitivity of 59% and a specificity of 81%. The area under curve (AUC) of FTIR PCA model for prostate cancer detection in the cases with 4–20 ng/mL PSA was 0.7, while the AUC for PSA alone was 0.437, suggesting the analysis of urinary EVs described in this study may offer a novel strategy for the development of a noninvasive additional test for prostate cancer screening.

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Crucial Role of Extracellular Vesicles in Bronchial Asthma

International Journal of Molecular Sciences ◽

10.3390/ijms20102589 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2589 ◽

Cited By ~ 7

Author(s):

Tatsuya Nagano ◽

Masahiro Katsurada ◽

Ryota Dokuni ◽

Daisuke Hazama ◽

Tatsunori Kiriu ◽

...

Keyword(s):

Bronchial Asthma ◽

Extracellular Vesicles ◽

Bronchoalveolar Lavage Fluid ◽

Cell Types ◽

Lavage Fluid ◽

Generation Process ◽

Intracellular Proteins ◽

Novel Biomarkers ◽

Microarray Analyses

Extracellular vesicles (EVs) are circulating vesicles secreted by various cell types. EVs are classified into three groups according to size, structural components, and generation process of vesicles: exosomes, microvesicles, and apoptotic bodies. Recently, EVs have been considered to be crucial for cell-to-cell communications and homeostasis because they contain intracellular proteins and nucleic acids. Epithelial cells from mice suffering from bronchial asthma (BA) secrete more EVs and suppress inflammation-induced EV production. Moreover, microarray analyses of bronchoalveolar lavage fluid have revealed that several microRNAs are useful novel biomarkers of BA. Mesenchymal stromal cell-derived EVs are possible candidates of novel BA therapy. In this review, we highlight the biologic roles of EVs in BA and review novel EV-targeted therapy to help understanding by clinicians and biologists.

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Multiplexed profiling of single-cell extracellular vesicles secretion

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1814348116 ◽

2019 ◽

Vol 116 (13) ◽

pp. 5979-5984 ◽

Cited By ~ 22

Author(s):

Yahui Ji ◽

Dongyuan Qi ◽

Linmei Li ◽

Haoran Su ◽

Xiaojie Li ◽

...

Keyword(s):

Single Cell ◽

Cell Lines ◽

Extracellular Vesicles ◽

Single Cell Analysis ◽

Comprehensive Evaluation ◽

Single Cells ◽

Deep Understanding ◽

Principal Component ◽

Cell Heterogeneity ◽

Indispensable Tool

Extracellular vesicles (EVs) are important intercellular mediators regulating health and diseases. Conventional methods for EV surface marker profiling, which was based on population measurements, masked the cell-to-cell heterogeneity in the quantity and phenotypes of EV secretion. Herein, by using spatially patterned antibody barcodes, we realized multiplexed profiling of single-cell EV secretion from more than 1,000 single cells simultaneously. Applying this platform to profile human oral squamous cell carcinoma (OSCC) cell lines led to a deep understanding of previously undifferentiated single-cell heterogeneity underlying EV secretion. Notably, we observed that the decrement of certain EV phenotypes (e.g.,CD63+EV) was associated with the invasive feature of both OSCC cell lines and primary OSCC cells. We also realized multiplexed detection of EV secretion and cytokines secretion simultaneously from the same single cells to investigate the multidimensional spectrum of cellular communications, from which we resolved tiered functional subgroups with distinct secretion profiles by visualized clustering and principal component analysis. In particular, we found that different cell subgroups dominated EV secretion and cytokine secretion. The technology introduced here enables a comprehensive evaluation of EV secretion heterogeneity at single-cell level, which may become an indispensable tool to complement current single-cell analysis and EV research.

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Small Extracellular Vesicles Isolated from Serum May Serve as Signal-Enhancers for the Monitoring of CNS Tumors

International Journal of Molecular Sciences ◽

10.3390/ijms21155359 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5359 ◽

Cited By ~ 1

Author(s):

Gabriella Dobra ◽

Matyas Bukva ◽

Zoltan Szabo ◽

Bella Bruszel ◽

Maria Harmati ◽

...

Keyword(s):

Extracellular Vesicles ◽

Serum Proteins ◽

Lumbar Disc ◽

Principal Component ◽

Cns Tumors ◽

Serum Samples ◽

Force Microscopy ◽

Isolation And Characterization ◽

Atomic Force ◽

Patient Groups

Liquid biopsy-based methods to test biomarkers (e.g., serum proteins and extracellular vesicles) may help to monitor brain tumors. In this proteomics-based study, we aimed to identify a characteristic protein fingerprint associated with central nervous system (CNS) tumors. Overall, 96 human serum samples were obtained from four patient groups, namely glioblastoma multiforme (GBM), non-small-cell lung cancer brain metastasis (BM), meningioma (M) and lumbar disc hernia patients (CTRL). After the isolation and characterization of small extracellular vesicles (sEVs) by nanoparticle tracking analysis (NTA) and atomic force microscopy (AFM), liquid chromatography -mass spectrometry (LC-MS) was performed on two different sample types (whole serum and serum sEVs). Statistical analyses (ratio, Cohen’s d, receiver operating characteristic; ROC) were carried out to compare patient groups. To recognize differences between the two sample types, pairwise comparisons (Welch’s test) and ingenuity pathway analysis (IPA) were performed. According to our knowledge, this is the first study that compares the proteome of whole serum and serum-derived sEVs. From the 311 proteins identified, 10 whole serum proteins and 17 sEV proteins showed the highest intergroup differences. Sixty-five proteins were significantly enriched in sEV samples, while 129 proteins were significantly depleted compared to whole serum. Based on principal component analysis (PCA) analyses, sEVs are more suitable to discriminate between the patient groups. Our results support that sEVs have greater potential to monitor CNS tumors, than whole serum.

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Interferon-γ and Hypoxia Priming Have Limited Effect on the miRNA Landscape of Human Mesenchymal Stromal Cells-Derived Extracellular Vesicles

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.581436 ◽

2020 ◽

Vol 8 ◽

Author(s):

Juliette Peltzer ◽

Kyle Lund ◽

Marie-Emmanuelle Goriot ◽

Marion Grosbot ◽

Jean-Jacques Lataillade ◽

...

Keyword(s):

Extracellular Vesicles ◽

Principal Component ◽

Interferon Γ ◽

Biological Action ◽

Individual Variability ◽

Substantial Part ◽

Beneficial Effects ◽

Healthy Donors ◽

Micro Rnas ◽

Serum Free Condition

Mesenchymal stromal cell (MSC)-based cell therapy has received great interest in regenerative medicine. Priming the cells during the culture phase can improve their efficacy and/or survival after injection. The literature suggests that MSC extracellular vesicles (EV) can recapitulate a substantial part of the beneficial effects of the cells they originate from, and that micro-RNAs (miRNAs) are important players in EV biological action. Here, our aim was to determine if two classical priming methods of MSC, interferon-gamma (IFNγ) and hypoxia (HYP), could modify their EV miRNA content. Human bone marrow MSCs (BM-MSCs) from five healthy donors were cultured with IFNγ or in HYP or in control (CONT) conditions. The conditioned media were collected after 48 h in serum-free condition and EV were isolated by ultracentrifugation. Total RNA was isolated, pools of CONT, IFN, and HYP cDNA were prepared, and a miRNA profiling was performed using RT-qPCR. Then, miRNAs were selected based on their detectability and measured on each individual EV sample. Priming had no effect on EV amount or size distribution. A set of 81 miRNAs was detected in at least one of the pools of EVs. They were measured on each individual sample; 41 miRNAs were detected in all samples. The principal component analysis (PCA) failed to discriminate the groups. HYP induced a significant decrease in EV hsa-miR-34a-3p content and IFN induced a significant increase in five miRNAs (hsa-miR-25-3p, hsa-miR-106a-5p, hsa-miR-126-3p, hsa-miR-451a, and hsa-miR-665). Taken together, we found only limited alterations in the miRNA landscape of MSC EV with a high inter-individual variability.

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