PubMed

Ecotoxicol Environ Saf. 2024 Jun 27;281:116594. doi: 10.1016/j.ecoenv.2024.116594. Online ahead of print.ABSTRACTChromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults. The Cr exposure-related metabolomic changes are not well elucidated. This study recruited 608 students from a university in Shandong Province, China in 2019. We used cohort design fitted with linear mixed-effects models to assess the association between blood Cr concentration and lung function. In addition, we performed metabolomic and lipidomic analyses of baseline serum samples (N = 582) using liquid chromatography-mass spectrometry. Two-step statistical analysis (analysis of variance and mixed-linear effect model) was used to evaluate the effect of blood Cr exposure on metabolites. We found that blood Cr was associated with decreased lung function in young adults. Each 2-fold increase in blood Cr concentrations was significantly associated with decreased FEV1 and FVC by 35.26 mL (95 % CI: -60.75, -9.78) and 38.56 mL (95 % CI: -66.60, -10.51), respectively. In the metabolomics analysis, blood Cr exposure was significantly associated with 14 key metabolites. The changed metabolites were mainly enriched in six pathways including lipid metabolism, amino acid metabolism, and cofactor vitamin metabolism. Blood Cr may affect lung function through oxidative stress and inflammation related pathways.PMID:38941662 | DOI:10.1016/j.ecoenv.2024.116594

Sci Adv. 2024 Jun 28;10(26):eadn5228. doi: 10.1126/sciadv.adn5228. Epub 2024 Jun 28.ABSTRACTLiver fibrosis is characterized by the activation of perivascular hepatic stellate cells (HSCs), the release of fibrogenic nanosized extracellular vesicles (EVs), and increased HSC glycolysis. Nevertheless, how glycolysis in HSCs coordinates fibrosis amplification through tissue zone-specific pathways remains elusive. Here, we demonstrate that HSC-specific genetic inhibition of glycolysis reduced liver fibrosis. Moreover, spatial transcriptomics revealed a fibrosis-mediated up-regulation of EV-related pathways in the liver pericentral zone, which was abrogated by glycolysis genetic inhibition. Mechanistically, glycolysis in HSCs up-regulated the expression of EV-related genes such as Ras-related protein Rab-31 (RAB31) by enhancing histone 3 lysine 9 acetylation on the promoter region, which increased EV release. Functionally, these glycolysis-dependent EVs increased fibrotic gene expression in recipient HSC. Furthermore, EVs derived from glycolysis-deficient mice abrogated liver fibrosis amplification in contrast to glycolysis-competent mouse EVs. In summary, glycolysis in HSCs amplifies liver fibrosis by promoting fibrogenic EV release in the hepatic pericentral zone, which represents a potential therapeutic target.PMID:38941469 | DOI:10.1126/sciadv.adn5228

J Agric Food Chem. 2024 Jun 28. doi: 10.1021/acs.jafc.3c08874. Online ahead of print.ABSTRACTNumerous studies have highlighted the potential of Lactic acid bacteria (LAB) fermentation of whey proteins for alleviating allergies. Nonetheless, the impact of LAB-derived metabolites on whey proteins antigenicity during fermentation remains uncertain. Our objective was to elucidate the impact of small molecular metabolites on the antigenicity of α-lactalbumin (α-LA) and β-lactoglobulin (β-LG). Through metabolomic analysis, we picked 13 bioactive small molecule metabolites from Lactobacillus delbrueckii subsp. bulgaricus DLPU F-36 for coincubation with α-LA and β-LG, respectively. The outcomes revealed that valine, arginine, benzoic acid, 2-keto butyric acid, and glutaric acid significantly diminished the sensitization potential of α-LA and β-LG, respectively. Moreover, chromatographic analyses unveiled the varying influence of small molecular metabolites on the structure of α-LA and β-LG, respectively. Notably, molecular docking underscored that the primary active sites of α-LA and β-LG involved in protein binding to IgE antibodies aligned with the interaction sites of small molecular metabolites. In essence, LAB-produced metabolites wield a substantial influence on the antigenic properties of whey proteins.PMID:38941263 | DOI:10.1021/acs.jafc.3c08874

Reproduction. 2024 Jun 1:REP-23-0480. doi: 10.1530/REP-23-0480. Online ahead of print.ABSTRACTThere has been remarkable progress in the conservation and reproduction of giant pandas. However, the physiology of the gestation period in pandas remains poorly understood. The metabolic processes from estrus to pregnancy are dynamic and precisely regulated, playing a crucial role in pregnancy and related dysfunctions. In this study, we conducted a metabolomic analysis of 37 blood samples collected from pandas in estrus, acyclic, potential pregnant states, employing rigorous screening to minimize the influence of diet. Our findings suggest that a reduced appetite can serve as an indicator for evaluating implantation time, representing a characteristic response to pregnancy and aiding in the prediction of delivery time in pregnant pandas. Metabolomic results indicate great metabolism variation from estrus to pregnancy, and highlight the association between amino acid metabolism and pregnancy outcomes. Compared to other pandas, individuals which successfully bred exhibit significantly elevated levels of arginine and histidine, even 2 months before experiencing reduced appetite. Furthermore, the lipid profile undergoes distinct dynamic changes only in estrus samples. In summary, our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas.PMID:38941177 | DOI:10.1530/REP-23-0480

Metabolomics. 2024 Jun 28;20(4):68. doi: 10.1007/s11306-024-02133-y.ABSTRACTINTRODUCTION: Exploring metabolic changes within host E. coli through an untargeted metabolomic study of T7L variants overexpression to optimize engineered endolysins for clinical/therapeutic use.AIM AND OBJECTIVE: This study aims to assess the impact of overexpressing T7L variants on the metabolic profiles of E. coli. The two variants considered include T7L-H37A, which has enhanced lytic activity compared to its wild-type protein, and T7L-H48K, a dead mutant with no significant activity.METHODS: 1H NMR-based metabolomics was employed to compare the metabolic profiles of E. coli cells overexpressing T7L wild-type protein and its variants.RESULTS: Overexpression of the T7L wild-type (T7L-WT) protein and its variants (T7L-H48K and T7L-H37A) was compared to RNAP overexpression in E. coli cells using 1H NMR-based metabolomics, analyzing a total of 75 annotated metabolites, including organic acids, amino acids, sugars, and nucleic acids. The results showed distinct clustering patterns for the two T7L variant groups compared with the WT, in which the dead mutant (H48K) group showed clustering close to that of RNAP. Pathway impact analysis revealed different effects of T7L variants on E. coli metabolic profiles, with T7L-H48K showing minimal alterations in energy and amino acid pathways linked to osmotic stress compared to noticeable alterations in these pathways for both T7L-H37A and T7L-WT.CONCLUSIONS: This study uncovered distinct metabolic fingerprints when comparing the overexpression of active and inactive mutants of T7L lytic enzymes in E. coli cells. These findings could contribute to the optimization and enhancement of suitable endolysins as potential alternatives to antibiotics.PMID:38941046 | DOI:10.1007/s11306-024-02133-y

Methods Mol Biol. 2024;2820:155-164. doi: 10.1007/978-1-0716-3910-8_14.ABSTRACTThe oral cavity is a habitat for different microorganisms, of which bacteria are best described. Studying different bacterial taxa and their proteins is crucial to understanding their interactions with the host and other microbes. Also, for bacteria with virulence potential, identifying novel antigenic proteins is essential to finding candidates for the development of vaccines.Here, a workflow for gel-free and label-free protein analysis of oral bacterial species grown in vitro as a biofilm and a planktonic culture is described. Details on cultivation, protein extraction and digestion, peptide cleanup, LC-MS/MS run parameters, and subsequent bioinformatics analysis are included. Challenging steps in the workflow, such as growing different types of bacteria and selecting a suitable protein database, are also discussed. This protocol provides a valuable guide for metaproteomic experiments using multi-species models of oral bacteria.PMID:38941022 | DOI:10.1007/978-1-0716-3910-8_14

Metabolomics. 2024 Jun 28;20(4):69. doi: 10.1007/s11306-024-02122-1.ABSTRACTBACKGROUND: Metabolomics data is often complex due to the high number of metabolites, chemical diversity, and dependence on sample preparation. This makes it challenging to detect significant differences between factor levels and to obtain accurate and reliable data. To address these challenges, the use of Design of Experiments (DoE) techniques in the setup of metabolomic experiments is crucial. DoE techniques can be used to optimize the experimental design space, ensuring that the maximum amount of information is obtained from a limited sample space.AIM OF REVIEW: This review aims at providing a baseline workflow for applying DoE when generating metabolomics data.KEY SCIENTIFIC CONCEPTS OF REVIEW: The review provides insights into the theory of DoE. The review showcases the theory being put into practice by highlighting different examples DoE being applied in metabolomics throughout the literature, considering both targeted and untargeted metabolomic studies in which the data was acquired using both nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry techniques. In addition, the review presents DoE concepts not currently being applied in metabolomics, highlighting these as potential future prospects.PMID:38941008 | DOI:10.1007/s11306-024-02122-1

Diabetologia. 2024 Jun 28. doi: 10.1007/s00125-024-06199-0. Online ahead of print.NO ABSTRACTPMID:38940920 | DOI:10.1007/s00125-024-06199-0

Anal Bioanal Chem. 2024 Jun 28. doi: 10.1007/s00216-024-05404-8. Online ahead of print.ABSTRACTIn recent years, instrumental improvements have enabled the spread of mass spectrometry-based lipidomics platforms in biomedical research. In mass spectrometry, the reliability of generated data varies for each compound, contingent on, among other factors, the availability of labeled internal standards. It is challenging to evaluate the data for lipids without specific labeled internal standards, especially when dozens to hundreds of lipids are measured simultaneously. Thus, evaluation of the performance of these platforms at the individual lipid level in interlaboratory studies is generally not feasible in a time-effective manner. Herein, using a focused subset of sphingolipids, we present an in-house validation methodology for individual lipid reliability assessment, tailored to the statistical analysis to be applied. Moreover, this approach enables the evaluation of various methodological aspects, including discerning coelutions sharing identical selected reaction monitoring transitions, pinpointing optimal labeled internal standards and their concentrations, and evaluating different extraction techniques. While the full validation according to analytical guidelines for all lipids included in a lipidomics method is currently not possible, this process shows areas to focus on for subsequent method development iterations as well as the robustness of data generated across diverse methodologies.PMID:38940870 | DOI:10.1007/s00216-024-05404-8

Metabolomics. 2024 Jun 28;20(4):67. doi: 10.1007/s11306-024-02130-1.ABSTRACTINTRODUCTION: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma associated with Plasmodium falciparum and Epstein-Barr virus, both of which affect metabolic pathways. The metabolomic patterns of BL is unknown.MATERIALS AND METHODS: We measured 627 metabolites in pre-chemotherapy treatment plasma samples from 25 male children (6-11 years) with BL and 25 cancer-free area- and age-frequency-matched male controls from the Epidemiology of Burkitt Lymphoma in East African Children and Minors study in Uganda using liquid chromatography-tandem mass spectrometry. Unconditional, age-adjusted logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for the BL association with 1-standard deviation increase in the log-metabolite concentration, adjusting for multiple comparisons using false discovery rate (FDR) thresholds and Bonferroni correction.RESULTS: Compared to controls, levels for 42 metabolite concentrations differed in BL cases (FDR < 0.001), including triacylglyceride (18:0_38:6), alpha-aminobutyric acid (AABA), ceramide (d18:1/20:0), phosphatidylcholine ae C40:6 and phosphatidylcholine C38:6 as the top signals associated with BL (ORs = 6.9 to 14.7, P < 2.4✕10- 4). Two metabolites (triacylglyceride (18:0_38:6) and AABA) selected using stepwise logistic regression discriminated BL cases from controls with an area under the curve of 0.97 (95% CI: 0.94, 1.00).CONCLUSION: Our findings warrant further examination of plasma metabolites as potential biomarkers for BL risk/diagnosis.PMID:38940866 | DOI:10.1007/s11306-024-02130-1

Arch Microbiol. 2024 Jun 28;206(7):329. doi: 10.1007/s00203-024-04058-5.ABSTRACTThe ability of cold-adapted bacteria to survive in extreme cold and diverse temperatures is due to their unique attributes like cell membrane stability, up-regulation of peptidoglycan biosynthesis, increased production of extracellular polymeric substances, and expansion of membrane pigment. Various cold-adapted proteins, including ice-nucleating proteins (INPs), antifreeze proteins (AFPs), cold shock proteins (Csps), and cold-acclimated proteins (CAPs), help the bacteria to survive in these environments. To sustain cells from extreme cold conditions and maintain stability in temperature fluctuations, survival strategies at the molecular level and their mechanism play significant roles in adaptations in cryospheric conditions. Furthermore, cold shock domains present in the multifunctional cold shock proteins play crucial roles in their adaptation strategies. The considerable contribution of lipopeptides, osmolytes, and membrane pigments plays an integral part in their survival in extreme environments. This review summarizes the evolutionary history of cold-adapted bacteria and their molecular and cellular adaptation strategies to thrive in harsh cold environments. It also discusses the importance of carotenoids produced, lipid composition, cryoprotectants, proteins, and chaperones related to this adaptation. Furthermore, the functions and mechanisms of adaptations within the cell are discussed briefly. One can utilize and explore their potential in various biotechnology applications and their evolutionary journey by knowing the inherent mechanism of their molecular and cellular adaptation to cold climatic conditions. This review will help all branches of the life science community understand the basic microbiology of psychrophiles and their hidden prospect in life science research.PMID:38940837 | DOI:10.1007/s00203-024-04058-5

Mass Spectrom Rev. 2024 Jun 28. doi: 10.1002/mas.21896. Online ahead of print.ABSTRACTDental caries, a prevalent global infectious condition affecting over 95% of adults, remains elusive in its precise etiology. Addressing the complex dynamics of caries demands a thorough exploration of taxonomic, potential, active, and encoded functions within the oral ecosystem. Metabolomic profiling emerges as a crucial tool, offering immediate insights into microecosystem physiology and linking directly to the phenotype. Identified metabolites, indicative of caries status, play a pivotal role in unraveling the metabolic processes underlying the disease. Despite challenges in metabolite variability, the use of metabolomics, particularly via mass spectrometry and nuclear magnetic resonance spectroscopy, holds promise in caries research. This review comprehensively examines metabolomics in caries prevention, diagnosis, and treatment, highlighting distinct metabolite expression patterns and their associations with disease-related bacterial communities. Pioneering in approach, it integrates singular and combinatory metabolomics methodologies, diverse biofluids, and study designs, critically evaluating prior limitations while offering expert insights for future investigations. By synthesizing existing knowledge, this review significantly advances our comprehension of caries, providing a foundation for improved prevention and treatment strategies.PMID:38940512 | DOI:10.1002/mas.21896

Skin Res Technol. 2024 Jul;30(7):e13792. doi: 10.1111/srt.13792.ABSTRACTBACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15%-30% of children and 10% of adults globally, with its incidence being influenced by genetic, environmental, and various other factors. While the immune plays a crucial role in the development, the composition of gut microbiota and serum metabolites also contribute to its pathogenesis.SUBJECT: Study the characteristics of gut microbiota and serum metabolites in patients with atopic dermatitis METHOD: In this study, we collected stool and serum samples from 28 AD patients and 23 healthy individuals (NC) for metagenomic sequencing of gut microbiota and non-targeted metabolomic sequencing of serum.RESULT: Our results revealed a lower diversity of gut microbiota in the AD group compared to the NC group. The predominant Phylum in AD patients were Bacteroidetes, Pseudomonas, and Verrucomicrobia, with the most dominant bacterial genus being Faecalibacterium. At the species level, Prevotella copri and Faecalibacterium prausnitzii were found to be the most abundant bacteria. Significant differences in serum metabolite profiles were observed between NC and AD patients, with noticeable variations in metabolite expression levels. The majority of metabolites in the serum of AD patients exhibited low expression, while a few showed high expression levels. Notably, metabolites such as Cholesterol glucuronide, Styrene, Lutein, Betaine, Phosphorylcholine, Taurine, and Creatinine displayed the most pronounced alterations.CONCLUSION: These findings contribute to a further understanding of the complexities underlying this disease.PMID:38940462 | DOI:10.1111/srt.13792

J Extracell Biol. 2022 Nov 23;1(11):e66. doi: 10.1002/jex2.66. eCollection 2022 Nov.ABSTRACTPlasma extracellular vesicle (EV) number and composition are altered following myocardial infarction (MI), but to properly understand the significance of these changes it is essential to appreciate how the different isolation methods affect EV characteristics, proteome and sphingolipidome. Here, we compared plasma EV isolated from platelet-poor plasma from four healthy donors and six MI patients at presentation and 1-month post-MI using ultracentrifugation (UC), polyethylene glycol precipitation, acoustic trapping, size-exclusion chromatography (SEC) and immunoaffinity capture. The isolated EV were evaluated by Nanoparticle Tracking Analysis (NTA), Western blot, transmission electron microscopy (TEM), an EV-protein array, untargeted proteomics (LC-MS/MS) and targeted sphingolipidomics (LC-MS/MS). The application of the five different plasma EV isolation methods in patients presenting with MI showed that the choice of plasma EV isolation method influenced the ability to distinguish elevations in plasma EV concentration following MI, enrichment of EV-cargo (EV-proteins and sphingolipidomics) and associations with the size of the infarct determined by cardiac magnetic resonance imaging 6 months post-MI. Despite the selection bias imposed by each method, a core of EV-associated proteins and lipids was detectable using all approaches. However, this study highlights how each isolation method comes with its own idiosyncrasies and makes the comparison of data acquired by different techniques in clinical studies problematic.PMID:38939906 | PMC:PMC11080728 | DOI:10.1002/jex2.66

J Extracell Biol. 2024 Feb 22;3(2):e140. doi: 10.1002/jex2.140. eCollection 2024 Feb.ABSTRACTExtracellular vesicles (EVs) have been involved in metabolic syndrome, although their specific role in the development of the pathology is still unknown. To further study the role of EVs, we have analysed by Raman tweezers microspectroscopy and mass spectrometry-based lipidomics the small EVs population secreted by fatty (ZF) and lean (ZL) hepatocytes obtained from Zucker rats. We have also explored in vivo and ex vivo biodistribution of these EVs through fluorine-18-radiolabelling using a positron emission tomography imaging. Based on the proportion of proteins to lipids and the types of lipids, our results indicate that within the range of small EVs, primary hepatocytes secrete different subpopulations of particles. These differences were observed in the enrichment of triglyceride species in EVs secreted by ZF hepatocytes. Biodistribution experiments showed accumulation in the brain, heart, lungs, kidney and specially in bladder after intravenous administration. In summary, we show that EVs released by a fatty hepatocytes carry a different lipid signature compared to their lean counterpart. Biodistribution experiment has shown no difference in the distribution of EVs secreted by ZF and ZL hepatocytes but has given us a first view of possible target organs for these particles. Our results might open a door to both pathology studies and therapeutic interventions.PMID:38939902 | PMC:PMC11080883 | DOI:10.1002/jex2.140

J Extracell Biol. 2023 Mar 31;2(4):e76. doi: 10.1002/jex2.76. eCollection 2023 Apr.ABSTRACTThe standardization of clinical studies using extracellular vesicles (EVs) has mainly focused on the procedures employed for their isolation and characterization; however, preanalytical aspects of sample collection, handling and storage also significantly impact the reproducibility of results. We conducted an online survey based on SPREC (Standard PREanalytical Code) among members of GEIVEX (Grupo Español de Investigación en Vesiculas Extracelulares) to explore how different laboratories handled fluid biospecimens destined for EV analyses. We received 70 surveys from forty-three different laboratories: 44% focused on plasma, 9% on serum and 16% on urine. The survey indicated that variability in preanalytical approaches reaches 94%. Moreover, in some cases, researchers had no access to all relevant preanalytical details of samples, with some sample aspects with potential impact on EV isolation/characterisation not coded within the current version of SPREC. Our study highlights the importance of working with common standard operating procedures (SOP) to control preanalytical conditions. The application of SPREC represents a suitable approach to codify and register preanalytical conditions. Integrating SPREC into the SOPs of laboratories/biobanks will provide a valuable source of information and constitute an advance for EV research by improving reproducibility and credibility.PMID:38939690 | PMC:PMC11080825 | DOI:10.1002/jex2.76

JACC Adv. 2023 Jan 27;2(1):100174. doi: 10.1016/j.jacadv.2022.100174. eCollection 2023 Jan.ABSTRACTBACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are cardiac biomarkers commonly detected in adults with type 2 diabetes (T2D) and are associated with heart failure risk.OBJECTIVES: The purpose of this study was to evaluate the effects of exercise training (ET) on hs-cTnT and NT-proBNP and evaluate the associations of these biomarkers with cardiorespiratory fitness among adults with T2D.METHODS: Participants of the HART-D (Health Benefits of Aerobic and Resistance Training in Individuals with Type 2 Diabetes) trial who were randomly assigned to one of 3 ET groups or a non-exercise control group were included. Cardiac biomarkers and cardiorespiratory fitness (evaluated by peak oxygen uptake [VO2peak]) were assessed at baseline and after 9 months. The effects of ET (3 ET groups pooled) vs non-exercise control on hs-cTnT and NT-proBNP were assessed using separate analysis of covariance models. Multivariable-adjusted linear regression was performed to identify factors associated with follow-up biomarkers and ΔVO2peak.RESULTS: The present study included 166 participants randomized to the ET (n = 135) and non-exercise control (n = 31) groups. Compared with the non-exercise control, ET did not significantly change hs-cTnT or NT-proBNP. In adjusted analysis, each ET group and ΔVO2peak were not significantly associated with hs-cTnT or NT-proBNP levels on follow-up. Among individuals in the ET group, baseline hs-cTnT was inversely associated with ΔVO2peak [per 1 SD higher log (hs-cTnT): β = -0.08 (95% CI = -0.15 to -0.01)].CONCLUSIONS: Among individuals with T2D, ET did not modify cardiac biomarkers. Higher baseline hs-cTnT was associated with blunted cardiorespiratory fitness improvement in response to exercise.PMID:38939024 | PMC:PMC11198483 | DOI:10.1016/j.jacadv.2022.100174

JACC Adv. 2023 Jan 27;2(1):100170. doi: 10.1016/j.jacadv.2022.100170. eCollection 2023 Jan.NO ABSTRACTPMID:38939018 | PMC:PMC11198037 | DOI:10.1016/j.jacadv.2022.100170

J Extracell Biol. 2024 Apr 22;3(4):e149. doi: 10.1002/jex2.149. eCollection 2024 Apr.ABSTRACTIsolation of extracellular vesicles (EV) has been developing rapidly in parallel with the interest in EVs. However, commonly utilized protocols may not suit more challenging sample matrixes and could potentially yield suboptimal results. Knowing and assessing the pitfalls of isolation procedure to be used, should be involved to some extent for EV analytics. EVs in cow milk are of great interest due to their abundancy and large-scale availability as well as their cross-species bioavailability and possible use as drug carriers. However, the characteristics of milk EVs overlap with those of other milk components. This makes it difficult to isolate and study EVs individually. There exists also a lack of consensus for isolation methods. In this study, we demonstrated the differences between various differential centrifugation-based approaches for isolation of large quantities of EVs from cow milk. Samples were further purified with gradient centrifugation and size exclusion chromatography (SEC) and differences were analyzed. Quality measurements were conducted on multiple independent platforms. Particle analysis, electron microscopy and RNA analysis were used, to comprehensively characterize the isolated samples and to identify the limitations and possible sources of contamination in the EV isolation protocols. Vesicle concentration to protein ratio and RNA to protein ratios were observed to increase as samples were purified, suggesting co-isolation with major milk proteins in direct differential centrifugation protocols. We demonstrated a novel size assessment of vesicles using a particle mobility analyzer that matched the sizing using electron microscopy in contrast to commonly utilized nanoparticle tracking analysis. Based on the standards of the International Society for Extracellular Vesicles and the quick checklist of EV-Track.org for EV isolation, we emphasize the need for complete characterization and validation of the isolation protocol with all EV-related work to ensure the accuracy of results and allow further analytics and experiments.PMID:38938848 | PMC:PMC11080921 | DOI:10.1002/jex2.149

J Extracell Biol. 2022 Mar 15;1(2):e32. doi: 10.1002/jex2.32. eCollection 2022 Feb.ABSTRACTThe composition of extracellular vesicles (EVs) is altered in many pathological conditions, and their molecular content provides essential information on features of parent cells and mechanisms of crosstalk between cells and organs. Metabolic Syndrome (MetS) is a cluster of clinical manifestations including obesity, insulin resistance, dyslipidemia and hypertension that increases the risk of cardiovascular disease and type 2 diabetes mellitus. Here, we investigated the crosstalk between liver and adipocytes by characterizing EVs secreted by primary hepatocytes isolated from Zucker rat model, and studied the effect they have on 3T3-L1 adipocytes. We found that steatotic hepatocytes secrete EVs with significantly reduced exosomal markers in comparison with their lean counterpart. Moreover, proteomic analysis revealed that those EVs reflect the metabolic state of the parent cell in that the majority of proteins upregulated relate to fat metabolism, fatty acid synthesis, glycolysis, and pentose phosphate pathway. In addition, hepatocytes-secreted EVs influenced lipolysis and insulin sensitivity in recipient 3T3-L1 adipocytes. Untargeted metabolomic analysis detected alterations in different adipocyte metabolic pathways in cells treated with hepatic EVs. In summary, our work showed that steatosis has a significant impact in the amount and composition of EVs secreted by hepatocytes. Moreover, our data point to the involvement of hepatic-EVs in the development of pathologies associated with MetS.PMID:38938664 | PMC:PMC11080919 | DOI:10.1002/jex2.32