Metabolomics : Official journal of the Metabolomic Society最新文献

{"title":"NMR-based metabolic profiling of children with premature adrenarche.","authors":"Konstantina Matzarapi,&nbsp;Aristeidis Giannakopoulos,&nbsp;Styliani A Chasapi,&nbsp;Dimitra Kritikou,&nbsp;Alexandra Efthymiadou,&nbsp;Dionisios Chrysis,&nbsp;Georgios A Spyroulias","doi":"10.1007/s11306-022-01941-4","DOIUrl":"https://doi.org/10.1007/s11306-022-01941-4","url":null,"abstract":"<p><strong>Introduction: </strong>Premature adrenarche (PA) for long time was considered a benign condition but later has been connected to various diseases in childhood and adulthood which remains controversial.</p><p><strong>Objective: </strong>To investigate the effect of premature adrenarche on the metabolic phenotype, and correlate the clinical and biochemical data with the metabolic profile of children with PA.</p><p><strong>Methods: </strong>Nuclear magnetic resonance (NMR)-based untargeted and targeted metabolomic approach in combination with multivariate and univariate statistical analysis applied to study the metabolic profiles of children with PA. Plasma, serum, and urine samples were collected from fifty-two children with Idiopathic PA and forty-eight age-matched controls from the division of Pediatric Endocrinology of the University Hospital of Patras were enrolled.</p><p><strong>Results: </strong>Metabolomic results showed that plasma and serum glucose, myo-inositol, amino acids, a population of unsaturated lipids, and esterified cholesterol were higher and significantly different in PA children. In the metabolic profiles of children with PA and age-matched control group a gradual increase of glucose and myo-inositol levels was observed in serum and plasma, which was positively correlated their body mass index standard deviation score (BMI SDS) values respectively. Urine ¹H NMR metabolic fingerprint of PA children showed positive correlation and a clustering-dependent relationship with their BMI and bone age (BA) respectively.</p><p><strong>Conclusion: </strong>This study provides evidence that PA driven metabolic changes begin during the childhood and PA may has an inductive role in a BMI-driven increase of specific metabolites. Finally, urine may be considered as the best biofluid for identification of the PA metabolism as it reflects more clearly the PA metabolic fingerprint.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"78"},"PeriodicalIF":3.6,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33538803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutathione, polyamine, and lysophosphatidylcholine synthesis pathways are associated with circulating pro-inflammatory cytokines.","authors":"Ming Liu,&nbsp;Hongwei Zhang,&nbsp;Zikun Xie,&nbsp;Yiheng Huang,&nbsp;Guang Sun,&nbsp;Dake Qi,&nbsp;Andrew Furey,&nbsp;Edward W Randell,&nbsp;Proton Rahman,&nbsp;Guangju Zhai","doi":"10.1007/s11306-022-01932-5","DOIUrl":"https://doi.org/10.1007/s11306-022-01932-5","url":null,"abstract":"<p><strong>Introduction: </strong>Pro-inflammatory cytokines are responsible for initiating an effective defense against exogenous pathogens, and their regulation has a vital role in maintaining physiological homeostasis. The involvement of pro-inflammatory cytokines in pathological conditions have been explored in great detail, however, studies investigating metabolic pathways associated with these cytokines under normal homeostatic conditions are scarce.</p><p><strong>Objectives: </strong>The aim of the current study was to identify metabolites and metabolic pathways associated with circulating pro-inflammatory cytokines under homeostatic conditions using a metabolomics approach.</p><p><strong>Methods: </strong>The study participants (n = 133) were derived from the Newfoundland Osteoarthritis Study (NFOAS) and the Complex Diseases in the Newfoundland population: Environment and Genetics (CODING) study. Plasma concentrations of cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and macrophage migration inhibitory factor (MIF) were assessed by enzyme-linked immunosorbent assay. Targeted metabolomic profiling on fasting plasma samples was performed using Biocrates MxP® Quant 500 kit which measures a total of 630 metabolites. Associations between natural log-transformed metabolite concentrations and metabolite sums/ratios and cytokine levels were assessed using linear regression with adjustment for age, sex, body mass index (BMI), and osteoarthritis status.</p><p><strong>Results: </strong>Seven metabolites and 11 metabolite sums/ratios were found to be significantly associated with TNF-α, IL-1β, and MIF (all p ≤ 5.13 × 10^- 5) after controlling multiple testing with Bonferroni method, indicating the association between glutathione (GSH), polyamine, and lysophosphatidylcholine (lysoPC) synthesis pathways and these pro-inflammatory cytokines.</p><p><strong>Conclusion: </strong>GSH, polyamine, and lysoPC synthesis pathways were positively associated with circulating TNF-α, IL-1β, and MIF levels under homeostatic conditions.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"76"},"PeriodicalIF":3.6,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40384451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of acute intravenous lipopolysaccharide administration on the plasma lipidome and metabolome in lactating Holstein cows experiencing hyperlipidemia.","authors":"Awais Javaid,&nbsp;Feiran Wang,&nbsp;Erin A Horst,&nbsp;M Elena Diaz-Rubio,&nbsp;Lin F Wang,&nbsp;Lance H Baumgard,&nbsp;Joseph W McFadden","doi":"10.1007/s11306-022-01928-1","DOIUrl":"https://doi.org/10.1007/s11306-022-01928-1","url":null,"abstract":"<p><strong>Introduction: </strong>The effects of lipopolysaccharides (i.e., endotoxin; LPS) on metabolism are poorly defined in lactating dairy cattle experiencing hyperlipidemia.</p><p><strong>Objectives: </strong>Our objective was to explore the effects of acute intravenous LPS administration on metabolism in late-lactation Holstein cows experiencing hyperlipidemia induced by intravenous triglyceride infusion and feed restriction.</p><p><strong>Methods: </strong>Ten non-pregnant lactating Holstein cows (273 ± 35 d in milk) were administered a single bolus of saline (3 mL of saline; n [Formula: see text] 5) or LPS (0.375 [Formula: see text]g of LPS/kg of body weight; n [Formula: see text] 5). Simultaneously, cows were intravenously infused a triglyceride emulsion and feed restricted for 16 h to induce hyperlipidemia in an attempt to model the periparturient period. Blood was sampled at routine intervals. Changes in circulating total fatty acid concentrations and inflammatory parameters were measured. Plasma samples were analyzed using untargeted lipidomics and metabolomics.</p><p><strong>Results: </strong>Endotoxin increased circulating serum amyloid A, LPS-binding protein, and cortisol concentrations. Endotoxin administration decreased plasma lysophosphatidylcholine (LPC) concentrations and increased select plasma ceramide concentrations. These outcomes suggest modulation of the immune response and insulin action. Lipopolysaccharide decreased the ratio of phosphatidylcholine to phosphatidylethanomanine, which potentially indicate a decrease in the hepatic activation of phosphatidylethanolamine N-methyltransferase and triglyceride export. Endotoxin administration also increased plasma concentrations of pyruvic and lactic acids, and decreased plasma citric acid concentrations, which implicate the upregulation of glycolysis and downregulation of the citric acid cycle (i.e., the Warburg effect), potentially in leukocytes.</p><p><strong>Conclusion: </strong>Acute intravenous LPS administration decreased circulating LPC concentrations, modified ceramide and glycerophospholipid concentrations, and influenced intermediary metabolism in dairy cows experiencing hyperlipidemia.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"75"},"PeriodicalIF":3.6,"publicationDate":"2022-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40372032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolites derived from fungi and bacteria suppress in vitro growth of Gnomoniopsis smithogilvyi, a major threat to the global chestnut industry.","authors":"Matias Silva-Campos,&nbsp;Damien L Callahan,&nbsp;David M Cahill","doi":"10.1007/s11306-022-01933-4","DOIUrl":"https://doi.org/10.1007/s11306-022-01933-4","url":null,"abstract":"<p><strong>Introduction: </strong>Chestnut rot caused by the fungus Gnomoniopsis smithogilvyi is a disease present in the world's major chestnut growing regions. The disease is considered a significant threat to the global production of nuts from the sweet chestnut (Castanea sativa). Conventional fungicides provide some control, but little is known about the potential of biological control agents (BCAs) as alternatives to manage the disease.</p><p><strong>Objective: </strong>Evaluate whether formulated BCAs and their secreted metabolites inhibit the in vitro growth of G. smithogilvyi.</p><p><strong>Methods: </strong>The antifungal potential of BCAs was assessed against the pathogen through an inverted plate assay for volatile compounds (VOCs), a diffusion assay for non-volatile compounds (nVOCs) and in dual culture. Methanolic extracts of nVOCs from the solid medium were further evaluated for their effect on conidia germination and were screened through an LC-MS-based approach for antifungal metabolites.</p><p><strong>Results: </strong>Isolates of Trichoderma spp., derived from the BCAs, significantly suppressed the pathogen through the production of VOCs and nVOCs. The BCA from which Bacillus subtilis was isolated was more effective in growth inhibition through the production of nVOCs. The LC-MS based metabolomics on the nVOCs derived from the BCAs showed the presence of several antifungal compounds.</p><p><strong>Conclusion: </strong>The results show that G. smithogilvyi can be effectively controlled by the BCAs tested and that their use may provide a more ecological alternative for managing chestnut rot. The in vitro analysis should now be expanded to the field to assess the effectiveness of these alternatives for chestnut rot management.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"74"},"PeriodicalIF":3.6,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9474450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40358254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An approach to assess and adjust for the influence of multicollinear covariates on metabolomics association patterns-applied to a study of the associations between a comprehensive lipoprotein profile and the homeostatic model assessment of insulin resistance.","authors":"Olav M Kvalheim,&nbsp;Tarja Rajalahti,&nbsp;Eivind Aadland","doi":"10.1007/s11306-022-01931-6","DOIUrl":"https://doi.org/10.1007/s11306-022-01931-6","url":null,"abstract":"<p><strong>Introduction: </strong>Comprehensive lipoprotein profiling using proton nuclear magnetic resonance (NMR) spectroscopy of serum represents an alternative to the homeostatic model assessment of insulin resistance (HOMA-IR). Both adiposity and physical (in)activity associate to insulin resistance, but quantification of the influence of these two lifestyle related factors on the association pattern of HOMA-IR to lipoproteins suffers from lack of appropriate methods to handle multicollinear covariates.</p><p><strong>Objectives: </strong>We aimed at (i) developing an approach for assessment and adjustment of the influence of multicollinear and even linear dependent covariates on regression models, and (ii) to use this approach to examine the influence of adiposity and physical activity on the association pattern between HOMA-IR and the lipoprotein profile.</p><p><strong>Methods: </strong>For 841 children, lipoprotein profiles were obtained from serum proton NMR and physical activity (PA) intensity profiles from accelerometry. Adiposity was measured as body mass index, the ratio of waist circumference to height, and skinfold thickness. Target projections were used to assess and isolate the influence of adiposity and PA on the association pattern of HOMA-IR to the lipoproteins.</p><p><strong>Results: </strong>Adiposity explained just over 50% of the association pattern of HOMA-IR to the lipoproteins with strongest influence on high-density lipoprotein features. The influence of PA was mainly attributed to a strong inverse association between adiposity and moderate and high-intensity physical activity.</p><p><strong>Conclusion: </strong>The presented covariate projection approach to obtain net association patterns, made it possible to quantify and interpret the influence of adiposity and physical (in)activity on the association pattern of HOMA-IR to the lipoprotein features.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"72"},"PeriodicalIF":3.6,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9439979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40343307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality assurance and quality control reporting in untargeted metabolic phenotyping: mQACC recommendations for analytical quality management.","authors":"Jennifer A Kirwan,&nbsp;Helen Gika,&nbsp;Richard D Beger,&nbsp;Dan Bearden,&nbsp;Warwick B Dunn,&nbsp;Royston Goodacre,&nbsp;Georgios Theodoridis,&nbsp;Michael Witting,&nbsp;Li-Rong Yu,&nbsp;Ian D Wilson","doi":"10.1007/s11306-022-01926-3","DOIUrl":"https://doi.org/10.1007/s11306-022-01926-3","url":null,"abstract":"<p><strong>Background: </strong>Demonstrating that the data produced in metabolic phenotyping investigations (metabolomics/metabonomics) is of good quality is increasingly seen as a key factor in gaining acceptance for the results of such studies. The use of established quality control (QC) protocols, including appropriate QC samples, is an important and evolving aspect of this process. However, inadequate or incorrect reporting of the QA/QC procedures followed in the study may lead to misinterpretation or overemphasis of the findings and prevent future metanalysis of the body of work.</p><p><strong>Objective: </strong>The aim of this guidance is to provide researchers with a framework that encourages them to describe quality assessment and quality control procedures and outcomes in mass spectrometry and nuclear magnetic resonance spectroscopy-based methods in untargeted metabolomics, with a focus on reporting on QC samples in sufficient detail for them to be understood, trusted and replicated. There is no intent to be proscriptive with regard to analytical best practices; rather, guidance for reporting QA/QC procedures is suggested. A template that can be completed as studies progress to ensure that relevant data is collected, and further documents, are provided as on-line resources.</p><p><strong>Key reporting practices: </strong>Multiple topics should be considered when reporting QA/QC protocols and outcomes for metabolic phenotyping data. Coverage should include the role(s), sources, types, preparation and uses of the QC materials and samples generally employed in the generation of metabolomic data. Details such as sample matrices and sample preparation, the use of test mixtures and system suitability tests, blanks and technique-specific factors are considered and methods for reporting are discussed, including the importance of reporting the acceptance criteria for the QCs. To this end, the reporting of the QC samples and results are considered at two levels of detail: \"minimal\" and \"best reporting practice\" levels.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"70"},"PeriodicalIF":3.6,"publicationDate":"2022-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40421084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic signatures of hepatolithiasis using ultra-high performance liquid chromatography-tandem mass spectrometry.","authors":"Cong Wang,&nbsp;Jun Yang,&nbsp;Enliang Li,&nbsp;Shuaiwu Luo,&nbsp;Chi Sun,&nbsp;Yuting Liao,&nbsp;Min Li,&nbsp;Jin Ge,&nbsp;Jun Lei,&nbsp;Fan Zhou,&nbsp;Linquan Wu,&nbsp;Wenjun Liao","doi":"10.1007/s11306-022-01927-2","DOIUrl":"https://doi.org/10.1007/s11306-022-01927-2","url":null,"abstract":"<p><strong>Background & aims: </strong>A metabolomic study of hepatolithiasis has yet to be performed. The purpose of the present study was to characterize the metabolite profile and identify potential biomarkers of hepatolithiasis using a metabolomic approach.</p><p><strong>Methods: </strong>We comprehensively analyzed the serum metabolites from 30 patients with hepatolithiasis and 20 healthy individuals using ultra-high performance liquid chromatography-tandem mass spectrometry operated in negative and positive ionization modes. Statistical analyses were performed using univariate (Student's t-test) and multivariate (orthogonal partial least-squares discriminant analysis) statistics and R language. Receiver operator characteristic (ROC) curve analysis was performed to identify potential predictors of hepatolithiasis.</p><p><strong>Results: </strong>We identified 277 metabolites that were significantly different between hepatolithiasis serum group and healthy control serum group. These metabolites were principally lipids and lipid-like molecules and amino acid metabolites. The steroid hormone biosynthesis pathway was enriched in hepatolithiasis serum group. In all specific metabolites, 75 metabolites were over-expressed in hepatolithiasis serum group. The AUC values for 60 metabolites exceeded 0.70, 4 metabolites including 18-β-Glycyrrhetinic acid, FMH, Rifampicin and PC (4:0/16:2) exceeded 0.90.</p><p><strong>Conclusions: </strong>We have identified serum metabolites that are associated with hepatolithiasis for the first time. 60 potential metabolic biomarkers were identified, 18-β-Glycyrrhetinic acid, FMH, Rifampicin and PC (4:0/16:2) may have the potential clinical utility in hepatolithiasis.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"69"},"PeriodicalIF":3.6,"publicationDate":"2022-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40620178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic changes in cats with renal disease and calcium oxalate uroliths.","authors":"Dennis E Jewell,&nbsp;Selena K Tavener,&nbsp;Regina L Hollar,&nbsp;Kiran S Panickar","doi":"10.1007/s11306-022-01925-4","DOIUrl":"https://doi.org/10.1007/s11306-022-01925-4","url":null,"abstract":"<p><strong>Introduction: </strong>There is a significant incidence of cats with renal disease (RD) and calcium oxalate (CaOx) kidney uroliths in domesticated cats. Foods which aid in the management of these diseases may be enhanced through understanding the underlying metabolomic changes.</p><p><strong>Objective: </strong>Assess the metabolomic profile with a view to identifying metabolomic targets which could aid in the management of renal disease and CaOx uroliths.</p><p><strong>Method: </strong>This is a retrospective investigation of 42 cats: 19 healthy kidney controls, 11 with RD, and 12 that formed CaOx nephroliths. Cats were evaluated as adults (2 through 7 years) and at the end of life for plasma metabolomics, body composition, and markers of renal dysfunction. Kidney sections were assessed by Pizzolato stain at the end of life for detection of CaOx crystals. CaOx stone presence was also assessed by analysis of stones removed from the kidney at the end of life.</p><p><strong>Results: </strong>There were 791 metabolites identified with 91 having significant (p < 0.05, q < 0.1) changes between groups. Many changes in metabolite concentrations could be explained by the loss of renal function being most acute in the cats with RD while the cats with CaOx stones were intermediate between control and RD (e.g., urea, creatinine, pseudouridine, dimethylarginines). However, the concentrations of some metabolites differentiated RD from CaOx stone forming cats. These were either increased in the RD cats (e.g., cystathionine, dodecanedioate, 3-(3-amino-3-carboxypropyl) uridine, 5-methyl-2'-deoxycytidine) or comparatively increased in the CaOx stone forming cats (phenylpyruvate, 4-hydroxyphenylpyruvate, alpha-ketobutyrate, retinal).</p><p><strong>Conclusions: </strong>The metabolomic changes show specific metabolites which respond generally to both renal diseases while the metabolomic profile still differentiates cats with RD and cats with CaOx uroliths.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"68"},"PeriodicalIF":3.6,"publicationDate":"2022-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40694426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin mutation and mycobacterial infection lead non-synergistically to a similar metabolic syndrome.","authors":"Yi Ding,&nbsp;Mariëlle C Haks,&nbsp;Susan J F van den Eeden,&nbsp;Tom H M Ottenhoff,&nbsp;Amy C Harms,&nbsp;Thomas Hankemeier,&nbsp;Muhamed N H Eeza,&nbsp;Jörg Matysik,&nbsp;A Alia,&nbsp;Herman P Spaink","doi":"10.1007/s11306-022-01921-8","DOIUrl":"https://doi.org/10.1007/s11306-022-01921-8","url":null,"abstract":"<p><strong>Introduction: </strong>The leptin signaling pathway plays an important role as a key regulator of glucose homeostasis, metabolism control and systemic inflammatory responses. However, the metabolic effects of leptin on infectious diseases, for example tuberculosis (TB), are still little known.</p><p><strong>Objectives: </strong>In this study, we aim to investigate the role of leptin on metabolism in the absence and presence of mycobacterial infection in zebrafish larvae and mice.</p><p><strong>Methods: </strong>Metabolites in entire zebrafish larvae and the blood of mice were studied using high-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and mass spectrometry, respectively. For transcriptome studies of zebrafish larvae, deep RNA sequencing was used.</p><p><strong>Results: </strong>The results show that leptin mutation leads to a similar metabolic syndrome as caused by mycobacterial infection in the two species, characterized by the decrease of 11 amine metabolites. In both species, this metabolic syndrome was not aggravated further when the leptin mutant was infected by mycobacteria. Therefore, we conclude that leptin and mycobacterial infection are both impacting metabolism non-synergistically. In addition, we studied the transcriptomes of lepb^ibl54 mutant zebrafish larvae and wild type (WT) siblings after mycobacterial infection. These studies showed that mycobacteria induced a very distinct transcriptome signature in the lepb^ibl54 mutant zebrafish compared to WT sibling control larvae. Furthermore, lepb^ibl55 Tg (pck1:luc1) zebrafish line was constructed and confirmed this difference in transcriptional responses.</p><p><strong>Conclusions: </strong>Leptin mutation and TB lead non-synergistically to a similar metabolic syndrome. Moreover, different transcriptomic responses in the lepb^ibl54  mutant and TB can lead to the similar metabolic end states.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"67"},"PeriodicalIF":3.6,"publicationDate":"2022-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40674244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis of ventilator-induced lung injury: metabolomics analysis of the lung and plasma.","authors":"Yanfei Mao,&nbsp;Zhixin Ma,&nbsp;Chufan Xu,&nbsp;Zhou Lv,&nbsp;Wenwen Dong,&nbsp;Xinru Liu","doi":"10.1007/s11306-022-01914-7","DOIUrl":"https://doi.org/10.1007/s11306-022-01914-7","url":null,"abstract":"<p><strong>Introduction: </strong>Nowadays,the mechanical ventilation (MV) aims to rest the respiratory muscles while providing adequate gas exchange, and it has been a part of basic life support during general anesthesia as well as in critically ill patients with and without respiratory failure. However, MV itself has the potential to cause or worsen lung injury, which is also known as ventilator-induced lung injury (VILI). Thus, the early diagnosis of VILI is of great importance for the prevention and treatment of VILI.</p><p><strong>Objective: </strong>This study aimed to investigate the metabolomes in the lung and plasma of mice receiving mechanical ventilation (MV).</p><p><strong>Methods: </strong>Healthy mice were randomly assigned into control group; (2) high volume tidal (HV) group (30 ml/kg); (3) low volume tidal (LV) group (6 ml/kg). After ventilation for 4 h, mice were sacrificed and the lung tissue and plasma were collected. The lung and plasma were processed for the metabolomics analysis. We also performed histopathological examination on the lung tissue.</p><p><strong>Results: </strong>We detected moderate inflammatory damage with alveolar septal thickening in the HV group compared with the normal and LV groups.The metabolomics analysis results showed MV altered the metabolism which was characterized by the dysregulation of γ-amino butyric acid (GABA) system and urea cycle (desregulations in plasma and lung guanidinosuccinic acid, argininosuccinic acid, succinic acid semialdehyde and lung GABA ), Disturbance of citric acid cycle (CAC) (increased plasma glutamine and lung phosphoenol pyruvate) and redox imbalance (desregulations in plasma and/or lung ascorbic acid, chenodeoxycholic acid, uric acid, oleic acid, stearidonic acid, palmitoleic acid and docosahexaenoic acid). Moreover, the lung and plasma metabolomes were also significantly different between LV and HV groups.</p><p><strong>Conclusions: </strong>Some lung and plasma metabolites related to the GABA system and urea cycle, citric acid cycle and redox balance were significantly altered, and they may be employed for the evaluation of VILI and serve as targets in the treatment of VILI.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"66"},"PeriodicalIF":3.6,"publicationDate":"2022-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40581117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}