Metabolomics最新文献

{"title":"A predictive model for neoadjuvant therapy response in breast cancer.","authors":"Rafael Nambo-Venegas, Virginia Isabel Enríquez-Cárcamo, Marcela Vela-Amieva, Isabel Ibarra-González, Lourdes Lopez-Castro, Sara Aileen Cabrera-Nieto, Juan E Bargalló-Rocha, Cynthia M Villarreal-Garza, Alejandro Mohar, Berenice Palacios-González, Juan P Reyes-Grajeda, Fernanda Sarahí Fajardo-Espinoza, Marlid Cruz-Ramos","doi":"10.1007/s11306-025-02230-6","DOIUrl":"10.1007/s11306-025-02230-6","url":null,"abstract":"<p><p>Neoadjuvant therapy is a standard treatment for breast cancer, but its effectiveness varies among patients. This highlights the importance of developing accurate predictive models. Our study uses metabolomics and machine learning to predict the response to neoadjuvant therapy in breast cancer patients.</p><p><strong>Objective: </strong>To develop and validate predictive models using machine learning and circulating metabolites for forecasting responses to neoadjuvant therapy among breast cancer patients, enhancing personalized treatment strategies.</p><p><strong>Methods: </strong>Based on pathological analysis after neoadjuvant chemotherapy and surgery, this retrospective study analyzed 30 young women breast cancer patients from a single institution, categorized as responders or non-responders. Utilizing liquid chromatography-tandem mass spectrometry, we investigated the plasma metabolome, explicitly targeting 40 metabolites, to identify relevant biomarkers linked to therapy response, using machine learning to generate a predictive model and validate the results.</p><p><strong>Results: </strong>Eighteen significant biomarkers were identified, including specific acylcarnitines and amino acids. The most effective predictive model demonstrated a remarkable accuracy of 90.7% and an Area Under the Curve (AUC) of 0.999 at 95% confidence, illustrating its potential utility as a web-based application for future patient management. This model's reliability underscores the significant role of circulating metabolites in predicting therapy outcomes.</p><p><strong>Conclusion: </strong>Our study's findings highlight the crucial role of metabolomics in advancing personalized medicine for breast cancer treatment by effectively identifying metabolite biomarkers correlated with neoadjuvant therapy response. This approach signifies a critical step towards tailoring treatment plans based on individual metabolic profiles, ultimately improving patient outcomes in breast cancer care.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 2","pages":"28"},"PeriodicalIF":3.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic signature of renal cell carcinoma tumours and its correlation with the urinary metabolome.","authors":"Filipa Amaro, Márcia Carvalho, Carina Carvalho-Maia, Carmen Jerónimo, Rui Henrique, Maria de Lourdes Bastos, Paula Guedes de Pinho, Joana Pinto","doi":"10.1007/s11306-024-02212-0","DOIUrl":"10.1007/s11306-024-02212-0","url":null,"abstract":"<p><strong>Introduction: </strong>Despite considerable advances in cancer research, the increasing prevalence and high mortality rate of clear cell renal cell carcinoma (ccRCC) remain a significant challenge. A more detailed comprehension of the distinctive metabolic characteristics of ccRCC is vital to enhance diagnostic, prognostic, and therapeutic strategies.</p><p><strong>Objectives: </strong>This study aimed to investigate the metabolic signatures of ccRCC tumours and, for the first time, their correlation with the urinary metabolome of the same patients.</p><p><strong>Methods: </strong>We applied a gas chromatography-mass spectrometry (GC-MS)-based metabolomic approach to analyse matched tissue and urine samples from a cohort of 18 ccRCC patients and urine samples from 18 cancer-free controls. Multivariate and univariate statistical methods, as well as pathway and correlation analyses, were performed to assess metabolic dysregulations and correlations between tissue and urine.</p><p><strong>Results: </strong>The results showed a ccRCC metabolic signature characterized by reprogramming in amino acid, energy, and sugar and inositol phosphate metabolisms. Our study identified, for the first time, significantly decreased levels of asparagine, proline, gluconate, 3-aminoisobutanoate, 4-aminobutanoate and urea in ccRCC tumours, highlighting the involvement of arginine biosynthesis, β-alanine metabolism and purine and pyrimidine metabolism in ccRCC. The correlations between tissue and urine metabolomes provide evidence for the potential usefulness of urinary metabolites in understanding systemic metabolic changes driven by RCC tumours.</p><p><strong>Conclusions: </strong>These findings significantly advance our understanding of metabolic reprogramming in ccRCC and the systemic metabolic changes associated with the disease. Future research is needed to validate these findings in larger cohorts and to determine their potential implications for diagnosis and targeted therapies.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 2","pages":"26"},"PeriodicalIF":3.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of salivary metabolomics in chronic periodontitis: bridging oral and systemic diseases.","authors":"Jawaher Albahri, Heather Allison, Kathryn A Whitehead, Howbeer Muhamadali","doi":"10.1007/s11306-024-02220-0","DOIUrl":"10.1007/s11306-024-02220-0","url":null,"abstract":"<p><strong>Background: </strong>Chronic periodontitis is a condition impacting approximately 50% of the world's population. As chronic periodontitis progresses, the bacteria in the oral cavity change resulting in new microbial interactions which in turn influence metabolite production. Chronic periodontitis manifests with inflammation of the periodontal tissues, which is progressively developed due to bacterial infection and prolonged bacterial interaction with the host immune response. The bi-directional relationship between periodontitis and systemic diseases has been reported in many previous studies. Traditional diagnostic methods for chronic periodontitis and systemic diseases such as chronic kidney diseases (CKD) have limitations due to their invasiveness, requiring practised individuals for sample collection, frequent blood collection, and long waiting times for the results. More rapid methods are required to detect such systemic diseases, however, the metabolic profiles of the oral cavity first need to be determined.</p><p><strong>Aim of review: </strong>In this review, we explored metabolomics studies that have investigated salivary metabolic profiles associated with chronic periodontitis and systemic illnesses including CKD, oral cancer, Alzheimer's disease, Parkinsons's disease, and diabetes to highlight the most recent methodologies that have been applied in this field.</p><p><strong>Key scientific concepts of the review: </strong>Of the rapid, high throughput techniques for metabolite profiling, Nuclear magnetic resonance (NMR) spectroscopy was the most applied technique, followed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Furthermore, Raman spectroscopy was the most used vibrational spectroscopic technique for comparison of the saliva from periodontitis patients to healthy individuals, whilst Fourier Transform Infra-Red Spectroscopy (FT-IR) was not utilised as much in this field. A recommendation for cultivating periodontal bacteria in a synthetic medium designed to replicate the conditions and composition of saliva in the oral environment is suggested to facilitate the identification of their metabolites. This approach is instrumental in assessing the potential of these metabolites as biomarkers for systemic illnesses.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 1","pages":"24"},"PeriodicalIF":3.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potential biomarkers for coronary slow flow using untargeted metabolomics.","authors":"Yunxian Chen, Jiarong Liang, Sujuan Chen, Baofeng Chen, Fenglei Guan, Xiangying Liu, Xiangyang Liu, Yuanlin Zhao, Liangqiu Tang","doi":"10.1007/s11306-025-02223-5","DOIUrl":"10.1007/s11306-025-02223-5","url":null,"abstract":"<p><strong>Background: </strong>Coronary slow flow (CSF) is associated with poor cardiovascular prognosis. However, its pathogenesis is unclear. This study aimed to identify potential characteristic biomarkers in patients with CSF using untargeted metabolomics.</p><p><strong>Methods: </strong>We prospectively enrolled 30 patients with CSF, 30 with coronary artery disease (CAD), and 30 with normal coronary arteries (NCA), all of whom were age-matched, according to the results of coronary angiography. Serum metabolomics were analyzed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Differentially expressed metabolites were identified through orthogonal partial least squares-discriminant analysis (OPLS-DA) combined with univariate fold-change and VIP value analysis. Pathway enrichment of these metabolites was performed using the KEGG database, and ROC curves were plotted to assess the diagnostic value of the metabolites in CSF patients.</p><p><strong>Results: </strong>Compared to the CAD and NCA groups, 256 metabolites showed specific expression in CSF, with 18 meeting stringent screening criteria (VIP > 1, FC ≥ 2, or FC ≤ 0.5, and P < 0.05). Seven metabolites demonstrated high diagnostic value for CSF: inositol 1,3,4-trisphosphate (AUC: 1.0), Cer (d24:1/18:0 (2OH)) (AUC: 0.984), Creosol (AUC: 0.976), Chaps (AUC: 0.904), Arg-Thr-Lys-Arg (AUC: 0.929), Ser-Tyr-Arg (AUC: 0.912), and Methyl Indole-3-Acetate (AUC: 0.909). Pathway analysis highlighted the HIF-1 signaling pathway as the most significant metabolic pathway.</p><p><strong>Conclusions: </strong>We identified seven metabolites that may serve as serum biomarkers for predicting and diagnosing CSF through untargeted metabolomics. The HIF-1 signaling pathway appears to be crucial in the development of CSF.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 1","pages":"23"},"PeriodicalIF":3.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the metabolomic profile of growth hormone deficiency children using NMR spectroscopy.","authors":"Eftychia A Aggelaki, Aristeidis Giannakopoulos, Panagiota D Georgiopoulou, Styliani A Chasapi, Alexandra Efthymiadou, Dimitra Kritikou, Dionisios Chrysis, Georgios A Spyroulias","doi":"10.1007/s11306-024-02217-9","DOIUrl":"10.1007/s11306-024-02217-9","url":null,"abstract":"<p><strong>Introduction: </strong>The diagnosis of Growth Hormone Deficiency (GHD) during childhood has been the subject of much controversy over the last few years. Aiming to accurate medical treatment, there is a need for biomarker discovery.</p><p><strong>Objective: </strong>To characterize the metabolic profile of GHD children, examine the effect of GH administration on the metabolic signature, and investigate the correlations between metabolites and IGF-1.</p><p><strong>Methods: </strong>Nuclear Magnetic Resonance (NMR)-based untargeted and targeted metabolomic approach applied to study the metabolic profiles of children with GHD. Plasma, serum, and urine samples were collected from twenty-two children diagnosed with GHD and forty-eight age matched controls from the Pediatric Endocrinology Unit of the University Hospital of Patras. Experimental data were examined by both multivariate and univariate statistical analysis.</p><p><strong>Results: </strong>The results of this pilot study revealed a different metabolic fingerprint of children with GHD in comparison to age-matched healthy individuals. However, the detected alterations in the metabolite patterns before and after GH treatment were subtle and of minor discriminative statistical power.</p><p><strong>Conclusions: </strong>This study provides evidence that metabolome plays a pivotal role in GHD, but large-scale multicenter studies are warranted to validate the results.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 1","pages":"25"},"PeriodicalIF":3.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic profiles of meconium in preeclamptic and normotensive pregnancies.","authors":"Elli Toivonen, Jutta Sikkinen, Anne Salonen, Olli Kärkkäinen, Ville Koistinen, Anton Klåvus, Topi Meuronen, Tuomas Heini, Arina Maltseva, Mikael Niku, Tiina Jääskeläinen, Hannele Laivuori","doi":"10.1007/s11306-025-02224-4","DOIUrl":"10.1007/s11306-025-02224-4","url":null,"abstract":"<p><strong>Introduction: </strong>Preeclampsia (PE) is a common vascular pregnancy disorder affecting maternal and fetal metabolism with severe immediate and long-term consequences in mothers and infants. During pregnancy, metabolites in the maternal circulation pass through the placenta to the fetus. Meconium, a first stool of the neonate, offers a view to maternal and fetoplacental unit metabolism and could add to knowledge on the effects of PE on the fetus and newborn.</p><p><strong>Objectives: </strong>To compare meconium metabolome of infants from PE and normotensive pregnancies.</p><p><strong>Methods: </strong>A cohort of preeclamptic parturients and normotensive controls were recruited in Tampere University Hospital during 2019-2022. Meconium was sampled and its metabolome analyzed using liquid chromatography- mass spectrometry in 48 subjects in each group.</p><p><strong>Results: </strong>Differences in abundances of 1263 compounds, of which 19 could be annotated, were detected between the two groups. Several acylcarnitines, androsterone sulfate, three bile acids, amino acid derivatives (phenylacetylglutamine, epsilon-(gamma-glutamyl)lysine and N-(phenylacetyl)glutamic acid), as well as caffeine and paraxanthine were lower in the PE group compared to the control group. Urea and progesterone were higher in the PE group.</p><p><strong>Conclusion: </strong>PE is associated with alterations in the meconium metabolome of infants. The differing abundances of several metabolites show alterations in the interaction between the fetoplacental unit and mother in PE, but whether they are a cause or an effect of the disorder remains to be further investigated.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 1","pages":"21"},"PeriodicalIF":3.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: High-quality identification of volatile organic compounds (VOCs) originating from breath.","authors":"Wisenave Arulvasan, Hsuan Chou, Julia Greenwood, Madeleine L Ball, Owen Birch, Simon Coplowe, Patrick Gordon, Andreea Ratiu, Elizabeth Lam, Ace Hatch, Monika Szkatulska, Steven Levett, Ella Mead, Chloe Charlton-Peel, Louise Nicholson-Scott, Shane Swann, Frederik-Jan van Schooten, Billy Boyle, Max Allsworth","doi":"10.1007/s11306-024-02203-1","DOIUrl":"10.1007/s11306-024-02203-1","url":null,"abstract":"","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 1","pages":"22"},"PeriodicalIF":3.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns.","authors":"Jagadeesh Puvvula, Lucie C Song, Klaudia J Zalewska, Ariel Alexander, Kathrine E Manz, Joseph M Braun, Kurt D Pennell, Emily A DeFranco, Shuk-Mei Ho, Yuet-Kin Leung, Shouxiong Huang, Ann M Vuong, Stephani S Kim, Zana Percy, Priyanka Bhashyam, Raymund Lee, Dean P Jones, Vilinh Tran, Dasom V Kim, Antonia M Calafat, Julianne C Botelho, Aimin Chen","doi":"10.1007/s11306-024-02219-7","DOIUrl":"10.1007/s11306-024-02219-7","url":null,"abstract":"<p><strong>Background: </strong>Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.</p><p><strong>Methods: </strong>This study included 75 pregnant individuals who delivered at the University of Cincinnati Hospital from 2014 to 2017. We measured maternal urinary biomarkers of paraben/phenol (12), phthalate (13), and phthalate replacements (4) from the samples collected during the delivery visit. Global serum metabolome profiles were analyzed from maternal blood (n = 72) and newborn (n = 63) cord blood samples collected at delivery. Fifteen of the 29 urinary biomarkers were excluded due to low detection frequency or potential exposures during hospital stay. We assessed metabolome-wide associations between 14 maternal urinary biomarkers and maternal/newborn metabolome profiles. Additionally, performed enrichment analysis to identify potential alterations in metabolic pathways.</p><p><strong>Results: </strong>We observed metabolome-wide associations between maternal urinary concentrations of phthalate metabolites (mono-isobutyl phthalate), phthalate replacements (mono-2-ethyl-5-carboxypentyl terephthalate, mono-2-ethyl-5-hydroxyhexyl terephthalate) and phenols (bisphenol-A, bisphenol-S) and maternal serum metabolome, using q-value < 0.2 as a threshold. Additionally, associations of phthalate metabolites (mono-n-butyl phthalate, monobenzyl phthalate) and phenols (2,5-dichlorophenol, BPA) with the newborn metabolome were noted. Enrichment analyses revealed associations (p-gamma < 0.05) with amino acid, carbohydrate, lipid, glycan, vitamin, and other cofactor metabolism pathways.</p><p><strong>Conclusion: </strong>Maternal paraben, phenol, phthalate, and phthalate replacement biomarker concentrations at delivery were associated with maternal and newborn serum global metabolome.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 1","pages":"20"},"PeriodicalIF":3.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-targeted metabolomics-based molecular networking enables the chemical characterization of Rumex sanguineus, a wild edible plant.","authors":"Valentina Ramundi, Mitja M Zdouc, Enrica Donati, Justin J J van der Hooft, Sara Cimini, Laura Righetti","doi":"10.1007/s11306-024-02210-2","DOIUrl":"10.1007/s11306-024-02210-2","url":null,"abstract":"<p><strong>Introduction and objective: </strong>Rumex sanguineus, a traditional medicinal plant of the Polygonaceae family, is gaining popularity as an edible resource. However, despite its historical and nutritional significance, its chemical composition remains poorly understood. To deepen the understanding of the of Rumex sanguineus composition, an in-depth analysis using non-targeted, mass spectrometry-based metabolomics was performed.  METHODS: Rumex roots, stems and leaves samples were analyzed by UHPLC-HRMS and subsequently subjected to feature-based molecular networking.</p><p><strong>Results and conclusion: </strong>Overall, 347 primary and specialized metabolites grouped into 8 biochemical classes were annotated. Most of these metabolites (60%) belong to the polyphenols and anthraquinones classes. To investigate potential' toxicity due to the presence of anthraquinones, the amount of emodin was quantified with analytical standard, revealing higher accumulation in leaves compared to stems and roots. This highlights the need for thorough metabolomic studies to understand both beneficial and harmful compounds, especially in plants with historical medicinal use transitioning to modern culinary use.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 1","pages":"19"},"PeriodicalIF":3.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wall shear stress modulates metabolic pathways in endothelial cells.","authors":"Rita Simões-Faria, Margo Daems, Hanna M Peacock, Mathias Declercq, Anton Willems, Elizabeth A V Jones, Bart Ghesquière","doi":"10.1007/s11306-024-02214-y","DOIUrl":"10.1007/s11306-024-02214-y","url":null,"abstract":"<p><strong>Introduction: </strong>Hemodynamic forces play a crucial role in modulating endothelial cell (EC) behavior, significantly influencing blood vessel responses. While traditional in vitro studies often explore ECs under static conditions, ECs are exposed to various hemodynamic forces in vivo. This study investigates how wall shear stress (WSS) influences EC metabolism, focusing on the interplay between WSS and key metabolic pathways.</p><p><strong>Objectives: </strong>The aim of this study is to examine the effects of WSS on EC metabolism, specifically evaluating its impact on central carbon metabolism and glycolysis using transcriptomics and tracer metabolomics approaches.</p><p><strong>Methods: </strong>ECs were exposed to WSS, and transcriptomic analysis was performed to assess gene expression changes related to metabolic pathways. Tracer metabolomics was used to track metabolic fluxes, focusing on glutamine and glycolytic metabolism. Additionally, chemical inhibition of glutamate dehydrogenase was conducted to evaluate its role in EC fitness under WSS.</p><p><strong>Results: </strong>Transcriptomic data revealed upregulation of glutamine and glutamate pathways, alongside downregulation of glycolytic activity in ECs exposed to WSS. Tracer metabolomics confirmed that WSS promotes glutamine anaplerosis into the Krebs cycle, while decreasing glycolytic metabolism. Suppression of glutamate dehydrogenase impaired EC fitness under WSS conditions.</p><p><strong>Conclusion: </strong>Our findings illuminate that ECs subjected to WSS exhibit a preference for glutamine as a key nutrient source for central carbon metabolism pathways, indicating diminished reliance on glycolysis. This study elucidates the nutritional predilections and regulatory mechanisms governing EC metabolism under WSS in vitro, underscoring the pivotal role of physical stimuli in shaping EC metabolic responses.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 1","pages":"16"},"PeriodicalIF":3.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}