MetabolomicsPub Date : 2026-05-07DOI: 10.1007/s11306-026-02437-1
Marion Pradeau, Julie-Catherine Coll, Ana Berteaux, Véronique Paquet, Isabelle Robillard Frayne, Stéphanie Ferland, Matthieu Ruiz, Anne-Marie Carreau
{"title":"Metabolomic and lipidomic plasma profiles according to metabolic dysfunction-associated steatotic liver diseases (MASLD) stages in the absence of type 2 diabetes (T2D).","authors":"Marion Pradeau, Julie-Catherine Coll, Ana Berteaux, Véronique Paquet, Isabelle Robillard Frayne, Stéphanie Ferland, Matthieu Ruiz, Anne-Marie Carreau","doi":"10.1007/s11306-026-02437-1","DOIUrl":"https://doi.org/10.1007/s11306-026-02437-1","url":null,"abstract":"<p><strong>Introduction: </strong>Amino acids (AAs), tricarboxylic acid (TCA) cycle intermediates, and acylcarnitines (ACs) can reflect energetic metabolism. Metabolic dysfunction-associated steatotic liver (MASLD) has been associated with the modification of plasma AAs, ACs and TCA cycle intermediates' profiles, but the changes in advanced fibrosis without type 2 diabetes (T2D) are not well studied.</p><p><strong>Objectives: </strong>The objective of this pilot study was to describe the targeted plasma metabolomic profile in individuals with advanced fibrosis to test research hypotheses concerning hepatic energy metabolism.</p><p><strong>Methods: </strong>We compared plasma fasting concentrations of 21 AAs, 11 organic acids (including ketone bodies and TCA cycle intermediates) and 14 ACs between individuals with advanced fibrosis stages (F3-F4/4) (n = 10) and individuals with no advanced fibrosis (n = 10), all without T2D and with similar clinical characteristics.</p><p><strong>Results: </strong>Median age (IQR) (51 [43-67] vs. 57 [43-66] years), sex (30 vs. 50% men) and BMI (35 [28-37] vs. 37 [32-39] kg/m<sup>2</sup>) were comparable between groups. The advanced fibrosis (AF) group presented higher plasma tyrosine (p = 0.04), α-ketoglutarate (p = 0.04), and a lower level of medium-chain ACs C8 and C10 (p = 0.04). The glutamate-glycine-serine (GSG) index, which combines AAs involved in glutathione metabolism, was higher in the AF group (p = 0.04).</p><p><strong>Conclusion: </strong>Overall, our results suggest impaired AAs catabolism and mitochondrial dysfunction. While the limited sample size and study design preclude causal inferences, these findings highlight potential metabolic signatures of advanced fibrosis in MASLD. They also underscore the need for larger, longitudinal studies to clarify their origin, significance, and clinical implications.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840108","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}
MetabolomicsPub Date : 2026-05-07DOI: 10.1007/s11306-026-02399-4
Joanna Bogusiewicz, Ivana Stanimirova, Magdalena Gaca-Tabaszewska, Paulina Szeliska, Krystyna Soszyńska, Anna Majdańska, Agata Ryfa, Alicja Bartoszewska-Kubiak, Jacek Furtak, Marcin Birski, Marek Harat, Barbara Bojko
{"title":"Lipidomic profile of meningiomas harboring different NF2 mutation status.","authors":"Joanna Bogusiewicz, Ivana Stanimirova, Magdalena Gaca-Tabaszewska, Paulina Szeliska, Krystyna Soszyńska, Anna Majdańska, Agata Ryfa, Alicja Bartoszewska-Kubiak, Jacek Furtak, Marcin Birski, Marek Harat, Barbara Bojko","doi":"10.1007/s11306-026-02399-4","DOIUrl":"https://doi.org/10.1007/s11306-026-02399-4","url":null,"abstract":"<p><strong>Introduction: </strong>Meningiomas are mainly benign brain tumors, but they can evolve to higher grades. The phenomena of these changes are not well-known. Therefore, more basic research is needed. This study attempted to assess the lipidome profile in meningiomas harboring different NF2 mutation statuses (wildtype and mutated). Solid-phase microextraction (SPME) probes were used to sample and extract the metabolites and reduce the invasiveness of lipidomic analysis.</p><p><strong>Objectives: </strong>This study aimed to select the set of lipids distinguishing meningiomas with different genotypes using two chromatography methods (hydrophilic interaction chromatography (HILIC) and reversed-phase chromatography (RPLC) in two ionization modes.</p><p><strong>Methods: </strong>Brain tumors were obtained during neurosurgical procedures. Then, sampling using SPME fibers was performed directly after the lesion excision. After collecting the whole batch of samples, desorption using an isopropanol-methanol solution was performed. Subsequently, instrumental analysis was carried out using liquid chromatography coupled with high-resolution mass spectrometry. The remaining part of the lesion was stored as paraffin tissue blocks, and then genetic testing was performed to determine the presence of mutations in the NF2 gene.</p><p><strong>Results: </strong>Genetic profiling of meningiomas revealed that most lesions had a mutation in the NF2 gene. A wide range of analytes was extracted from the studied tumors using SPME probes. A set of 34 lipids was selected as crucial metabolites in tumor differentiation. A combination of analytes detected in more than one analysis mode demonstrated higher sensitivity and specificity compared to the individual models and increased the differentiation of mutant and wildtype samples.</p><p><strong>Conclusions: </strong>SPME coupled liquid chromatography and mass spectrometry, can be successfully applied to the screening of lipids in meningiomas with different NF mutation statuses.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840143","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}
MetabolomicsPub Date : 2026-05-06DOI: 10.1007/s11306-026-02436-2
André Nunes Silva, Djaceli Sampaio de Oliveira Dembogurski, Amanda Galdi Boaretto, Carlos Alexandre Carollo, Flavio Macedo Alves, Denise Brentan Silva
{"title":"Seasonality and fruiting converge on megastigmanes to shape foliar metabolic plasticity in Miconia albicans (Swartz) Triana (Melastomataceae).","authors":"André Nunes Silva, Djaceli Sampaio de Oliveira Dembogurski, Amanda Galdi Boaretto, Carlos Alexandre Carollo, Flavio Macedo Alves, Denise Brentan Silva","doi":"10.1007/s11306-026-02436-2","DOIUrl":"10.1007/s11306-026-02436-2","url":null,"abstract":"<p><strong>Introduction: </strong>Miconia albicans is a medicinal plant widely used in traditional medicine and represents a promising candidate for phytotherapeutic drug development. Despite its widespread use, the influence of environmental seasonality and phenological state on its foliar metabolome remains poorly understood, particularly in seasonal ecosystems such as the Brazilian savanna (Cerrado Biome).</p><p><strong>Objectives: </strong>This study aimed to evaluate the influence of seasonality and phenological state on the foliar metabolome of M. albicans by untargeted metabolomics and chemometric approaches.</p><p><strong>Methods: </strong>Leaves of M. albicans were collected from the same individuals over an 18-month period, encompassing dry and rainy seasons and contrasting phenological states (fruiting and budding). Samples were analyzed using LC-MS-based untargeted metabolomics, and data were evaluated through multivariate analyses and univariate mixed-effects models.</p><p><strong>Results: </strong>Twenty-five metabolites were annotated, including flavonoids, megastigmanes, tannins, and triterpenes. Fruiting exerted the strongest effect on global metabolic structure, being associated with marked convergence of foliar metabolomes and coordinated responses of specific chemical classes, such as megastigmanes and tannins. Seasonality mainly affected megastigmanes, which exhibited higher intensities in the dry season. Budding had the weakest effect with responses restricted to the triterpene pathway. Univariate analyses also revealed that all annotated megastigmanes had higher intensities in both fruiting individuals and the dry season.</p><p><strong>Conclusion: </strong>These results demonstrate that foliar specialized metabolism in M. albicans integrates environmental and phenological signals, with megastigmanes participate in a central axis of foliar metabolic plasticity within M. albicans under dry and fruiting conditions.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840065","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}
MetabolomicsPub Date : 2026-05-06DOI: 10.1007/s11306-026-02445-1
Ana Carolina Pinto, Helena Beatriz Ferreira, Samuel Barbosa, Tiago Sousa, Tânia Melo, Lúcio Lara Santos, Rita Ferreira, Daniel Moreira-Gonçalves, Maria do Rosário Domingues
{"title":"Deciphering the circulating lipidome signature associated with physical performance in gastric cancer patients: an exploratory study.","authors":"Ana Carolina Pinto, Helena Beatriz Ferreira, Samuel Barbosa, Tiago Sousa, Tânia Melo, Lúcio Lara Santos, Rita Ferreira, Daniel Moreira-Gonçalves, Maria do Rosário Domingues","doi":"10.1007/s11306-026-02445-1","DOIUrl":"10.1007/s11306-026-02445-1","url":null,"abstract":"<p><strong>Introduction: </strong>Physical performance strongly influences peri-treatment outcomes in gastric cancer (GC), yet simple molecular markers reflecting functional status are lacking. Lipidomics may help identify circulating biomarkers linked to physical fitness.</p><p><strong>Objectives: </strong>To assess whether physical performance is associated with distinct plasma lipidomic profiles in GC patients.</p><p><strong>Methods: </strong>Nineteen male GC patients (60-75 years) from the PROTECT trial were classified as high- (HighP) or low-performance (LowP) based on the 6-min walk test. Plasma lipidomics (LC-MS/MS) quantified 232 lipid species and a total of 25 fatty acids were quantified by gas chromatography-MS. Multivariate and univariate analyses, group comparisons, and correlations examined associations with clinical, anthropometric, and fitness parameters.</p><p><strong>Results: </strong>Lipid profiles differed by performance status. HighP patients showed higher phosphatidylinositol (PI 36:2) and trends toward increased plasmalogen phosphatidylethanolamines (PE), whereas sphingomyelin (SM 43:2) was higher in LowP patients. Plasmenyl-PE species correlated positively with functional tests, muscle mass, body mass index, and nutritional status; SM 43:2 correlated negatively. Acylcarnitines showed minimal associations.</p><p><strong>Conclusion: </strong>GC patients with different physical performance status display distinct circulating lipid signatures. PI 36:2, PE plasmalogens, and SM 43:2 species appear linked to physical fitness, suggesting potential value as preoperative biomarkers. Validation in larger cohorts is warranted.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840048","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}
MetabolomicsPub Date : 2026-04-29DOI: 10.1007/s11306-026-02425-5
Kaylie I Kirkwood-Donelson, Dylan J Johnson, Payam Noroozi Farhadi, Kakali Sarkar, Adam I Schiffenbauer, Frederick W Miller, Gregory Kudzin, Erin S Baker, Jian-Liang Li, Lisa G Rider, Alan K Jarmusch
{"title":"Untargeted metabolomics reveals serum metabolites related to energy metabolism and inflammation associated with juvenile dermatomyositis.","authors":"Kaylie I Kirkwood-Donelson, Dylan J Johnson, Payam Noroozi Farhadi, Kakali Sarkar, Adam I Schiffenbauer, Frederick W Miller, Gregory Kudzin, Erin S Baker, Jian-Liang Li, Lisa G Rider, Alan K Jarmusch","doi":"10.1007/s11306-026-02425-5","DOIUrl":"10.1007/s11306-026-02425-5","url":null,"abstract":"<p><strong>Introduction: </strong>Juvenile dermatomyositis (JDM) is a rare autoimmune inflammatory myopathy characterized by muscle weakness and distinctive skin rashes. Despite advancements in the clinical understanding of JDM, metabolic disturbances underlying the disease remain poorly understood.</p><p><strong>Objectives: </strong>This study aimed to investigate serum metabolite differences in JDM compared to age- and sex-matched unaffected siblings (US) and unrelated healthy controls (HC), and to identify metabolite abundance differences associated with disease severity.</p><p><strong>Methods: </strong>Serum samples from JDM (n = 16) and adult dermatomyositis (DM; n = 15) patients and corresponding US and HC underwent untargeted metabolomics profiling. Multivariate, univariate, and correlation analyses were employed to identify metabolites differentiating groups and correlating with Physician Global Damage (PGD) scores.</p><p><strong>Results: </strong>JDM patients exhibited modest but discernible alterations in serum metabolites compared to controls, many of which also correlated with PGD. Several bioactive lipids and pyroglutamic acid were upregulated in JDM and positively correlated with PGD. Changes in xanthine, methionine and N-acetylneuraminic acid also indicated increased oxidative stress and inflammation. Markers of increased energy demand and muscle damage, including acylcarnitines, creatine, 4-guanidinobutyric acid, glutamine, and phenylacetylglutamine, were differential and correlated with PGD in some cases. A metabolite abundance gradient from JDM to US to HC groups suggests that siblings help account for genetic and environmental influences on the metabolome. DM patients did not show significant serum changes compared to US.</p><p><strong>Conclusion: </strong>Untargeted metabolomics revealed distinct serum metabolite alterations in JDM, providing insights into disease-related metabolic perturbations. These findings enhance understanding of JDM pathophysiology and inform future large-scale, targeted studies.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775726","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}
MetabolomicsPub Date : 2026-04-29DOI: 10.1007/s11306-026-02432-6
Annika Kneipp, Inge Kirchberger, Dennis Freuer, Christine Meisinger, Jakob Linseisen
{"title":"Urinary metabolites and fatigue in a population-based metabolomics study: an exploratory analysis.","authors":"Annika Kneipp, Inge Kirchberger, Dennis Freuer, Christine Meisinger, Jakob Linseisen","doi":"10.1007/s11306-026-02432-6","DOIUrl":"10.1007/s11306-026-02432-6","url":null,"abstract":"<p><strong>Introduction: </strong>Nearly every fifth adult person suffers from chronic fatigue, but its etiology and related mechanisms are poorly understood. Metabolomics data offer new possibilities for identifying metabolites related to disease etiology.</p><p><strong>Objectives: </strong>This study aimed to investigate the association between urinary metabolites and fatigue in the general population.</p><p><strong>Methods: </strong>Fatigue severity was assessed using the Fatigue Assessment Scale (FAS). 51 urinary metabolites were quantified via ¹H nuclear magnetic resonance (¹H-NMR). Multivariable linear regression models adjusted for possible confounders were performed on data of 570 participants of the Metabolism, Nutrition and Immune System in Augsburg (MEIA) study to explore the associations between urinary metabolites and fatigue.</p><p><strong>Results: </strong>Four urinary metabolites showed significant associations with fatigue, namely hypoxanthine (β = 0.932, 95% CI 0.168-1.697, p = 0.017), 3-hydroxyhippurate (β = 0.213, 95% CI 0.003-0.424, p = 0.047), dimethylamine (β = 0.756, 95% CI 0.255-1.257, p = 0.003), and trimethylamine-N-oxide (β = 0.088, 95% CI 0.002-0.174, p = 0.045). Stratified analyses showed that the association of hypoxanthine was limited to individuals with obesity (BMI ≥ 30 kg/m<sup>2</sup>; β = 3.186, 95% CI 1.742-4.629, p < 0.001). After correction for multiple testing (false discovery rate), none of these associations remained statistically significant.</p><p><strong>Conclusion: </strong>Urinary metabolites related to purine degradation and gut microbial metabolism may reflect fatigue-related biological processes, demonstrating the potential of urinary metabolomics to identify biochemical alterations and possible mechanisms of fatigue pathophysiology.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775662","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}
MetabolomicsPub Date : 2026-04-29DOI: 10.1007/s11306-026-02443-3
Stephanie Seneff, László G Boros
{"title":"The essential role of hydrogen gas recycling by gut microbes in reducing deuterium load in host mitochondria: is trimethylamine oxide a deuterium sensor?","authors":"Stephanie Seneff, László G Boros","doi":"10.1007/s11306-026-02443-3","DOIUrl":"10.1007/s11306-026-02443-3","url":null,"abstract":"<p><strong>Background: </strong>The human gut microbiome plays many essential roles, but an often-overlooked role is to maintain an abundant supply of deuterium depleted (deupleted) nutrients to fuel the host mitochondria. Excess deuterium (heavy hydrogen) damages mitochondrial ATP synthase nanomotors, leading to a decrease in matrix water production with increased reactive oxygen species (ROS) and inefficient ATP production. A microbial metabolite, trimethylamine N-oxide (TMAO) is a powerful signaling molecule whose plasma levels are high in association with many chronic diseases, including diabetes, fatty liver disease, and atherosclerosis, as well as cancer and dementia. Thus, TMAO is an important gut-host signaling molecule that serves as a marker for an imbalanced microbiome that is unable to fully metabolize trimethylamine (TMA), an important step in maintaining a deupleted nutrient supply.</p><p><strong>Aim of review: </strong>In this paper, we present a hypothesis that TMAO is a marker for deuterium overload in the methylation pathway, in addition to its role as an indicator of a disrupted gut microbiome. The original study that brought attention to TMAO involved feeding mice synthetic choline with fully deuterated methyl groups. Fully deuterated TMAO was subsequently detected in the plasma. By contrast, a diet rich in eggs, a natural source of choline (a precursor to TMAO), does not raise TMAO levels. Many of the pathologies that are linked to elevated TMAO can also be viewed as strategies to promote the supply of deupleted water to the mitochondria, systemically.</p><p><strong>Key scientific concepts: </strong>The mantra that \"food is medicine\" is well supported by the powerful role that gut dysbiosis plays in influencing human health and disease.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775123","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}
MetabolomicsPub Date : 2026-04-29DOI: 10.1007/s11306-026-02441-5
Kara Wegermann, Mengshu He, Lydia Coulter Kwee, Christopher B Newgard, Serhiy Hnatyshyn, Petia Shipkova, Svati H Shah, Cynthia A Moylan
{"title":"Metabolic markers of kidney function and oxidative stress are associated with heart failure with preserved ejection fraction (HFpEF) in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD).","authors":"Kara Wegermann, Mengshu He, Lydia Coulter Kwee, Christopher B Newgard, Serhiy Hnatyshyn, Petia Shipkova, Svati H Shah, Cynthia A Moylan","doi":"10.1007/s11306-026-02441-5","DOIUrl":"10.1007/s11306-026-02441-5","url":null,"abstract":"<p><strong>Background and aim: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with heart failure with preserved ejection fraction (HFpEF), independent of shared risk factors. The aim of this study was to discover metabolic pathways associated with HFpEF in individuals with MASLD to explore shared mechanisms and identify biomarkers of risk.</p><p><strong>Methods: </strong>We examined HFpEF cases and non-HF controls in the Duke CATHeterization GENetics (CATHGEN) study. HFpEF was defined as left ventricular ejection fraction (LVEF) ≥ 45%, diastolic dysfunction grade ≥ 1 on transthoracic echocardiogram (TTE), and history of clinical heart failure. MASLD was phenotyped using ICD codes or hepatic steatosis index (HSI) > 36, in the presence of ≥ 1 metabolic risk factor. Metabolomic profiling was performed in fasting plasma using targeted tandem flow injection (absolute quantification, n = 60) and non-targeted (relative quantification, n = 210) mass spectrometry. Logistic regression models tested the association between metabolite factors and HFpEF. An interaction term analyzed the influence of MASLD on associations between metabolites and HFpEF.</p><p><strong>Results: </strong>A total of 430 participants were included; 247 (57.4%) had HFpEF. In participants with MASLD (N = 222, 51.6%), a factor composed of markers of kidney function, acylcarnitines, and modified amino acids was associated with HFpEF (OR: 2.2, 95% CI: 1.5-3.2, FDR-adjusted p-value = 0.002). The association of a PC composed primarily of ketoglutarate and phenyl sulfate with HFpEF was modified by MASLD (unadjusted p-value = 0.03).</p><p><strong>Conclusions: </strong>Markers of kidney function and mitochondrial metabolism were associated with HFpEF in participants with MASLD. Mitochondrial energy pathways may link MASLD to HFpEF.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775987","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}
MetabolomicsPub Date : 2026-04-29DOI: 10.1007/s11306-026-02440-6
Yaowu He, Yupeng Li, Jing Geng, Hong Chen, Huaping Dai
{"title":"ILDMDB: a manually curated database of metabolite-disease associations in interstitial lung diseases.","authors":"Yaowu He, Yupeng Li, Jing Geng, Hong Chen, Huaping Dai","doi":"10.1007/s11306-026-02440-6","DOIUrl":"10.1007/s11306-026-02440-6","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolomics analysis shows great promise in identifying non-invasive biomarkers for interstitial lung diseases (ILDs). However, the relevant data are scattered across numerous disparate publications, hindering their full utilization.</p><p><strong>Objectives: </strong>To comprehensively leverage the metabolomic data disseminated throughout the literature, we manually curated and integrated them into the ILDMDB database ( https://ildmdb.shinyapps.io/ILDMDB/ ). This database will be regularly updated and maintained.</p><p><strong>Methods: </strong>We conducted a systematic literature search and extracted key metabolomics data, including changes in metabolites, relevant clinical parameters, and predictive model performance metrics etc. These data were then manually integrated into the ILDMDB database.</p><p><strong>Results: </strong>The current version of ILDMDB contains 3,969 entries, representing 20 ILD types and over 1,000 metabolites derived from Homo sapiens, animal models, and cell line experiments. Each entry comprises detailed information, including the metabolite name, disease type, and original reference. In addition, we have incorporated model data on metabolites used for ILD diagnosis, disease severity, and prognosis, along with information on metabolites associated with clinical parameters. Users can search for target metabolites freely, view their expression patterns and detailed information, and manage metabolite collections in the database.</p><p><strong>Conclusion: </strong>ILDMDB serves as an exploratory platform designed to assist researchers in swiftly and conveniently accessing the metabolic landscape of ILDs, thereby advancing research into the diagnosis, prognosis, and treatment of ILDs from a metabolic perspective.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775994","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}
MetabolomicsPub Date : 2026-04-29DOI: 10.1007/s11306-026-02438-0
Dongwei Sun, Alex Postajian, Edgmin Rostomian, Yu Chen, Junyoung O Park, Vedi Hatamian, Kevin Babakhan Vartanian, Finosh G Thankam
{"title":"Integrated metabolomic profiling reveals metabolomic responses by epicardial and myocardial stromal cells to ischemia.","authors":"Dongwei Sun, Alex Postajian, Edgmin Rostomian, Yu Chen, Junyoung O Park, Vedi Hatamian, Kevin Babakhan Vartanian, Finosh G Thankam","doi":"10.1007/s11306-026-02438-0","DOIUrl":"10.1007/s11306-026-02438-0","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiac ischemia induces substantial metabolomic reprogramming, which dysregulates cardiomyocytes (CMs) and non-myocyte stromal cell populations. The stromal cells derived from epicardial adipose tissue (EAT) and ventricle are critical for extracellular matrix (ECM) remodeling, paracrine signaling, and myocardial homeostasis. However, the metabolomic content and responses of EAT-derived stromal cells (EATDS) and ventricular stromal cells (VSCs) remain unknown.</p><p><strong>Methodology: </strong>This study employed untargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics to characterize ischemia-driven metabolic reprogramming in EATDS and VSCs harvested from swine hearts. Ischemia was simulated using the standard ischemic buffer (pH 6.2) for 2 h.</p><p><strong>Results: </strong>Metabolomic screening revealed 65 and 68 metabolites, respectively, for EATDS and VSCs. Results revealed extensive downregulation of amino acid biosynthesis, redox pathways, and mitochondrial metabolism, alongside selective upregulation of glycolytic and cofactor-associated metabolites. Pathway enrichment analyses indicated significant suppression of the TCA cycle, one-carbon metabolism, glutathione cycling, and branched-chain amino acid degradation, reflecting impaired bioenergetic and antioxidant capacity. Adaptive responses included the enrichment of glycolysis, β-alanine, and glyoxylate/dicarboxylate metabolism, consistent with metabolic plasticity under hypoxic conditions. Network-based analyses linked these metabolic shifts to inflammatory pathways. Functional assays demonstrated that sarcosine, pyroglutamic acid, and 3-hydroxypropionic acid modulate the gene expression of cardiac regenerative biomarkers, including GATA4, Nkx2.5, TROP-I, LGALS1, TBX5, and IRX4.</p><p><strong>Conclusions: </strong>These findings suggest that ischemia-induced metabolomic changes exert transcriptional control over cardiac remodeling programs, emphasizing the regulatory potential of metabolite-gene interactions. Such an integrated metabolomic transcriptional response highlights novel therapeutic targets for modulating cellular resilience and heart regeneration following ischemic heart disease.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"22 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775984","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}