Metabolites

2 pages, 167 KiB

Open AccessLetter

Letter to the Editor of Metabolites

by Maureen R. Hanson and Arnaud Germain

Metabolites 2020, 10(5), 216; https://doi.org/10.3390/metabo10050216 - 25 May 2020

Cited by 8 | Viewed by 5386

Abstract

Dear Editor, [...] Full article

14 pages, 3770 KiB

Open AccessArticle

Insights into the Metabolome of the Cyanobacterium Leibleinia gracilis from the Lagoon of Tahiti and First Inspection of Its Variability

by Hiren Solanki, Manon Pierdet, Olivier P. Thomas and Mayalen Zubia

Metabolites 2020, 10(5), 215; https://doi.org/10.3390/metabo10050215 - 24 May 2020

Cited by 7 | Viewed by 3376

Abstract

Cyanobacteria are known to produce a large diversity of specialized metabolites that can cause severe (eco)toxicological effects. In the lagoon of Tahiti, the benthic cyanobacterium Leibleinia gracilis is commonly found overgrowing the proliferative macroalga Turbinaria ornata or dead branching corals. The specialized metabolome [...] Read more.

Cyanobacteria are known to produce a large diversity of specialized metabolites that can cause severe (eco)toxicological effects. In the lagoon of Tahiti, the benthic cyanobacterium Leibleinia gracilis is commonly found overgrowing the proliferative macroalga Turbinaria ornata or dead branching corals. The specialized metabolome of the cyanobacterium L. gracilis was therefore investigated together with its variability on both substrates and changes in environmental parameters. For the study of the metabolome variability, replicates of L. gracilis were collected in the same location of the lagoon of Tahiti before and after a raining event, both on dead corals and on T. ornata. The variability in the metabolome was inferred from a comparative non-targeted metabolomic using high resolution mass spectrometry (MS) data and a molecular network analysis built through MS/MS analyses. Oxidized fatty acid derivatives including the unusual 11-oxopalmitelaidic acid were found as major constituents of the specialized metabolome of this species. Significant variations in the metabolome of the cyanobacteria were observed, being more important with a change in environmental factors. Erucamide was found to be the main chemical marker highly present when the cyanobacterium grows on the macroalga. This study highlights the importance of combined approaches in metabolomics and molecular networks to inspect the variability in the metabolome of cyanobacteria with applications for ecological questions. Full article

(This article belongs to the Special Issue Metabolomics in Chemical Ecology)

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15 pages, 3104 KiB

Open AccessArticle

Metabolomic Profiling of Nicotiana Spp. Nectars Indicate That Pollinator Feeding Preference Is a Stronger Determinant Than Plant Phylogenetics in Shaping Nectar Diversity

by Fredy A. Silva, Elizabeth C. Chatt, Siti-Nabilla Mahalim, Adel Guirgis, Xingche Guo, Daniel S. Nettleton, Basil J. Nikolau and Robert W. Thornburg

Metabolites 2020, 10(5), 214; https://doi.org/10.3390/metabo10050214 - 22 May 2020

Cited by 10 | Viewed by 3589

Abstract

Floral nectar is a rich secretion produced by the nectary gland and is offered as reward to attract pollinators leading to improved seed set. Nectars are composed of a complex mixture of sugars, amino acids, proteins, vitamins, lipids, organic and inorganic acids. This [...] Read more.

Floral nectar is a rich secretion produced by the nectary gland and is offered as reward to attract pollinators leading to improved seed set. Nectars are composed of a complex mixture of sugars, amino acids, proteins, vitamins, lipids, organic and inorganic acids. This composition is influenced by several factors, including floral morphology, mechanism of nectar secretion, time of flowering, and visitation by pollinators. The objective of this study was to determine the contributions of flowering time, plant phylogeny, and pollinator selection on nectar composition in Nicotiana. The main classes of nectar metabolites (sugars and amino acids) were quantified using gas chromatography/mass spectrometric analytical platforms to identify differences among fifteen Nicotiana species representing day- and night-flowering plants from ten sections of the genus that are visited by five different primary pollinators. The nectar metabolomes of different Nicotiana species can predict the feeding preferences of the target pollinator(s) of each species, and the nectar sugars (i.e., glucose, fructose, and sucrose) are a distinguishing feature of Nicotiana species phylogeny. Moreover, comparative statistical analysis indicate that pollinators are a stronger determinant of nectar composition than plant phylogeny. Full article

(This article belongs to the Special Issue Plant Metabolomics)

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14 pages, 1945 KiB

Open AccessArticle

Impact of Pre-Blood Collection Factors on Plasma Metabolomic Profiles

by Sheetal Hardikar, Richard D. Albrechtsen, David Achaintre, Tengda Lin, Svenja Pauleck, Mary Playdon, Andreana N. Holowatyj, Biljana Gigic, Petra Schrotz-King, Juergen Boehm, Nina Habermann, Stefanie Brezina, Andrea Gsur, Eline H. van Roekel, Matty P. Weijenberg, Pekka Keski-Rahkonen, Augustin Scalbert, Jennifer Ose and Cornelia M. Ulrich

Metabolites 2020, 10(5), 213; https://doi.org/10.3390/metabo10050213 - 21 May 2020

Cited by 9 | Viewed by 2771

Abstract

Demographic, lifestyle and biospecimen-related factors at the time of blood collection can influence metabolite levels in epidemiological studies. Identifying the major influences on metabolite concentrations is critical to designing appropriate sample collection protocols and considering covariate adjustment in metabolomics analyses. We examined the [...] Read more.

Demographic, lifestyle and biospecimen-related factors at the time of blood collection can influence metabolite levels in epidemiological studies. Identifying the major influences on metabolite concentrations is critical to designing appropriate sample collection protocols and considering covariate adjustment in metabolomics analyses. We examined the association of age, sex, and other short-term pre-blood collection factors (time of day, season, fasting duration, physical activity, NSAID use, smoking and alcohol consumption in the days prior to collection) with 133 targeted plasma metabolites (acylcarnitines, amino acids, biogenic amines, sphingolipids, glycerophospholipids, and hexoses) among 108 individuals that reported exposures within 48 h before collection. The differences in mean metabolite concentrations were assessed between groups based on pre-collection factors using two-sided t-tests and ANOVA with FDR correction. Percent differences in metabolite concentrations were negligible across season, time of day of collection, fasting status or lifestyle behaviors at the time of collection, including physical activity or the use of tobacco, alcohol or NSAIDs. The metabolites differed in concentration between the age and sex categories for 21.8% and 14.3% metabolites, respectively. In conclusion, extrinsic factors in the short period prior to collection were not meaningfully associated with concentrations of selected endogenous metabolites in a cross-sectional sample, though metabolite concentrations differed by age and sex. Larger studies with more coverage of the human metabolome are warranted. Full article

(This article belongs to the Special Issue Integrative-Metabolomics in Epidemiological Studies)

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26 pages, 1829 KiB

Open AccessArticle

An NMR-Based Approach to Identify Urinary Metabolites Associated with Acute Physical Exercise and Cardiorespiratory Fitness in Healthy Humans—Results of the KarMeN Study

by Sina Kistner, Manuela J. Rist, Maik Döring, Claudia Dörr, Rainer Neumann, Sascha Härtel and Achim Bub

Metabolites 2020, 10(5), 212; https://doi.org/10.3390/metabo10050212 - 21 May 2020

Cited by 12 | Viewed by 3703

Abstract

Knowledge on metabolites distinguishing the metabolic response to acute physical exercise between fit and less fit individuals could clarify mechanisms and metabolic pathways contributing to the beneficial adaptations to exercise. By analyzing data from the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study, we [...] Read more.

Knowledge on metabolites distinguishing the metabolic response to acute physical exercise between fit and less fit individuals could clarify mechanisms and metabolic pathways contributing to the beneficial adaptations to exercise. By analyzing data from the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study, we characterized the acute effects of a standardized exercise tolerance test on urinary metabolites of 255 healthy women and men. In a second step, we aimed to detect a urinary metabolite pattern associated with the cardiorespiratory fitness (CRF), which was determined by measuring the peak oxygen uptake (VO_2peak) during incremental exercise. Spot urine samples were collected pre- and post-exercise and 47 urinary metabolites were identified by nuclear magnetic resonance (NMR) spectroscopy. While the univariate analysis of pre-to-post-exercise differences revealed significant alterations in 37 urinary metabolites, principal component analysis (PCA) did not show a clear separation of the pre- and post-exercise urine samples. Moreover, both bivariate correlation and multiple linear regression analyses revealed only weak relationships between the VO_2peak and single urinary metabolites or urinary metabolic pattern, when adjusting for covariates like age, sex, menopausal status, and lean body mass (LBM). Taken as a whole, our results show that several urinary metabolites (e.g., lactate, pyruvate, alanine, and acetate) reflect acute exercise-induced alterations in the human metabolism. However, as neither pre- and post-exercise levels nor the fold changes of urinary metabolites substantially accounted for the variation of the covariate-adjusted VO_2peak, our results furthermore indicate that the urinary metabolites identified in this study do not allow to draw conclusions on the individual’s physical fitness status. Studies investigating the relationship between the human metabolome and functional variables like the CRF should adjust for confounders like age, sex, menopausal status, and LBM. Full article

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14 pages, 4439 KiB

Open AccessArticle

Alterations in Tissue Metabolite Profiles with Amifostine-Prophylaxed Mice Exposed to Gamma Radiation

by Amrita K. Cheema, Yaoxiang Li, Michael Girgis, Meth Jayatilake, Oluseyi O. Fatanmi, Stephen Y. Wise, Thomas M. Seed and Vijay K. Singh

Metabolites 2020, 10(5), 211; https://doi.org/10.3390/metabo10050211 - 21 May 2020

Cited by 21 | Viewed by 3077

Abstract

Acute exposure to high-dose ionizing irradiation has the potential to severely injure the hematopoietic system and its capacity to produce vital blood cells that innately serve to ward off infections and excessive bleeding. Developing a medical radiation countermeasure that can protect individuals from [...] Read more.

Acute exposure to high-dose ionizing irradiation has the potential to severely injure the hematopoietic system and its capacity to produce vital blood cells that innately serve to ward off infections and excessive bleeding. Developing a medical radiation countermeasure that can protect individuals from the damaging effects of irradiation remains a significant, unmet need and an area of great public health interest and concern. Despite significant advancements in the field of radiation countermeasure development to find a nontoxic and effective prophylactic agent for acute radiation syndrome, no such drug has yet been approved by the Food and Drug Administration. This study focuses on examining the metabolic corrections elicited by amifostine, a potent radioprotector, on tissues of vital body organs, such as the heart, spleen, and kidney. Our findings indicate that prophylaxis with this drug offers significant protection against potentially lethal radiation injury, in part, by correction of radiation-induced metabolic pathway perturbations. Full article

(This article belongs to the Special Issue Metabolomics/Lipidomics in Radiation Research)

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24 pages, 2890 KiB

Open AccessArticle

Metabolic Profiling of PGPR-Treated Tomato Plants Reveal Priming-Related Adaptations of Secondary Metabolites and Aromatic Amino Acids

by Msizi I. Mhlongo, Lizelle A. Piater, Paul A. Steenkamp, Nico Labuschagne and Ian A. Dubery

Metabolites 2020, 10(5), 210; https://doi.org/10.3390/metabo10050210 - 20 May 2020

Cited by 49 | Viewed by 5861

Abstract

Plant growth–promoting rhizobacteria (PGPR) are beneficial microbes in the rhizosphere that can directly or indirectly stimulate plant growth. In addition, some can prime plants for enhanced defense against a broad range of pathogens and insect herbivores. In this study, four PGPR strains ( [...] Read more.

Plant growth–promoting rhizobacteria (PGPR) are beneficial microbes in the rhizosphere that can directly or indirectly stimulate plant growth. In addition, some can prime plants for enhanced defense against a broad range of pathogens and insect herbivores. In this study, four PGPR strains (Pseudomonas fluorescens N04, P. koreensis N19, Paenibacillus alvei T19, and Lysinibacillus sphaericus T22) were used to induce priming in Solanum lycopersicum (cv. Moneymaker) plants. Plants were inoculated with each of the four PGPRs, and plant tissues (roots, stems, and leaves) were harvested at 24 h and 48 h post-inoculation. Methanol-extracted metabolites were analyzed by ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS). Chemometric methods were applied to mine the data and characterize the differential metabolic profiles induced by the PGPR. The results revealed that all four strains induced defense-related metabolic reprogramming in the plants, characterized by dynamic changes to the metabolomes involving hydroxycinnamates, benzoates, flavonoids, and glycoalkaloids. In addition, targeted analysis of aromatic amino acids indicated differential quantitative increases or decreases over a two-day period in response to the four PGPR strains. The metabolic alterations point to an altered or preconditioned state that renders the plants primed for enhanced defense responses. The results contribute to ongoing efforts in investigating and unraveling the biochemical processes that define the PGPR priming phenomenon. Full article

(This article belongs to the Special Issue Plant Metabolomics)

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18 pages, 2252 KiB

Open AccessArticle

Cross-Species Comparison of Fruit-Metabolomics to Elucidate Metabolic Regulation of Fruit Polyphenolics Among Solanaceous Crops

by Carla Lenore F. Calumpang, Tomoki Saigo, Mutsumi Watanabe and Takayuki Tohge

Metabolites 2020, 10(5), 209; https://doi.org/10.3390/metabo10050209 - 19 May 2020

Cited by 21 | Viewed by 4624

Abstract

Many solanaceous crops are an important part of the human daily diet. Fruit polyphenolics are plant specialized metabolites that are recognized for their human health benefits and their defensive role against plant abiotic and biotic stressors. Flavonoids and chlorogenates are the major polyphenolic [...] Read more.

Many solanaceous crops are an important part of the human daily diet. Fruit polyphenolics are plant specialized metabolites that are recognized for their human health benefits and their defensive role against plant abiotic and biotic stressors. Flavonoids and chlorogenates are the major polyphenolic compounds found in solanaceous fruits that vary in quantity, physiological function, and structural diversity among and within plant species. Despite their biological significance, the elucidation of metabolic shifts of polyphenols during fruit ripening in different fruit tissues, has not yet been well-characterized in solanaceous crops, especially at a cross-species and cross-cultivar level. Here, we performed a cross-species comparison of fruit-metabolomics to elucidate the metabolic regulation of fruit polyphenolics from three representative crops of Solanaceae (tomato, eggplant, and pepper), and a cross-cultivar comparison among different pepper cultivars (Capsicum annuum cv.) using liquid chromatography-mass spectrometry (LC-MS). We observed a metabolic trade-off between hydroxycinnamates and flavonoids in pungent pepper and anthocyanin-type pepper cultivars and identified metabolic signatures of fruit polyphenolics in each species from each different tissue-type and fruit ripening stage. Our results provide additional information for metabolomics-assisted crop improvement of solanaceous fruits towards their improved nutritive properties and enhanced stress tolerance. Full article

(This article belongs to the Special Issue Fruit Metabolism and Metabolomics)

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19 pages, 3129 KiB

Open AccessArticle

Tryptophan Metabolism, Inflammation, and Oxidative Stress in Patients with Neurovascular Disease

by Martin Hajsl, Alzbeta Hlavackova, Karolina Broulikova, Martin Sramek, Martin Maly, Jan E. Dyr and Jiri Suttnar

Metabolites 2020, 10(5), 208; https://doi.org/10.3390/metabo10050208 - 19 May 2020

Cited by 51 | Viewed by 5547

Abstract

Atherosclerosis is a leading cause of major vascular events, myocardial infarction, and ischemic stroke. Tryptophan (TRP) catabolism was recognized as an important player in inflammation and immune response having together with oxidative stress (OS) significant effects on each phase of atherosclerosis. The aim [...] Read more.

Atherosclerosis is a leading cause of major vascular events, myocardial infarction, and ischemic stroke. Tryptophan (TRP) catabolism was recognized as an important player in inflammation and immune response having together with oxidative stress (OS) significant effects on each phase of atherosclerosis. The aim of the study is to analyze the relationship of plasma levels of TRP metabolites, inflammation, and OS in patients with neurovascular diseases (acute ischemic stroke (AIS), significant carotid artery stenosis (SCAS)) and in healthy controls. Blood samples were collected from 43 patients (25 with SCAS, 18 with AIS) and from 25 healthy controls. The concentrations of twelve TRP metabolites, riboflavin, neopterin (NEO, marker of inflammation), and malondialdehyde (MDA, marker of OS) were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Concentrations of seven TRP metabolites (TRP, kynurenine (KYN), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), anthranilic acid (AA), melatonin (MEL), tryptamine (TA)), NEO, and MDA were significantly different in the studied groups. Significantly lower concentrations of TRP, KYN, 3-HAA, MEL, TA, and higher MDA concentrations were found in AIS compared to SCAS patients. MDA concentration was higher in both AIS and SCAS group (p < 0.001, p = 0.004, respectively) compared to controls, NEO concentration was enhanced (p < 0.003) in AIS. MDA did not directly correlate with TRP metabolites in the study groups, except for 1) a negative correlation with kynurenine acid and 2) the activity of kynurenine aminotransferase in AIS patients (r = −0.552, p = 0.018; r = −0.504, p = 0.033, respectively). In summary, TRP metabolism is clearly more deregulated in AIS compared to SCAS patients; the effect of TRP metabolites on OS should be further elucidated. Full article

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13 pages, 738 KiB

Open AccessReview

Systems Biology ARDS Research with a Focus on Metabolomics

by Sayed M. Metwaly and Brent W. Winston

Metabolites 2020, 10(5), 207; https://doi.org/10.3390/metabo10050207 - 19 May 2020

Cited by 16 | Viewed by 4801

Abstract

Acute respiratory distress syndrome (ARDS) is a clinical syndrome that inflicts a considerably heavy toll in terms of morbidity and mortality. While there are multitudes of conditions that can lead to ARDS, the vast majority of ARDS cases are caused by a relatively [...] Read more.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome that inflicts a considerably heavy toll in terms of morbidity and mortality. While there are multitudes of conditions that can lead to ARDS, the vast majority of ARDS cases are caused by a relatively small number of diseases, especially sepsis and pneumonia. Currently, there is no clinically agreed upon reliable diagnostic test for ARDS, and the detection or diagnosis of ARDS is based on a constellation of laboratory and radiological tests in the absence of evidence of left ventricular dysfunction, as specified by the Berlin definition of ARDS. Virtually all the ARDS biomarkers to date have been proven to be of very limited clinical utility. Given the heterogeneity of ARDS due to the wide variation in etiology, clinical and molecular manifestations, there is a current scientific consensus agreement that ARDS is not just a single entity but rather a spectrum of conditions that need further study for proper classification, the identification of reliable biomarkers and the adequate institution of therapeutic targets. This scoping review aims to elucidate ARDS omics research, focusing on metabolomics and how metabolomics can boost the study of ARDS biomarkers and help to facilitate the identification of ARDS subpopulations. Full article

(This article belongs to the Special Issue Integrative-Metabolomics in Epidemiological Studies)

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15 pages, 3119 KiB

Open AccessArticle

Cross-Omics: Integrating Genomics with Metabolomics in Clinical Diagnostics

by Marten H. P. M. Kerkhofs, Hanneke A. Haijes, A. Marcel Willemsen, Koen L. I. van Gassen, Maria van der Ham, Johan Gerrits, Monique G. M. de Sain-van der Velden, Hubertus C. M. T. Prinsen, Hanneke W. M. van Deutekom, Peter M. van Hasselt, Nanda M. Verhoeven-Duif and Judith J. M. Jans

Metabolites 2020, 10(5), 206; https://doi.org/10.3390/metabo10050206 - 18 May 2020

Cited by 22 | Viewed by 3708

Abstract

Next-generation sequencing and next-generation metabolic screening are, independently, increasingly applied in clinical diagnostics of inborn errors of metabolism (IEM). Integrated into a single bioinformatic method, these two –omics technologies can potentially further improve the diagnostic yield for IEM. Here, we present cross-omics: a [...] Read more.

Next-generation sequencing and next-generation metabolic screening are, independently, increasingly applied in clinical diagnostics of inborn errors of metabolism (IEM). Integrated into a single bioinformatic method, these two –omics technologies can potentially further improve the diagnostic yield for IEM. Here, we present cross-omics: a method that uses untargeted metabolomics results of patient’s dried blood spots (DBSs), indicated by Z-scores and mapped onto human metabolic pathways, to prioritize potentially affected genes. We demonstrate the optimization of three parameters: (1) maximum distance to the primary reaction of the affected protein, (2) an extension stringency threshold reflecting in how many reactions a metabolite can participate, to be able to extend the metabolite set associated with a certain gene, and (3) a biochemical stringency threshold reflecting paired Z-score thresholds for untargeted metabolomics results. Patients with known IEMs were included. We performed untargeted metabolomics on 168 DBSs of 97 patients with 46 different disease-causing genes, and we simulated their whole-exome sequencing results in silico. We showed that for accurate prioritization of disease-causing genes in IEM, it is essential to take into account not only the primary reaction of the affected protein but a larger network of potentially affected metabolites, multiple steps away from the primary reaction. Full article

(This article belongs to the Special Issue Metabolomics–Integration of Technology and Bioinformatics)

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15 pages, 933 KiB

Open AccessArticle

Sedentariness and Urinary Metabolite Profile in Type 2 Diabetic Patients, a Cross-Sectional Study

by Elisa Benetti, Erica Liberto, Davide Bressanello, Valentina Bordano, Arianna C. Rosa, Gianluca Miglio, Jonida Haxhi, Giuseppe Pugliese, Stefano Balducci and Chiara Cordero

Metabolites 2020, 10(5), 205; https://doi.org/10.3390/metabo10050205 - 18 May 2020

Cited by 7 | Viewed by 2773

Abstract

Recent findings indicate a significant association between sedentary (SED)-time and type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether different levels of SED-time could impact on biochemical and physiological processes occurring in sedentary and physically inactive T2DM patients. [...] Read more.

Recent findings indicate a significant association between sedentary (SED)-time and type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether different levels of SED-time could impact on biochemical and physiological processes occurring in sedentary and physically inactive T2DM patients. In particular, patients from the “Italian Diabetes and Exercise Study (IDES)_2 trial belonging to the first and fourth quartile of SED-time were compared. Urine samples were analyzed by comprehensive two-dimensional gas chromatography (GC × GC) with parallel detection by mass spectrometry and flame ionization detection (GC × 2GC-MS/FID). This platform enables accurate profiling and fingerprinting of urinary metabolites while maximizing the overall information capacity, quantitation reliability, and response linearity. Moreover, using advanced pattern recognition, the fingerprinting process was extended to untargeted and targeted features, revealing diagnostic urinary fingerprints between groups. Quantitative metabolomics was then applied to analytes of relevance for robust comparisons. Increased levels of glycine, L-valine, L-threonine, L-phenylalanine, L-leucine, L-alanine, succinic acid, 2-ketoglutaric acid, xylitol, and ribitol were revealed in samples from less sedentary women. In conclusion, SED-time is associated with changes in urine metabolome signatures. These preliminary results suggest that reducing SED-time could be a strategy to improve the health status of a large proportion of diabetic patients. Full article

(This article belongs to the Special Issue Metabolomics in Clinical Research)

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11 pages, 2550 KiB

Open AccessArticle

Modulatory Effect of Nicotinic Acid on the Metabolism of Caco-2 Cells Exposed to IL-1β and LPS

by Maria Laura Santoru, Cristina Piras, Federica Murgia, Martina Spada, Laura Tronci, Vera Piera Leoni, Gabriele Serreli, Monica Deiana and Luigi Atzori

Metabolites 2020, 10(5), 204; https://doi.org/10.3390/metabo10050204 - 16 May 2020

Cited by 17 | Viewed by 3542

Abstract

Inflammatory bowel diseases (IBD) are the most common gastrointestinal inflammatory pathologies. Previous work evidenced a lower content of nicotinic acid (NA) in feces of IBD patients compared to healthy subjects. In the present study, we aimed to understand the effects of NA on [...] Read more.

Inflammatory bowel diseases (IBD) are the most common gastrointestinal inflammatory pathologies. Previous work evidenced a lower content of nicotinic acid (NA) in feces of IBD patients compared to healthy subjects. In the present study, we aimed to understand the effects of NA on intestinal inflammation, as several studies reported its possible beneficial effect, and investigate its influence on inflammation-driven metabolism. NA was tested on a Caco-2 in-vitro model in which inflammation was induced with interleukin-1β (IL-1β) and lipopolysaccharide (LPS), two mayor proinflammatory compounds produced in IBD, that stimulate the production of cytokines, such as interleukin 8. A metabolomics approach, with gas chromatography–mass spectrometry (GC-MS) and nuclear proton magnetic resonance (¹H-NMR), was applied to study the metabolic changes. The results showed that NA significantly reduced the level of IL-8 produced in both LPS and IL-1β stimulated cells, confirming the anti-inflammatory effect of NA also on intestinal inflammation. Moreover, it was demonstrated that NA treatment had a restoring effect on several metabolites whose levels were modified by treatments with IL-1β or LPS. This study points out a possible use of NA as anti-inflammatory compound and might be considered as a promising starting point in understanding the beneficial effect of NA in IBD. Full article

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13 pages, 1905 KiB

Open AccessArticle

Evaluation of Non-Uniform Sampling 2D ¹H–¹³C HSQC Spectra for Semi-Quantitative Metabolomics

by Bo Zhang, Robert Powers and Elizabeth M. O’Day

Metabolites 2020, 10(5), 203; https://doi.org/10.3390/metabo10050203 - 16 May 2020

Cited by 22 | Viewed by 4338

Abstract

Metabolomics is the comprehensive study of metabolism, the biochemical processes that sustain life. By comparing metabolites between healthy and disease states, new insights into disease mechanisms can be uncovered. NMR is a powerful analytical method to detect and quantify metabolites. Standard one-dimensional (1D) [...] Read more.

Metabolomics is the comprehensive study of metabolism, the biochemical processes that sustain life. By comparing metabolites between healthy and disease states, new insights into disease mechanisms can be uncovered. NMR is a powerful analytical method to detect and quantify metabolites. Standard one-dimensional (1D) ¹H-NMR metabolite profiling is informative but challenged by significant chemical shift overlap. Multi-dimensional NMR can increase resolution, but the required long acquisition times lead to limited throughput. Non-uniform sampling (NUS) is a well-accepted mode of acquiring multi-dimensional NMR data, enabling either reduced acquisition times or increased sensitivity in equivalent time. Despite these advantages, the technique is not widely applied to metabolomics. In this study, we evaluated the utility of NUS ¹H–¹³C heteronuclear single quantum coherence (HSQC) for semi-quantitative metabolomics. We demonstrated that NUS improved sensitivity compared to uniform sampling (US). We verified that the NUS measurement maintains linearity, making it possible to detect metabolite changes across samples and studies. Furthermore, we calculated the lower limit of detection and quantification (LOD/LOQ) of common metabolites. Finally, we demonstrate that the measurements are repeatable on the same system and across different systems. In conclusion, our results detail the analytical capability of NUS and, in doing so, empower the future use of NUS ¹H–¹³C HSQC in metabolomic studies. Full article

(This article belongs to the Special Issue New Tools for Metabolomics)

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35 pages, 1844 KiB

Open AccessEditor’s ChoiceReview

Metabolomics and Multi-Omics Integration: A Survey of Computational Methods and Resources

by Tara Eicher, Garrett Kinnebrew, Andrew Patt, Kyle Spencer, Kevin Ying, Qin Ma, Raghu Machiraju and Ewy A. Mathé

Metabolites 2020, 10(5), 202; https://doi.org/10.3390/metabo10050202 - 15 May 2020

Cited by 74 | Viewed by 14173

Abstract

As researchers are increasingly able to collect data on a large scale from multiple clinical and omics modalities, multi-omics integration is becoming a critical component of metabolomics research. This introduces a need for increased understanding by the metabolomics researcher of computational and statistical [...] Read more.

As researchers are increasingly able to collect data on a large scale from multiple clinical and omics modalities, multi-omics integration is becoming a critical component of metabolomics research. This introduces a need for increased understanding by the metabolomics researcher of computational and statistical analysis methods relevant to multi-omics studies. In this review, we discuss common types of analyses performed in multi-omics studies and the computational and statistical methods that can be used for each type of analysis. We pinpoint the caveats and considerations for analysis methods, including required parameters, sample size and data distribution requirements, sources of a priori knowledge, and techniques for the evaluation of model accuracy. Finally, for the types of analyses discussed, we provide examples of the applications of corresponding methods to clinical and basic research. We intend that our review may be used as a guide for metabolomics researchers to choose effective techniques for multi-omics analyses relevant to their field of study. Full article

(This article belongs to the Special Issue Metabolomics and Multi-Omics Integration)

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19 pages, 7059 KiB

Open AccessArticle

Metabolite Genome-Wide Association Study (mGWAS) and Gene-Metabolite Interaction Network Analysis Reveal Potential Biomarkers for Feed Efficiency in Pigs

by Xiao Wang and Haja N. Kadarmideen

Metabolites 2020, 10(5), 201; https://doi.org/10.3390/metabo10050201 - 15 May 2020

Cited by 19 | Viewed by 5616

Abstract

Metabolites represent the ultimate response of biological systems, so metabolomics is considered the link between genotypes and phenotypes. Feed efficiency is one of the most important phenotypes in sustainable pig production and is the main breeding goal trait. We utilized metabolic and genomic [...] Read more.

Metabolites represent the ultimate response of biological systems, so metabolomics is considered the link between genotypes and phenotypes. Feed efficiency is one of the most important phenotypes in sustainable pig production and is the main breeding goal trait. We utilized metabolic and genomic datasets from a total of 108 pigs from our own previously published studies that involved 59 Duroc and 49 Landrace pigs with data on feed efficiency (residual feed intake (RFI)), genotype (PorcineSNP80 BeadChip) data, and metabolomic data (45 final metabolite datasets derived from LC-MS system). Utilizing these datasets, our main aim was to identify genetic variants (single-nucleotide polymorphisms (SNPs)) that affect 45 different metabolite concentrations in plasma collected at the start and end of the performance testing of pigs categorized as high or low in their feed efficiency (based on RFI values). Genome-wide significant genetic variants could be then used as potential genetic or biomarkers in breeding programs for feed efficiency. The other objective was to reveal the biochemical mechanisms underlying genetic variation for pigs’ feed efficiency. In order to achieve these objectives, we firstly conducted a metabolite genome-wide association study (mGWAS) based on mixed linear models and found 152 genome-wide significant SNPs (p-value < 1.06 × 10⁻⁶) in association with 17 metabolites that included 90 significant SNPs annotated to 52 genes. On chromosome one alone, 51 significant SNPs associated with isovalerylcarnitine and propionylcarnitine were found to be in strong linkage disequilibrium (LD). SNPs in strong LD annotated to FBXL4, and CCNC consisted of two haplotype blocks where three SNPs (ALGA0004000, ALGA0004041, and ALGA0004042) were in the intron regions of FBXL4 and CCNC. The interaction network revealed that CCNC and FBXL4 were linked by the hub gene N6AMT1 that was associated with isovalerylcarnitine and propionylcarnitine. Moreover, three metabolites (i.e., isovalerylcarnitine, propionylcarnitine, and pyruvic acid) were clustered in one group based on the low-high RFI pigs. This study performed a comprehensive metabolite-based genome-wide association study (GWAS) analysis for pigs with differences in feed efficiency and provided significant metabolites for which there is significant genetic variation as well as biological interaction networks. The identified metabolite genetic variants, genes, and networks in high versus low feed efficient pigs could be considered as potential genetic or biomarkers for feed efficiency. Full article

(This article belongs to the Special Issue Metabolomic Applications in Animal Science)

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13 pages, 2926 KiB

Open AccessArticle

Design, Synthesis, and Biological Evaluation of 1,2,3-Triazole-linked triazino[5,6-b]indole-benzene sulfonamide Conjugates as Potent Carbonic Anhydrase I, II, IX, and XIII Inhibitors

by Krishna Kartheek Chinchilli, Andrea Angeli, Pavitra S. Thacker, Laxman Naik Korra, Rashmita Biswas, Mohammed Arifuddin and Claudiu T. Supuran

Metabolites 2020, 10(5), 200; https://doi.org/10.3390/metabo10050200 - 15 May 2020

Cited by 12 | Viewed by 3352

Abstract

A series of 1,2,3-triazole-linked triazino[5,6-b]indole-benzene sulfonamide hybrids (6a–6o) was synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against the human (h) isoforms hCA I, II, XIII (cytosolic isoforms), and hCA IX (transmembrane tumor-associated isoform). The results revealed that [...] Read more.

A series of 1,2,3-triazole-linked triazino[5,6-b]indole-benzene sulfonamide hybrids (6a–6o) was synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against the human (h) isoforms hCA I, II, XIII (cytosolic isoforms), and hCA IX (transmembrane tumor-associated isoform). The results revealed that the compounds 6a–6o exhibited K_i values in the low to medium nanomolar range against hCA II and hCA IX (K_is ranging from 7.7 nM to 41.3 nM) and higher K_i values against hCA I and hCA XIII. Compound 6i showed potent inhibition of hCA II (K_i = 7.7nM), being more effective compared to the standard inhibitor acetazolamide (AAZ) (K_i = 12.1 nM). Compounds 6b and 6d showed moderate activity against hCA XIII (K_i = 69.8 and 65.8 nM). Hence, compound 6i could be consider as potential lead candidate for the design of potent and selective hCA II inhibitors. Full article

(This article belongs to the Section Pharmacology and Drug Metabolism)

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15 pages, 1839 KiB

Open AccessArticle

Using Metabolomics to Identify Cell Line-Independent Indicators of Growth Inhibition for Chinese Hamster Ovary Cell-Based Bioprocesses

by Nicholas Alden, Ravali Raju, Kyle McElearney, James Lambropoulos, Rashmi Kshirsagar, Alan Gilbert and Kyongbum Lee

Metabolites 2020, 10(5), 199; https://doi.org/10.3390/metabo10050199 - 15 May 2020

Cited by 18 | Viewed by 4905

Abstract

Chinese hamster ovary (CHO) cells are widely used for the production of biopharmaceuticals. Efforts to improve productivity through medium design and feeding strategy optimization have focused on preventing the depletion of essential nutrients and managing the accumulation of lactate and ammonia. In addition [...] Read more.

Chinese hamster ovary (CHO) cells are widely used for the production of biopharmaceuticals. Efforts to improve productivity through medium design and feeding strategy optimization have focused on preventing the depletion of essential nutrients and managing the accumulation of lactate and ammonia. In addition to ammonia and lactate, many other metabolites accumulate in CHO cell cultures, although their effects remain largely unknown. Elucidating these effects has the potential to further improve the productivity of CHO cell-based bioprocesses. This study used untargeted metabolomics to identify metabolites that accumulate in fed-batch cultures of monoclonal antibody (mAb) producing CHO cells. The metabolomics experiments profiled six cell lines that are derived from two different hosts, produce different mAbs, and exhibit different growth profiles. Comparing the cell lines’ metabolite profiles at different growth stages, we found a strong negative correlation between peak viable cell density (VCD) and a tryptophan metabolite, putatively identified as 5-hydroxyindoleacetaldehyde (5-HIAAld). Amino acid supplementation experiments showed strong growth inhibition of all cell lines by excess tryptophan, which correlated with the accumulation of 5-HIAAld in the culture medium. Prospectively, the approach presented in this study could be used to identify cell line- and host-independent metabolite markers for clone selection and bioprocess development. Full article

(This article belongs to the Special Issue Metabolic Engineering and Synthetic Biology Volume 2)

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12 pages, 2137 KiB

Open AccessArticle

Dynamic Flux Balance Analysis to Evaluate the Strain Production Performance on Shikimic Acid Production in Escherichia coli

by Yuki Kuriya and Michihiro Araki

Metabolites 2020, 10(5), 198; https://doi.org/10.3390/metabo10050198 - 15 May 2020

Cited by 15 | Viewed by 3520

Abstract

Flux balance analysis (FBA) is used to improve the microbial production of useful compounds. However, a large gap often exists between the FBA solution and the experimental yield, because of growth and byproducts. FBA has been extended to dynamic FBA (dFBA), which is [...] Read more.

Flux balance analysis (FBA) is used to improve the microbial production of useful compounds. However, a large gap often exists between the FBA solution and the experimental yield, because of growth and byproducts. FBA has been extended to dynamic FBA (dFBA), which is applicable to time-varying processes, such as batch or fed-batch cultures, and has significantly contributed to metabolic and cultural engineering applications. On the other hand, the performance of the experimental strains has not been fully evaluated. In this study, we applied dFBA to the production of shikimic acid from glucose in Escherichia coli, to evaluate the production performance of the strain as a case study. The experimental data of glucose consumption and cell growth were used as FBA constraints. Bi-level FBA optimization with maximized growth and shikimic acid production were the objective functions. Results suggest that the shikimic acid concentration in the high-shikimic-acid-producing strain constructed in the experiment reached up to 84% of the maximum value by simulation. Thus, this method can be used to evaluate the performance of strains and estimate the milestones of strain improvement. Full article

(This article belongs to the Special Issue Metabolomics-Driven Biotechnology)

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21 pages, 1123 KiB

Open AccessReview

Metabolomics for Evaluating Flavor-Associated Metabolites in Plant-Based Products

by Shruti Pavagadhi and Sanjay Swarup

Metabolites 2020, 10(5), 197; https://doi.org/10.3390/metabo10050197 - 15 May 2020

Cited by 27 | Viewed by 4896

Abstract

Plant-based diets (PBDs) are associated with environmental benefits, human health promotion and animal welfare. There is a worldwide shift towards PBDs, evident from the increased global demand for fresh plant-based products (PBPs). Such shifts in dietary preferences accompanied by evolving food palates, create [...] Read more.

Plant-based diets (PBDs) are associated with environmental benefits, human health promotion and animal welfare. There is a worldwide shift towards PBDs, evident from the increased global demand for fresh plant-based products (PBPs). Such shifts in dietary preferences accompanied by evolving food palates, create opportunities to leverage technological advancements and strict quality controls in developing PBPs that can drive consumer acceptance. Flavor, color and texture are important sensory attributes of a food product and, have the largest influence on consumer appeal and acceptance. Among these, flavor is considered the most dominating quality attribute that significantly affects overall eating experience. Current state-of-art technologies rely on physicochemical estimations and sensory-based tests to assess flavor-related attributes in fresh PBPs. However, these methodologies often do not provide any indication about the metabolic features associated with unique flavor profiles and, consequently, can be used in a limited way to define the quality attributes of PBPs. To this end, a systematic understanding of metabolites that contribute to the flavor profiles of PBPs is warranted to complement the existing methodologies. This review will discuss the use of metabolomics for evaluating flavor-associated metabolites in fresh PBPs at post-harvest stage, alongside its applications for quality assessment and grading. We will summarize the current research in this area, discuss technical challenges and considerations pertaining to sampling and analytical techniques, as well as s provide future perspectives and directions for government organizations, industries and other stakeholders associated with the quality assessment of fresh PBPs. Full article

(This article belongs to the Special Issue Metabolomics Application for Food Authentication and Quality Assessment)

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14 pages, 1630 KiB

Open AccessArticle

Mapping Metabolite and ICD-10 Associations

by Egon Taalberg and Kalle Kilk

Metabolites 2020, 10(5), 196; https://doi.org/10.3390/metabo10050196 - 14 May 2020

Cited by 1 | Viewed by 2432

Abstract

The search for novel metabolic biomarkers is intense but has had limited practical outcomes for medicine. Part of the problem is that we lack knowledge of how different comorbidities influence biomarkers’ performance. In this study, 49 metabolites were measured by targeted LC/MS protocols [...] Read more.

The search for novel metabolic biomarkers is intense but has had limited practical outcomes for medicine. Part of the problem is that we lack knowledge of how different comorbidities influence biomarkers’ performance. In this study, 49 metabolites were measured by targeted LC/MS protocols in the serum of 1011 volunteers. Their performance as potential biomarkers was evaluated by the area under the curve of receiver operator characteristics (AUC-ROC) for 105 diagnosis codes or code groups from the 10th revision of the international classification of diseases (ICD-10). Additionally, the interferences between diagnosis codes were investigated. The highest AUC-ROC values for individual metabolites and ICD-10 code combinations reached a moderate (0.7) range. Most metabolites that were found to be potential markers remained so independently of the control group composition or comorbidities. The precise value of the AUC-ROC, however, could vary depending on the comorbidities. Moreover, networks of metabolite and disease associations were built in order to map diseases, which may interfere with metabolic biomarker research on other diseases. Full article

(This article belongs to the Section Advances in Metabolomics)

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11 pages, 813 KiB

Open AccessArticle

Dyslipidemia: A Trigger for Coronary Heart Disease in Romanian Patients with Diabetes

by Mihnea-Alexandru Găman, Matei-Alexandru Cozma, Elena-Codruța Dobrică, Nicolae Bacalbașa, Ovidiu Gabriel Bratu and Camelia Cristina Diaconu

Metabolites 2020, 10(5), 195; https://doi.org/10.3390/metabo10050195 - 14 May 2020

Cited by 40 | Viewed by 4461

Abstract

Previous studies have reported age and gender disparities in the occurrence and therapeutic approach of dyslipidemia and (or) coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate these differences in Romanian patients with T2DM. A cross-sectional, [...] Read more.

Previous studies have reported age and gender disparities in the occurrence and therapeutic approach of dyslipidemia and (or) coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate these differences in Romanian patients with T2DM. A cross-sectional, observational, retrospective study was conducted using the medical records of T2DM patients who attended the outpatient facility of the Internal Medicine Clinic of the Clinical Emergency Hospital of Bucharest, Romania for routine check-ups in a six-month period. We analyzed the records of 217 diabetic patients (mean age 69 ± 11 years; 51.15% women). We found no significant gender differences in the occurrence of dyslipidemia, CHD or CHD + dyslipidemia or in terms of statin prescription. However; patients aged 65 years or older were significantly more affected by dyslipidemia, CHD or CHD + dyslipidemia, versus subjects aged <65 years. Further, they were more likely to be prescribed statin therapy (p < 0.0001 for all). Statins were prescribed to 67.24% of the patients with dyslipidemia; 61.01% of the subjects with CHD; and to 91.48% of the patients who had both conditions. e recorded no gender differences in the occurrence of CHD and (or) dyslipidemia in Romanian T2DM patients. Patients aged 65 years or older had a higher prevalence of CHD and/or dyslipidemia, and were more likely to be prescribed statins, versus younger counterparts. However, many T2DM patients with CHD and (or) dyslipidemia were undertreated: Nearly 33% of the subjects with dyslipidemia, and nearly 40% of the ones with CHD were not prescribed statins. Full article

(This article belongs to the Special Issue Cardiometabolic Challenges-Present and Future)

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18 pages, 3095 KiB

Open AccessArticle

A Metabolomic Approach for Predicting Diurnal Changes in Cortisol

by Jarrett Eshima, Trenton J. Davis, Heather D. Bean, John Fricks and Barbara S. Smith

Metabolites 2020, 10(5), 194; https://doi.org/10.3390/metabo10050194 - 13 May 2020

Cited by 8 | Viewed by 2961

Abstract

Introduction: The dysregulation of cortisol secretion has been associated with a number of mental health and mood disorders. However, diagnostics for mental health and mood disorders are behavioral and lack biological contexts. Objectives: The goal of this work is to identify volatile metabolites [...] Read more.

Introduction: The dysregulation of cortisol secretion has been associated with a number of mental health and mood disorders. However, diagnostics for mental health and mood disorders are behavioral and lack biological contexts. Objectives: The goal of this work is to identify volatile metabolites capable of predicting changes in total urinary cortisol across the diurnal cycle for long-term stress monitoring in psychological disorders. Methods: We applied comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry to sample the urinary volatile metabolome using an untargeted approach across three time points in a single day for 60 subjects. Results: The finalized multiple regression model includes 14 volatile metabolites and 7 interaction terms. A review of the selected metabolites suggests pyrrole, 6-methyl-5-hepten-2-one and 1-iodo-2-methylundecane may originate from endogenous metabolic mechanisms influenced by glucocorticoid signaling mechanisms. Conclusion: This analysis demonstrated the feasibility of using specific volatile metabolites for the prediction of secreted cortisol across time. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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19 pages, 3096 KiB

Open AccessArticle

Role of the Mitochondrial Citrate-malate Shuttle in Hras12V-Induced Hepatocarcinogenesis: A Metabolomics-Based Analysis

by Chuanyi Lei, Jun Chen, Huiling Li, Tingting Fan, Xu Zheng, Hong Wang, Nan Zhang, Yang Liu, Xiaoqin Luo, Jingyu Wang and Aiguo Wang

Metabolites 2020, 10(5), 193; https://doi.org/10.3390/metabo10050193 - 13 May 2020

Cited by 5 | Viewed by 2815

Abstract

The activation of the Ras signaling pathway is a crucial process in hepatocarcinogenesis. Till now, no reports have scrutinized the role of dynamic metabolic changes in Ras oncogene-induced transition of the normal and precancerous liver cells to hepatocellular carcinoma in vivo. In the [...] Read more.

The activation of the Ras signaling pathway is a crucial process in hepatocarcinogenesis. Till now, no reports have scrutinized the role of dynamic metabolic changes in Ras oncogene-induced transition of the normal and precancerous liver cells to hepatocellular carcinoma in vivo. In the current study, we attempted a comprehensive investigation of Hras12V transgenic mice (Ras-Tg) by concatenating nontargeted metabolomics, transcriptomics analysis, and targeted-metabolomics incorporating [U-¹³C] glucose. A total of 631 peaks were detected, out of which 555 metabolites were screened. Besides, a total of 122 differently expressed metabolites (DEMs) were identified, and they were categorized and subtyped with the help of variation tendency analysis of the normal (W), precancerous (P), and hepatocellular carcinoma (T) liver tissues. Thus, the positive or negative association between metabolites and the hepatocellular carcinoma and Ras oncogene were identified. The bioinformatics analysis elucidated the hepatocarcinogenesis-associated significant metabolic pathways: glycolysis, mitochondrial citrate-malate shuttle, lipid biosynthesis, pentose phosphate pathway (PPP), cholesterol and bile acid biosynthesis, and glutathione metabolism. The key metabolites and enzymes identified in this analysis were further validated. Moreover, we confirmed the PPP, glycolysis, and conversion of pyruvate to cytosol acetyl-CoA by mitochondrial citrate-malate shuttle, in vivo, by incorporating [U-¹³C] glucose. In summary, the current study presented the comprehensive bioinformatics analysis, depicting the Ras oncogene-induced dynamic metabolite variations in hepatocarcinogenesis. A significant finding of our study was that the mitochondrial citrate-malate shuttle plays a crucial role in detoxification of lactic acid, maintenance of mitochondrial integrity, and enhancement of lipid biosynthesis, which, in turn, promotes hepatocarcinogenesis. Full article

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13 pages, 2823 KiB

Open AccessArticle

Metabolomics Analysis Reveals Global Metabolic Changes in the Evolved E. coli Strain with Improved Growth and 1-Butanol Production in Minimal Medium

by Walter A. Laviña, Sana Subhan Memon Sakurai, Sammy Pontrelli, Sastia Prama Putri and Eiichiro Fukusaki

Metabolites 2020, 10(5), 192; https://doi.org/10.3390/metabo10050192 - 13 May 2020

Cited by 4 | Viewed by 3526

Abstract

Production of 1-butanol from microorganisms has garnered significant interest due to its prospect as a drop-in biofuel and precursor for a variety of commercially relevant chemicals. Previously, high 1-butanol titer has been reported in Escherichia coli strain JCL166, which contains a modified clostridial [...] Read more.

Production of 1-butanol from microorganisms has garnered significant interest due to its prospect as a drop-in biofuel and precursor for a variety of commercially relevant chemicals. Previously, high 1-butanol titer has been reported in Escherichia coli strain JCL166, which contains a modified clostridial 1-butanol pathway. Although conventional and metabolomics-based strain improvement strategies of E. coli strain JCL166 have been successful in improving production in rich medium, 1-butanol titer was severely limited in minimal medium. To further improve growth and consequently 1-butanol production in minimal medium, adaptive laboratory evolution (ALE) using mutD5 mutator plasmid was done on JCL166. Comparative metabolomics analysis of JCL166 and BP1 revealed global perturbations in the evolved strain BP1 compared to JCL166 (44 out of 64 metabolites), encompassing major metabolic pathways such as glycolysis, nucleotide biosynthesis, and CoA-related processes. Collectively, these metabolic changes in BP1 result in improved growth and, consequently, 1-butanol production in minimal medium. Furthermore, we found that the mutation in ihfB caused by ALE had a significant effect on the metabolome profile of the evolved strain. This study demonstrates how metabolomics was utilized for characterization of ALE-developed strains to understand the overall effect of mutations acquired through evolution. Full article

(This article belongs to the Special Issue Metabolic Engineering and Synthetic Biology Volume 2)

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13 pages, 912 KiB

Open AccessArticle

The Effect of Bee Venom Peptides Melittin, Tertiapin, and Apamin on the Human Erythrocytes Ghosts: A Preliminary Study

by Agata Światły-Błaszkiewicz, Lucyna Mrówczyńska, Eliza Matuszewska, Jan Lubawy, Arkadiusz Urbański, Zenon J. Kokot, Grzegorz Rosiński and Jan Matysiak

Metabolites 2020, 10(5), 191; https://doi.org/10.3390/metabo10050191 - 13 May 2020

Cited by 13 | Viewed by 3567

Abstract

Red blood cells (RBCs) are the most abundant cells in the human blood that have been extensively studied under morphology, ultrastructure, biochemical and molecular functions. Therefore, RBCs are excellent cell models in the study of biologically active compounds like drugs and toxins on [...] Read more.

Red blood cells (RBCs) are the most abundant cells in the human blood that have been extensively studied under morphology, ultrastructure, biochemical and molecular functions. Therefore, RBCs are excellent cell models in the study of biologically active compounds like drugs and toxins on the structure and function of the cell membrane. The aim of the present study was to explore erythrocyte ghost’s proteome to identify changes occurring under the influence of three bee venom peptides-melittin, tertiapin, and apamin. We conducted preliminary experiments on the erythrocyte ghosts incubated with these peptides at their non-hemolytic concentrations. Such preparations were analyzed using liquid chromatography coupled with tandem mass spectrometry. It was found that when higher concentrations of melittin and apamin were used, fewer proteins were identified. Moreover, the results clearly indicated that apamin demonstrates the greatest influence on the RBCs ghosts proteome. Interestingly, the data also suggest that tertiapin exerted a stabilizing effect on the erythrocyte membrane. The experiments carried out show the great potential of proteomic research in the projects focused on the toxin’s properties as membrane active agents. However, to determine the specificity of the effect of selected bee venom peptides on the erythrocyte ghosts, further proteomic research should be focused on the quantitative analysis. Full article

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16 pages, 1926 KiB

Open AccessArticle

JUMPm: A Tool for Large-Scale Identification of Metabolites in Untargeted Metabolomics

by Xusheng Wang, Ji-Hoon Cho, Suresh Poudel, Yuxin Li, Drew R. Jones, Timothy I. Shaw, Haiyan Tan, Boer Xie and Junmin Peng

Metabolites 2020, 10(5), 190; https://doi.org/10.3390/metabo10050190 - 12 May 2020

Cited by 8 | Viewed by 4845

Abstract

Metabolomics is increasingly important for biomedical research, but large-scale metabolite identification in untargeted metabolomics is still challenging. Here, we present Jumbo Mass spectrometry-based Program of Metabolomics (JUMPm) software, a streamlined software tool for identifying potential metabolite formulas and structures in mass spectrometry. During [...] Read more.

Metabolomics is increasingly important for biomedical research, but large-scale metabolite identification in untargeted metabolomics is still challenging. Here, we present Jumbo Mass spectrometry-based Program of Metabolomics (JUMPm) software, a streamlined software tool for identifying potential metabolite formulas and structures in mass spectrometry. During database search, the false discovery rate is evaluated by a target-decoy strategy, where the decoys are produced by breaking the octet rule of chemistry. We illustrated the utility of JUMPm by detecting metabolite formulas and structures from liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analyses of unlabeled and stable-isotope labeled yeast samples. We also benchmarked the performance of JUMPm by analyzing a mixed sample from a commercially available metabolite library in both hydrophilic and hydrophobic LC-MS/MS. These analyses confirm that metabolite identification can be significantly improved by estimating the element composition in formulas using stable isotope labeling, or by introducing LC retention time during a spectral library search, which are incorporated into JUMPm functions. Finally, we compared the performance of JUMPm and two commonly used programs, Compound Discoverer 3.1 and MZmine 2, with respect to putative metabolite identifications. Our results indicate that JUMPm is an effective tool for metabolite identification of both unlabeled and labeled data in untargeted metabolomics. Full article

(This article belongs to the Special Issue Metabolomics–Integration of Technology and Bioinformatics)

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16 pages, 642 KiB

Open AccessArticle

Effects of Cyclic High Ambient Temperature and Dietary Supplementation of Orotic Acid, a Pyrimidine Precursor, on Plasma and Muscle Metabolites in Broiler Chickens

by Saki Shimamoto, Kiriko Nakamura, Shozo Tomonaga, Satoru Furukawa, Akira Ohtsuka and Daichi Ijiri

Metabolites 2020, 10(5), 189; https://doi.org/10.3390/metabo10050189 - 12 May 2020

Cited by 7 | Viewed by 4014

Abstract

The aim of this study was to evaluate the effects of high ambient temperature (HT) and orotic acid supplementation on the plasma and muscle metabolomic profiles in broiler chickens. Thirty-two 14-day-old broiler chickens were divided into four treatment groups that were fed diets [...] Read more.

The aim of this study was to evaluate the effects of high ambient temperature (HT) and orotic acid supplementation on the plasma and muscle metabolomic profiles in broiler chickens. Thirty-two 14-day-old broiler chickens were divided into four treatment groups that were fed diets with or without 0.7% orotic acid under thermoneutral (25 ± 1 °C) or cyclic HT (35 ± 1 °C for 8 h/day) conditions for 2 weeks. The chickens exposed to HT had higher plasma malondialdehyde concentrations, suggesting an increase in lipid peroxidation, which is alleviated by orotic acid supplementation. The HT environment also affected the serine, glutamine, and tyrosine plasma concentrations, while orotic acid supplementation affected the aspartic acid, glutamic acid, and tyrosine plasma concentrations. Untargeted gas chromatography–triple quadrupole mass spectrometry (GC-MS/MS)-based metabolomics analysis identified that the HT affected the plasma levels of metabolites involved in purine metabolism, ammonia recycling, pyrimidine metabolism, homocysteine degradation, glutamate metabolism, urea cycle, β-alanine metabolism, glycine and serine metabolism, and aspartate metabolism, while orotic acid supplementation affected metabolites involved in pyrimidine metabolism, β-alanine metabolism, the malate–aspartate shuttle, and aspartate metabolism. Our results suggest that cyclic HT affects various metabolic processes in broiler chickens, and that orotic acid supplementation ameliorates HT-induced increases in lipid peroxidation. Full article

(This article belongs to the Special Issue Metabolomic Applications in Animal Science)

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23 pages, 1537 KiB

Open AccessEditor’s ChoiceReview

MEATabolomics: Muscle and Meat Metabolomics in Domestic Animals

by Susumu Muroya, Shuji Ueda, Tomohiko Komatsu, Takuya Miyakawa and Per Ertbjerg

Metabolites 2020, 10(5), 188; https://doi.org/10.3390/metabo10050188 - 11 May 2020

Cited by 93 | Viewed by 7591

Abstract

In the past decades, metabolomics has been used to comprehensively understand a variety of food materials for improvement and assessment of food quality. Farm animal skeletal muscles and meat are one of the major targets of metabolomics for the characterization of meat and [...] Read more.

In the past decades, metabolomics has been used to comprehensively understand a variety of food materials for improvement and assessment of food quality. Farm animal skeletal muscles and meat are one of the major targets of metabolomics for the characterization of meat and the exploration of biomarkers in the production system. For identification of potential biomarkers to control meat quality, studies of animal muscles and meat with metabolomics (MEATabolomics) has been conducted in combination with analyses of meat quality traits, focusing on specific factors associated with animal genetic background and sensory scores, or conditions in feeding system and treatments of meat in the processes such as postmortem storage, processing, and hygiene control. Currently, most of MEATabolomics approaches combine separation techniques (gas or liquid chromatography, and capillary electrophoresis)–mass spectrometry (MS) or nuclear magnetic resonance (NMR) approaches with the downstream multivariate analyses, depending on the polarity and/or hydrophobicity of the targeted metabolites. Studies employing these approaches provide useful information to monitor meat quality traits efficiently and to understand the genetic background and production system of animals behind the meat quality. MEATabolomics is expected to improve the knowledge and methodologies in animal breeding and feeding, meat storage and processing, and prediction of meat quality. Full article

(This article belongs to the Special Issue Metabolomic Applications in Animal Science)

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24 pages, 401 KiB

Open AccessEditor’s ChoiceReview

Metabolite Changes during Postharvest Storage: Effects on Fruit Quality Traits

by Delphine M. Pott, José G. Vallarino and Sonia Osorio

Metabolites 2020, 10(5), 187; https://doi.org/10.3390/metabo10050187 - 8 May 2020

Cited by 110 | Viewed by 7816

Abstract

Metabolic changes occurring in ripe or senescent fruits during postharvest storage lead to a general deterioration in quality attributes, including decreased flavor and ‘off-aroma’ compound generation. As a consequence, measures to reduce economic losses have to be taken by the fruit industry and [...] Read more.

Metabolic changes occurring in ripe or senescent fruits during postharvest storage lead to a general deterioration in quality attributes, including decreased flavor and ‘off-aroma’ compound generation. As a consequence, measures to reduce economic losses have to be taken by the fruit industry and have mostly consisted of storage at cold temperatures and the use of controlled atmospheres or ripening inhibitors. However, the biochemical pathways and molecular mechanisms underlying fruit senescence in commercial storage conditions are still poorly understood. In this sense, metabolomic platforms, enabling the profiling of key metabolites responsible for organoleptic and health-promoting traits, such as volatiles, sugars, acids, polyphenols and carotenoids, can be a powerful tool for further understanding the biochemical basis of postharvest physiology and have the potential to play a critical role in the identification of the pathways affected by fruit senescence. Here, we provide an overview of the metabolic changes during postharvest storage, with special attention to key metabolites related to fruit quality. The potential use of metabolomic approaches to yield metabolic markers useful for chemical phenotyping or even storage and marketing decisions is highlighted. Full article

(This article belongs to the Special Issue Fruit Metabolism and Metabolomics)

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