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Metabolites
Volume 9
Issue 12
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Metabolites, Volume 9, Issue 12 (December 2019) – 27 articles

Cover Story (view full-size image): The orphan endothelial cell adhesion G protein-coupled receptor (aGPCR) ADGRL4/ELTD1 regulates physiological and tumour angiogenesis. To better characterise ADGRL4/ELTD1’s role in endothelial cell biology, we silenced ADGRL4/ELTD1 using two independent siRNAs in human umbilical vein endothelial cells (HUVECS) followed by transcriptional profiling, target gene validation and metabolomics using liquid chromatography-mass spectrometry. ADGRL4/ELTD1 expression impacts core components of endothelial metabolism (ACLY, SLC25A1), affecting metabolite levels within pyrimidine, amino acid and sugar metabolic pathways, and regulates genes involved in endothelial differentiation/homeostasis (KIT) and Notch signalling (JAG1, DLL4, HES2). This work establishes a new role for ADGRL4/ELTD1 as a regulator of endothelial metabolism. View this paper
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30 pages, 3229 KiB  
Review
From Samples to Insights into Metabolism: Uncovering Biologically Relevant Information in LC-HRMS Metabolomics Data
by Julijana Ivanisevic and Elizabeth J. Want
Metabolites 2019, 9(12), 308; https://doi.org/10.3390/metabo9120308 - 17 Dec 2019
Cited by 61 | Viewed by 9306
Abstract
Untargeted metabolomics (including lipidomics) is a holistic approach to biomarker discovery and mechanistic insights into disease onset and progression, and response to intervention. Each step of the analytical and statistical pipeline is crucial for the generation of high-quality, robust data. Metabolite identification remains [...] Read more.
Untargeted metabolomics (including lipidomics) is a holistic approach to biomarker discovery and mechanistic insights into disease onset and progression, and response to intervention. Each step of the analytical and statistical pipeline is crucial for the generation of high-quality, robust data. Metabolite identification remains the bottleneck in these studies; therefore, confidence in the data produced is paramount in order to maximize the biological output. Here, we outline the key steps of the metabolomics workflow and provide details on important parameters and considerations. Studies should be designed carefully to ensure appropriate statistical power and adequate controls. Subsequent sample handling and preparation should avoid the introduction of bias, which can significantly affect downstream data interpretation. It is not possible to cover the entire metabolome with a single platform; therefore, the analytical platform should reflect the biological sample under investigation and the question(s) under consideration. The large, complex datasets produced need to be pre-processed in order to extract meaningful information. Finally, the most time-consuming steps are metabolite identification, as well as metabolic pathway and network analysis. Here we discuss some widely used tools and the pitfalls of each step of the workflow, with the ultimate aim of guiding the reader towards the most efficient pipeline for their metabolomics studies. Full article
(This article belongs to the Special Issue Metabolomics Data Processing and Data Analysis—Current Best Practices)
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23 pages, 2374 KiB  
Article
Soluble Sugar and Lipid Readjustments in the Yarrowia lipolytica Yeast at Various Temperatures and pH
by Varvara Yu Sekova, Daria I. Dergacheva, Elena P. Isakova, Natalya N. Gessler, Vera M. Tereshina and Yulia I. Deryabina
Metabolites 2019, 9(12), 307; https://doi.org/10.3390/metabo9120307 - 17 Dec 2019
Cited by 24 | Viewed by 3978
Abstract
Microorganisms cope with a wide range of environmental challenges using different mechanisms. Their ability to prosper at extreme ambient pH and high temperatures has been well reported, but the adaptation mechanism often remains unrevealed. In this study, we addressed the dynamics of lipid [...] Read more.
Microorganisms cope with a wide range of environmental challenges using different mechanisms. Their ability to prosper at extreme ambient pH and high temperatures has been well reported, but the adaptation mechanism often remains unrevealed. In this study, we addressed the dynamics of lipid and sugar profiles upon different cultivation conditions. The results showed that the cells grown at various pH and optimal temperature contained mannitol as the major cytosol sugar alcohol. The elevated temperature of 38 °C led to a two- to three-fold increase in total cytosol sugars with concurrent substitution of mannitol for trehalose. Lipid composition in the cells at optimal temperature changed insignificantly at any pH tested. The increase in the temperature caused some drop in the storage and membrane lipid levels, remarkable changes in their composition, and the degree of unsaturated fatty acids. It was shown that the fatty acid composition of some membrane phospholipids varied considerably at changing pH and temperature values. The data showed a pivotal role and flexibility of the sugar and lipid composition of Y. lipolytica W29 in adaptation to unfavorable environmental conditions. Full article
(This article belongs to the Special Issue Metabolomics in Yeast and Fermentation)
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22 pages, 4168 KiB  
Article
Barth Syndrome: Exploring Cardiac Metabolism with Induced Pluripotent Stem Cell-Derived Cardiomyocytes
by Erica M. Fatica, Gina A. DeLeonibus, Alisha House, Jillian V. Kodger, Ryan W. Pearce, Rohan R. Shah, Liraz Levi and Yana Sandlers
Metabolites 2019, 9(12), 306; https://doi.org/10.3390/metabo9120306 - 17 Dec 2019
Cited by 16 | Viewed by 4776
Abstract
Barth syndrome (BTHS) is an X-linked recessive multisystem disorder caused by mutations in the TAZ gene (TAZ, G 4.5, OMIM 300394) that encodes for the acyltransferase tafazzin. This protein is highly expressed in the heart and plays a significant role in cardiolipin biosynthesis. [...] Read more.
Barth syndrome (BTHS) is an X-linked recessive multisystem disorder caused by mutations in the TAZ gene (TAZ, G 4.5, OMIM 300394) that encodes for the acyltransferase tafazzin. This protein is highly expressed in the heart and plays a significant role in cardiolipin biosynthesis. Heart disease is the major clinical manifestation of BTHS with a high incidence in early life. Although the genetic basis of BTHS and tetralinoleoyl cardiolipin deficiency in BTHS-affected individuals are well-established, downstream metabolic changes in cardiac metabolism are still uncovered. Our study aimed to characterize TAZ-induced metabolic perturbations in the heart. Control (PGP1-TAZWT) and TAZ mutant (PGP1-TAZ517delG) iPS-CM were incubated with 13C6-glucose and 13C5-glutamine and incorporation of 13C into downstream Krebs cycle intermediates was traced. Our data reveal that TAZ517delG induces accumulation of cellular long chain acylcarnitines and overexpression of fatty acid binding protein (FABP4). We also demonstrate that TAZ517delG induces metabolic alterations in pathways related to energy production as reflected by high glucose uptake, an increase in glycolytic lactate production and a decrease in palmitate uptake. Moreover, despite mitochondrial dysfunction, in the absence of glucose and fatty acids, TAZ517delG-iPS-CM can use glutamine as a carbon source to replenish the Krebs cycle. Full article
(This article belongs to the Special Issue Metabolites in Cardio-Metabolic Disease: Unravelling New Markers and Mechanisms)
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14 pages, 570 KiB  
Article
Impact of Bovine Diet on Metabolomic Profile of Skim Milk and Whey Protein Ingredients
by Jonathan B. Magan, Tom F. O’Callaghan, Jiamin Zheng, Lun Zhang, Rupasri Mandal, Deirdre Hennessy, Mark A. Fenelon, David S. Wishart, Alan L. Kelly and Noel A. McCarthy
Metabolites 2019, 9(12), 305; https://doi.org/10.3390/metabo9120305 - 17 Dec 2019
Cited by 20 | Viewed by 3625
Abstract
The influence of bovine diet on the metabolome of reconstituted skim milk powder (SMP) and protein ingredients produced from the milk of cows fed on pasture or concentrate-based diets was investigated. Cows were randomly assigned to diets consisting of perennial ryegrass only (GRS), [...] Read more.
The influence of bovine diet on the metabolome of reconstituted skim milk powder (SMP) and protein ingredients produced from the milk of cows fed on pasture or concentrate-based diets was investigated. Cows were randomly assigned to diets consisting of perennial ryegrass only (GRS), perennial ryegrass/white clover sward (CLV), or indoor total mixed ration (TMR) for an entire lactation. Raw milk obtained from each group was processed at pilot scale, to produce SMP and sweet whey, and SMP was further processed at laboratory scale, to yield ideal whey and acid whey. The total amino acid composition and metabolome of each sample were analyzed, using high-performance cation exchange and a targeted combination of direct-injection mass spectrometry and reverse-phase liquid chromatography–tandem mass spectrometry (LC–MS/MS), respectively. The nitrogen composition of the products from each of the diets was similar, with one exception being the significantly higher nonprotein nitrogen content in TMR-derived skim milk powder than that from the GRS system. Total amino acid analysis showed significantly higher concentrations of glycine in GRS- and CLV-derived sweet whey and acid whey than in those from TMR. The cysteine contents of CLV-derived ideal whey and acid whey were significantly higher than for TMR, while the valine content of GRS-derived acid whey was significantly higher than TMR. The phenylalanine content of GRS-derived ideal whey was significantly higher than that from CLV. Metabolomic analysis showed significantly higher concentrations of the metabolites glutamine, valine, and phosphocreatine in each ingredient type derived from TMR than those from GRS or CLV, while the serine content of each GRS-derived ingredient type was significantly higher than that in TMR-derived ingredients. These results demonstrate that the type of bovine feeding system used can have a significant effect on the amino acid composition and metabolome of skim milk and whey powders and may aid in the selection of raw materials for product manufacture, while the clear separation between the samples gives further evidence for distinguishing milk products produced from different feeding systems based on LC–MS/MS. Full article
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21 pages, 2854 KiB  
Article
Single Spheroid Metabolomics: Optimizing Sample Preparation of Three-Dimensional Multicellular Tumor Spheroids
by Mate Rusz, Evelyn Rampler, Bernhard K. Keppler, Michael A. Jakupec and Gunda Koellensperger
Metabolites 2019, 9(12), 304; https://doi.org/10.3390/metabo9120304 - 14 Dec 2019
Cited by 17 | Viewed by 3858
Abstract
Tumor spheroids are important model systems due to the capability of capturing in vivo tumor complexity. In this work, the experimental design of metabolomics workflows using three-dimensional multicellular tumor spheroid (3D MTS) models is addressed. Non-scaffold based cultures of the HCT116 colon carcinoma [...] Read more.
Tumor spheroids are important model systems due to the capability of capturing in vivo tumor complexity. In this work, the experimental design of metabolomics workflows using three-dimensional multicellular tumor spheroid (3D MTS) models is addressed. Non-scaffold based cultures of the HCT116 colon carcinoma cell line delivered highly reproducible MTSs with regard to size and other key parameters (such as protein content and fraction of viable cells) as a prerequisite. Carefully optimizing the multiple steps of sample preparation, the developed procedure enabled us to probe the metabolome of single MTSs (diameter range 790 ± 22 µm) in a highly repeatable manner at a considerable throughput. The final protocol consisted of rapid washing of the spheroids on the cultivation plate, followed by cold methanol extraction. 13C enriched internal standards, added upon extraction, were key to obtaining the excellent analytical figures of merit. Targeted metabolomics provided absolute concentrations with average biological repeatabilities of <20% probing MTSs individually. In a proof of principle study, MTSs were exposed to two metal-based anticancer drugs, oxaliplatin and the investigational anticancer drug KP1339 (sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]), which exhibit distinctly different modes of action. This difference could be recapitulated in individual metabolic shifts observed from replicate single MTSs. Therefore, biological variation among single spheroids can be assessed using the presented analytical strategy, applicable for in-depth anticancer drug metabolite profiling. Full article
(This article belongs to the Special Issue Sample Preparation in Metabolomics)
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37 pages, 2386 KiB  
Review
Metabolomics: A Way Forward for Crop Improvement
by Ali Razzaq, Bushra Sadia, Ali Raza, Muhammad Khalid Hameed and Fozia Saleem
Metabolites 2019, 9(12), 303; https://doi.org/10.3390/metabo9120303 - 14 Dec 2019
Cited by 148 | Viewed by 11025
Abstract
Metabolomics is an emerging branch of “omics” and it involves identification and quantification of metabolites and chemical footprints of cellular regulatory processes in different biological species. The metabolome is the total metabolite pool in an organism, which can be measured to characterize genetic [...] Read more.
Metabolomics is an emerging branch of “omics” and it involves identification and quantification of metabolites and chemical footprints of cellular regulatory processes in different biological species. The metabolome is the total metabolite pool in an organism, which can be measured to characterize genetic or environmental variations. Metabolomics plays a significant role in exploring environment–gene interactions, mutant characterization, phenotyping, identification of biomarkers, and drug discovery. Metabolomics is a promising approach to decipher various metabolic networks that are linked with biotic and abiotic stress tolerance in plants. In this context, metabolomics-assisted breeding enables efficient screening for yield and stress tolerance of crops at the metabolic level. Advanced metabolomics analytical tools, like non-destructive nuclear magnetic resonance spectroscopy (NMR), liquid chromatography mass-spectroscopy (LC-MS), gas chromatography-mass spectrometry (GC-MS), high performance liquid chromatography (HPLC), and direct flow injection (DFI) mass spectrometry, have sped up metabolic profiling. Presently, integrating metabolomics with post-genomics tools has enabled efficient dissection of genetic and phenotypic association in crop plants. This review provides insight into the state-of-the-art plant metabolomics tools for crop improvement. Here, we describe the workflow of plant metabolomics research focusing on the elucidation of biotic and abiotic stress tolerance mechanisms in plants. Furthermore, the potential of metabolomics-assisted breeding for crop improvement and its future applications in speed breeding are also discussed. Mention has also been made of possible bottlenecks and future prospects of plant metabolomics. Full article
(This article belongs to the Special Issue Metabolomics of Plant Response to Environmental Stress)
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15 pages, 2577 KiB  
Article
Blood Metabolites Associate with Prognosis in Endometrial Cancer
by Elin Strand, Ingvild L. Tangen, Kristine E. Fasmer, Havjin Jacob, Mari K. Halle, Erling A. Hoivik, Bert Delvoux, Jone Trovik, Ingfrid S. Haldorsen, Andrea Romano and Camilla Krakstad
Metabolites 2019, 9(12), 302; https://doi.org/10.3390/metabo9120302 - 14 Dec 2019
Cited by 12 | Viewed by 3102
Abstract
Endometrial cancer has a high prevalence among post-menopausal women in developed countries. We aimed to explore whether certain metabolic patterns could be related to the characteristics of aggressive disease and poorer survival among endometrial cancer patients in Western Norway. Patients with endometrial cancer [...] Read more.
Endometrial cancer has a high prevalence among post-menopausal women in developed countries. We aimed to explore whether certain metabolic patterns could be related to the characteristics of aggressive disease and poorer survival among endometrial cancer patients in Western Norway. Patients with endometrial cancer with short survival (n = 20) were matched according to FIGO (International Federation of Gynecology and Obstetrics, 2009 criteria) stage, histology, and grade, with patients with long survival (n = 20). Plasma metabolites were measured on a multiplex system including 183 metabolites, which were subsequently determined using liquid chromatography-mass spectrometry. Partial least square discriminant analysis, together with hierarchical clustering, was used to identify patterns which distinguished short from long survival. A proposed signature of metabolites related to survival was suggested, and a multivariate receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.820–0.965 (p ≤ 0.001). Methionine sulfoxide seems to be particularly strongly associated with poor survival rates in these patients. In a subgroup with preoperative contrast-enhanced computed tomography data, selected metabolites correlated with the estimated abdominal fat distribution parameters. Metabolic signatures may predict prognosis and be promising supplements when evaluating phenotypes and exploring metabolic pathways related to the progression of endometrial cancer. In the future, this may serve as a useful tool in cancer management. Full article
(This article belongs to the Special Issue Metabolomics in the Study of Disease)
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16 pages, 483 KiB  
Review
Emerging Insights into the Metabolic Alterations in Aging Using Metabolomics
by Sarika Srivastava
Metabolites 2019, 9(12), 301; https://doi.org/10.3390/metabo9120301 - 13 Dec 2019
Cited by 68 | Viewed by 7294
Abstract
Metabolomics is the latest ‘omics’ technology and systems biology science that allows for comprehensive profiling of small-molecule metabolites in biological systems at a specific time and condition. Metabolites are cellular intermediate products of metabolic reactions, which reflect the ultimate response to genomic, transcriptomic, [...] Read more.
Metabolomics is the latest ‘omics’ technology and systems biology science that allows for comprehensive profiling of small-molecule metabolites in biological systems at a specific time and condition. Metabolites are cellular intermediate products of metabolic reactions, which reflect the ultimate response to genomic, transcriptomic, proteomic, or environmental changes in a biological system. Aging is a complex biological process that is characterized by a gradual and progressive decline in molecular, cellular, tissue, organ, and organismal functions, and it is influenced by a combination of genetic, environmental, diet, and lifestyle factors. The precise biological mechanisms of aging remain unknown. Metabolomics has emerged as a powerful tool to characterize the organism phenotypes, identify altered metabolites, pathways, novel biomarkers in aging and disease, and offers wide clinical applications. Here, I will provide a comprehensive overview of our current knowledge on metabolomics led studies in aging with particular emphasis on studies leading to biomarker discovery. Based on the data obtained from model organisms and humans, it is evident that metabolites associated with amino acids, lipids, carbohydrate, and redox metabolism may serve as biomarkers of aging and/or longevity. Current challenges and key questions that should be addressed in the future to advance our understanding of the biological mechanisms of aging are discussed. Full article
(This article belongs to the Special Issue Metabolomics to Probe Metabolism in Ageing and Age-related Neurodegenerative Diseases)
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14 pages, 1394 KiB  
Article
Metabolomics of Small Intestine Neuroendocrine Tumors and Related Hepatic Metastases
by Alessio Imperiale, Gilles Poncet, Pietro Addeo, Elisa Ruhland, Colette Roche, Stephanie Battini, A. Ercument Cicek, Marie Pierrette Chenard, Valérie Hervieu, Bernard Goichot, Philippe Bachellier, Thomas Walter and Izzie Jacques Namer
Metabolites 2019, 9(12), 300; https://doi.org/10.3390/metabo9120300 - 11 Dec 2019
Cited by 8 | Viewed by 3093
Abstract
To assess the metabolomic fingerprint of small intestine neuroendocrine tumors (SI-NETs) and related hepatic metastases, and to investigate the influence of the hepatic environment on SI-NETs metabolome. Ninety-four tissue samples, including 46 SI-NETs, 18 hepatic NET metastases and 30 normal SI and liver [...] Read more.
To assess the metabolomic fingerprint of small intestine neuroendocrine tumors (SI-NETs) and related hepatic metastases, and to investigate the influence of the hepatic environment on SI-NETs metabolome. Ninety-four tissue samples, including 46 SI-NETs, 18 hepatic NET metastases and 30 normal SI and liver samples, were analyzed using 1H-magic angle spinning (HRMAS) NMR nuclear magnetic resonance (NMR) spectroscopy. Twenty-seven metabolites were identified and quantified. Differences between primary NETs vs. normal SI and primary NETs vs. hepatic metastases, were assessed. Network analysis was performed according to several clinical and pathological features. Succinate, glutathion, taurine, myoinositol and glycerophosphocholine characterized NETs. Normal SI specimens showed higher levels of alanine, creatine, ethanolamine and aspartate. PLS-DA revealed a continuum-like distribution among normal SI, G1-SI-NETs and G2-SI-NETs. The G2-SI-NET distribution was closer and clearly separated from normal SI tissue. Lower concentration of glucose, serine and glycine, and increased levels of choline-containing compounds, taurine, lactate and alanine, were found in SI-NETs with more aggressive tumors. Higher abundance of acetate, succinate, choline, phosphocholine, taurine, lactate and aspartate discriminated liver metastases from normal hepatic parenchyma. Higher levels of alanine, ethanolamine, glycerophosphocholine and glucose was found in hepatic metastases than in primary SI-NETs. The present work gives for the first time a snapshot of the metabolomic characteristics of SI-NETs, suggesting the existence of complex metabolic reality, maybe characteristic of different tumor evolution. Full article
(This article belongs to the Special Issue Cancer Metabolomics 2019)
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15 pages, 2493 KiB  
Article
Acupuncture on ST36, CV4 and KI1 Suppresses the Progression of Methionine- and Choline-Deficient Diet-Induced Nonalcoholic Fatty Liver Disease in Mice
by Xiangjin Meng, Xin Guo, Jing Zhang, Junji Moriya, Junji Kobayashi, Reimon Yamaguchi and Sohsuke Yamada
Metabolites 2019, 9(12), 299; https://doi.org/10.3390/metabo9120299 - 09 Dec 2019
Cited by 16 | Viewed by 4008
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and its treatment remain a constant challenge. A number of clinical trials have shown that acupuncture treatment has beneficial effects for patients with NAFLD, but the molecular mechanisms [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and its treatment remain a constant challenge. A number of clinical trials have shown that acupuncture treatment has beneficial effects for patients with NAFLD, but the molecular mechanisms underlying its action are still largely unknown. In this study, we established a mouse model of NAFLD by administering a methionine- and choline-deficient (MCD) diet and selected three acupoints (ST36, CV4, and KI1) or nonacupoints (sham) for needling. We then investigated the effects of acupuncture treatment on the progression of NAFLD and the underlying mechanisms. After two weeks of acupuncture treatment, the liver in the needling-nonapcupoint group (NG) mice appeared pale and yellowish in color, while that in the needling-acupoint group (AG) showed a bright red color. Histologically, fewer lipid droplets and inflammatory foci were observed in the AG liver than in the NG liver. Furthermore, the expression of proinflammatory signaling factors was significantly downregulated in the AG liver. A lipid analysis showed that the levels of triglyceride (TG) and free fatty acid (FFA) were lower in the AG liver than in the NG liver, with an altered expression of lipid metabolism-related factors as well. Moreover, the numbers of 8-hydroxy-2′-deoxyguanosine (8-OHdG)-positive hepatocytes and levels of hepatic thiobarbituric acid reactive substances (TBARS) were significantly lower in AG mice than in NG mice. In line with these results, a higher expressions of antioxidant factors was found in the AG liver than in the NG liver. Our results indicate that acupuncture repressed the progression of NAFLD by inhibiting inflammatory reactions, reducing oxidative stress, and promoting lipid metabolism of hepatocytes, suggesting that this approach might be an important complementary treatment for NAFLD. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
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14 pages, 6652 KiB  
Article
Plasma Homocysteine and Polymorphisms of Genes Involved in Folate Metabolism Correlate with DNMT1 Gene Methylation Levels
by Fabio Coppedè, Andrea Stoccoro, Pierpaola Tannorella and Lucia Migliore
Metabolites 2019, 9(12), 298; https://doi.org/10.3390/metabo9120298 - 07 Dec 2019
Cited by 7 | Viewed by 3625
Abstract
DNA methyltransferase 1 (DNMT1) is responsible for the maintenance of DNA methylation patterns during cell division. Several human diseases are characterized by impaired DNMT1 gene methylation, but less is known about the factors that regulate DNMT1 promoter methylation levels. Dietary folates and related [...] Read more.
DNA methyltransferase 1 (DNMT1) is responsible for the maintenance of DNA methylation patterns during cell division. Several human diseases are characterized by impaired DNMT1 gene methylation, but less is known about the factors that regulate DNMT1 promoter methylation levels. Dietary folates and related B-vitamins are essential micronutrients for DNA methylation processes, and we performed the present study to investigate the contribution of circulating folate, vitamin B12, homocysteine, and common polymorphisms in folate pathway genes to the DNMT1 gene methylation levels. We investigated DNMT1 gene methylation levels in peripheral blood DNA samples from 215 healthy individuals. All the DNA samples were genotyped for MTHFR 677C > T (rs1801133) and 1298A > C (rs1801131), MTRR 66A > G (rs1801394), MTR 2756A > G (rs1805087), SLC19A1 (RFC1) 80G > A (rs1051266), TYMS 28-bp tandem repeats (rs34743033) and 1494 6-bp insertion/deletion (indel) (rs34489327), DNMT3A -448A > G (rs1550117), and DNMT3B -149C > T (rs2424913) polymorphisms. Circulating homocysteine, folate, and vitamin B12 levels were available from 158 of the recruited individuals. We observed an inverse correlation between plasma homocysteine and DNMT1 methylation levels. Furthermore, both MTR rs1805087 and TYMS rs34743033 polymorphisms showed a statistically significant effect on DNMT1 methylation levels. The present study revealed several correlations between the folate metabolic pathway and DNMT1 promoter methylation that could be of relevance for those disorders characterized by altered DNA methylation. Full article
(This article belongs to the Special Issue Folate Absorption and Metabolism)
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18 pages, 3458 KiB  
Article
Short-Term Temporal Metabolic Behavior in Halophilic Cyanobacterium Synechococcus sp. Strain PCC 7002 after Salt Shock
by Shimpei Aikawa, Atsumi Nishida, Tomohisa Hasunuma, Jo-Shu Chang and Akihiko Kondo
Metabolites 2019, 9(12), 297; https://doi.org/10.3390/metabo9120297 - 05 Dec 2019
Cited by 12 | Viewed by 3513
Abstract
In response to salt stress, cyanobacteria increases the gene expression of Na+/H+ antiporter and K+ uptake system proteins and subsequently accumulate compatible solutes. However, alterations in the concentrations of metabolic intermediates functionally related to the early stage of the [...] Read more.
In response to salt stress, cyanobacteria increases the gene expression of Na+/H+ antiporter and K+ uptake system proteins and subsequently accumulate compatible solutes. However, alterations in the concentrations of metabolic intermediates functionally related to the early stage of the salt stress response have not been investigated. The halophilic cyanobacterium Synechococcus sp. PCC 7002 was subjected to salt shock with 0.5 and 1 M NaCl, then we performed metabolomics analysis by capillary electrophoresis/mass spectrometry (CE/MS) and gas chromatography/mass spectrometry (GC/MS) after cultivation for 1, 3, 10, and 24 h. Gene expression profiling using a microarray after 1 h of salt shock was also conducted. We observed suppression of the Calvin cycle and activation of glycolysis at both NaCl concentrations. However, there were several differences in the metabolic changes after salt shock following exposure to 0.5 M and 1 M NaCl: (i): the main compatible solute, glucosylglycerol, accumulated quickly at 0.5 M NaCl after 1 h but increased gradually for 10 h at 1 M NaCl; (ii) the oxidative pentose phosphate pathway and the tricarboxylic acid cycle were activated at 0.5 M NaCl; and (iii) the multi-functional compound spermidine greatly accumulated at 1 M NaCl. Our results show that Synechococcus sp. PCC 7002 acclimated to different levels of salt through a salt stress response involving the activation of different metabolic pathways. Full article
(This article belongs to the Special Issue Metabolomics-Driven Biotechnology)
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15 pages, 1894 KiB  
Article
Genomic Survey, Transcriptome, and Metabolome Analysis of Apocynum venetum and Apocynum hendersonii to Reveal Major Flavonoid Biosynthesis Pathways
by Gang Gao, Ping Chen, Jikang Chen, Kunmei Chen, Xiaofei Wang, Aminu Shehu Abubakar, Ning Liu, Chunming Yu and Aiguo Zhu
Metabolites 2019, 9(12), 296; https://doi.org/10.3390/metabo9120296 - 05 Dec 2019
Cited by 28 | Viewed by 3191
Abstract
Apocynum plants, especially A. venetum and A. hendersonii, are rich in flavonoids. In the present study, a whole genome survey of the two species was initially carried out to optimize the flavonoid biosynthesis-correlated gene mining. Then, the metabolome and transcriptome analyses were combined [...] Read more.
Apocynum plants, especially A. venetum and A. hendersonii, are rich in flavonoids. In the present study, a whole genome survey of the two species was initially carried out to optimize the flavonoid biosynthesis-correlated gene mining. Then, the metabolome and transcriptome analyses were combined to elucidate the flavonoid biosynthesis pathways. Both species have small genome sizes of 232.80 Mb (A. venetum) and 233.74 Mb (A. hendersonii) and showed similar metabolite profiles with flavonols being the main differentiated flavonoids between the two specie. Positive correlation of gene expression levels (flavonone-3 hydroxylase, anthocyanidin reductase, and flavonoid 3-O-glucosyltransferase) and total flavonoid content were observed. The contents of quercitrin, hyperoside, and total anthocyanin in A. venetum were found to be much higher than in A. hendersonii, and such was thought to be the reason for the morphological difference in color of A. venetum and A. hendersonii. This study provides valuable genomic and metabolome information for understanding of A. venetum and A. hendersonii, and lays a foundation for elucidating Apocynum genus plant flavonoid biosynthesis. Full article
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19 pages, 3051 KiB  
Article
Metabolomic Profiling Reveals the Difference on Reproductive Performance between High and Low Lactational Weight Loss Sows
by Liang Hu, Lianqiang Che, Chen Wu, Mihai Victor Curtasu, Fali Wu, Zhengfeng Fang, Yan Lin, Shengyu Xu, Bin Feng, Jian Li, Yong Zhuo, Peter Kappel Theil and De Wu
Metabolites 2019, 9(12), 295; https://doi.org/10.3390/metabo9120295 - 04 Dec 2019
Cited by 9 | Viewed by 3030
Abstract
Sows suffering excess weight loss during lactation may delay weaning to estrus interval (WEI) and have a detrimental effect on subsequent reproductive performance, however, the underlying mechanism is not completely clear. Therefore, the goal of this study was to investigate physiological profiles manifested [...] Read more.
Sows suffering excess weight loss during lactation may delay weaning to estrus interval (WEI) and have a detrimental effect on subsequent reproductive performance, however, the underlying mechanism is not completely clear. Therefore, the goal of this study was to investigate physiological profiles manifested in plasma originating from high (HWL) and low lactational weight loss (LWL) sows. The plasma biochemical parameters, hormones, antioxidant parameters, and milk compositions were assessed. Furthermore, plasma metabolites were analyzed using ultrahigh-performance liquid chromatography/time-of-flight mass spectrometry in positive and negative ion modes. Results showed that HWL sows had a lower feed intake and higher lactational weight loss and prolonged WEI, but had similar litter performance and milk composition compared to LWL sows. These changes were associated with lower plasma insulin-like growth factor 1 and higher fibroblast growth factor 21 levels in the HWL sows. Moreover, HWL led to a severe oxidative stress and metabolic damage, as accompanied by excessive protein breakdown and lipids mobilization at weaning. Metabolomic analysis revealed differences in 46 compounds between HWL and LWL sows, and the identified compounds were enriched in metabolic pathways related to amino acids metabolism, fatty acids oxidation metabolism, bile acids biosynthesis, and nucleoside metabolism. These results provide the evidence for physiological mechanism in sows with excessive lactational weight loss that delayed the WEI. Metabolomic data provides essential information and gives rise to potential targets for the development of nutritional intervention strategies. Full article
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22 pages, 1907 KiB  
Article
Insights on Salt Tolerance of Two Endemic Limonium Species from Spain
by Sara González-Orenga, P. Pablo Ferrer-Gallego, Emilio Laguna, M. Pilar López-Gresa, Maria P. Donat-Torres, Mercedes Verdeguer, Oscar Vicente and Monica Boscaiu
Metabolites 2019, 9(12), 294; https://doi.org/10.3390/metabo9120294 - 29 Nov 2019
Cited by 20 | Viewed by 3177
Abstract
We have analysed the salt tolerance of two endemic halophytes of the genus Limonium, with high conservation value. In the present study, seed germination and growth parameters as well as different biomarkers—photosynthetic pigments, mono and divalent ion contents—associated to salt stress were [...] Read more.
We have analysed the salt tolerance of two endemic halophytes of the genus Limonium, with high conservation value. In the present study, seed germination and growth parameters as well as different biomarkers—photosynthetic pigments, mono and divalent ion contents—associated to salt stress were evaluated in response to high levels of NaCl. The study was completed with an untargeted metabolomics analysis of the primary compounds including carbohydrates, phosphoric and organic acids, and amino acids, identified by using a gas chromatography and mass spectrometry platform. Limonium albuferae proved to be more salt-tolerant than L. doufourii, both at the germination stage and during vegetative growth. The degradation of photosynthetic pigments and the increase of Na+/K+ ratio under salt stress were more accentuated in the less tolerant second species. The metabolomics analysis unravelled several differences between the two species. The higher salt tolerance of L. albuferae may rely on its specific accumulation of fructose and glucose under high salinity conditions, the first considered as a major osmolyte in this genus. In addition, L. albuferae showed steady levels of citric and malic acids, whereas the glutamate family pathway was strongly activated under stress in both species, leading to the accumulation of proline (Pro) and γ-aminobutyric acid (GABA). Full article
(This article belongs to the Special Issue Metabolomics in Plant Environmental Physiology)
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14 pages, 1899 KiB  
Article
Degradation of Extracellular NAD+ Intermediates in Cultures of Human HEK293 Cells
by Veronika Kulikova, Konstantin Shabalin, Kirill Nerinovski, Alexander Yakimov, Maria Svetlova, Ljudmila Solovjeva, Andrey Kropotov, Mikhail Khodorkovskiy, Marie E. Migaud, Mathias Ziegler and Andrey Nikiforov
Metabolites 2019, 9(12), 293; https://doi.org/10.3390/metabo9120293 - 29 Nov 2019
Cited by 30 | Viewed by 8823
Abstract
Nicotinamide adenine dinucleotide (NAD) is an essential redox carrier, whereas its degradation is a key element of important signaling pathways. Human cells replenish their NAD contents through NAD biosynthesis from extracellular precursors. These precursors encompass bases nicotinamide (Nam) and nicotinic acid and their [...] Read more.
Nicotinamide adenine dinucleotide (NAD) is an essential redox carrier, whereas its degradation is a key element of important signaling pathways. Human cells replenish their NAD contents through NAD biosynthesis from extracellular precursors. These precursors encompass bases nicotinamide (Nam) and nicotinic acid and their corresponding nucleosides nicotinamide riboside (NR) and nicotinic acid riboside (NAR), now collectively referred to as vitamin B3. In addition, extracellular NAD+ and nicotinamide mononucleotide (NMN), and potentially their deamidated counterparts, nicotinic acid adenine dinucleotide (NAAD) and nicotinic acid mononucleotide (NAMN), may serve as precursors of intracellular NAD. However, it is still debated whether nucleotides enter cells directly or whether they are converted to nucleosides and bases prior to uptake into cells. Here, we studied the metabolism of extracellular NAD+ and its derivatives in human HEK293 cells using normal and serum-free culture medium. Using medium containing 10% fetal bovine serum (FBS), mono- and dinucleotides were degraded to the corresponding nucleosides. In turn, the nucleosides were cleaved to their corresponding bases. Degradation was also observed in culture medium alone, in the absence of cells, indicating that FBS contains enzymatic activities which degrade NAD+ intermediates. Surprisingly, NR was also rather efficiently hydrolyzed to Nam in the absence of FBS. When cultivated in serum-free medium, HEK293 cells efficiently cleaved NAD+ and NAAD to NMN and NAMN. NMN exhibited rather high stability in cell culture, but was partially metabolized to NR. Using pharmacological inhibitors of plasma membrane transporters, we also showed that extracellular cleavage of NAD+ and NMN to NR is a prerequisite for using these nucleotides to maintain intracellular NAD contents. We also present evidence that, besides spontaneous hydrolysis, NR is intensively metabolized in cell culture by intracellular conversion to Nam. Our results demonstrate that both the cultured cells and the culture medium mediate a rather active conversion of NAD+ intermediates. Consequently, in studies of precursor supplementation and uptake, the culture conditions need to be carefully defined. Full article
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15 pages, 1785 KiB  
Article
Ammonium Fluoride as Suitable Additive for HILIC-Based LC-HRMS Metabolomics
by Luca Narduzzi, Anne-Lise Royer, Emmanuelle Bichon, Yann Guitton, Corinne Buisson, Bruno Le Bizec and Gaud Dervilly-Pinel
Metabolites 2019, 9(12), 292; https://doi.org/10.3390/metabo9120292 - 27 Nov 2019
Cited by 17 | Viewed by 5307
Abstract
Hydrophilic Interaction Liquid Chromatography (HILIC) chromatography is widely applied in metabolomics as a complementary strategy to reverse phase chromatography. Nevertheless, it still faces several issues in terms of peak shape and compounds ionization, limiting the automatic de-convolution and data semi-quantification performed through dedicated [...] Read more.
Hydrophilic Interaction Liquid Chromatography (HILIC) chromatography is widely applied in metabolomics as a complementary strategy to reverse phase chromatography. Nevertheless, it still faces several issues in terms of peak shape and compounds ionization, limiting the automatic de-convolution and data semi-quantification performed through dedicated software. A way to improve the chromatographic and ionization performance of a HILIC method is to modify the electrostatic interactions of the analytes with both mobile and stationary phases. In this study, using a ZIC-HILIC chromatographic phase, we evaluated the performance of ammonium fluoride (AF) as additive salt, comparing its performance to ammonium acetate (AA). Three comparative criteria were selected: (1) identification and peak quality of 34 standards following a metabolomics-specific evaluation approach, (2) an intraday repeatability test with real samples and (3) performing two real metabolomics fingerprints with the AF method to evaluate its inter-day repeatability. The AF method showed not only higher ionization efficiency and signal-to-noise ratio but also better repeatability and robustness than the AA approach. A tips and tricks section is then added, aiming at improving method replicability for further users. In conclusion, ammonium fluoride as additive salt presents several advantages and might be considered as a step forward in the application of robust HILIC methods in metabolomics. Full article
(This article belongs to the Special Issue Metabolomics 2019)
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15 pages, 1414 KiB  
Article
Mucosal Metabolomic Profiling and Pathway Analysis Reveal the Metabolic Signature of Ulcerative Colitis
by Joseph Diab, Terkel Hansen, Rasmus Goll, Hans Stenlund, Einar Jensen, Thomas Moritz, Jon Florholmen and Guro Forsdahl
Metabolites 2019, 9(12), 291; https://doi.org/10.3390/metabo9120291 - 27 Nov 2019
Cited by 24 | Viewed by 5199
Abstract
The onset of ulcerative colitis (UC) is characterized by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host–microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve [...] Read more.
The onset of ulcerative colitis (UC) is characterized by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host–microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies. This study aims to explore the mucosal metabolomic profile in UC patients, and to define the UC metabolic signature. Treatment- naïve UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopies. Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acyl carnitine, and amino acid profiles. Several pathways were found perturbed according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as tryptophan metabolism) to fatty acid metabolism, namely linoleic and butyrate. These metabolic changes during UC reflect the homeostatic disturbance in the gut, and highlight the importance of system biology approaches to identify key drivers of pathogenesis which prerequisite personalized medicine. Full article
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18 pages, 969 KiB  
Communication
Metabolic Fingerprint of Chronic Obstructive Lung Diseases: A New Diagnostic Perspective
by Dimitris Tsoukalas, Evangelia Sarandi, Maria Thanasoula, Anca Oana Docea, Gerasimos Tsilimidos, Daniela Calina and Aristides Tsatsakis
Metabolites 2019, 9(12), 290; https://doi.org/10.3390/metabo9120290 - 26 Nov 2019
Cited by 21 | Viewed by 6805
Abstract
Chronic obstructive lung disease (COLD) is a group of airway diseases, previously known as emphysema and chronic bronchitis. The heterogeneity of COLD does not allow early diagnosis and leads to increased morbidity and mortality. The increasing number of COLD incidences stresses the need [...] Read more.
Chronic obstructive lung disease (COLD) is a group of airway diseases, previously known as emphysema and chronic bronchitis. The heterogeneity of COLD does not allow early diagnosis and leads to increased morbidity and mortality. The increasing number of COLD incidences stresses the need for precision medicine approaches that are specific to the patient. Metabolomics is an emerging technology that allows for the discrimination of metabolic changes in the cell as a result of environmental factors and specific genetic background. Thus, quantification of metabolites in human biofluids can provide insights into the metabolic state of the individual in real time and unravel the presence of, or predisposition to, a disease. In this article, the advantages of and potential barriers to putting metabolomics into clinical practice for COLD are discussed. Today, metabolomics is mostly lab-based, and research studies with novel COLD-specific biomarkers are continuously being published. Several obstacles in the research and the market field hamper the translation of these data into clinical practice. However, technological and computational advances will facilitate the clinical interpretation of data and provide healthcare professionals with the tools to prevent, diagnose, and treat COLD with precision in the coming decades. Full article
(This article belongs to the Special Issue Metabolomics and Chronic Obstructive Lung Diseases)
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18 pages, 1135 KiB  
Article
Untargeted Metabolomics-Based Screening Method for Inborn Errors of Metabolism using Semi-Automatic Sample Preparation with an UHPLC- Orbitrap-MS Platform
by Ramon Bonte, Michiel Bongaerts, Serwet Demirdas, Janneke G. Langendonk, Hidde H. Huidekoper, Monique Williams, Willem Onkenhout, Edwin H. Jacobs, Henk J. Blom and George J. G. Ruijter
Metabolites 2019, 9(12), 289; https://doi.org/10.3390/metabo9120289 - 26 Nov 2019
Cited by 29 | Viewed by 4956
Abstract
Routine diagnostic screening of inborn errors of metabolism (IEM) is currently performed by different targeted analyses of known biomarkers. This approach is time-consuming, targets a limited number of biomarkers and will not identify new biomarkers. Untargeted metabolomics generates a global metabolic phenotype and [...] Read more.
Routine diagnostic screening of inborn errors of metabolism (IEM) is currently performed by different targeted analyses of known biomarkers. This approach is time-consuming, targets a limited number of biomarkers and will not identify new biomarkers. Untargeted metabolomics generates a global metabolic phenotype and has the potential to overcome these issues. We describe a novel, single platform, untargeted metabolomics method for screening IEM, combining semi-automatic sample preparation with pentafluorophenylpropyl phase (PFPP)-based UHPLC- Orbitrap-MS. We evaluated analytical performance and diagnostic capability of the method by analysing plasma samples of 260 controls and 53 patients with 33 distinct IEM. Analytical reproducibility was excellent, with peak area variation coefficients below 20% for the majority of the metabolites. We illustrate that PFPP-based chromatography enhances identification of isomeric compounds. Ranked z-score plots of metabolites annotated in IEM samples were reviewed by two laboratory specialists experienced in biochemical genetics, resulting in the correct diagnosis in 90% of cases. Thus, our untargeted metabolomics platform is robust and differentiates metabolite patterns of different IEMs from those of controls. We envision that the current approach to diagnose IEM, using numerous tests, will eventually be replaced by untargeted metabolomics methods, which also have the potential to discover novel biomarkers and assist in interpretation of genetic data. Full article
(This article belongs to the Special Issue Genetic Metabolic Diagnostics)
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14 pages, 912 KiB  
Article
1H-NMR Urinary Metabolic Profile, A Promising Tool for the Management of Infants with Human Cytomegalovirus-Infection
by Marie Antoinette Frick, Ignasi Barba, Marina Fenoy-Alejandre, Paula López-López, Fernando Baquero-Artigao, Paula Rodríguez-Molino, Antoni Noguera-Julian, Marta Nicolás-López, Asunción de la Fuente-Juárez, Maria Gemma Codina-Grau, Juliana Esperalba Esquerra, Ángeles Linde-Sillo and Pere Soler-Palacín
Metabolites 2019, 9(12), 288; https://doi.org/10.3390/metabo9120288 - 25 Nov 2019
Cited by 6 | Viewed by 2638
Abstract
Congenital human cytomegalovirus (HCMV) infection is the most common mother-to-child transmitted infection in the developed world. Certain aspects of its management remain a challenge. Urinary metabolic profiling is a promising tool for use in pediatric conditions. The aim of this study was to [...] Read more.
Congenital human cytomegalovirus (HCMV) infection is the most common mother-to-child transmitted infection in the developed world. Certain aspects of its management remain a challenge. Urinary metabolic profiling is a promising tool for use in pediatric conditions. The aim of this study was to investigate the urinary metabolic profile in HCMV-infected infants and controls during acute care hospitalization. Urine samples were collected from 53 patients at five hospitals participating in the Spanish congenital HCMV registry. Thirty-one cases of HCMV infection and 22 uninfected controls were included. Proton nuclear magnetic resonance (1H-NMR) spectra were obtained using NOESYPR1D pulse sequence. The dataset underwent orthogonal projection on latent structures discriminant analysis to identify candidate variables affecting the urinary metabolome: HCMV infection, type of infection, sex, chronological age, gestational age, type of delivery, twins, and diet. Statistically significant discriminative models were obtained only for HCMV infection (p = 0.03) and chronological age (p < 0.01). No significant differences in the metabolomic profile were found between congenital and postnatal HCMV infection. When the HCMV-infected group was analyzed according to chronological age, a statistically significant model was obtained only in the neonatal group (p = 0.01), with the differentiating metabolites being betaine, glycine, alanine, and dimethylamine. Despite the considerable variation in urinary metabolic profiles in a real-life setting, clinical application of metabolomics to the study of HCMV infection seems feasible. Full article
(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)
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13 pages, 1812 KiB  
Article
ADGRL4/ELTD1 Silencing in Endothelial Cells Induces ACLY and SLC25A1 and Alters the Cellular Metabolic Profile
by David M. Favara, Christos E. Zois, Syed Haider, Elisabete Pires, Helen Sheldon, James McCullagh, Alison H. Banham and Adrian L. Harris
Metabolites 2019, 9(12), 287; https://doi.org/10.3390/metabo9120287 - 25 Nov 2019
Cited by 13 | Viewed by 4389
Abstract
Adhesion G Protein-Coupled Receptor L4 (ADGRL4/ELTD1) is an endothelial cell adhesion G protein-coupled receptor (aGPCR) which regulates physiological and tumour angiogenesis, providing an attractive target for anti-cancer therapeutics. To date, ADGRL4/ELTD1′s full role and mechanism of function within endothelial biology remains unknown, as [...] Read more.
Adhesion G Protein-Coupled Receptor L4 (ADGRL4/ELTD1) is an endothelial cell adhesion G protein-coupled receptor (aGPCR) which regulates physiological and tumour angiogenesis, providing an attractive target for anti-cancer therapeutics. To date, ADGRL4/ELTD1′s full role and mechanism of function within endothelial biology remains unknown, as do its ligand(s). In this study, ADGRL4/ELTD1 silencing, using two independent small interfering RNAs (siRNAs), was performed in human umbilical vein endothelial cells (HUVECS) followed by transcriptional profiling, target gene validation, and metabolomics using liquid chromatography-mass spectrometry in order to better characterise ADGRL4/ELTD1′s role in endothelial cell biology. We show that ADGRL4/ELTD1 silencing induced expression of the cytoplasmic metabolic regulator ATP Citrate Lyase (ACLY) and the mitochondria-to-cytoplasm citrate transporter Solute Carrier Family 25 Member 1 (SLC25A1) but had no apparent effect on pathways downstream of ACLY (fatty acid and cholesterol synthesis or acetylation). Silencing induced KIT expression and affected the Notch signalling pathway, upregulating Delta Like Canonical Notch Ligand 4 (DLL4) and suppressing Jagged Canonical Notch Ligand 1 (JAG1) and Hes Family BHLH Transcription Factor 2 (HES2). The effect of ADGRL4/ELTD1 silencing on the cellular metabolic profile was modest but several metabolites were significantly affected. Cis-aconitic acid, uridine diphosphate (UDP)-glucoronate, fructose 2,6-diphosphate, uridine 5-diphosphate, and aspartic acid were all elevated as a result of silencing and phosphocreatine, N-acetylglutamic acid, taurine, deoxyadenosine triphosphate, and cytidine monophosphate were depleted. Metabolic pathway analysis implicated ADGRL4/ELTD1 in pyrimidine, amino acid, and sugar metabolism. In summary, this study shows that ADGRL4/ELTD1 impacts core components of endothelial metabolism and regulates genes involved in endothelial differentiation/homeostasis and Notch signalling. Full article
(This article belongs to the Special Issue Metabolomics in the Study of Disease)
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10 pages, 1119 KiB  
Article
Detecting Pulmonary Oxygen Toxicity Using eNose Technology and Associations between Electronic Nose and Gas Chromatography–Mass Spectrometry Data
by Thijs T. Wingelaar, Paul Brinkman, Rianne de Vries, Pieter-Jan A.M. van Ooij, Rigo Hoencamp, Anke-Hilse Maitland-van der Zee, Markus W. Hollmann and Rob A. van Hulst
Metabolites 2019, 9(12), 286; https://doi.org/10.3390/metabo9120286 - 22 Nov 2019
Cited by 5 | Viewed by 2727
Abstract
Exposure to oxygen under increased atmospheric pressures can induce pulmonary oxygen toxicity (POT). Exhaled breath analysis using gas chromatography–mass spectrometry (GC–MS) has revealed that volatile organic compounds (VOCs) are associated with inflammation and lipoperoxidation after hyperbaric–hyperoxic exposure. Electronic nose (eNose) technology would be [...] Read more.
Exposure to oxygen under increased atmospheric pressures can induce pulmonary oxygen toxicity (POT). Exhaled breath analysis using gas chromatography–mass spectrometry (GC–MS) has revealed that volatile organic compounds (VOCs) are associated with inflammation and lipoperoxidation after hyperbaric–hyperoxic exposure. Electronic nose (eNose) technology would be more suited for the detection of POT, since it is less time and resource consuming. However, it is unknown whether eNose technology can detect POT and whether eNose sensor data can be associated with VOCs of interest. In this randomized cross-over trial, the exhaled breath from divers who had made two dives of 1 h to 192.5 kPa (a depth of 9 m) with either 100% oxygen or compressed air was analyzed, at several time points, using GC–MS and eNose. We used a partial least square discriminant analysis, eNose discriminated oxygen and air dives at 30 min post dive with an area under the receiver operating characteristics curve of 79.9% (95%CI: 61.1–98.6; p = 0.003). A two-way orthogonal partial least square regression (O2PLS) model analysis revealed an R² of 0.50 between targeted VOCs obtained by GC–MS and eNose sensor data. The contribution of each sensor to the detection of targeted VOCs was also assessed using O2PLS. When all GC–MS fragments were included in the O2PLS model, this resulted in an R² of 0.08. Thus, eNose could detect POT 30 min post dive, and the correlation between targeted VOCs and eNose data could be assessed using O2PLS. Full article
(This article belongs to the Special Issue Volatile Metabolites’ New Frontier for Metabolomics)
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16 pages, 472 KiB  
Review
Experimental Design and Sample Preparation in Forest Tree Metabolomics
by Ana M. Rodrigues, Ana I. Ribeiro-Barros and Carla António
Metabolites 2019, 9(12), 285; https://doi.org/10.3390/metabo9120285 - 22 Nov 2019
Cited by 29 | Viewed by 5391
Abstract
Appropriate experimental design and sample preparation are key steps in metabolomics experiments, highly influencing the biological interpretation of the results. The sample preparation workflow for plant metabolomics studies includes several steps before metabolite extraction and analysis. These include the optimization of laboratory procedures, [...] Read more.
Appropriate experimental design and sample preparation are key steps in metabolomics experiments, highly influencing the biological interpretation of the results. The sample preparation workflow for plant metabolomics studies includes several steps before metabolite extraction and analysis. These include the optimization of laboratory procedures, which should be optimized for different plants and tissues. This is particularly the case for trees, whose tissues are complex matrices to work with due to the presence of several interferents, such as oleoresins, cellulose. A good experimental design, tree tissue harvest conditions, and sample preparation are crucial to ensure consistency and reproducibility of the metadata among datasets. In this review, we discuss the main challenges when setting up a forest tree metabolomics experiment for mass spectrometry (MS)-based analysis covering all technical aspects from the biological question formulation and experimental design to sample processing and metabolite extraction and data acquisition. We also highlight the importance of forest tree metadata standardization in metabolomics studies. Full article
(This article belongs to the Special Issue Sample Preparation in Metabolomics)
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7 pages, 374 KiB  
Case Report
Serum Steroid Profiling by Liquid Chromatography–Tandem Mass Spectrometry for the Rapid Confirmation and Early Treatment of Congenital Adrenal Hyperplasia: A Neonatal Case Report
by Ilaria Cicalini, Stefano Tumini, Paola Irma Guidone, Damiana Pieragostino, Mirco Zucchelli, Sara Franchi, Gabriele Lisi, Pierluigi Lelli Chiesa, Liborio Stuppia, Vincenzo De Laurenzi and Claudia Rossi
Metabolites 2019, 9(12), 284; https://doi.org/10.3390/metabo9120284 - 21 Nov 2019
Cited by 8 | Viewed by 2748
Abstract
Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders of steroid biosynthesis, in 95% of cases due to 21-hydroxylase deficiency. The resulting hormonal imbalances lead to increased 17-hydroxyprogesterone and androgens levels, at the expense of decreased concentrations of glucocorticoids and, in [...] Read more.
Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders of steroid biosynthesis, in 95% of cases due to 21-hydroxylase deficiency. The resulting hormonal imbalances lead to increased 17-hydroxyprogesterone and androgens levels, at the expense of decreased concentrations of glucocorticoids and, in some cases, of mineralocorticoids. A variety of clinical presentations accompany a range of severities, which are described as different forms of CAH, and are the result of these hormonal imbalances. The incidence of CAH worldwide is approximately 1 in 15,000 live births, and is population-dependent; thus, its inclusion in neonatal screening tests is widely discussed. Diagnosis of CAH is based on the quantification of 17-hydroxyprogesterone, usually by immunoassay, which has low specificity and high false-positive rates, resulting in a relatively high demand for a second-tier confirmation test. We report a case of a newborn recognized as female at birth, but showing ambiguous genitalia and other CAH clinical features, including hypernatremia, in the first days of life. In addition to the classical assays, liquid chromatography–tandem mass spectrometry was used to determine the serum steroid profile, allowing for the accurate and simultaneous quantification of seven steroids in the same analysis. Such an application immediately revealed an alteration in the levels of specific steroids related to CAH, leading to an early intervention by hormone replacement therapy. Subsequently, the diagnosis of classic CAH due to 21-hydroxylase deficiency was further confirmed by molecular testing. Full article
(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)
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2 pages, 138 KiB  
Editorial
The Application of Metabolomic Techniques in Research Investigating Neurodegenerative Diseases
by Brian D. Green
Metabolites 2019, 9(12), 283; https://doi.org/10.3390/metabo9120283 - 20 Nov 2019
Viewed by 1904
Abstract
We live in a world posing many new and different challenges for human health, and one such challenge is the rapidly expanding number of cases of human neurodegenerative disease [...] Full article
(This article belongs to the Special Issue Metabolomics in Neurodegenerative Disease)
14 pages, 2239 KiB  
Review
Glucose-6 Phosphate, a Central Hub for Liver Carbohydrate Metabolism
by Fabienne Rajas, Amandine Gautier-Stein and Gilles Mithieux
Metabolites 2019, 9(12), 282; https://doi.org/10.3390/metabo9120282 - 20 Nov 2019
Cited by 54 | Viewed by 17836
Abstract
Cells efficiently adjust their metabolism according to the abundance of nutrients and energy. The ability to switch cellular metabolism between anabolic and catabolic processes is critical for cell growth. Glucose-6 phosphate is the first intermediate of glucose metabolism and plays a central role [...] Read more.
Cells efficiently adjust their metabolism according to the abundance of nutrients and energy. The ability to switch cellular metabolism between anabolic and catabolic processes is critical for cell growth. Glucose-6 phosphate is the first intermediate of glucose metabolism and plays a central role in the energy metabolism of the liver. It acts as a hub to metabolically connect glycolysis, the pentose phosphate pathway, glycogen synthesis, de novo lipogenesis, and the hexosamine pathway. In this review, we describe the metabolic fate of glucose-6 phosphate in a healthy liver and the metabolic reprogramming occurring in two pathologies characterized by a deregulation of glucose homeostasis, namely type 2 diabetes, which is characterized by fasting hyperglycemia; and glycogen storage disease type I, where patients develop severe hypoglycemia during short fasting periods. In these two conditions, dysfunction of glucose metabolism results in non-alcoholic fatty liver disease, which may possibly lead to the development of hepatic tumors. Moreover, we also emphasize the role of the transcription factor carbohydrate response element-binding protein (ChREBP), known to link glucose and lipid metabolisms. In this regard, comparing these two metabolic diseases is a fruitful approach to better understand the key role of glucose-6 phosphate in liver metabolism in health and disease. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
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