Metabolites

16 pages, 1872 KiB

Open AccessArticle

iNovo479: Metabolic Modeling Provides a Roadmap to Optimize Bioproduct Yield from Deconstructed Lignin Aromatics by Novosphingobium aromaticivorans

by Alexandra M. Linz, Yanjun Ma, Samuel Scholz, Daniel R. Noguera and Timothy J. Donohue

Metabolites 2022, 12(4), 366; https://doi.org/10.3390/metabo12040366 - 18 Apr 2022

Cited by 4 | Viewed by 2249

Abstract

Lignin is an abundant renewable source of aromatics and precursors for the production of other organic chemicals. However, lignin is a heterogeneous polymer, so the mixture of aromatics released during its depolymerization can make its conversion to chemicals challenging. Microbes are a potential [...] Read more.

Lignin is an abundant renewable source of aromatics and precursors for the production of other organic chemicals. However, lignin is a heterogeneous polymer, so the mixture of aromatics released during its depolymerization can make its conversion to chemicals challenging. Microbes are a potential solution to this challenge, as some can catabolize multiple aromatic substrates into one product. Novosphingobium aromaticivorans has this ability, and its use as a bacterial chassis for lignin valorization could be improved by the ability to predict product yields based on thermodynamic and metabolic inputs. In this work, we built a genome-scale metabolic model of N. aromaticivorans, iNovo479, to guide the engineering of strains for aromatic conversion into products. iNovo479 predicted product yields from single or multiple aromatics, and the impact of combinations of aromatic and non-aromatic substrates on product yields. We show that enzyme reactions from other organisms can be added to iNovo479 to predict the feasibility and profitability of producing additional products by engineered strains. Thus, we conclude that iNovo479 can help guide the design of bacteria to convert lignin aromatics into valuable chemicals. Full article

(This article belongs to the Special Issue The Thermodynamic Regulation of Microbial Metabolisms by Environmental Factors)

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12 pages, 1253 KiB

Open AccessArticle

Early Effects of Metabolic Syndrome on ATP-Sensitive Potassium Channels from Rat Pancreatic Beta Cells

by Iskra Cruz-Cruz, Germán Bernate-Obando, Carlos Larqué, Rene Escalona, Rodolfo Pinto-Almazán and Myrian Velasco

Metabolites 2022, 12(4), 365; https://doi.org/10.3390/metabo12040365 - 18 Apr 2022

Cited by 3 | Viewed by 2022

Abstract

Metabolic syndrome (MS) is a cluster of metabolic signs that increases the risk of developing type 2 two diabetes mellitus and cardiovascular diseases. MS leads to pancreatic beta cell exhaustion and decreased insulin secretion through unknown mechanisms in a time-dependent manner. ATP-sensitive potassium [...] Read more.

Metabolic syndrome (MS) is a cluster of metabolic signs that increases the risk of developing type 2 two diabetes mellitus and cardiovascular diseases. MS leads to pancreatic beta cell exhaustion and decreased insulin secretion through unknown mechanisms in a time-dependent manner. ATP-sensitive potassium channels (K_ATP channels), common targets of anti-diabetic drugs, participate in the glucose-stimulated insulin secretion, coupling the metabolic status and electrical activity of pancreatic beta cells. We investigated the early effects of MS on the conductance, ATP and glybenclamide sensitivity of the K_ATP channels. We used Wistar rats fed with a high-sucrose diet (HSD) for 8 weeks as a MS model. In excised membrane patches, control and HSD channels showed similar unitary conductance and ATP sensitivity pancreatic beta cells in their K_ATP channels_. In contrast, MS produced variability in the sensitivity to glybenclamide of K_ATP channels. We observed two subpopulations of pancreatic beta cells, one with similar (Gly1) and one with increased (Gly2) glybenclamide sensitivity compared to the control group. This study shows that the early effects of MS produced by consuming high-sugar beverages can affect the pharmacological properties of K_ATP channels to one of the drugs used for diabetes treatment. Full article

(This article belongs to the Special Issue Frontiers in the Study of Metabolic Diseases Using Rodent Models)

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19 pages, 5605 KiB

Open AccessArticle

Flavin-Containing Monooxygenase 3 (FMO3) Is Critical for Dioxin-Induced Reorganization of the Gut Microbiome and Host Insulin Sensitivity

by William Massey, Lucas J. Osborn, Rakhee Banerjee, Anthony Horak, Kevin K. Fung, Danny Orabi, E. Ricky Chan, Naseer Sangwan, Zeneng Wang and J. Mark Brown

Metabolites 2022, 12(4), 364; https://doi.org/10.3390/metabo12040364 - 18 Apr 2022

Cited by 7 | Viewed by 3926

Abstract

Exposure to some environmental pollutants can have potent endocrine-disrupting effects, thereby promoting hormone imbalance and cardiometabolic diseases such as non-alcoholic fatty liver disease (NAFLD), diabetes, and cardiorenal diseases. Recent evidence also suggests that many environmental pollutants can reorganize the gut microbiome to potentially [...] Read more.

Exposure to some environmental pollutants can have potent endocrine-disrupting effects, thereby promoting hormone imbalance and cardiometabolic diseases such as non-alcoholic fatty liver disease (NAFLD), diabetes, and cardiorenal diseases. Recent evidence also suggests that many environmental pollutants can reorganize the gut microbiome to potentially impact these diverse human diseases. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is among the most potent endocrine-disrupting dioxin pollutants, yet our understanding of how TCDD impacts the gut microbiome and systemic metabolism is incompletely understood. Here, we show that TCDD exposure in mice profoundly stimulates the hepatic expression of flavin-containing monooxygenase 3 (Fmo3), which is a hepatic xenobiotic metabolizing enzyme that is also responsible for the production of the gut microbiome-associated metabolite trimethylamine N-oxide (TMAO). Interestingly, an enzymatic product of FMO3 (TMAO) has been associated with the same cardiometabolic diseases that these environmental pollutants promote. Therefore, here, we examined TCDD-induced alterations in the gut microbiome, host liver transcriptome, and glucose tolerance in Fmo3^+/+ and Fmo3^−/− mice. Our results show that Fmo3 is a critical component of the transcriptional response to TCDD, impacting the gut microbiome, host liver transcriptome, and systemic glucose tolerance. Collectively, this work uncovers a previously underappreciated role for Fmo3 in integrating diet–pollutant–microbe–host interactions. Full article

(This article belongs to the Special Issue Insights into How Gut Microbial Metabolites Regulate Innate Immune Responses)

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15 pages, 1207 KiB

Open AccessArticle

Effects of Water Stress, Defoliation and Crop Thinning on Vitis vinifera L. cv. Solaris: Part I: Plant Responses, Fruit Development and Fruit Quality

by Violetta Aru, Andreas Paul Nittnaus, Klavs Martin Sørensen, Søren Balling Engelsen and Torben Bo Toldam-Andersen

Metabolites 2022, 12(4), 363; https://doi.org/10.3390/metabo12040363 - 18 Apr 2022

Cited by 7 | Viewed by 2980

Abstract

Viticultural practices and irrigation have a major impact on fruit development and yield, and ultimately on must quality. The effects of water deficit (WD), defoliation (Def), and crop-thinning (CT) on Solaris plants and fruit development, as well as on the chemical composition of [...] Read more.

Viticultural practices and irrigation have a major impact on fruit development and yield, and ultimately on must quality. The effects of water deficit (WD), defoliation (Def), and crop-thinning (CT) on Solaris plants and fruit development, as well as on the chemical composition of grape juice were investigated. WD was induced at three periods during fruit development (pre-veraison, veraison, and ripening) in pot-grown plants, while Def and CT were carried out on field-grown plants. Environmental and vegetative parameters were monitored during the experiments. The bulk chemical composition of the fruits was determined in juice by Fourier Transform-Infrared (FT-IR) spectroscopy throughout fruit ripening and at final harvest. The results showed that WD reduced soil water content and leaf water status. CT significantly reduced yield per vine, but increased cluster size. Mid to late WD reduced soluble solids by 1%. CT increased sugar content in juice, while Def decreased sugar accumulation. Total acids were higher in the juice from the field vines. Yet, CT lowered malic and tartaric acids. Def increased tartaric acid. Ammonia and alpha amino nitrogen were higher in the juice from pot-grown vines, while pH was lowered by Def and raised by CT. It is concluded that Solaris has a remarkable ability to tolerate and recover from WD. CT and Def significantly affected the bulk chemical composition of grapes in terms of total acidity and sugar accumulation, with CT grapes having the highest sugar content and the lowest total acidity and Def the opposite. Full article

(This article belongs to the Special Issue Grape and Wine Metabolome Analysis)

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26 pages, 5016 KiB

Open AccessArticle

HBM4EU Chromates Study: Urinary Metabolomics Study of Workers Exposed to Hexavalent Chromium

by Lucyna Kozłowska, Tiina Santonen, Radu Corneliu Duca, Lode Godderis, Karolina Jagiello, Beata Janasik, An Van Nieuwenhuyse, Katrien Poels, Tomasz Puzyn, Paul T. J. Scheepers, Monika Sijko, Maria João Silva, Anita Sosnowska, Susana Viegas, Jelle Verdonck, Wojciech Wąsowicz, on behalf of HBM4EU Chromates Study Team and on behalf of Statistical Team

Metabolites 2022, 12(4), 362; https://doi.org/10.3390/metabo12040362 - 18 Apr 2022

Cited by 8 | Viewed by 3750

Abstract

Exposure to hexavalent chromium Cr(VI) may occur in several occupational activities, placing workers in many industries at risk for potential related health outcomes. Untargeted metabolomics was applied to investigate changes in metabolic pathways in response to Cr(VI) exposure. We obtained our data from [...] Read more.

Exposure to hexavalent chromium Cr(VI) may occur in several occupational activities, placing workers in many industries at risk for potential related health outcomes. Untargeted metabolomics was applied to investigate changes in metabolic pathways in response to Cr(VI) exposure. We obtained our data from a study population of 220 male workers with exposure to Cr(VI) and 102 male controls from Belgium, Finland, Poland, Portugal and the Netherlands within the HBM4EU Chromates Study. Urinary metabolite profiles were determined using liquid chromatography mass spectrometry, and differences between post-shift exposed workers and controls were analyzed using principal component analysis. Based on the first two principal components, we observed clustering by industrial chromate application, such as welding, chrome plating, and surface treatment, distinct from controls and not explained by smoking status or alcohol use. The changes in the abundancy of excreted metabolites observed in workers reflect fatty acid and monoamine neurotransmitter metabolism, oxidative modifications of amino acid residues, the excessive formation of abnormal amino acid metabolites and changes in steroid and thyrotropin-releasing hormones. The observed responses could also have resulted from work-related factors other than Cr(VI). Further targeted metabolomics studies are needed to better understand the observed modifications and further explore the suitability of urinary metabolites as early indicators of adverse effects associated with exposure to Cr(VI). Full article

(This article belongs to the Special Issue Toxicometabolomics)

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15 pages, 2515 KiB

Open AccessArticle

Analysis of Metabolomic Changes in Xylem and Phloem Sap of Cucumber under Phosphorus Stresses

by Jingjing Sun, Qinglin Li, Hui Xu and Wentao Zhang

Metabolites 2022, 12(4), 361; https://doi.org/10.3390/metabo12040361 - 18 Apr 2022

Cited by 6 | Viewed by 2450

Abstract

Cucumber xylem and phloem sap is a key link in nutrient distribution, transportation and signal transduction of cucumber plants; however, the metabolic response mechanism of cucumber xylem and phloem sap under phosphorus stress has not been clearly revealed. In this study, gas chromatography-mass [...] Read more.

Cucumber xylem and phloem sap is a key link in nutrient distribution, transportation and signal transduction of cucumber plants; however, the metabolic response mechanism of cucumber xylem and phloem sap under phosphorus stress has not been clearly revealed. In this study, gas chromatography-mass spectrometry (GC-MS) combined with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to analyze the metabolites in cucumber xylem and phloem sap under different phosphorus stress. A total of 22 differential metabolites were screened from xylem and phloem sap, respectively. Through the analysis of metabolic pathways of differential metabolites, four and three key metabolic pathways were screened, respectively. The results showed that compared with the normal phosphorus level, the content of most amino acids in the key metabolic pathway increased in xylem but decreased in phloem both under low and high phosphorus stress levels. The contents of sucrose and glucose in phloem glycolysis pathway showed a positive correlation with the change of phosphorus nutrient levels. The tricarboxylic acid cycle was promoted in xylem and phloem of cucumber under low and high phosphorus nutrient levels, and the contents of malic acid and citric acid increased significantly. This study provided abundant biochemical information for the metabolic response and regulation strategies of cucumber xylem and phloem under phosphorus stress, and is committed to looking for more sensitive markers to evaluate the supply level of phosphorus nutrients in cucumber. Full article

(This article belongs to the Special Issue Advances in Metabolic Studies in Plant Extraction)

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20 pages, 684 KiB

Open AccessReview

Exploring Thermal Sensitivities and Adaptations of Oxidative Phosphorylation Pathways

by Hélène Lemieux and Pierre U. Blier

Metabolites 2022, 12(4), 360; https://doi.org/10.3390/metabo12040360 - 17 Apr 2022

Cited by 10 | Viewed by 4352

Abstract

Temperature shifts are a major challenge to animals; they drive adaptations in organisms and species, and affect all physiological functions in ectothermic organisms. Understanding the origin and mechanisms of these adaptations is critical for determining whether ectothermic organisms will be able to survive [...] Read more.

Temperature shifts are a major challenge to animals; they drive adaptations in organisms and species, and affect all physiological functions in ectothermic organisms. Understanding the origin and mechanisms of these adaptations is critical for determining whether ectothermic organisms will be able to survive when faced with global climate change. Mitochondrial oxidative phosphorylation is thought to be an important metabolic player in this regard, since the capacity of the mitochondria to produce energy greatly varies according to temperature. However, organism survival and fitness depend not only on how much energy is produced, but, more precisely, on how oxidative phosphorylation is affected and which step of the process dictates thermal sensitivity. These questions need to be addressed from a new perspective involving a complex view of mitochondrial oxidative phosphorylation and its related pathways. In this review, we examine the effect of temperature on the commonly measured pathways, but mainly focus on the potential impact of lesser-studied pathways and related steps, including the electron-transferring flavoprotein pathway, glycerophosphate dehydrogenase, dihydroorotate dehydrogenase, choline dehydrogenase, proline dehydrogenase, and sulfide:quinone oxidoreductase. Our objective is to reveal new avenues of research that can address the impact of temperature on oxidative phosphorylation in all its complexity to better portray the limitations and the potential adaptations of aerobic metabolism. Full article

(This article belongs to the Special Issue Ectotherms Metabolism: Plasticity and Adaptation)

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14 pages, 894 KiB

Open AccessArticle

Metabolomic Associations of Asthma in the Hispanic Community Health Study/Study of Latinos

by Yura Lee, Han Chen, Wei Chen, Qibin Qi, Majid Afshar, Jianwen Cai, Martha L. Daviglus, Bharat Thyagarajan, Kari E. North, Stephanie J. London, Eric Boerwinkle, Juan C. Celedón, Robert C. Kaplan and Bing Yu

Metabolites 2022, 12(4), 359; https://doi.org/10.3390/metabo12040359 - 16 Apr 2022

Cited by 2 | Viewed by 3151

Abstract

Asthma disproportionally affects Hispanic and/or Latino backgrounds; however, the relation between circulating metabolites and asthma remains unclear. We conducted a cross-sectional study associating 640 individual serum metabolites, as well as twelve metabolite modules, with asthma in 3347 Hispanic/Latino background participants (514 asthmatics, 15.36%) [...] Read more.

Asthma disproportionally affects Hispanic and/or Latino backgrounds; however, the relation between circulating metabolites and asthma remains unclear. We conducted a cross-sectional study associating 640 individual serum metabolites, as well as twelve metabolite modules, with asthma in 3347 Hispanic/Latino background participants (514 asthmatics, 15.36%) from the Hispanic/Latino Community Health Study/Study of Latinos. Using survey logistic regression, per standard deviation (SD) increase in 1-arachidonoyl-GPA (20:4) was significantly associated with 32% high odds of asthma after accounting for clinical risk factors (p = 6.27 × 10⁻⁵), and per SD of the green module, constructed using weighted gene co-expression network, was suggestively associated with 25% high odds of asthma (p = 0.006). In the stratified analyses by sex and Hispanic and/or Latino backgrounds, the effect of 1-arachidonoyl-GPA (20:4) and the green module was predominantly observed in women (OR = 1.24 and 1.37, p < 0.001) and people of Cuban and Puerto-Rican backgrounds (OR = 1.25 and 1.27, p < 0.01). Mutations in Fatty Acid Desaturase 2 (FADS2) affected the levels of 1-arachidonoyl-GPA (20:4), and Mendelian Randomization analyses revealed that high genetically regulated 1-arachidonoyl-GPA (20:4) levels were associated with increased odds of asthma (p < 0.001). The findings reinforce a molecular basis for asthma etiology, and the potential causal effect of 1-arachidonoyl-GPA (20:4) on asthma provides an opportunity for future intervention. Full article

(This article belongs to the Special Issue Metabolomics of Complex Traits II)

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9 pages, 1054 KiB

Open AccessArticle

ProBDNF as an Indicator of Improvement among Women with Depressive Episodes

by Weronika Zwolińska, Maria Skibinska, Agnieszka Słopień and Monika Dmitrzak-Węglarz

Metabolites 2022, 12(4), 358; https://doi.org/10.3390/metabo12040358 - 16 Apr 2022

Cited by 3 | Viewed by 2211

Abstract

Depression is a chronic psychiatric disorder with a heavy socioeconomic burden. Studies on biomarkers are needed to comprehend the pathophysiology of depression and to improve treatment outcomes. Research points to the importance of imbalance between mature brain-derived neurotrophic factor (BDNF) and its precursor, [...] Read more.

Depression is a chronic psychiatric disorder with a heavy socioeconomic burden. Studies on biomarkers are needed to comprehend the pathophysiology of depression and to improve treatment outcomes. Research points to the importance of imbalance between mature brain-derived neurotrophic factor (BDNF) and its precursor, pro–brain–derived neurotrophic factor (proBDNF), in the pathophysiology of mood disorders and the potential neurodegenerative role of calcium-binding protein B (S100B). Our objective was to compare BDNF, proBDNF, and S100B serum levels before and after the treatment of acute depressive episodes and to assess their correlation with the severity of symptoms and history of stress. We also aimed to investigate the differences in BDNF, proBDNF, and S100B levels between depression in the course of bipolar disorder (BD) and major depressive disorder (MDD). We recruited 31 female patients diagnosed with BD or MDD who were hospitalized due to current depressive episodes. The patients had their serum BDNF, proBDNF, and S100B levels evaluated using the ELISA method upon admission and after the symptoms improved, at discharge. We found that proBDNF levels decreased significantly with the treatment (p = 0.0478), while BDNF and S100B levels were not altered significantly. No differences in biochemical parameters between MDD and BD subjects were observed. Consequently, we concluded that a decrease in serum proBDNF levels could be considered a biomarker of recovery from depressive episodes. Full article

(This article belongs to the Special Issue Altered Metabolism in Depressive Disorders)

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20 pages, 18194 KiB

Open AccessReview

Guide to Metabolomics Analysis: A Bioinformatics Workflow

by Yang Chen, En-Min Li and Li-Yan Xu

Metabolites 2022, 12(4), 357; https://doi.org/10.3390/metabo12040357 - 15 Apr 2022

Cited by 107 | Viewed by 21861

Abstract

Metabolomics is an emerging field that quantifies numerous metabolites systematically. The key purpose of metabolomics is to identify the metabolites corresponding to each biological phenotype, and then provide an analysis of the mechanisms involved. Although metabolomics is important to understand the involved biological [...] Read more.

Metabolomics is an emerging field that quantifies numerous metabolites systematically. The key purpose of metabolomics is to identify the metabolites corresponding to each biological phenotype, and then provide an analysis of the mechanisms involved. Although metabolomics is important to understand the involved biological phenomena, the approach’s ability to obtain an exhaustive description of the processes is limited. Thus, an analysis-integrated metabolomics, transcriptomics, proteomics, and other omics approach is recommended. Such integration of different omics data requires specialized statistical and bioinformatics software. This review focuses on the steps involved in metabolomics research and summarizes several main tools for metabolomics analyses. We also outline the most abnormal metabolic pathways in several cancers and diseases, and discuss the importance of multi-omics integration algorithms. Overall, our goal is to summarize the current metabolomics analysis workflow and its main analysis software to provide useful insights for researchers to establish a preferable pipeline of metabolomics or multi-omics analysis. Full article

(This article belongs to the Section Bioinformatics and Data Analysis)

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15 pages, 1434 KiB

Open AccessSystematic Review

Metabolites Associated with Memory and Gait: A Systematic Review

by Qu Tian, Brendan A. Mitchell, Abigail E. Corkum, Ruin Moaddel and Luigi Ferrucci

Metabolites 2022, 12(4), 356; https://doi.org/10.3390/metabo12040356 - 15 Apr 2022

Cited by 8 | Viewed by 2335

Abstract

We recently found that dual decline in memory and gait speed was consistently associated with an increased risk of dementia compared to decline in memory or gait only or no decline across six aging cohorts. The mechanisms underlying this relationship are unknown. We [...] Read more.

We recently found that dual decline in memory and gait speed was consistently associated with an increased risk of dementia compared to decline in memory or gait only or no decline across six aging cohorts. The mechanisms underlying this relationship are unknown. We hypothesize that individuals who experience dual decline may have specific pathophysiological pathways to dementia which can be indicated by specific metabolomic signatures. Here, we summarize blood-based metabolites that are associated with memory and gait from existing literature and discuss their relevant pathways. A total of 39 eligible studies were included in this systematic review. Metabolites that were associated with memory and gait belonged to five shared classes: sphingolipids, fatty acids, phosphatidylcholines, amino acids, and biogenic amines. The sphingolipid metabolism pathway was found to be enriched in both memory and gait impairments. Existing data may suggest that metabolites from sphingolipids and the sphingolipid metabolism pathway are important for both memory and gait impairments. Future studies using empirical data across multiple cohorts are warranted to identify metabolomic signatures of dual decline in memory and gait and to further understand its relationship with future dementia risk. Full article

(This article belongs to the Section Lipid Metabolism)

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11 pages, 2347 KiB

Open AccessArticle

High Correlation among Brain-Derived Major Protein Levels in Cerebrospinal Fluid: Implication for Amyloid-Beta and Tau Protein Changes in Alzheimer’s Disease

by Kyoka Hoshi, Mayumi Kanno, Mitsunari Abe, Takenobu Murakami, Yoshikazu Ugawa, Aya Goto, Takashi Honda, Takashi Saito, Takaomi C. Saido, Yoshiki Yamaguchi, Masakazu Miyajima, Katsutoshi Furukawa, Hiroyuki Arai and Yasuhiro Hashimoto

Metabolites 2022, 12(4), 355; https://doi.org/10.3390/metabo12040355 - 15 Apr 2022

Cited by 3 | Viewed by 2920 | Correction

Abstract

The cerebrospinal fluid (CSF) plays an important role in homeostasis of the brain. We previously demonstrated that major CSF proteins such as lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin (Tf) that are biosynthesized in the brain could be biomarkers of altered CSF production. [...] Read more.

The cerebrospinal fluid (CSF) plays an important role in homeostasis of the brain. We previously demonstrated that major CSF proteins such as lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin (Tf) that are biosynthesized in the brain could be biomarkers of altered CSF production. Here we report that the levels of these brain-derived CSF proteins correlated well with each other across various neurodegenerative diseases, including Alzheimer’s disease (AD). In addition, protein levels tended to be increased in the CSF samples of AD patients compared with the other diseases. Patients at memory clinics were classified into three categories, consisting of AD (n = 61), mild cognitive impairment (MCI) (n = 42), and cognitively normal (CN) (n = 23), with MMSE scores of 20.4 ± 4.2, 26.9 ± 1.7, and 29.0 ± 1.6, respectively. In each category, CSF protein levels were highly correlated with each other. In CN subjects, increased CSF protein levels correlated well with those of AD markers, including amyloid-β and tau protein, whereas in MCI and AD subjects, correlations declined with AD markers except p-tau. Future follow-up on each clinical subject may provide a clue that the CSF proteins would be AD-related biomarkers. Full article

(This article belongs to the Special Issue Metabolite Profiles Analysis to Elucidate Candidate Biomarkers that Associate with Cognition)

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14 pages, 4225 KiB

Open AccessArticle

TRACES: A Lightweight Browser for Liquid Chromatography–Multiple Reaction Monitoring–Mass Spectrometry Chromatograms

by Yoshihiro Kita, Suzumi M. Tokuoka, Yoshiya Oda and Takao Shimizu

Metabolites 2022, 12(4), 354; https://doi.org/10.3390/metabo12040354 - 15 Apr 2022

Cited by 4 | Viewed by 2601

Abstract

In targeted metabolomic analysis using liquid chromatography–multiple reaction monitoring–mass spectrometry (LC-MRM-MS), hundreds of MRMs are performed in a single run, yielding a large dataset containing thousands of chromatographic peaks. Automation tools for processing large MRM datasets have been reported, but a visual review [...] Read more.

In targeted metabolomic analysis using liquid chromatography–multiple reaction monitoring–mass spectrometry (LC-MRM-MS), hundreds of MRMs are performed in a single run, yielding a large dataset containing thousands of chromatographic peaks. Automation tools for processing large MRM datasets have been reported, but a visual review of chromatograms is still critical, as real samples with biological matrices often cause complex chromatographic patterns owing to non-specific, insufficiently separated, isomeric, and isotopic components. Herein, we report the development of new software, TRACES, a lightweight chromatogram browser for MRM-based targeted LC-MS analysis. TRACES provides rapid access to all MRM chromatograms in a dataset, allowing users to start ad hoc data browsing without preparations such as loading compound libraries. As a special function of the software, we implemented a chromatogram-level deisotoping function that facilitates the identification of regions potentially affected by isotopic signals. Using MRM libraries containing precursor and product formulae, the algorithm reveals all possible isotopic interferences in the dataset and generates deisotoped chromatograms. To validate the deisotoping function in real applications, we analyzed mouse tissue phospholipids in which isotopic interference by molecules with different fatty-acyl unsaturation levels is known. TRACES successfully removed isotopic signals within the MRM chromatograms, helping users avoid inappropriate regions for integration. Full article

(This article belongs to the Special Issue Metabolomics Data Analysis and Quality Assessment)

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18 pages, 2253 KiB

Open AccessArticle

Identification of Metabolomic Biomarkers of Long-Term Stress Using NMR Spectroscopy in a Diving Duck

by Asha Perera, Catherine Soos and Karen Machin

Metabolites 2022, 12(4), 353; https://doi.org/10.3390/metabo12040353 - 15 Apr 2022

Viewed by 2105

Abstract

Human-induced environmental changes that act as long-term stressors pose significant impacts on wildlife health. Energy required for maintenance or other functions may be re-routed towards coping with stressors, ultimately resulting in fluctuations in metabolite levels associated with energy metabolism. While metabolomics approaches are [...] Read more.

Human-induced environmental changes that act as long-term stressors pose significant impacts on wildlife health. Energy required for maintenance or other functions may be re-routed towards coping with stressors, ultimately resulting in fluctuations in metabolite levels associated with energy metabolism. While metabolomics approaches are used increasingly to study environmental stressors, its use in studying stress in birds is in its infancy. We implanted captive lesser scaup (Aythya affinis) with either a biodegradable corticosterone (CORT) pellet to mimic the effects of a prolonged stressor or a placebo pellet. 1D ¹H nuclear magnetic resonance (NMR) spectroscopy was performed on serum samples collected over 20 days after implant surgery. We hypothesized that CORT pellet-induced physiological stress would alter energy metabolism and result in distinct metabolite profiles in ducks compared with placebo (control). Quantitative targeted metabolite analysis revealed that metabolites related to energy metabolism: glucose, formate, lactate, glutamine, 3-hydroxybutyrate, ethanolamine, indole-3- acetate, and threonine differentiated ducks with higher circulatory CORT from controls on day 2. These metabolites function as substrates or intermediates in metabolic pathways related to energy production affected by elevated serum CORT. The use of metabolomics shows promise as a novel tool to identify and characterize physiological responses to stressors in wild birds. Full article

(This article belongs to the Special Issue Metabolites Focused on Wildlife and Conservation Biology)

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17 pages, 3669 KiB

Open AccessReview

Old but New: Group IIA Phospholipase A₂ as a Modulator of Gut Microbiota

by Yoshitaka Taketomi, Yoshimi Miki and Makoto Murakami

Metabolites 2022, 12(4), 352; https://doi.org/10.3390/metabo12040352 - 14 Apr 2022

Cited by 13 | Viewed by 3405

Abstract

Among the phospholipase A₂ (PLA₂) superfamily, the secreted PLA₂ (sPLA₂) family contains 11 mammalian isoforms that exhibit unique tissue or cellular distributions and enzymatic properties. Current studies using sPLA₂-deficient or -overexpressed mouse strains, along with [...] Read more.

Among the phospholipase A₂ (PLA₂) superfamily, the secreted PLA₂ (sPLA₂) family contains 11 mammalian isoforms that exhibit unique tissue or cellular distributions and enzymatic properties. Current studies using sPLA₂-deficient or -overexpressed mouse strains, along with mass spectrometric lipidomics to determine sPLA₂-driven lipid pathways, have revealed the diverse pathophysiological roles of sPLA₂s in various biological events. In general, individual sPLA₂s exert their specific functions within tissue microenvironments, where they are intrinsically expressed through hydrolysis of extracellular phospholipids. Recent studies have uncovered a new aspect of group IIA sPLA₂ (sPLA₂-IIA), a prototypic sPLA₂ with the oldest research history among the mammalian PLA₂s, as a modulator of the gut microbiota. In the intestine, Paneth cell-derived sPLA₂-IIA acts as an antimicrobial protein to shape the gut microbiota, thereby secondarily affecting inflammation, allergy, and cancer in proximal and distal tissues. Knockout of intestinal sPLA₂-IIA in BALB/c mice leads to alterations in skin cancer, psoriasis, and anaphylaxis, while overexpression of sPLA₂-IIA in Pla2g2a-null C57BL/6 mice induces systemic inflammation and exacerbates arthritis. These phenotypes are associated with notable changes in gut microbiota and fecal metabolites, are variable in different animal facilities, and are abrogated after antibiotic treatment, co-housing, or fecal transfer. These studies open a new mechanistic action of this old sPLA₂ and add the sPLA₂ family to the growing list of endogenous factors capable of affecting the microbe–host interaction and thereby systemic homeostasis and diseases. Full article

(This article belongs to the Special Issue Multipurpose Enzymes in Lipid Metabolism)

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18 pages, 1765 KiB

Open AccessArticle

Untargeted Metabolomics of Slc13a5 Deficiency Reveal Critical Liver–Brain Axis for Lipid Homeostasis

by Sofia Milosavljevic, Kevin E. Glinton, Xiqi Li, Cláudia Medeiros, Patrick Gillespie, John R. Seavitt, Brett H. Graham and Sarah H. Elsea

Metabolites 2022, 12(4), 351; https://doi.org/10.3390/metabo12040351 - 14 Apr 2022

Cited by 8 | Viewed by 3541

Abstract

Though biallelic variants in SLC13A5 are known to cause severe encephalopathy, the mechanism of this disease is poorly understood. SLC13A5 protein deficiency reduces citrate transport into the cell. Downstream abnormalities in fatty acid synthesis and energy generation have been described, though biochemical signs [...] Read more.

Though biallelic variants in SLC13A5 are known to cause severe encephalopathy, the mechanism of this disease is poorly understood. SLC13A5 protein deficiency reduces citrate transport into the cell. Downstream abnormalities in fatty acid synthesis and energy generation have been described, though biochemical signs of these perturbations are inconsistent across SLC13A5 deficiency patients. To investigate SLC13A5-related disorders, we performed untargeted metabolic analyses on the liver, brain, and serum from a Slc13a5-deficient mouse model. Metabolomic data were analyzed using the connect-the-dots (CTD) methodology and were compared to plasma and CSF metabolomics from SLC13A5-deficient patients. Mice homozygous for the Slc13a5^tm1b/tm1b null allele had perturbations in fatty acids, bile acids, and energy metabolites in all tissues examined. Further analyses demonstrated that for several of these molecules, the ratio of their relative tissue concentrations differed widely in the knockout mouse, suggesting that deficiency of Slc13a5 impacts the biosynthesis and flux of metabolites between tissues. Similar findings were observed in patient biofluids, indicating altered transport and/or flux of molecules involved in energy, fatty acid, nucleotide, and bile acid metabolism. Deficiency of SLC13A5 likely causes a broader state of metabolic dysregulation than previously recognized, particularly regarding lipid synthesis, storage, and metabolism, supporting SLC13A5 deficiency as a lipid disorder. Full article

(This article belongs to the Special Issue I'm Not Dead Yet in Metabolic Regulation)

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30 pages, 2026 KiB

Open AccessReview

Reprogramming of Fatty Acid Metabolism in Gynaecological Cancers: Is There a Role for Oestradiol?

by Azilleo Kristo Mozihim, Ivy Chung, Nur Akmarina B. M. Said and Amira Hajirah Abd Jamil

Metabolites 2022, 12(4), 350; https://doi.org/10.3390/metabo12040350 - 14 Apr 2022

Cited by 7 | Viewed by 3422

Abstract

Gynaecological cancers are among the leading causes of cancer-related death among women worldwide. Cancer cells undergo metabolic reprogramming to sustain the production of energy and macromolecules required for cell growth, division and survival. Emerging evidence has provided significant insights into the integral role [...] Read more.

Gynaecological cancers are among the leading causes of cancer-related death among women worldwide. Cancer cells undergo metabolic reprogramming to sustain the production of energy and macromolecules required for cell growth, division and survival. Emerging evidence has provided significant insights into the integral role of fatty acids on tumourigenesis, but the metabolic role of high endogenous oestrogen levels and increased gynaecological cancer risks, notably in obesity, is less understood. This is becoming a renewed research interest, given the recently established association between obesity and incidence of many gynaecological cancers, including breast, ovarian, cervical and endometrial cancers. This review article, hence, comprehensively discusses how FA metabolism is altered in these gynaecological cancers, highlighting the emerging role of oestradiol on the actions of key regulatory enzymes of lipid metabolism, either directly through its classical ER pathways, or indirectly via the IGIFR pathway. Given the dramatic rise in obesity and parallel increase in the prevalence of gynaecological cancers among premenopausal women, further clarifications of the complex mechanisms underpinning gynaecological cancers are needed to inform future prevention efforts. Hence, in our review, we also highlight opportunities where metabolic dependencies can be exploited as viable therapeutic targets for these hormone-responsive cancers. Full article

(This article belongs to the Special Issue Cancer Associated Changes in Metabolism)

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10 pages, 1983 KiB

Open AccessArticle

N-Chlorotaurine Reduces the Lung and Systemic Inflammation in LPS-Induced Pneumonia in High Fat Diet-Induced Obese Mice

by Nguyen Khanh Hoang, Eiji Maegawa, Shigeru Murakami, Stephen W. Schaffer and Takashi Ito

Metabolites 2022, 12(4), 349; https://doi.org/10.3390/metabo12040349 - 14 Apr 2022

Cited by 7 | Viewed by 2653

Abstract

Lung infection can evoke pulmonary and systemic inflammation, which is associated with systemic severe symptoms, such as skeletal muscle wasting. While N-chlorotaurine (also known as taurine chloramine; TauCl) has anti-inflammatory effects in cells, its effects against pulmonary and systemic inflammation after lung [...] Read more.

Lung infection can evoke pulmonary and systemic inflammation, which is associated with systemic severe symptoms, such as skeletal muscle wasting. While N-chlorotaurine (also known as taurine chloramine; TauCl) has anti-inflammatory effects in cells, its effects against pulmonary and systemic inflammation after lung infection has not been elucidated. In the present study, we evaluated the anti-inflammatory effect of the taurine derivative, TauCl against Escherichia coli-derived lipopolysaccharide (LPS)-induced pneumonia in obese mice maintained on a high fat diet. In this study, TauCl was injected intraperitoneally 1 h before intratracheal LPS administration. While body weight was decreased by 7.5% after LPS administration, TauCl treatment suppressed body weight loss. TauCl also attenuated the increase in lung weight due to lung edema. While LPS-induced acute pneumonia caused an increase in cytokine/chemokine mRNA expression, including that of IL-1β, -6, TNF-α, MCP-1, TauCl treatment attenuated IL-6, and TNF-alpha expression, but not IL-1β and MCP-1. TauCl treatment partly attenuated the elevation of the serum cytokines. Furthermore, TauCl treatment alleviated skeletal muscle wasting. Importantly, LPS-induced expression of Atrogin-1, MuRF1 and IκB, direct or indirect targets for NFκB, were suppressed by TauCl treatment. These findings suggest that intraperitoneal TauCl treatment attenuates acute pneumonia-related pulmonary and systemic inflammation, including muscle wasting, in vivo. Full article

(This article belongs to the Special Issue Regulation and Effect of Taurine on Metabolism)

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20 pages, 962 KiB

Open AccessReview

Advances in Cell Engineering of the Komagataella phaffii Platform for Recombinant Protein Production

by Cristina Bustos, Johan Quezada, Rhonda Veas, Claudia Altamirano, Stephanie Braun-Galleani, Patrick Fickers and Julio Berrios

Metabolites 2022, 12(4), 346; https://doi.org/10.3390/metabo12040346 - 14 Apr 2022

Cited by 23 | Viewed by 4676

Abstract

Komagataella phaffii (formerly known as Pichia pastoris) has become an increasingly important microorganism for recombinant protein production. This yeast species has gained high interest in an industrial setting for the production of a wide range of proteins, including enzymes and biopharmaceuticals. During [...] Read more.

Komagataella phaffii (formerly known as Pichia pastoris) has become an increasingly important microorganism for recombinant protein production. This yeast species has gained high interest in an industrial setting for the production of a wide range of proteins, including enzymes and biopharmaceuticals. During the last decades, relevant bioprocess progress has been achieved in order to increase recombinant protein productivity and to reduce production costs. More recently, the improvement of cell features and performance has also been considered for this aim, and promising strategies with a direct and substantial impact on protein productivity have been reported. In this review, cell engineering approaches including metabolic engineering and energy supply, transcription factor modulation, and manipulation of routes involved in folding and secretion of recombinant protein are discussed. A lack of studies performed at the higher-scale bioreactor involving optimisation of cultivation parameters is also evidenced, which highlights new research aims to be considered. Full article

(This article belongs to the Special Issue Microbial Metabolic Engineering)

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15 pages, 1851 KiB

Open AccessArticle

Modeling the Amino Acid Effect on Glucagon Secretion from Pancreatic Alpha Cells

by Jan Zmazek, Vladimir Grubelnik, Rene Markovič and Marko Marhl

Metabolites 2022, 12(4), 348; https://doi.org/10.3390/metabo12040348 - 13 Apr 2022

Cited by 3 | Viewed by 2684

Abstract

Type 2 Diabetes Mellitus (T2DM) is a burdensome problem in modern society, and intensive research is focused on better understanding the underlying cellular mechanisms of hormone secretion for blood glucose regulation. T2DM is a bi-hormonal disease, and in addition to 100 years of [...] Read more.

Type 2 Diabetes Mellitus (T2DM) is a burdensome problem in modern society, and intensive research is focused on better understanding the underlying cellular mechanisms of hormone secretion for blood glucose regulation. T2DM is a bi-hormonal disease, and in addition to 100 years of increasing knowledge about the importance of insulin, the second hormone glucagon, secreted by pancreatic alpha cells, is becoming increasingly important. We have developed a mathematical model for glucagon secretion that incorporates all major metabolic processes of glucose, fatty acids, and glutamine as the most abundant postprandial amino acid in blood. In addition, we consider cAMP signaling in alpha cells. The model predictions quantitatively estimate the relative importance of specific metabolic and signaling pathways and particularly emphasize the important role of glutamine in promoting glucagon secretion, which is in good agreement with known experimental data. Full article

(This article belongs to the Section Bioinformatics and Data Analysis)

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15 pages, 1913 KiB

Open AccessArticle

Prenatal Supplementation in Beef Cattle and Its Effects on Plasma Metabolome of Dams and Calves

by Fernando José Schalch Junior, Guilherme Henrique Gebim Polizel, Fernando Augusto Correia Queiroz Cançado, Arícia Christofaro Fernandes, Isabela Mortari, Pedro Ratto Lisboa Pires, Heidge Fukumasu, Miguel Henrique de Almeida Santana and Arlindo Saran Netto

Metabolites 2022, 12(4), 347; https://doi.org/10.3390/metabo12040347 - 13 Apr 2022

Cited by 16 | Viewed by 2728

Abstract

This study investigated the effect of different prenatal nutrition on the plasma metabolome of Nellore dams and their offspring. For that purpose, three nutritional treatments were used in 126 cows during pregnancy: NP—(control) only mineral supplementation; PP—protein-energy supplementation in the final third; and [...] Read more.

This study investigated the effect of different prenatal nutrition on the plasma metabolome of Nellore dams and their offspring. For that purpose, three nutritional treatments were used in 126 cows during pregnancy: NP—(control) only mineral supplementation; PP—protein-energy supplementation in the final third; and FP—protein-energy supplementation during the entire pregnancy. Targeted metabolomics were analyzed in plasma at the beginning of pregnancy and in pre-delivery of cows (n = 27) as well as in calves (n = 27, 30 ± 9.6 days of age). Data were analyzed by the analysis of variance, partial least squares discriminant analysis, and the principal component analysis (PCA). The PCA showed a clear clustering in the periods investigated only in cows (early gestation and pre-delivery). We found significant metabolites in both supervised analyses (p < 0.05 and VIP score > 1) for cows (Taurine, Glutamic acid, Histidine, and PC aa C42:2) and for calves (Carnosine, Alanine, and PC aa C26:0). The enrichment analysis revealed biological processes (p < 0.1) common among cows and calves (histidine metabolism and beta-alanine metabolism), which may be indicative of transgenerational epigenetic changes. In general, fetal programming affected mainly the metabolism of amino acids. Full article

(This article belongs to the Special Issue Insights into Increasing Meat Production Using Omics Technologies)

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14 pages, 2684 KiB

Open AccessArticle

Synthesis of Human Phase I and Phase II Metabolites of Hop (Humulus lupulus) Prenylated Flavonoids

by Lance Buckett, Sabrina Schönberger, Veronika Spindler, Nadine Sus, Christian Schoergenhofer, Jan Frank, Oliver Frank and Michael Rychlik

Metabolites 2022, 12(4), 345; https://doi.org/10.3390/metabo12040345 - 12 Apr 2022

Cited by 5 | Viewed by 4147

Abstract

Hop prenylated flavonoids have been investigated for their in vivo activities due to their broad spectrum of positive health effects. Previous studies on the metabolism of xanthohumol using untargeted methods have found that it is first degraded into 8-prenylnaringenin and 6-prenylnaringenin, by spontaneous [...] Read more.

Hop prenylated flavonoids have been investigated for their in vivo activities due to their broad spectrum of positive health effects. Previous studies on the metabolism of xanthohumol using untargeted methods have found that it is first degraded into 8-prenylnaringenin and 6-prenylnaringenin, by spontaneous cyclisation into isoxanthohumol, and subsequently demethylated by gut bacteria. Further combinations of metabolism by hydroxylation, sulfation, and glucuronidation result in an unknown number of isomers. Most investigations involving the analysis of prenylated flavonoids used surrogate or untargeted approaches in metabolite identification, which is prone to errors in absolute identification. Here, we present a synthetic approach to obtaining reference standards for the identification of human xanthohumol metabolites. The synthesised metabolites were subsequently analysed by qTOF LC-MS/MS, and some were matched to a human blood sample obtained after the consumption of 43 mg of micellarised xanthohumol. Additionally, isomers of the reference standards were identified due to their having the same mass fragmentation pattern and different retention times. Overall, the methods unequivocally identified the metabolites of xanthohumol that are present in the blood circulatory system. Lastly, in vitro bioactive testing should be applied using metabolites and not original compounds, as free compounds are scarcely found in human blood. Full article

(This article belongs to the Section Nutrition and Metabolism)

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16 pages, 755 KiB

Open AccessReview

Role of Polyamines and Hypusine in β Cells and Diabetes Pathogenesis

by Abhishek Kulkarni, Cara M. Anderson, Raghavendra G. Mirmira and Sarah A. Tersey

Metabolites 2022, 12(4), 344; https://doi.org/10.3390/metabo12040344 - 12 Apr 2022

Cited by 22 | Viewed by 5548

Abstract

The polyamines—putrescine, spermidine, and spermine—are polycationic, low molecular weight amines with cellular functions primarily related to mRNA translation and cell proliferation. Polyamines partly exert their effects via the hypusine pathway, wherein the polyamine spermidine provides the aminobutyl moiety to allow posttranslational modification of [...] Read more.

The polyamines—putrescine, spermidine, and spermine—are polycationic, low molecular weight amines with cellular functions primarily related to mRNA translation and cell proliferation. Polyamines partly exert their effects via the hypusine pathway, wherein the polyamine spermidine provides the aminobutyl moiety to allow posttranslational modification of the translation factor eIF5A with the rare amino acid hypusine (hydroxy putrescine lysine). The “hypusinated” eIF5A (eIF5A^hyp) is considered to be the active form of the translation factor necessary for the translation of mRNAs associated with stress and inflammation. Recently, it has been demonstrated that activity of the polyamines-hypusine circuit in insulin-producing islet β cells contributes to diabetes pathogenesis under conditions of inflammation. Elevated levels of polyamines are reported in both exocrine and endocrine cells of the pancreas, which may contribute to endoplasmic reticulum stress, oxidative stress, inflammatory response, and autophagy. In this review, we have summarized the existing research on polyamine-hypusine metabolism in the context of β-cell function and diabetes pathogenesis. Full article

(This article belongs to the Special Issue The Role of β Cells in Diabetes)

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15 pages, 15297 KiB

Open AccessReview

Metabolites and Biomarker Compounds of Neurodegenerative Diseases in Cerebrospinal Fluid

by Keiji Wakamatsu, Yoichi Chiba, Ryuta Murakami, Yumi Miyai, Koichi Matsumoto, Masaki Kamada, Wakako Nonaka, Naoya Uemura, Ken Yanase and Masaki Ueno

Metabolites 2022, 12(4), 343; https://doi.org/10.3390/metabo12040343 - 12 Apr 2022

Cited by 12 | Viewed by 3534

Abstract

Despite recent advances in diagnostic procedures for neurological disorders, it is still difficult to definitively diagnose some neurodegenerative diseases without neuropathological examination of autopsied brain tissue. As pathological processes in the brain are frequently reflected in the components of cerebrospinal fluid (CSF), CSF [...] Read more.

Despite recent advances in diagnostic procedures for neurological disorders, it is still difficult to definitively diagnose some neurodegenerative diseases without neuropathological examination of autopsied brain tissue. As pathological processes in the brain are frequently reflected in the components of cerebrospinal fluid (CSF), CSF samples are sometimes useful for diagnosis. After CSF is secreted from the choroid plexus epithelial cells in the ventricles, some flows in the brain, some is mixed with intracerebral interstitial fluid, and some is excreted through two major drainage pathways, i.e., the intravascular periarterial drainage pathway and the glymphatic system. Accordingly, substances produced by metabolic and pathological processes in the brain may be detectable in CSF. Many papers have reported changes in the concentration of substances in the CSF of patients with metabolic and neurological disorders, some of which can be useful biomarkers of the disorders. In this paper, we show the significance of glucose- and neurotransmitter-related CSF metabolites, considering their transporters in the choroid plexus; summarize the reported candidates of CSF biomarkers for neurodegenerative diseases, including amyloid-β, tau, α-synuclein, microRNAs, and mitochondrial DNA; and evaluate their potential as efficient diagnostic tools. Full article

(This article belongs to the Special Issue Cerebrospinal Fluid Biomarkers for Understanding Disease Pathogenesis)

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14 pages, 822 KiB

Open AccessReview

Effects of Arachidonic Acid and Its Metabolites on Functional Beta-Cell Mass

by Karin J. Bosma, Cecilia E. Kaiser, Michelle E. Kimple and Maureen Gannon

Metabolites 2022, 12(4), 342; https://doi.org/10.3390/metabo12040342 - 12 Apr 2022

Cited by 22 | Viewed by 3997

Abstract

Arachidonic acid (AA) is a polyunsaturated 20-carbon fatty acid present in phospholipids in the plasma membrane. The three primary pathways by which AA is metabolized are mediated by cyclooxygenase (COX) enzymes, lipoxygenase (LOX) enzymes, and cytochrome P450 (CYP) enzymes. These three pathways produce [...] Read more.

Arachidonic acid (AA) is a polyunsaturated 20-carbon fatty acid present in phospholipids in the plasma membrane. The three primary pathways by which AA is metabolized are mediated by cyclooxygenase (COX) enzymes, lipoxygenase (LOX) enzymes, and cytochrome P450 (CYP) enzymes. These three pathways produce eicosanoids, lipid signaling molecules that play roles in biological processes such as inflammation, pain, and immune function. Eicosanoids have been demonstrated to play a role in inflammatory, renal, and cardiovascular diseases as well type 1 and type 2 diabetes. Alterations in AA release or AA concentrations have been shown to affect insulin secretion from the pancreatic beta cell, leading to interest in the role of AA and its metabolites in the regulation of beta-cell function and maintenance of beta-cell mass. In this review, we discuss the metabolism of AA by COX, LOX, and CYP, the roles of these enzymes and their metabolites in beta-cell mass and function, and the possibility of targeting these pathways as novel therapies for treating diabetes. Full article

(This article belongs to the Special Issue The Role of β Cells in Diabetes)

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18 pages, 2246 KiB

Open AccessArticle

High Fructose and High Fat Diet Impair Different Types of Memory through Oxidative Stress in a Sex- and Hormone-Dependent Manner

by Edwin Chávez-Gutiérrez, Claudia Erika Fuentes-Venado, Lorena Rodríguez-Páez, Christian Guerra-Araiza, Carlos Larqué, Erick Martínez-Herrera, María Esther Ocharan-Hernández, Joel Lomelí, Marco A. Loza-Mejía, Juan Rodrigo Salazar, Dulce María Meneses-Ruiz, Juan Manuel Gallardo and Rodolfo Pinto-Almazán

Metabolites 2022, 12(4), 341; https://doi.org/10.3390/metabo12040341 - 12 Apr 2022

Cited by 5 | Viewed by 2873

Abstract

Metabolic syndrome (MetS) contributes to the spread of cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. Evaluation of sex- and hormone-dependent changes in body weight, blood pressure, blood lipids, oxidative stress markers, and alterations in different types of memory in Sprague–Dawley rats [...] Read more.

Metabolic syndrome (MetS) contributes to the spread of cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. Evaluation of sex- and hormone-dependent changes in body weight, blood pressure, blood lipids, oxidative stress markers, and alterations in different types of memory in Sprague–Dawley rats fed with a high fat and high fructose (HFHF) diet were evaluated. After 12 weeks of feeding the male and female rats with HFHF, body weight gain, increase in blood pressure, and generation of dyslipidemia compared to the animals fed with chow diet were observed. Regarding memory, it was noted that gonadectomy reverted the effects of HFHF in the 24 h novel object recognition task and in spatial learning/memory analyzed through Morris water maze, males being more affected than females. Nevertheless, gonadectomy did not revert long-term memory impairment in the passive avoidance task induced by HFHF nor in male or female rats. On the other hand, sex-hormone–diet interaction was observed in the plasma concentration of malondialdehyde and nitric oxide. These results suggest that the changes observed in the memory and learning of MetS animals are sex- and hormone-dependent and correlate to an increase in oxidative stress. Full article

(This article belongs to the Special Issue Frontiers in the Study of Metabolic Diseases Using Rodent Models)

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10 pages, 2112 KiB

Open AccessBrief Report

Serum Cholesteryl Ester Transfer Protein (CETP) and Sortilin (SORT) in Patients with Psoriasis with Relation to Systemic Treatment

by Julia Nowowiejska, Anna Baran, Julita A. Krahel, Tomasz W. Kamiński, Magdalena Maciaszek and Iwona Flisiak

Metabolites 2022, 12(4), 340; https://doi.org/10.3390/metabo12040340 - 9 Apr 2022

Cited by 3 | Viewed by 2021

Abstract

Psoriasis is a common inflammatory skin disease, which is tightly associated with metabolic disorders. Cholesteryl ester transfer protein (CETP) and sortilin (SORT) are molecules engaged in lipid metabolism of proatherogenic properties. They have been hardly ever studied in psoriasis before. Serum CETP and [...] Read more.

Psoriasis is a common inflammatory skin disease, which is tightly associated with metabolic disorders. Cholesteryl ester transfer protein (CETP) and sortilin (SORT) are molecules engaged in lipid metabolism of proatherogenic properties. They have been hardly ever studied in psoriasis before. Serum CETP and SORT concentrations were measured in 33 patients with plaque-type psoriasis before and after 12 weeks of treatment with methotrexate or acitretin. There was no significant difference in CEPT and SORT serum concentrations between patients and controls. Positive correlations between CETP after the treatment with acitretin and activity of transaminases (R = 0.65, R = 0.56, respectively) were noted. CETP was positively related with triglycerides (R = 0.49), glucose (R = 0.54) and CRP (R = 0.64) before the treatment with methotrexate, which all disappeared afterwards. Systemic therapy with methotrexate caused normalization of SORT concentration. There was significant correlation between SORT and WBC (p < 0.01) and CRP (p < 0.05). CETP and SORT cannot be used as individual biomarkers. Nevertheless, they show some interesting relations with other parameters. Increased concentration of CETP perhaps could investigated as a marker of liver side effects of acitretin treatment in psoriatics. SORT could be considered as a new indicator of metabolically induced inflammation in psoriasis. Methotrexate may be preferred in patients with high SORT concentrations. Further studies are needed to establish their exact role in psoriatic patients. Full article

(This article belongs to the Special Issue Metabolites for Screening and Evaluation of Cardiometabolic Risk)

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21 pages, 2611 KiB

Open AccessArticle

Metabolomic Abnormalities in Serum from Untreated and Treated Dogs with Hyper- and Hypoadrenocorticism

by Carolin Anna Imbery, Frank Dieterle, Claudia Ottka, Corinna Weber, Götz Schlotterbeck, Elisabeth Müller, Hannes Lohi and Urs Giger

Metabolites 2022, 12(4), 339; https://doi.org/10.3390/metabo12040339 - 9 Apr 2022

Cited by 2 | Viewed by 2975

Abstract

The adrenal glands play a major role in metabolic processes, and both excess and insufficient serum cortisol concentrations can lead to serious metabolic consequences. Hyper- and hypoadrenocorticism represent a diagnostic and therapeutic challenge. Serum samples from dogs with untreated hyperadrenocorticism (n = [...] Read more.

The adrenal glands play a major role in metabolic processes, and both excess and insufficient serum cortisol concentrations can lead to serious metabolic consequences. Hyper- and hypoadrenocorticism represent a diagnostic and therapeutic challenge. Serum samples from dogs with untreated hyperadrenocorticism (n = 27), hyperadrenocorticism undergoing treatment (n = 28), as well as with untreated (n = 35) and treated hypoadrenocorticism (n = 23) were analyzed and compared to apparently healthy dogs (n = 40). A validated targeted proton nuclear magnetic resonance (¹H NMR) platform was used to quantify 123 parameters. Principal component analysis separated the untreated endocrinopathies. The serum samples of dogs with untreated endocrinopathies showed various metabolic abnormalities with often contrasting results particularly in serum concentrations of fatty acids, and high- and low-density lipoproteins and their constituents, which were predominantly increased in hyperadrenocorticism and decreased in hypoadrenocorticism, while amino acid concentrations changed in various directions. Many observed serum metabolic abnormalities tended to normalize with medical treatment, but normalization was incomplete when compared to levels in apparently healthy dogs. Application of machine learning models based on the metabolomics data showed good classification, with misclassifications primarily observed in treated groups. Characterization of metabolic changes enhances our understanding of these endocrinopathies. Further assessment of the recognized incomplete reversal of metabolic alterations during medical treatment may improve disease management. Full article

(This article belongs to the Special Issue Metabolism and Diseases)

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10 pages, 241 KiB

Open AccessReview

The Impact of Mineral Supplementation on Polycystic Ovarian Syndrome

by Tahra ElObeid, Marwa Osman Awad, Vijay Ganji and Joyce Moawad

Metabolites 2022, 12(4), 338; https://doi.org/10.3390/metabo12040338 - 8 Apr 2022

Cited by 8 | Viewed by 4410

Abstract

Polycystic ovary syndrome (PCOS) is an endocrinopathy that is common among women of reproductive age. It is a heterogeneous disorder with an unknown etiology. Different strategies have been proposed for the treatment of PCOS. Recent studies recommend supplementation with specific minerals for treating [...] Read more.

Polycystic ovary syndrome (PCOS) is an endocrinopathy that is common among women of reproductive age. It is a heterogeneous disorder with an unknown etiology. Different strategies have been proposed for the treatment of PCOS. Recent studies recommend supplementation with specific minerals for treating various PCOS phenotypes. We searched PubMed, Google Scholar, and SCOPUS databases by using search terms combining PCOS with the supplementation of magnesium, zinc, selenium, or chromium. This review presents a narrative concerning the association between PCOS and magnesium, zinc, selenium, and chromium supplementation. We review findings from various randomized controlled trials and meta-analyses conducted in women of childbearing age with PCOS. Recent reports highlight the beneficial effect of minerals on the clinical and metabolic symptoms of PCOS. Further studies are required to establish the appropriate dosage level of these minerals for ameliorating the pathologies associated with PCOS because of the potential health risks linked with higher doses. Full article

(This article belongs to the Special Issue Human Reproductive Health and Metabolism)

16 pages, 3620 KiB

Open AccessArticle

Independent and Interactive Effects of Genetic Background and Sex on Tissue Metabolomes of Adipose, Skeletal Muscle, and Liver in Mice

by Ann E. Wells, William T. Barrington, Stephen Dearth, Nikhil Milind, Gregory W. Carter, David W. Threadgill, Shawn R. Campagna and Brynn H. Voy

Metabolites 2022, 12(4), 337; https://doi.org/10.3390/metabo12040337 - 8 Apr 2022

Cited by 1 | Viewed by 2772

Abstract

Genetics play an important role in the development of metabolic diseases. However, the relative influence of genetic variation on metabolism is not well defined, particularly in tissues, where metabolic dysfunction that leads to disease occurs. We used inbred strains of laboratory mice to [...] Read more.

Genetics play an important role in the development of metabolic diseases. However, the relative influence of genetic variation on metabolism is not well defined, particularly in tissues, where metabolic dysfunction that leads to disease occurs. We used inbred strains of laboratory mice to evaluate the impact of genetic variation on the metabolomes of tissues that play central roles in metabolic diseases. We chose a set of four common inbred strains that have different levels of susceptibility to obesity, insulin resistance, and other common metabolic disorders. At the ages used, and under standard husbandry conditions, these lines are not overtly diseased. Using global metabolomics profiling, we evaluated water-soluble metabolites in liver, skeletal muscle, and adipose from A/J, C57BL/6J, FVB/NJ, and NOD/ShiLtJ mice fed a standard mouse chow diet. We included both males and females to assess the relative influence of strain, sex, and strain-by-sex interactions on metabolomes. The mice were also phenotyped for systems level traits related to metabolism and energy expenditure. Strain explained more variation in the metabolite profile than did sex or its interaction with strain across each of the tissues, especially in liver. Purine and pyrimidine metabolism and pathways related to amino acid metabolism were identified as pathways that discriminated strains across all three tissues. Based on the results from ANOVA, sex and sex-by-strain interaction had modest influence on metabolomes relative to strain, suggesting that the tissue metabolome remains largely stable across sexes consuming the same diet. Our data indicate that genetic variation exerts a fundamental influence on tissue metabolism. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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