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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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11 pages, 431 KiB  
Review
Sex and Age Differences in the Impact of Metabolic Syndrome on Heart Failure Development
by Tae-Eun Kim, Do Young Kim, Hyeongsu Kim and Sung Hea Kim
Metabolites 2024, 14(12), 653; https://doi.org/10.3390/metabo14120653 - 25 Nov 2024
Cited by 1 | Viewed by 1109
Abstract
Metabolic syndrome (MetS), a cluster of metabolic dysregulations, is recognized as a significant risk factor for the development of heart failure (HF). The pathophysiological mechanisms linking MetS to HF are complex and multifaceted, with the components of MetS contributing to cardiac deterioration through [...] Read more.
Metabolic syndrome (MetS), a cluster of metabolic dysregulations, is recognized as a significant risk factor for the development of heart failure (HF). The pathophysiological mechanisms linking MetS to HF are complex and multifaceted, with the components of MetS contributing to cardiac deterioration through impaired myocardial energy metabolism, increased inflammation, and endothelial dysfunction. Numerous clinical studies have confirmed the relationship between MetS and HF. Multiple studies have demonstrated that the impact of MetS on HF varies by sex and age. Metabolic disorders, including MetS, have a greater impact on HF incidence in younger adults compared to the elderly population and in women compared to men. Although the reasons for these differences are not yet fully understood, recognizing the sex- and age-related variations is crucial for developing targeted strategies to prevent HF in individuals with MetS. Future research should continue to investigate the underlying mechanisms behind these variations and identify optimal management approaches that account for both sex and age in reducing HF risk. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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14 pages, 2796 KiB  
Article
Metabolic Aging as an Increased Risk for Chronic Obstructive Pulmonary Disease
by Claire J. Guo, Suneeta Godbole, Wassim W. Labaki, Katherine A. Pratte, Jeffrey L. Curtis, Robert Paine, Eric Hoffman, Meilan Han, Jill Ohar, Christopher Cooper, Katerina J. Kechris, Dawn L. DeMeo and Russell P. Bowler
Metabolites 2024, 14(12), 647; https://doi.org/10.3390/metabo14120647 - 21 Nov 2024
Viewed by 1763
Abstract
Background/Objectives: Both aging and chronic obstructive pulmonary disease (COPD) are strongly associated with changes in the metabolome; however, it is unknown whether there are common aging/COPD metabolomic signatures and if accelerated aging is associated with COPD. Methods: Plasma from 5704 subjects from the [...] Read more.
Background/Objectives: Both aging and chronic obstructive pulmonary disease (COPD) are strongly associated with changes in the metabolome; however, it is unknown whether there are common aging/COPD metabolomic signatures and if accelerated aging is associated with COPD. Methods: Plasma from 5704 subjects from the Genetic Epidemiology of COPD study (COPDGene) and 2449 subjects from Subpopulations and intermediate outcome measures in COPD study (SPIROMICS) were profiled using the Metabolon global metabolomics platform (1013 annotated metabolites). Post-bronchodilator spirometry measures of airflow obstruction (forced expiratory volume at one second (FEV1)/forced vital capacity (FVC) < 0.7) were used to define COPD. Elastic net regression was trained on never and former smokers with normal spirometry and no emphysema to create a metabolomic age score which was validated in SPIROMICS subjects. Results: Our metabolic age score was strongly associated with chronic age in the validation cohort (correlation coefficient = 0.8). COPD subjects with accelerated aging (>7 years difference between metabolic and actual age) had more severe disease compared with those who had decelerated aging (<−7 years difference between metabolic and actual age). COPD and aging metabolites were shared more than expected (p < 0.001), with amino acid and glutathione metabolism among pathways overrepresented. Conclusions: These findings suggest a common mechanism between aging and COPD and that COPD is associated with accelerated metabolic aging. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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19 pages, 14796 KiB  
Article
Effects of Ammonia Stress on Liver Tissue Structure, Enzyme Activities, and Metabolome of Juvenile Largemouth Bass Micropterus salmoides
by Decheng Pu, Zhengxi Wang, Jishu Zheng, Peiyuan Li, Xiuli Wei, Dongsheng Li, Lihong Gao, Lin Zhou and Yu Wang
Metabolites 2024, 14(12), 649; https://doi.org/10.3390/metabo14120649 - 21 Nov 2024
Cited by 1 | Viewed by 1212
Abstract
Background: Ammonia, a ubiquitous contaminant in aquatic ecosystems, poses multifaceted threats to fish species at elevated concentrations. Methods: In order to investigate the toxic effects of chronic ammonia stress on the liver of juvenile Micropterus salmoides, the present experiment was conducted to [...] Read more.
Background: Ammonia, a ubiquitous contaminant in aquatic ecosystems, poses multifaceted threats to fish species at elevated concentrations. Methods: In order to investigate the toxic effects of chronic ammonia stress on the liver of juvenile Micropterus salmoides, the present experiment was conducted to investigate the differences in changes in liver tissue structure, enzyme activities, and metabolomes after 28 days of ammonia exposure (0, 4, 8, and 16 mg/L). Results: The findings revealed that ammonia exposure induced significant oxidative stress in the liver, manifesting in decreased activities of antioxidant enzymes SOD and GSH-Px, elevated levels of GSH, GST, and MDA, and heightened activities of immune enzymes LZM, ALP, and ACP. An increase in ammonia concentration exacerbated liver tissue damage. Metabolome analysis further unveiled perturbations in liver metabolites of Micropterus salmoides exposed to ammonia, with Ala-His emerging as a potentially pivotal functional substance under chronic stress. Specifically, the 4 mg/L group responded to ammonia toxicity by augmenting GSH and L-Carnosine levels, the 8 mg/L group detoxified via upregulation of L-Glutamine, and the 16 mg/L group mitigated toxicity through the urea synthesis pathway. Conclusions: This research offers preliminary insights into the toxicological responses of Micropterus salmoides under chronic ammonia stress. It is suggested that the duration of ammonia concentration exceeding 4 mg/L in high-density aquaculture should not exceed 7 days. Full article
(This article belongs to the Section Environmental Metabolomics)
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21 pages, 6832 KiB  
Article
Identification of Spatial Specific Lipid Metabolic Signatures in Long-Standing Diabetic Kidney Disease
by Yiran Zhang, Hai-Long Piao and Di Chen
Metabolites 2024, 14(11), 641; https://doi.org/10.3390/metabo14110641 - 20 Nov 2024
Cited by 2 | Viewed by 1297
Abstract
Background: Diabetic kidney disease (DKD) is a major complication of diabetes leading to kidney failure. Methods: This study investigates lipid metabolism profiles of long-standing DKD (LDKD, diabetes duration > 10 years) by integrative analysis of available single-cell RNA sequencing and spatial multi-omics data [...] Read more.
Background: Diabetic kidney disease (DKD) is a major complication of diabetes leading to kidney failure. Methods: This study investigates lipid metabolism profiles of long-standing DKD (LDKD, diabetes duration > 10 years) by integrative analysis of available single-cell RNA sequencing and spatial multi-omics data (focusing on spatial continuity samples) from the Kidney Precision Medicine Project. Results: Two injured cell types, an injured thick ascending limb (iTAL) and an injured proximal tubule (iPT), were identified and significantly elevated in LDKD samples. Both iTAL and iPT exhibit increased lipid metabolic and biosynthetic activities and decreased lipid and fatty acid oxidative processes compared to TAL/PT cells. Notably, compared to PT, iPT shows significant upregulation of specific injury and fibrosis-related genes, including FSHR and BMP7. Meanwhile, comparing iTAL to TAL, inflammatory-related genes such as ANXA3 and IGFBP2 are significantly upregulated. Furthermore, spatial metabolomics analysis reveals regionally distributed clusters in the kidney and notably differentially expressed lipid metabolites, such as triglycerides, glycerophospholipids, and sphingolipids, particularly pronounced in the inner medullary regions. Conclusions: These findings provide an integrative description of the lipid metabolism landscape in LDKD, highlighting injury-associated cellular processes and potential molecular mechanisms. Full article
(This article belongs to the Special Issue New Analytical Techniques and Applications of Metabolomics and Lipidomics)
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13 pages, 1635 KiB  
Article
Modulation of Urea Transport Attenuates TLR2-Mediated Microglial Activation and Upregulates Microglial Metabolism In Vitro
by Najlaa A. Al-Thani, Dylan Zinck, Gavin S. Stewart and Derek A. Costello
Metabolites 2024, 14(11), 634; https://doi.org/10.3390/metabo14110634 - 17 Nov 2024
Cited by 4 | Viewed by 1390
Abstract
Background: Alzheimer’s disease (AD) is a neurodegenerative disorder traditionally characterised by the presence of amyloid beta (Aβ) plaques and neurofibrillary tau tangles in the brain. However, emerging research has highlighted additional metabolic hallmarks of AD pathology. These include the metabolic reprogramming of microglia [...] Read more.
Background: Alzheimer’s disease (AD) is a neurodegenerative disorder traditionally characterised by the presence of amyloid beta (Aβ) plaques and neurofibrillary tau tangles in the brain. However, emerging research has highlighted additional metabolic hallmarks of AD pathology. These include the metabolic reprogramming of microglia in favour of glycolysis over oxidative phosphorylation. This shift is attributed to an ‘M1′-like pro-inflammatory phenotype, which exacerbates neuroinflammation and contributes to neuronal damage. The urea cycle also presents as an altered metabolic pathway in AD, due to elevated urea levels and altered expression of urea cycle enzymes, metabolites, and transporters in the brain. However, to date, these changes remain largely unexplored. Methods: This study focuses on understanding the effects of extracellular urea and urea transporter-B (UT-B) inhibition on inflammatory changes in lipoteichoic acid (LTA)-stimulated BV2 microglia and on the viability of SH-SY5Y neuronal cells under oxidative stress and neurotoxic conditions. Results: In BV2 microglia, UT-B inhibition demonstrated a notable anti-inflammatory effect by reducing the formation of nitric oxide (NO) and the expression of tumour necrosis factor α (TNFα) and CCL2 in response to stimulation with the toll-like receptor (TLR)2 agonist, lipoteichoic acid (LTA). This was accompanied by a reduction in extracellular urea and upregulation of UT-B expression. The application of exogenous urea was also shown to mediate the inflammatory profile of BV2 cells in a similar manner but had only a modest impact on UT-B expression. While exposure to LTA alone did not alter the microglial metabolic profile, inhibition of UT-B upregulated the expression of genes associated with both glycolysis and fatty acid oxidation. Conversely, neither increased extracellular urea nor UT-B inhibition had a significant impact on cell viability or cytotoxicity in SH-SY5Y neurones exposed to oxidative stressors tert-butyl hydroperoxide (t-BHP) and 6-hydroxydopamine (6-OHDA). Conclusions: This study further highlights the involvement of urea transport in regulating the neuroinflammation associated with AD. Moreover, we reveal a novel role for UT-B in maintaining microglial metabolic homeostasis. Taken together, these findings contribute supporting evidence to the regulation of UT-B as a therapeutic target for intervention into neuroinflammatory and neurodegenerative disease. Full article
(This article belongs to the Section Cell Metabolism)
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25 pages, 1190 KiB  
Review
Understanding the Role of Alcohol in Metabolic Dysfunction and Male Infertility
by Valentina Annamaria Genchi, Angelo Cignarelli, Andrea Sansone, Dimitri Yannas, Leonardo Dalla Valentina, Daniele Renda Livraghi, Giorgia Spaggiari and Daniele Santi
Metabolites 2024, 14(11), 626; https://doi.org/10.3390/metabo14110626 - 15 Nov 2024
Cited by 2 | Viewed by 3432
Abstract
Purpose: Over the past 40–50 years, demographic shifts and the obesity epidemic have coincided with significant changes in lifestyle habits, including a rise in excessive alcohol consumption. This increase in alcohol intake is a major public health concern due to its far-reaching effects [...] Read more.
Purpose: Over the past 40–50 years, demographic shifts and the obesity epidemic have coincided with significant changes in lifestyle habits, including a rise in excessive alcohol consumption. This increase in alcohol intake is a major public health concern due to its far-reaching effects on human health, particularly on metabolic processes and male reproductive function. This narrative review focuses on the role of alcohol consumption in altering metabolism and impairing testicular function, emphasizing the potential damage associated with both acute and chronic alcohol intake. Conclusion: Chronic alcohol consumption has been shown to disrupt liver function, impair lipid metabolism, and dysregulate blood glucose levels, contributing to the development of obesity, metabolic syndrome, and related systemic diseases. In terms of male reproductive health, alcohol can significantly affect testicular function by lowering testosterone levels, reducing sperm quality, and impairing overall fertility. The extent of these effects varies, depending on the frequency, duration, and intensity of alcohol use, with chronic and abusive consumption posing greater risks. The complexity of alcohol’s impact is further compounded by individual variability and the interaction with other lifestyle factors such as diet, stress, and physical activity. Despite growing concern, research on alcohol’s effects remains inconclusive, with significant discrepancies across studies regarding the definition and reporting of alcohol consumption. These inconsistencies highlight the need for more rigorous, methodologically sound research to better understand how alcohol consumption influences metabolic and reproductive health. Ultimately, a clearer understanding is essential for developing targeted public health interventions, particularly in light of rising alcohol use, demographic changes, and the ongoing obesity crisis. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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21 pages, 3268 KiB  
Article
Comparison of Free Flavonoids and the Polyphenol Content in the Bran of a Newly Developed Sorghum Variety and Two Commercially Available Sorghum Varieties
by Mariely Cristine Dos Santos, Naoki Tanaka, Shigemitsu Kasuga, Kazuhiro Tanabe, Chihiro Hayashi, Masahiro Mizuno and Yoshihiko Amano
Metabolites 2024, 14(11), 628; https://doi.org/10.3390/metabo14110628 - 15 Nov 2024
Cited by 1 | Viewed by 980
Abstract
Background/Objectives: Sorghum bicolor is a source of many bioactive components, such as polyphenols. Those components are present mainly in its bran, often removed in industrial processes through decortication. In that sense, this work aimed to analyze the polyphenol content, especially free flavonoids, [...] Read more.
Background/Objectives: Sorghum bicolor is a source of many bioactive components, such as polyphenols. Those components are present mainly in its bran, often removed in industrial processes through decortication. In that sense, this work aimed to analyze the polyphenol content, especially free flavonoids, from the bran of a newly developed variety compared to other commercially available varieties. Methods: The samples were white sorghum TDN® Sorgho, red sorghum Mini Sorgho, and the newly developed red sorghum RILN-156. First, decortication was conducted to obtain the bran samples, which were triturated and then sieved. The use of colorimetric methods allowed the general quantification of the polyphenolic components. First, the polyphenol content was extracted using 70% methanol. Then, the samples’ total phenolic content, total flavonoid content, total tannin content, total anthocyanin content, and antioxidant potential were determined. To analyze the different components and identify the free flavonoids, an untargeted metabolomics analysis (with liquid chromatography coupled with mass spectrometer (LC/MS) and capillary electrophoresis coupled with a mass spectrometer (CE/MS)) was performed. Results: The results have shown that apart from anthocyanin and tannin, the newly developed variety, RILN-156, presented the highest concentration of polyphenolic content, including a higher antioxidant capacity. The exploratory analysis identified 19 flavonoids within the samples, with galangin and daidzein being the most abundant ones. Conclusions: These results show a promising finding for using this newly developed sorghum variety (RILN-156) industrially and further investigating its health benefits. They also elucidate the differences between colored sorghum within themselves and with white sorghum varieties. Full article
(This article belongs to the Section Plant Metabolism)
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Graphical abstract

17 pages, 2798 KiB  
Article
A Comprehensive LC–MS Metabolomics Assay for Quantitative Analysis of Serum and Plasma
by Lun Zhang, Jiamin Zheng, Mathew Johnson, Rupasri Mandal, Meryl Cruz, Miriam Martínez-Huélamo, Cristina Andres-Lacueva and David S. Wishart
Metabolites 2024, 14(11), 622; https://doi.org/10.3390/metabo14110622 - 14 Nov 2024
Viewed by 3105
Abstract
Background/Objectives: Targeted metabolomics is often criticized for the limited metabolite coverage that it offers. Indeed, most targeted assays developed or used by researchers measure fewer than 200 metabolites. In an effort to both expand the coverage and improve the accuracy of metabolite quantification [...] Read more.
Background/Objectives: Targeted metabolomics is often criticized for the limited metabolite coverage that it offers. Indeed, most targeted assays developed or used by researchers measure fewer than 200 metabolites. In an effort to both expand the coverage and improve the accuracy of metabolite quantification in targeted metabolomics, we decided to develop a comprehensive liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay that could quantitatively measure more than 700 metabolites in serum or plasma. Methods: The developed assay makes use of chemical derivatization followed by reverse phase LC–MS/MS and/or direct flow injection MS (DFI–MS) in both positive and negative ionization modes to separate metabolites. Multiple reaction monitoring (MRM), in combination with isotopic standards and multi-point calibration curves, is used to detect and absolutely quantify the targeted metabolites. The assay has been adapted to a 96-well plate format to enable automated, high-throughput sample analysis. Results: The assay (called MEGA) is able to detect and quantify 721 metabolites in serum/plasma, covering 20 metabolite classes and many commonly used clinical biomarkers. The limits of detection were determined to range from 1.4 nM to 10 mM, recovery rates were from 80% to 120%, and quantitative precision was within 20%. LC–MS/MS metabolite concentrations of the NIST® SRM®1950 plasma standard were found to be within 15% of NMR quantified levels. The MEGA assay was further validated in a large dietary intervention study. Conclusions: The MEGA assay should make comprehensive quantitative metabolomics much more affordable, accessible, automatable, and applicable to large-scale clinical studies. Full article
(This article belongs to the Special Issue Method Development in Metabolomics and Exposomics)
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13 pages, 2892 KiB  
Article
Analysis of In Vivo Plant Volatiles Using Active Sampling and TD-GC×GC-TOFMS
by Sheri A. Schmidt, Ewenet Yemane Mesfin, Chaminda De Silva Weeraddana, A. Paulina de la Mata, Alejandro C. Costamagna and James J. Harynuk
Metabolites 2024, 14(11), 623; https://doi.org/10.3390/metabo14110623 - 14 Nov 2024
Cited by 1 | Viewed by 1216
Abstract
Background: Plants constantly produce primary and secondary metabolites, and a significant fraction of these are volatile organic compounds (VOCs). Factors including the life stage of the plant, temperature, environment, and stress influence the abundance and types of VOCs emitted. The analysis of VOCs [...] Read more.
Background: Plants constantly produce primary and secondary metabolites, and a significant fraction of these are volatile organic compounds (VOCs). Factors including the life stage of the plant, temperature, environment, and stress influence the abundance and types of VOCs emitted. The analysis of VOCs released by plants during different stages or with different conditions provides insight into plant metabolism and stress responses. Collecting the VOC profiles of plants in vivo makes it possible to obtain a representative sample of the entire plant volatilome under controlled conditions with minimal invasiveness. In addition, in vivo sampling can also be used to compare the impacts of different environmental conditions or stressors on plants, i.e., the presence/absence of a pest or amount of nitrogen in soil. Methods: In this study, an in vivo plant sampling technique is introduced and validated using active sampling and thermal desorption (TD) tubes with comprehensive two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer (TD-GC×GC-TOFMS). The purpose of this work is to highlight a novel technique to analyze headspace secondary plant metabolites with a minimal invasiveness. Results: It was concluded that in vivo active sampling onto TD tubes provides a wider global coverage of compounds and larger peak areas when compared to extraction by solid-phase microextraction (SPME). Additionally, the Horwitz ratio of active sampling onto TD tubes was 0.893, demonstrating this technique to be a reliable and reproducible method. Lastly, a variety of plants were sampled to assess the versatility of this technique across various plant species with different sizes and volatile profiles. Hundreds of compounds were measured with this analysis, including terpenes, aldehydes, ketones, terpenoids, and alcohols. Conclusions: This novel in vivo active sampling method provides an additional technique for extracting and analyzing volatile secondary plant metabolites. Full article
(This article belongs to the Special Issue Method Development in Metabolomics and Exposomics)
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14 pages, 1597 KiB  
Article
Schinus terebinthifolia Raddi—Untargeted Metabolomics Approach to Investigate the Chemical Variation in Volatile and Non-Volatile Compounds
by Mara Junqueira Carneiro, Guilherme Perez Pinheiro, Elisa Ribeiro Miranda Antunes, Leandro Wang Hantao, Thomas Moritz and Alexandra Christine Helena Frankland Sawaya
Metabolites 2024, 14(11), 612; https://doi.org/10.3390/metabo14110612 - 11 Nov 2024
Viewed by 1214
Abstract
Context: Schinus terebinthifolia Raddi is used in Brazilian folk medicine due to the wound healing and antiseptic properties of its bark, and its fruit are used as a condiment. However, the aerial parts of this plant have been studied and present some bioactive [...] Read more.
Context: Schinus terebinthifolia Raddi is used in Brazilian folk medicine due to the wound healing and antiseptic properties of its bark, and its fruit are used as a condiment. However, the aerial parts of this plant have been studied and present some bioactive compounds as well. Objectives: The aim of this study was to investigate the variation in volatile and non-volatile composition of S. terebinthifolia leaves using untargeted metabolomics. Material and Methods: The leaves of four trees were collected over one year; ethanolic extracts were analyzed by UHPLC-MS and fresh leaves were analyzed by GC-MS using HS-SPME. The data were processed using online software. Results: The results suggest seasonality interfered little with the chemical composition of leaves. On the other hand, the sex of the plant clearly determined the chemical composition of both volatile and non-volatile compounds. Discussion and conclusions: Chemical variability between plants with male and female flowers is fundamental information for the standardized use of its leaves. Compounds with important biological activities were putatively identified, confirming the potential use of S. terebinthifolia leaves as a source of bioactive compounds, reducing waste and increasing economic gains for local farmers throughout the year. Full article
(This article belongs to the Special Issue Analysis of Specialized Metabolites in Natural Products)
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12 pages, 9300 KiB  
Article
Phenolic Metabolites Protocatechuic Acid and Vanillic Acid Improve Nitric Oxide Bioavailability via the Akt-eNOS Pathway in Response to TNF-α Induced Oxidative Stress and Inflammation in Endothelial Cells
by Joseph Festa, Aamir Hussain, Zakia Al-Hareth, Stephen J. Bailey, Harprit Singh and Mariasole Da Boit
Metabolites 2024, 14(11), 613; https://doi.org/10.3390/metabo14110613 - 11 Nov 2024
Cited by 2 | Viewed by 1172
Abstract
Background/Objectives: Reduced nitric oxide (NO) bioavailability secondary to excess-superoxide-driven oxidative stress is central to endothelial dysfunction. Previous studies suggest that phenolic metabolites may improve NO bioavailability, yet limited research is available in response to an inflammatory mediator. Therefore, we assessed the effects [...] Read more.
Background/Objectives: Reduced nitric oxide (NO) bioavailability secondary to excess-superoxide-driven oxidative stress is central to endothelial dysfunction. Previous studies suggest that phenolic metabolites may improve NO bioavailability, yet limited research is available in response to an inflammatory mediator. Therefore, we assessed the effects of cyanidin-3-glucoside (C3G) and its phenolic metabolites protocatechuic acid (PCA) and vanillic acid (VA) on NO bioavailability in a TNF-α induced inflammatory environment. Methods: Primary human umbilical vein endothelial cells (HUVECs) were supplemented with either C3G, PCA, or VA at 1 μM for 24 h before being stimulated with TNF-α 20 ng/mL for an additional 24 h. Measurements included cell viability, apoptosis, reactive oxygen species (ROS), nitrite concentrations, and endothelial nitric oxide synthase (eNOS) and Akt at the mRNA and protein level. Results: Phenolic metabolites did not increase the eNOS expression or nitrite levels in the unstimulated environment; rather, the metabolites mediated NO bioavailability in response to TNF-α induced oxidative stress, with increased viability, eNOS mRNA, phosphorylation, and nitrite levels. Conclusions: Phenolic metabolites, in the presence of TNF-α, can improve NO bioavailability at physiologically relevant concentrations via the Akt-eNOS pathway. This demonstrates that the induction of inflammation is a prerequisite for phenolic metabolites to promote protective properties in endothelial cells by activating the Akt-eNOS pathway. Full article
(This article belongs to the Section Cell Metabolism)
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16 pages, 2250 KiB  
Article
MS2Lipid: A Lipid Subclass Prediction Program Using Machine Learning and Curated Tandem Mass Spectral Data
by Nami Sakamoto, Takaki Oka, Yuki Matsuzawa, Kozo Nishida, Jayashankar Jayaprakash, Aya Hori, Makoto Arita and Hiroshi Tsugawa
Metabolites 2024, 14(11), 602; https://doi.org/10.3390/metabo14110602 - 7 Nov 2024
Cited by 2 | Viewed by 1551
Abstract
Background: Untargeted lipidomics using collision-induced dissociation-based tandem mass spectrometry (CID-MS/MS) is essential for biological and clinical applications. However, annotation confidence still relies on manual curation by analytical chemists, despite the development of various software tools for automatic spectral processing based on rule-based [...] Read more.
Background: Untargeted lipidomics using collision-induced dissociation-based tandem mass spectrometry (CID-MS/MS) is essential for biological and clinical applications. However, annotation confidence still relies on manual curation by analytical chemists, despite the development of various software tools for automatic spectral processing based on rule-based fragment annotations. Methods: In this study, we present a novel machine learning model, MS2Lipid, for the prediction of known lipid subclasses from MS/MS queries, providing an orthogonal approach to existing lipidomics software programs in determining the lipid subclass of ion features. We designed a new descriptor, MCH (mode of carbon and hydrogen), to increase the specificity of lipid subclass prediction in nominal mass resolution MS data. Results: The model, trained with 6760 and 6862 manually curated MS/MS spectra for the positive and negative ion modes, respectively, classified queries into one or several of 97 lipid subclasses, achieving an accuracy of 97.4% in the test set. The program was further validated using various datasets from different instruments and curators, with the average accuracy exceeding 87.2%. Using an integrated approach with molecular spectral networking, we demonstrated the utility of MS2Lipid by annotating microbiota-derived esterified bile acids, whose abundance was significantly increased in fecal samples of obese patients in a human cohort study. This suggests that the machine learning model provides an independent criterion for lipid subclass classification, enhancing the annotation of lipid metabolites within known lipid classes. Conclusions: MS2Lipid is a highly accurate machine learning model that enhances lipid subclass annotation from MS/MS data and provides an independent criterion. Full article
(This article belongs to the Special Issue Metabolomics and Bioinformatics Approaches to Studying Human Gut Microbiota-Derived Metabolites)
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13 pages, 2623 KiB  
Article
Metabolomics of Papanicolaou Tests for the Discovery of Ovarian Cancer Biomarkers
by Samyukta Sah, Elisabeth M. Schwiebert, Samuel G. Moore, Ying Liu, David A. Gaul, Kristin L. M. Boylan, Amy P. N. Skubitz and Facundo M. Fernández
Metabolites 2024, 14(11), 600; https://doi.org/10.3390/metabo14110600 - 7 Nov 2024
Viewed by 1401
Abstract
Background: Ovarian cancer (OC) remains one of the most lethal cancers among women due to most cases going undiagnosed until later stages. The early detection and treatment of this malignancy provides the best prognosis, but the lack of an accurate and sensitive [...] Read more.
Background: Ovarian cancer (OC) remains one of the most lethal cancers among women due to most cases going undiagnosed until later stages. The early detection and treatment of this malignancy provides the best prognosis, but the lack of an accurate and sensitive screening tool combined with ambiguous symptoms hinders these diagnoses. In contrast, screening for cervical cancer via Papanicolaou (Pap) tests is a widespread practice that greatly reduces the cancer’s mortality rates. Interestingly, previous studies show evidence of OC cells in Pap tests, suggesting that proteins, and potentially lipids, shed from ovarian tumors end up in the cervix. The goal of this study is to evaluate the practicality of using Pap tests as biospecimens for OC-screening-related metabolomics. Methods: To evaluate the effectiveness of using residual Pap test samples as biospecimens for potential metabolomics work, 29 Pap test samples, collected from women over the age of 50 with normal cytology and no visible blood contamination, were first obtained from the University of Minnesota, with IRB approval. These samples were centrifuged to recover the cell pellets from the supernatants. The cell pellets underwent a biphasic extraction, followed by an RP-LC-MS analysis, while the supernatants underwent two separate extractions and analyses, including RP-LC-MS and HILIC-LC-MS. Non-targeted features were detected in the range of 220–1000 m/z to determine the sensitivity and scope of the various extraction and analytical workflows, as well as evaluating residual Pap test samples as viable metabolomics biospecimens. Results: The biphasic extraction and subsequent RP-LC-MS analysis of the isolated cell pellets from all 29 samples yielded informative, exploratory data, highlighting the potential of using residual Pap test samples as biospecimens for metabolomics, specifically lipidomics, studies. Each sample was analyzed in both the positive and negative ion mode, yielding the detection of 7318 in the positive ion mode and 3733 in the negative ion mode. Using multiple reference libraries, 22.85% and 36.19% of these features were annotated in the positive and negative ion mode, respectively. Among these detected features, 453 unique lipids, representative of 20 different lipid subclasses, were annotated in all 29 samples. Of the various lipid subclasses represented from the detected lipids, ceramides, triacylglycerols, hexosylceramides, and phosphatidylcholines contributed to over half (53.3%) of the detected lipids at 16.2%, 13.0%, 12.8%, and 11.3%, respectively. Conclusions: The detection of these 453 common lipids across all patients establishes a relative lipidome baseline for women over the age of 50 with normal cervical cytology. This exploratory study is the first investigation to utilize residual Pap test samples as biospecimens in a metabolomics/lipidomics workflow. Full article
(This article belongs to the Special Issue Method Development in Metabolomics and Exposomics)
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17 pages, 2954 KiB  
Article
Integrated Metabolomic and Transcriptomic Analysis of Nitraria Berries Indicate the Role of Flavonoids in Adaptation to High Altitude
by Qing Zhao, Jie Zhang, Yanhong Li, Zufan Yang, Qian Wang and Qiangqiang Jia
Metabolites 2024, 14(11), 591; https://doi.org/10.3390/metabo14110591 - 1 Nov 2024
Cited by 2 | Viewed by 1213
Abstract
Background: Plants of Nitraria, belonging to the Zygophyllaceae family, are not only widely distributed at an altitude of about 1000 m but also at an altitude of about 3000 m, which is a rare phenomenon. However, little is known about the effect [...] Read more.
Background: Plants of Nitraria, belonging to the Zygophyllaceae family, are not only widely distributed at an altitude of about 1000 m but also at an altitude of about 3000 m, which is a rare phenomenon. However, little is known about the effect of altitude on the accumulation of metabolites in plants of Nitraria. Furthermore, the mechanism of the high–altitude adaptation of Nitraria has yet to be fully elucidated. Methods: In this study, metabolomics and transcriptomics were used to investigate the differential accumulation of metabolites of Nitraria berries and the regulatory mechanisms in different altitudes. Results: As a result, the biosynthesis of flavonoids is the most significant metabolic pathway in the process of adaptation to high altitude, and 5 Cyanidins, 1 Pelargonidin, 3 Petunidins, 1 Peonidin, and 4 Delphinidins are highly accumulated in high–altitude Nitraria. The results of transcriptomics showed that the structural genes C4H (2), F3H, 4CL (2), DFR (2), UFGT (2), and FLS (2) were highly expressed in high–altitude Nitraria. A network metabolism map of flavonoids was constructed, and the accumulation of differential metabolites and the expression of structural genes were analyzed for correlation. Conclusions: In summary, this study preliminarily offers a new understanding of metabolic differences and regulation mechanisms in plants of Nitraria from different altitudes. Full article
(This article belongs to the Section Plant Metabolism)
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21 pages, 1539 KiB  
Review
Exercise as a Therapeutic Strategy for Obesity: Central and Peripheral Mechanisms
by Yiyin Zhang, Ruwen Wang, Tiemin Liu and Ru Wang
Metabolites 2024, 14(11), 589; https://doi.org/10.3390/metabo14110589 - 30 Oct 2024
Cited by 1 | Viewed by 4255
Abstract
Obesity is a complex, multifactorial condition involving excessive fat accumulation due to an imbalance between energy intake and expenditure, with its global prevalence steadily rising. This condition significantly increases the risk of chronic diseases, including sarcopenia, type 2 diabetes, and cardiovascular diseases, highlighting [...] Read more.
Obesity is a complex, multifactorial condition involving excessive fat accumulation due to an imbalance between energy intake and expenditure, with its global prevalence steadily rising. This condition significantly increases the risk of chronic diseases, including sarcopenia, type 2 diabetes, and cardiovascular diseases, highlighting the need for effective interventions. Exercise has emerged as a potent non-pharmacological approach to combat obesity, targeting both central and peripheral mechanisms that regulate metabolism, energy expenditure, and neurological functions. In the central nervous system, exercise influences appetite, mood, and cognitive functions by modulating the reward system and regulating appetite-controlling hormones to manage energy intake. Concurrently, exercise promotes thermogenesis in adipose tissue and regulates endocrine path-ways and key metabolic organs, such as skeletal muscle and the liver, to enhance fat oxidation and support energy balance. Despite advances in understanding exercise’s role in obesity, the precise interaction between the neurobiological and peripheral metabolic pathways remains underexplored, particularly in public health strategies. A better understanding of these interactions could inform more comprehensive obesity management approaches by addressing both central nervous system influences on behavior and peripheral metabolic regulation. This review synthesizes recent insights into these roles, highlighting potential therapeutic strategies targeting both systems for more effective obesity interventions. Full article
(This article belongs to the Special Issue Exploring Pathological Mechanisms in Obesity, Diabetes, and Metabolic Syndrome)
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15 pages, 1886 KiB  
Article
Predicting the Pathway Involvement of All Pathway and Associated Compound Entries Defined in the Kyoto Encyclopedia of Genes and Genomes
by Erik D. Huckvale and Hunter N. B. Moseley
Metabolites 2024, 14(11), 582; https://doi.org/10.3390/metabo14110582 - 27 Oct 2024
Cited by 2 | Viewed by 1019
Abstract
Background/Objectives: Predicting the biochemical pathway involvement of a compound could facilitate the interpretation of biological and biomedical research. Prior prediction approaches have largely focused on metabolism, training machine learning models to solely predict based on metabolic pathways. However, there are many other [...] Read more.
Background/Objectives: Predicting the biochemical pathway involvement of a compound could facilitate the interpretation of biological and biomedical research. Prior prediction approaches have largely focused on metabolism, training machine learning models to solely predict based on metabolic pathways. However, there are many other types of pathways in cells and organisms that are of interest to biologists. Methods: While several publications have made use of the metabolites and metabolic pathways available in the Kyoto Encyclopedia of Genes and Genomes (KEGG), we downloaded all the compound entries with pathway annotations available in the KEGG. From these data, we constructed a dataset where each entry contained features representing compounds combined with features representing pathways, followed by a binary label indicating whether the given compound is associated with the given pathway. We trained multi-layer perceptron binary classifiers on variations of this dataset. Results: The models trained on 6485 KEGG compounds and 502 pathways scored an overall mean Matthews correlation coefficient (MCC) performance of 0.847, a median MCC of 0.848, and a standard deviation of 0.0098. Conclusions: This performance on all 502 KEGG pathways represents a roughly 6% improvement over the performance of models trained on only the 184 KEGG metabolic pathways, which had a mean MCC of 0.800 and a standard deviation of 0.021. These results demonstrate the capability to effectively predict biochemical pathways in general, in addition to those specifically related to metabolism. Moreover, the improvement in the performance demonstrates additional transfer learning with the inclusion of non-metabolic pathways. Full article
(This article belongs to the Special Issue Machine Learning Applications in Metabolomics Analysis)
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17 pages, 7552 KiB  
Article
Metabolomics Reveal Key Metabolic Pathway Responses to Anxiety State Regulated by Serotonin in Portunus trituberculatus
by Wei Zhai, Yuanyuan Fu, Lei Liu, Xinlian Huang and Sixiang Wang
Metabolites 2024, 14(10), 568; https://doi.org/10.3390/metabo14100568 - 21 Oct 2024
Cited by 1 | Viewed by 1722
Abstract
Background: Anxiety refers to the pathological persistence and intensification of emotional responses to danger, affecting health from psychological and physical aspects. Serotonin is an important neurotransmitter involved in the onset of anxiety. Methods and Results: To explore the biological changes in the formation [...] Read more.
Background: Anxiety refers to the pathological persistence and intensification of emotional responses to danger, affecting health from psychological and physical aspects. Serotonin is an important neurotransmitter involved in the onset of anxiety. Methods and Results: To explore the biological changes in the formation of anxiety in crustaceans under the regulation of serotonin, we applied the open field-like test method for assessing anxiety states of larval Portunus trituberculatus, a highly aggressive crustacean species with a more simple neural structure compared with rodents and mammals. Compared with the control group, serotonin treatment resulted in a significant decrease in the time spent by the larvae in the central zone, suggesting anxiety-like behavior. Clonazepam treatment reversed this result and provided further evidence that the behavior of larval P. trituberculatus displayed anxiety. Moreover, a non-targeted metabolomic analysis found a significant alteration in the metabolites involved in tryptophan metabolism pathways associated with anxiety, including L-kynurenine, N-acetyl serotonin, and serotonin. These metabolites are involved in the serotonin pathway, the kynurenine pathway, and other pathways that affect anxiety through tryptophan metabolism. There were no significant differences in tryptophan metabolism levels between the control and clonazepam treatment groups. Conclusions: Our results demonstrate the possible existence of anxiety-like behavior in the larvae of P. trituberculatus from two perspectives. Being a species with a simpler neural structure than that of mammals, the larvae of P. trituberculatus offer a convenient model for studying the mechanisms of anxiety in crustaceans. Full article
(This article belongs to the Special Issue Meeting the Challenge of Metabolomics Analysis by Using Multidimensional Gas Chromatography with Mass Spectrometry)
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19 pages, 658 KiB  
Review
Research Progress on Antioxidant Peptides from Fish By-Products: Purification, Identification, and Structure–Activity Relationship
by Xinru Liu, Qiuyue Hu, Yafang Shen, Yuxin Wu, Lu Gao, Xuechao Xu and Guijie Hao
Metabolites 2024, 14(10), 561; https://doi.org/10.3390/metabo14100561 - 20 Oct 2024
Cited by 1 | Viewed by 1853
Abstract
Background/Objectives: Excessive reactive oxygen species (ROS) can lead to oxidative stress, which has become an urgent problem requiring effective solutions. Due to the drawbacks of chemically synthesized antioxidants, there is a growing interest in natural antioxidants, particularly antioxidant peptides. Methods: By reviewing [...] Read more.
Background/Objectives: Excessive reactive oxygen species (ROS) can lead to oxidative stress, which has become an urgent problem requiring effective solutions. Due to the drawbacks of chemically synthesized antioxidants, there is a growing interest in natural antioxidants, particularly antioxidant peptides. Methods: By reviewing recent literature on antioxidant peptides, particularly those extracted from various parts of fish, summarize which fish by-products are more conducive to the extraction of antioxidant peptides and elaborate on their characteristics. Results: This article summarizes recent advancements in extracting antioxidant peptides from fish processing by-products, Briefly introduced the purification and identification process of antioxidant peptides, specifically focusing on the extraction of antioxidant peptides from various fish by-products. Additionally, this article comprehensively reviews the relationship between amino acid residues that compose antioxidant peptides and their potential mechanisms of action. It explores the impact of amino acid types, molecular weight, and structure–activity relationships on antioxidant efficacy. Conclusions: Different amino acid residues can contribute to the antioxidant activity of peptides by scavenging free radicals, chelating metal ions, and modulating enzyme activities. The smaller the molecular weight of the antioxidant peptide, the stronger its antioxidant activity. Additionally, the antioxidant activity of peptides is influenced by specific amino acids located at the C-terminus and N-terminus positions. Simultaneously, this review provides a more systematic analysis and a broader perspective based on existing research, concluded that fish viscera are more favorable for the extraction of antioxidant peptides, providing new insights for the practical application of fish by-products. This could increase the utilization of fish viscera and reduce the environmental pollution caused by their waste, offering valuable references for the study and application of antioxidant peptides from fish by-products. Full article
(This article belongs to the Special Issue Insights into the Metabolic Absorption of Bioactive Peptides Derived from Food Sources)
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20 pages, 1457 KiB  
Article
Detailed Profiling of 17-Hydroxygeranyllinalool Diterpene Glycosides from Nicotiana Species Reveals Complex Reaction Networks of Conjugation Isomers
by Alina Ebert, Saleh Alseekh, Lucio D’Andrea, Ute Roessner, Ralph Bock and Joachim Kopka
Metabolites 2024, 14(10), 562; https://doi.org/10.3390/metabo14100562 - 20 Oct 2024
Viewed by 1213
Abstract
Background: Specialised anti-herbivory metabolites are abundant in the solanaceous genus Nicotiana. These metabolites include the large family of 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs). Many HGL-DTGs occur exclusively within the Nicotiana genus, but information from the molecular model species N. tabacum, N. benthamiana [...] Read more.
Background: Specialised anti-herbivory metabolites are abundant in the solanaceous genus Nicotiana. These metabolites include the large family of 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs). Many HGL-DTGs occur exclusively within the Nicotiana genus, but information from the molecular model species N. tabacum, N. benthamiana, and the tree tobacco N. glauca is limited. Objectives: We studied HGL-DTG occurrence and complexity in these species with the aim of providing in-depth reference annotations and comprehensive HGL-DTG inventories. Methods: We analysed polar metabolite extracts in comparison to the previously investigated wild reference species N. attenuata using positive ESI(+) and negative ESI(-) mode electrospray ionisation LC-MS and MS/MS. Results: We provide annotations of 66 HGL-DTGs with in-source and MS/MS fragmentation spectra for selected HGL-DTGs with exemplary fragment interpretations of ESI(+) as well as less studied ESI(-) spectra. We assemble a potential biosynthesis pathway comparing the presence of HGL-DTGs in N. tabacum, N. glauca, and N. benthamiana to N. attenuata. Approximately one-third of HGL-DTGs are chromatographically resolved isomers of hexose, deoxyhexose, or malonate conjugates. The number of isomers is especially high for conjugates with low numbers of deoxyhexose moieties. Conclusions: We extend the number of known HGL-DTGs with a focus on Nicotiana model species and demonstrate that the HGL-DTG family of N. tabacum plants can be surprisingly complex. Our study provides an improved basis with detailed references to previous studies of wild Nicotiana species and enables inference of HGL-DTG pathways with required enzymes for the biosynthesis of this important family of specialised defence metabolites. Full article
(This article belongs to the Section Plant Metabolism)
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13 pages, 5623 KiB  
Article
Unveiling the Metabolic Trajectory of Pig Feces Across Different Ages and Senescence
by Chuanmin Qiao, Chengzhong Liu, Ruipei Ding, Shumei Wang and Maozhang He
Metabolites 2024, 14(10), 558; https://doi.org/10.3390/metabo14100558 - 17 Oct 2024
Viewed by 1401
Abstract
Porcine models are increasingly recognized for their similarities to humans and have been utilized in disease modeling and organ grafting research. While extensive metabolomics studies have been conducted in swine, primarily focusing on conventional cohorts or specific animal models, the composition and functions [...] Read more.
Porcine models are increasingly recognized for their similarities to humans and have been utilized in disease modeling and organ grafting research. While extensive metabolomics studies have been conducted in swine, primarily focusing on conventional cohorts or specific animal models, the composition and functions of fecal metabolites in pigs across different age groups—particularly in the elderly—remain inadequately understood. In this study, an untargeted metabolomics approach was employed to analyze the fecal metabolomes of pigs at three distinct age stages: young (one year), middle-aged (four years), and elderly (eight years). The objective was to elucidate age-associated changes in metabolite composition and functionality under standardized rearing conditions. The untargeted metabolomic analysis revealed a diverse array of age-related metabolites. Notably, L-methionine sulfoxide levels were found to increase with age, whereas cytidine-5-monophosphate levels exhibited a gradual decline throughout the aging process. These metabolites demonstrated alterations across various biological pathways, including energy metabolism, pyrimidine metabolism, lipid metabolism, and amino acid metabolism. Collectively, the identified key metabolites, such as L-methionine sulfoxide and Cholecalciferol, may serve as potential biomarkers of senescence, providing valuable insights into the mechanistic understanding of aging in pigs. Full article
(This article belongs to the Special Issue Bioactive Compounds in Animal Nutrition Resources and Animal By-Products)
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17 pages, 823 KiB  
Article
Maternal Dietary Deficiencies in Folic Acid and Choline Change Metabolites Levels in Offspring after Ischemic Stroke
by Faizan Anwar, Mary-Tyler Mosley, Paniz Jasbi, Jinhua Chi, Haiwei Gu and Nafisa M. Jadavji
Metabolites 2024, 14(10), 552; https://doi.org/10.3390/metabo14100552 - 16 Oct 2024
Cited by 1 | Viewed by 1399
Abstract
Background/objectives: Ischemic stroke is a major health concern, and nutrition is a modifiable risk factor that can influence recovery outcomes. This study investigated the impact of maternal dietary deficiencies in folic acid (FADD) or choline (ChDD) on the metabolite profiles of offspring [...] Read more.
Background/objectives: Ischemic stroke is a major health concern, and nutrition is a modifiable risk factor that can influence recovery outcomes. This study investigated the impact of maternal dietary deficiencies in folic acid (FADD) or choline (ChDD) on the metabolite profiles of offspring after ischemic stroke. Methods: A total of 32 mice (17 males and 15 females) were used to analyze sex-specific differences in response to these deficiencies. Results: At 1-week post-stroke, female offspring from the FADD group showed the greatest number of altered metabolites, including pathways involved in cholesterol metabolism and neuroprotection. At 4 weeks post-stroke, both FADD and ChDD groups exhibited significant disruptions in metabolites linked to inflammation, oxidative stress, and neurotransmission. Conclusions: These alterations were more pronounced in females compared to males, suggesting sex-dependent responses to maternal dietary deficiencies. The practical implications of these findings suggest that ensuring adequate maternal nutrition during pregnancy may be crucial for reducing stroke susceptibility and improving post-stroke recovery in offspring. Nutritional supplementation strategies targeting folic acid and choline intake could potentially mitigate the long-term adverse effects on metabolic pathways and promote better neurological outcomes. Future research should explore these dietary interventions in clinical settings to develop comprehensive guidelines for maternal nutrition and stroke prevention. Full article
(This article belongs to the Special Issue Neuronutrition: Metabolomic Insights and Perspectives)
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12 pages, 2076 KiB  
Article
Liraglutide Therapy in Obese Patients Alters Macrophage Phenotype and Decreases Their Tumor Necrosis Factor Alpha Release and Oxidative Stress Markers—A Pilot Study
by Łukasz Bułdak, Aleksandra Bołdys, Estera Skudrzyk, Grzegorz Machnik and Bogusław Okopień
Metabolites 2024, 14(10), 554; https://doi.org/10.3390/metabo14100554 - 16 Oct 2024
Viewed by 1351
Abstract
Introduction: Obesity is one of the major healthcare challenges. It affects one in eight people around the world and leads to several comorbidities, including type 2 diabetes, hyperlipidemia, and arterial hypertension. GLP-1 analogs have become major players in the therapy of obesity, [...] Read more.
Introduction: Obesity is one of the major healthcare challenges. It affects one in eight people around the world and leads to several comorbidities, including type 2 diabetes, hyperlipidemia, and arterial hypertension. GLP-1 analogs have become major players in the therapy of obesity, leading to significant weight loss in patients. However, benefits resulting from their usage seem to be greater than simple appetite reduction and glucose-lowering potential. Recent data show better cardiovascular outcomes, which are connected with the improvements in the course of atherosclerosis. Macrophages are crucial cells in the forming and progression of atherosclerotic lesions. Previously, it was shown that in vitro treatment with GLP-1 analogs can affect macrophage phenotype, but there is a paucity of in vivo data. Objective: To evaluate the influence of in vivo treatment with liraglutide on basic phenotypic and functional markers of macrophages. Methods: Basic phenotypic features were assessed (including inducible nitric oxide synthase, arginase 1 and mannose receptors), proinflammatory cytokine (IL-1β, TNFα) release, and oxidative stress markers (reactive oxygen species, malondialdehyde) in macrophages obtained prior and after 3-month therapy with liraglutide in patients with obesity. Results: Three-month treatment with subcutaneous liraglutide resulted in the alteration of macrophage phenotype toward alternative activation (M2) with accompanying reduction in the TNFα release and diminished oxidative stress markers. Conclusions: Our results show that macrophages in patients treated with GLP-1 can alter their phenotype and function. Those findings may at least partly explain the pleiotropic beneficial cardiovascular effects seen in subjects treated with GLP-1 analogs. Full article
(This article belongs to the Special Issue Lipid Metabolism and Atherosclerosis: Cell Specific Functions and Molecular Mechanism of the Disease)
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12 pages, 2854 KiB  
Article
Multi-Modal Investigation of Metabolism in Murine Breast Cancer Cell Lines Using Fluorescence Lifetime Microscopy and Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy
by Sarah Erickson-Bhatt, Benjamin L. Cox, Erin Macdonald, Jenu V. Chacko, Paul Begovatz, Patricia J. Keely, Suzanne M. Ponik, Kevin W. Eliceiri and Sean B. Fain
Metabolites 2024, 14(10), 550; https://doi.org/10.3390/metabo14100550 - 15 Oct 2024
Viewed by 1495
Abstract
Background/Objectives: Despite the role of metabolism in breast cancer metastasis, we still cannot predict which breast tumors will progress to distal metastatic lesions or remain dormant. This work uses metabolic imaging to study breast cancer cell lines (4T1, 4T07, and 67NR) with [...] Read more.
Background/Objectives: Despite the role of metabolism in breast cancer metastasis, we still cannot predict which breast tumors will progress to distal metastatic lesions or remain dormant. This work uses metabolic imaging to study breast cancer cell lines (4T1, 4T07, and 67NR) with differing metastatic potential in a 3D collagen gel bioreactor system. Methods: Within the bioreactor, hyperpolarized magnetic resonance spectroscopy (HP-MRS) is used to image lactate/pyruvate ratios, while fluorescence lifetime imaging microscopy (FLIM) of endogenous metabolites measures metabolism at the cellular scale. Results: HP-MRS results showed no lactate peak for 67NR and a comparatively large lactate/pyruvate ratio for both 4T1 and 4T07 cell lines, suggestive of greater pyruvate utilization with greater metastatic potential. Similar patterns were observed using FLIM with significant increases in FAD intensity, redox ratio, and NAD(P)H lifetime. The lactate/pyruvate ratio was strongly correlated to NAD(P)H lifetime, consistent with the role of NADH as an electron donor for the glycolytic pathway, suggestive of an overall upregulation of metabolism (both glycolytic and oxidative), for the 4T07 and 4T1 cell lines compared to the non-metastatic 67NR cell line. Conclusions: These findings support a complementary role for HP-MRS and FLIM enabled by a novel collagen gel bioreactor system to investigate metastatic potential and cancer metabolism. Full article
(This article belongs to the Section Cell Metabolism)
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31 pages, 1017 KiB  
Review
Nutritional Modulation of the Gut–Brain Axis: A Comprehensive Review of Dietary Interventions in Depression and Anxiety Management
by Mariana Merino del Portillo, Vicente Javier Clemente-Suárez, Pablo Ruisoto, Manuel Jimenez, Domingo Jesús Ramos-Campo, Ana Isabel Beltran-Velasco, Ismael Martínez-Guardado, Alejandro Rubio-Zarapuz, Eduardo Navarro-Jiménez and José Francisco Tornero-Aguilera
Metabolites 2024, 14(10), 549; https://doi.org/10.3390/metabo14100549 - 14 Oct 2024
Cited by 9 | Viewed by 7709
Abstract
Mental health is an increasing topic of focus since more than 500 million people in the world suffer from depression and anxiety. In this multifactorial disorder, parameters such as inflammation, the state of the microbiota and, therefore, the patient’s nutrition are receiving more [...] Read more.
Mental health is an increasing topic of focus since more than 500 million people in the world suffer from depression and anxiety. In this multifactorial disorder, parameters such as inflammation, the state of the microbiota and, therefore, the patient’s nutrition are receiving more attention. In addition, food products are the source of many essential ingredients involved in the regulation of mental processes, including amino acids, neurotransmitters, vitamins, and others. For this reason, this narrative review was carried out with the aim of analyzing the role of nutrition in depression and anxiety disorders. To reach the review aim, a critical review was conducted utilizing both primary sources, such as scientific publications and secondary sources, such as bibliographic indexes, web pages, and databases. The search was conducted in PsychINFO, MedLine (Pubmed), Cochrane (Wiley), Embase, and CinAhl. The results show a direct relationship between what we eat and the state of our nervous system. The gut–brain axis is a complex system in which the intestinal microbiota communicates directly with our nervous system and provides it with neurotransmitters for its proper functioning. An imbalance in our microbiota due to poor nutrition will cause an inflammatory response that, if sustained over time and together with other factors, can lead to disorders such as anxiety and depression. Changes in the functions of the microbiota–gut–brain axis have been linked to several mental disorders. It is believed that the modulation of the microbiome composition may be an effective strategy for a new treatment of these disorders. Modifications in nutritional behaviors and the use of ergogenic components are presented as important non-pharmacological interventions in anxiety and depression prevention and treatment. It is desirable that the choice of nutritional and probiotic treatment in individual patients be based on the results of appropriate biochemical and microbiological tests. Full article
(This article belongs to the Special Issue Advances in Food Sciences: Metabolomics to Unravel the Complexity of Food Metabolites)
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24 pages, 1102 KiB  
Review
Recent Advances in Metabolomics and Lipidomics Studies in Human and Animal Models of Multiple Sclerosis
by Petros Pousinis, Olga Begou, Marina Kleopatra Boziki, Nikolaos Grigoriadis, Georgios Theodoridis and Helen Gika
Metabolites 2024, 14(10), 545; https://doi.org/10.3390/metabo14100545 - 13 Oct 2024
Cited by 1 | Viewed by 2043
Abstract
Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease of the central nervous system (CNS) that leads to a loss of myelin. There are three main types of MS: relapsing-remitting MS (RRMS) and primary and secondary progressive disease (PPMS, SPMS). The differentiation in [...] Read more.
Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease of the central nervous system (CNS) that leads to a loss of myelin. There are three main types of MS: relapsing-remitting MS (RRMS) and primary and secondary progressive disease (PPMS, SPMS). The differentiation in the pathogenesis of these two latter courses is still unclear. The underlying mechanisms of MS are yet to be elucidated, and the treatment relies on immune-modifying agents. Recently, lipidomics and metabolomics studies using human biofluids, mainly plasma and cerebrospinal fluid (CSF), have suggested an important role of lipids and metabolites in the pathophysiology of MS. In this review, the results from studies on metabolomics and lipidomics analyses performed on biological samples of MS patients and MS-like animal models are presented and analyzed. Based on the collected findings, the biochemical pathways in human and animal cohorts involved were investigated and biological mechanisms and the potential role they have in MS are discussed. Limitations and challenges of metabolomics and lipidomics approaches are presented while concluding that metabolomics and lipidomics may provide a more holistic approach and provide biomarkers for early diagnosis of MS disease. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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20 pages, 2238 KiB  
Article
Detection and Validation of Organic Metabolites in Urine for Clear Cell Renal Cell Carcinoma Diagnosis
by Kiana L. Holbrook, George E. Quaye, Elizabeth Noriega Landa, Xiaogang Su, Qin Gao, Heinric Williams, Ryan Young, Sabur Badmos, Ahsan Habib, Angelica A. Chacon and Wen-Yee Lee
Metabolites 2024, 14(10), 546; https://doi.org/10.3390/metabo14100546 - 13 Oct 2024
Cited by 3 | Viewed by 1746
Abstract
Background: Clear cell renal cell carcinoma (ccRCC) comprises the majority, approximately 70–80%, of renal cancer cases and often remains asymptomatic until incidentally detected during unrelated abdominal imaging or at advanced stages. Currently, standardized screening tests for renal cancer are lacking, which presents challenges [...] Read more.
Background: Clear cell renal cell carcinoma (ccRCC) comprises the majority, approximately 70–80%, of renal cancer cases and often remains asymptomatic until incidentally detected during unrelated abdominal imaging or at advanced stages. Currently, standardized screening tests for renal cancer are lacking, which presents challenges in disease management and improving patient outcomes. This study aimed to identify ccRCC-specific volatile organic compounds (VOCs) in the urine of ccRCC-positive patients and develop a urinary VOC-based diagnostic model. Methods: This study involved 233 pretreatment ccRCC patients and 43 healthy individuals. VOC analysis utilized stir-bar sorptive extraction coupled with thermal desorption gas chromatography/mass spectrometry (SBSE-TD-GC/MS). A ccRCC diagnostic model was established via logistic regression, trained on 163 ccRCC cases versus 31 controls, and validated with 70 ccRCC cases versus 12 controls, resulting in a ccRCC diagnostic model involving 24 VOC markers. Results: The findings demonstrated promising diagnostic efficacy, with an Area Under the Curve (AUC) of 0.94, 86% sensitivity, and 92% specificity. Conclusions: This study highlights the feasibility of using urine as a reliable biospecimen for identifying VOC biomarkers in ccRCC. While further validation in larger cohorts is necessary, this study’s capability to differentiate between ccRCC and control groups, despite sample size limitations, holds significant promise. Full article
(This article belongs to the Special Issue Emerging Applications of Urinary Metabolomics in Cancer)
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24 pages, 3004 KiB  
Review
Non/Low-Caloric Artificial Sweeteners and Gut Microbiome: From Perturbed Species to Mechanisms
by Jiahao Feng, Jingya Peng, Yun-Chung Hsiao, Chih-Wei Liu, Yifei Yang, Haoduo Zhao, Taylor Teitelbaum, Xueying Wang and Kun Lu
Metabolites 2024, 14(10), 544; https://doi.org/10.3390/metabo14100544 - 11 Oct 2024
Cited by 4 | Viewed by 5518
Abstract
Background: Non/low-caloric artificial sweeteners (NAS) are recognized as chemical additives substituting sugars to avoid caloric intake and subsequent sugar-derived diseases such as diabetes and hyperglycemia. Six NAS have been claimed safe and are authorized by the US Food and Drug Administration (FDA) for [...] Read more.
Background: Non/low-caloric artificial sweeteners (NAS) are recognized as chemical additives substituting sugars to avoid caloric intake and subsequent sugar-derived diseases such as diabetes and hyperglycemia. Six NAS have been claimed safe and are authorized by the US Food and Drug Administration (FDA) for public use, with acceptable daily intake information available: aspartame, acesulfame-K, saccharin, sucralose, neotame, and advantame. However, the impacts of NAS on the gut microbiome have raised potential concerns, since sporadic research revealed NAS-induced microbial changes in the gastrointestinal tracts and alterations in the microbiome–host interactive metabolism. Methods: Given the fact that the gut microbiome influences kaleidoscopic physiological functions in host health, this review aimed to decipher the impacts of NAS on the gut microbiome by implementing a comprehensive two-stage literature analysis based on each NAS. Results: This review documented disturbed microbiomes due to NAS exposure to a maximal resolution of species level using taxonomic clustering analysis, and recorded metabolism alterations involved in gut microbiome–host interactions. Conclusions: The results elucidated that specific NAS exhibited discrepant impacts on the gut microbiome, even though overlapping on the genera and species were identified. Some NAS caused glucose tolerance impairment in the host, but the key metabolites and their underlying mechanisms were different. Furthermore, this review embodied the challenges and future directions of current NAS–gut microbiome research to inspire advanced examination of the NAS exposure–gut microbiome–host metabolism axis. Full article
(This article belongs to the Special Issue Effects of Environmental Exposure on Host and Microbial Metabolism)
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20 pages, 662 KiB  
Review
Hydrogen-Rich Water to Enhance Exercise Performance: A Review of Effects and Mechanisms
by Qiaorui Zhou, Huixin Li, Ye Zhang, Yirui Zhao, Can Wang and Chang Liu
Metabolites 2024, 14(10), 537; https://doi.org/10.3390/metabo14100537 - 7 Oct 2024
Cited by 2 | Viewed by 6080
Abstract
Background: Hydrogen-rich water (HRW) has garnered significant interest within the sports and exercise science community due to its selective antioxidant properties. Despite its potential benefits, comprehensive reviews specifically addressing its effects on athletic performance are limited. This review aims to assess the [...] Read more.
Background: Hydrogen-rich water (HRW) has garnered significant interest within the sports and exercise science community due to its selective antioxidant properties. Despite its potential benefits, comprehensive reviews specifically addressing its effects on athletic performance are limited. This review aims to assess the impact of HRW on sports performance and explore the underlying molecular biological mechanisms, with the goal of elucidating how HRW might enhance athletic performance. Methods: This review synthesizes research on HRW by examining articles published between 1980 and April 2024 in databases such as PubMed, the Cochrane Library, Embase, Scopus, and Web of Science. Results: It highlights HRW’s effects on various aspects of athletic performance, including endurance, strength, sprint times, lunge movements, countermovement jump height, and time to exhaustion. While the precise mechanisms by which HRW affects athletic performance remain unclear, this review investigates its general molecular biological mechanisms beyond the specific context of sports. This provides a theoretical foundation for future research aimed at understanding how HRW can enhance athletic performance. HRW targets the harmful reactive oxygen and nitrogen species produced during intense exercise, thereby reducing oxidative stress—a critical factor in muscle fatigue, inflammation, and diminished athletic performance. HRW helps to scavenge hydroxyl radicals and peroxynitrite, regulate antioxidant enzymes, mitigate lipid peroxidation, reduce inflammation, protect against mitochondrial dysfunction, and modulate cellular signaling pathways. Conclusions: In summary, while a few studies have indicated that HRW may not produce significant beneficial effects, the majority of research supports the conclusion that HRW may enhance athletic performance across various sports. The potential mechanisms underlying these benefits are thought to involve HRW’s role as a selective antioxidant, its impact on oxidative stress, and its regulation of redox homeostasis. However, the specific molecular biological mechanisms through which HRW improves athletic performance remain to be fully elucidated. Full article
(This article belongs to the Section Nutrition and Metabolism)
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13 pages, 600 KiB  
Article
Association between Inflammatory and Metabolic Biomarkers and Common Mental Disorders among Adults: 2015 Health Survey of São Paulo, SP, Brazil
by Letícia do Nascimento Maximiano Ferreira, Regina Mara Fisberg, Flavia Mori Sarti and Marcelo Macedo Rogero
Metabolites 2024, 14(10), 535; https://doi.org/10.3390/metabo14100535 - 5 Oct 2024
Cited by 1 | Viewed by 1088
Abstract
Recent studies suggest that plasma inflammatory biomarker concentrations may represent valuable indicators for the diagnosis and prognosis of mental disorders. At the same time, metabolic alterations may contribute to the development and progression of systemic low-grade inflammation. Background/Objectives: This study evaluated the [...] Read more.
Recent studies suggest that plasma inflammatory biomarker concentrations may represent valuable indicators for the diagnosis and prognosis of mental disorders. At the same time, metabolic alterations may contribute to the development and progression of systemic low-grade inflammation. Background/Objectives: This study evaluated the association between plasma inflammatory biomarkers and common mental disorders (CMD), exploring the relationship between metabolic biomarkers, metabolic syndrome (MetS), and inflammatory biomarkers in younger and older adults. Methods: This cross-sectional study used data from the 2015 Health Survey of São Paulo with a Focus on Nutrition Study. The occurrence of CMD was assessed through the Self-Reporting Questionnaire (SRQ-20). Blood samples were used to measure plasma concentrations of inflammatory and cardiometabolic biomarkers. MetS was defined according to the International Diabetes Federation Consensus. The Mann–Whitney test compared inflammatory biomarker concentrations across CMD groups and cardiometabolic conditions, and logistic regression models explored associations between inflammatory biomarker concentration and CMD. Results: The sample included 575 participants, 22.6% (n = 130) of whom had CMD. Concentrations of plasminogen activator inhibitor 1, C-reactive protein (CRP), and the systemic low-grade inflammation score varied significantly among CMD groups. CRP concentrations were positively associated with the presence of CMD, independent of confounding factors. Participants with insulin resistance, dyslipidemia, and MetS exhibited significantly higher CRP concentrations than individuals without these conditions. Conclusions: The findings suggest that increased plasma CRP concentrations may be a potential risk factor for CMD. Higher CRP concentrations were observed in individuals with insulin resistance, dyslipidemia, and MetS. Future interventional studies should explore these hypotheses in diverse populations. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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16 pages, 2225 KiB  
Article
Resistant Potato Starch Supplementation Reduces Serum Free Fatty Acid Levels and Influences Bile Acid Metabolism
by Jason R. Bush, Izuchukwu Iwuamadi, Jun Han, David J. Schibli, David R. Goodlett and Edward C. Deehan
Metabolites 2024, 14(10), 536; https://doi.org/10.3390/metabo14100536 - 5 Oct 2024
Cited by 1 | Viewed by 2686
Abstract
Background: Resistant starches, such as high-amylose maize starch and resistant potato starch (RPS), have prebiotic effects that are linked to improved metabolism at >15 g/day, but the effects at lower doses have not been reported. Methods: We performed an exploratory post [...] Read more.
Background: Resistant starches, such as high-amylose maize starch and resistant potato starch (RPS), have prebiotic effects that are linked to improved metabolism at >15 g/day, but the effects at lower doses have not been reported. Methods: We performed an exploratory post hoc analysis of free fatty acids (FFAs), bile acids (BAs), and ketone bodies in serum previously collected from a randomized, double-blind, placebo-controlled clinical trial evaluating the effects of one- and four-week consumption of 3.5 g/day RPS versus a placebo using two-way ANOVA adjusted by pFDR. Associations between week 4 changes in FFAs, BAs, and ketone bodies were assessed by Pearson’s correlations. Results: RPS consumption reduced total FFAs relative to the placebo, including multiple unsaturated FFAs and octanedioic acid, with reductions in taurine- and glycine-conjugated secondary BAs also detected (q < 0.05). No changes in ketone bodies were observed (q > 0.05). Changes in 7-ketodeoxycholic acid (r = −0.595) and glycolithocholic acid (r = −0.471) were inversely correlated with treatment-induced reductions in FFAs for RPS but not the placebo, suggesting the effects were from the prebiotic. Shifts in β-hydroxybutyrate were further correlated with FFA changes in both treatments (q < 0.05). Conclusions: These findings demonstrate that low doses of RPS positively influence fatty acid metabolism in humans, reducing circulating levels of FFA and conjugated BAs. Full article
(This article belongs to the Special Issue Functional Foods and Natural Bioactive Compounds: Strategies to Face Metabolic Syndrome and Related Non-Communicable Diseases)
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16 pages, 1838 KiB  
Article
Comparative Impact of Organic Grass-Fed and Conventional Cattle-Feeding Systems on Beef and Human Postprandial Metabolomics—A Randomized Clinical Trial
by Meghan Spears, Gwendolyn Cooper, Brett Sather, Marguerite Bailey, Jane A. Boles, Brian Bothner and Mary P. Miles
Metabolites 2024, 14(10), 533; https://doi.org/10.3390/metabo14100533 - 3 Oct 2024
Cited by 3 | Viewed by 6336
Abstract
Background/Objectives: Cattle-feeding systems may have health implications for consumers of beef products. Organic grass-fed (GRA) and conventional (CON) cattle-feeding systems may result in beef products with differing metabolite profiles and therefore could impact the postprandial metabolomic response of consumers. This study aims to [...] Read more.
Background/Objectives: Cattle-feeding systems may have health implications for consumers of beef products. Organic grass-fed (GRA) and conventional (CON) cattle-feeding systems may result in beef products with differing metabolite profiles and therefore could impact the postprandial metabolomic response of consumers. This study aims to measure whole beef metabolomics and postprandial metabolomic response of consumers between GRA and CON beef to elucidate potential health implications. Methods: This study followed a randomized double-blind crossover design with healthy male and female subjects (n = 10). Plasma samples were taken at fasting (0) and postprandially for four hours after consumption of a steak from each condition. Untargeted metabolomic analysis of whole beef and human plasma samples used LC/MS. Multivariate and pathway enrichment analysis in MetaboAnalyst was used to investigate metabolite and biochemical pathways that distinguished CON and GRA. Results: Cattle-feeding systems impacted both postprandial and whole beef steak metabolomic profiles. Metabolites that contributed to this variation included carnitine species (Proionylcarnitine), fatty acids, amino acids (L-valine), and Calamendiol. These metabolites have been associated with oxidative stress, inflammation, and cardiovascular health. Functional pathway enrichment analysis revealed numerous amino acid degradation pathways, especially branched-chain amino acids, and fatty acid degradation that changed throughout the postprandial time course. Conclusions: These findings suggest that CON and GRA cattle-feeding systems differentially impact whole beef metabolomics, as well as consumer postprandial metabolic responses and the associated health implications. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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15 pages, 8732 KiB  
Article
Machine Learning-Based Plasma Metabolomics in Liraglutide-Treated Type 2 Diabetes Mellitus Patients and Diet-Induced Obese Mice
by Seokjae Park and Eun-Kyoung Kim
Metabolites 2024, 14(9), 483; https://doi.org/10.3390/metabo14090483 - 2 Sep 2024
Viewed by 1641
Abstract
Liraglutide, a glucagon-like peptide-1 receptor agonist, is effective in the treatment of type 2 diabetes mellitus (T2DM) and obesity. Despite its benefits, including improved glycemic control and weight loss, the common metabolic changes induced by liraglutide and correlations between those in rodents and [...] Read more.
Liraglutide, a glucagon-like peptide-1 receptor agonist, is effective in the treatment of type 2 diabetes mellitus (T2DM) and obesity. Despite its benefits, including improved glycemic control and weight loss, the common metabolic changes induced by liraglutide and correlations between those in rodents and humans remain unknown. Here, we used advanced machine learning techniques to analyze the plasma metabolomic data in diet-induced obese (DIO) mice and patients with T2DM treated with liraglutide. Among the machine learning models, Support Vector Machine was the most suitable for DIO mice, and Gradient Boosting was the most suitable for patients with T2DM. Through the cross-evaluation of machine learning models, we found that liraglutide promotes metabolic shifts and interspecies correlations in these shifts between DIO mice and patients with T2DM. Our comparative analysis helped identify metabolic correlations influenced by liraglutide between humans and rodents and may guide future therapeutic strategies for T2DM and obesity. Full article
(This article belongs to the Special Issue Nutrition and Metabolism in Human Diseases 2nd Edition)
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16 pages, 4642 KiB  
Article
Sitting Interruption Modalities during Prolonged Sitting Acutely Improve Postprandial Metabolome in a Crossover Pilot Trial among Postmenopausal Women
by Jeffrey S. Patterson, Brinda K. Rana, Haiwei Gu and Dorothy D. Sears
Metabolites 2024, 14(9), 478; https://doi.org/10.3390/metabo14090478 - 30 Aug 2024
Cited by 2 | Viewed by 1675
Abstract
Older adults sit during most hours of the day; more than 30% are considered physically inactive. The accumulation of prolonged sitting time is an exercise-independent risk factor for aging-related conditions such as cardiometabolic disease and cancer. Archival plasma samples from a randomized controlled, [...] Read more.
Older adults sit during most hours of the day; more than 30% are considered physically inactive. The accumulation of prolonged sitting time is an exercise-independent risk factor for aging-related conditions such as cardiometabolic disease and cancer. Archival plasma samples from a randomized controlled, four-condition crossover study conducted in 10 postmenopausal women with overweight or obesity were analyzed. During 5-hour conditions completed on separate days, the trial tested three interruption modalities: two-minute stands each 20 min (STS), hourly ten-minute standing breaks (Stand), hourly two-minute walks (Walk), and a controlled sit. Fasting baseline and 5-hour end point (2 h postprandial) samples were used for targeted metabolomic profiling. Condition-associated metabolome changes were compared using paired t-tests. STS eliminated the postprandial elevation of amino acid metabolites that was observed in the control. A norvaline derivative shown to have anti-hypertensive and -hyperglycemic effects was significantly increased during Stand and STS. Post-hoc testing identified 19 significantly different metabolites across the interventions. Tight metabolite clustering by condition was driven by amino acid, vasoactive, and sugar metabolites, as demonstrated by partial least squares-discriminant analyses. This exploratory study suggests that brief, low-intensity modalities of interrupting prolonged sitting can acutely elucidate beneficial cardiometabolic changes in postmenopausal women with cardiometabolic risk. Full article
(This article belongs to the Special Issue The Emerging Role of Metabolomics in Epidemiological Studies of Atherosclerosis and Cardiovascular Disease)
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25 pages, 5241 KiB  
Article
Impact of Phenylketonuria on the Serum Metabolome and Plasma Lipidome: A Study in Early-Treated Patients
by Jorine C. van der Weerd, Annemiek M. J. van Wegberg, Theo S. Boer, Udo F. H. Engelke, Karlien L. M. Coene, Ron A. Wevers, Stephan J. L. Bakker, Pim de Blaauw, Joost Groen, Francjan J. van Spronsen and M. Rebecca Heiner-Fokkema
Metabolites 2024, 14(9), 479; https://doi.org/10.3390/metabo14090479 - 30 Aug 2024
Cited by 1 | Viewed by 1696
Abstract
Background: Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU). Methods: To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of [...] Read more.
Background: Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU). Methods: To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of matched controls. Samples (lipidomics in EDTA-plasma (22 PKU and 22 controls) and metabolomics in serum (35 PKU and 20 controls)) were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Data were subjected to multivariate (PCA, OPLS-DA) and univariate (Mann–Whitney U test, p < 0.05) analyses. Results: Levels of 33 (of 20,443) lipid features and 56 (of 5885) metabolite features differed statistically between PKU patients and controls. For lipidomics, findings include higher glycerolipids, glycerophospholipids, and sphingolipids species. Significantly lower values were found for sterols and glycerophospholipids species. Seven features had unknown identities. Total triglyceride content was higher. Higher Phe and Phe catabolites, tryptophan derivatives, pantothenic acid, and dipeptides were observed for metabolomics. Ornithine levels were lower. Twenty-six metabolite features were not annotated. Conclusions: This study provides insight into the metabolic phenotype of PKU patients. Additional studies are required to establish whether the observed changes result from PKU itself, diet, and/or an unknown reason. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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24 pages, 1235 KiB  
Systematic Review
Peripheral Lipid Signatures, Metabolic Dysfunction, and Pathophysiology in Schizophrenia Spectrum Disorders
by Sally Wu, Kristoffer J. Panganiban, Jiwon Lee, Dan Li, Emily C.C. Smith, Kateryna Maksyutynska, Bailey Humber, Tariq Ahmed, Sri Mahavir Agarwal, Kristen Ward and Margaret Hahn
Metabolites 2024, 14(9), 475; https://doi.org/10.3390/metabo14090475 - 28 Aug 2024
Cited by 1 | Viewed by 1515
Abstract
Metabolic dysfunction is commonly observed in schizophrenia spectrum disorders (SSDs). The causes of metabolic comorbidity in SSDs are complex and include intrinsic or biological factors linked to the disorder, which are compounded by antipsychotic (AP) medications. The exact mechanisms underlying SSD pathophysiology and [...] Read more.
Metabolic dysfunction is commonly observed in schizophrenia spectrum disorders (SSDs). The causes of metabolic comorbidity in SSDs are complex and include intrinsic or biological factors linked to the disorder, which are compounded by antipsychotic (AP) medications. The exact mechanisms underlying SSD pathophysiology and AP-induced metabolic dysfunction are unknown, but dysregulated lipid metabolism may play a role. Lipidomics, which detects lipid metabolites in a biological sample, represents an analytical tool to examine lipid metabolism. This systematic review aims to determine peripheral lipid signatures that are dysregulated among individuals with SSDs (1) with minimal exposure to APs and (2) during AP treatment. To accomplish this goal, we searched MEDLINE, Embase, and PsychINFO databases in February 2024 to identify all full-text articles written in English where the authors conducted lipidomics in SSDs. Lipid signatures reported to significantly differ in SSDs compared to controls or in relation to AP treatment and the direction of dysregulation were extracted as outcomes. We identified 46 studies that met our inclusion criteria. Most of the lipid metabolites that significantly differed in minimally AP-treated patients vs. controls comprised glycerophospholipids, which were mostly downregulated. In the AP-treated group vs. controls, the significantly different metabolites were primarily fatty acyls, which were dysregulated in conflicting directions between studies. In the pre-to-post AP-treated patients, the most impacted metabolites were glycerophospholipids and fatty acyls, which were found to be primarily upregulated and conflicting, respectively. These lipid metabolites may contribute to SSD pathophysiology and metabolic dysfunction through various mechanisms, including the modulation of inflammation, cellular membrane permeability, and metabolic signaling pathways. Full article
(This article belongs to the Special Issue Metabolomics in Disease Mechanisms and Drug Targets)
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24 pages, 377 KiB  
Review
An Overview of Pre-Analytical Factors Impacting Metabolomics Analyses of Blood Samples
by Amy Thachil, Li Wang, Rupasri Mandal, David Wishart and Tom Blydt-Hansen
Metabolites 2024, 14(9), 474; https://doi.org/10.3390/metabo14090474 - 28 Aug 2024
Cited by 5 | Viewed by 2493
Abstract
Discrepant sample processing remains a significant challenge within blood metabolomics research, introducing non-biological variation into the measured metabolome and biasing downstream results. Inconsistency during the pre-analytical phase can influence experimental processes, producing metabolome measurements that are non-representative of in vivo composition. To minimize [...] Read more.
Discrepant sample processing remains a significant challenge within blood metabolomics research, introducing non-biological variation into the measured metabolome and biasing downstream results. Inconsistency during the pre-analytical phase can influence experimental processes, producing metabolome measurements that are non-representative of in vivo composition. To minimize variation, there is a need to create and adhere to standardized pre-analytical protocols for blood samples intended for use in metabolomics analyses. This will allow for reliable and reproducible findings within blood metabolomics research. In this review article, we provide an overview of the existing literature pertaining to pre-analytical factors that influence blood metabolite measurements. Pre-analytical factors including blood tube selection, pre- and post-processing time and temperature conditions, centrifugation conditions, freeze–thaw cycles, and long-term storage conditions are specifically discussed, with recommendations provided for best practices at each stage. Full article
(This article belongs to the Special Issue Metabolomics and Machine Learning for Improved Diagnostics and as a Tool to Accelerate Drug Development)
17 pages, 1998 KiB  
Article
Disposition of Oral Nalbuphine and Its Metabolites in Healthy Subjects and Subjects with Hepatic Impairment: Preliminary Modeling Results Using a Continuous Intestinal Absorption Model with Enterohepatic Recirculation
by Swati Nagar, Amale Hawi, Thomas Sciascia and Ken Korzekwa
Metabolites 2024, 14(9), 471; https://doi.org/10.3390/metabo14090471 - 27 Aug 2024
Viewed by 1224
Abstract
Nalbuphine (NAL) is a mixed κ-agonist/μ-antagonist opioid with extensive first-pass metabolism. A phase 1 open-label study was conducted to characterize the pharmacokinetics (PKs) of NAL and select metabolites following single oral doses of NAL extended-release tablets in subjects with mild, moderate, and severe [...] Read more.
Nalbuphine (NAL) is a mixed κ-agonist/μ-antagonist opioid with extensive first-pass metabolism. A phase 1 open-label study was conducted to characterize the pharmacokinetics (PKs) of NAL and select metabolites following single oral doses of NAL extended-release tablets in subjects with mild, moderate, and severe hepatic impairment (Child–Pugh A, B, and C, respectively) compared to healthy matched subjects. NAL exposures were similar for subjects with mild hepatic impairment as compared to healthy subjects and nearly three-fold and eight-fold higher in subjects with moderate and severe hepatic impairment, respectively. Datasets obtained for healthy, moderate, and severe hepatic impaired groups were modeled with a mechanistic model that incorporated NAL hepatic metabolism and enterohepatic recycling of NAL and its glucuronidated metabolites. The mechanistic model includes a continuous intestinal absorption model linked to semi-physiological liver–gallbladder–compartmental PK models based on partial differential equations (termed the PDE-EHR model). In vitro studies indicated that cytochromes P450 CYP2C9 and CYP2C19 are the major CYPs involved in NAL oxidation, with glucuronidation mainly catalyzed by UGT1A8 and UGT2B7 isozymes. Complex formation and elimination kinetics of NAL and four main metabolites was well predicted by PDE-EHR. The model is expected to improve predictions of drug interactions and complex drug disposition. Full article
(This article belongs to the Special Issue The Role of Metabolites in Translational and Clinical Pharmacology)
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16 pages, 3813 KiB  
Article
Combining the Vaginal Microbiome and Serum Metabolome to Screen for Potential Biomarkers of Early Pregnancy in Cows
by Yan Luo, Zhen Wang, Xin Zhao, Jiankang Xing, Zhiliang Chen, Wenxue Zhao, Xiaoqing Long, Yanbing Zhang and Yongbin Shao
Metabolites 2024, 14(9), 469; https://doi.org/10.3390/metabo14090469 - 26 Aug 2024
Viewed by 1472
Abstract
Early pregnancy diagnostic techniques are of significant importance in livestock farming, particularly in dairy farming. This study aimed to screen artificially inseminated cows for potential biomarkers at day 21 of pregnancy using microbiota–metabolomics analysis. The microbiome analysis revealed significant changes (p < [...] Read more.
Early pregnancy diagnostic techniques are of significant importance in livestock farming, particularly in dairy farming. This study aimed to screen artificially inseminated cows for potential biomarkers at day 21 of pregnancy using microbiota–metabolomics analysis. The microbiome analysis revealed significant changes (p < 0.05) in the composition and abundance of the vaginal microbiota in cows after pregnancy. Notably, there was an increase in the abundance of [Eubacterium]_hallii_group (p < 0.05) associated with the production of short-chain fatty acids in the pregnant group compared with the non-pregnant group. Furthermore, significant alterations were observed in the serum metabolome, with notable changes in the concentrations of prolyl-hydroxyproline (Pro-Hyp) (p < 0.01) and bonactin (p < 0.01). The majority of differential metabolites clustered within the pathways of amino acid metabolism and lipid metabolism, with lipid metabolism exhibiting a higher proportion and playing a pivotal role in early pregnancy. An enzyme-linked immunosorbent assay was employed to quantify three key metabolites of the arachidonic acid pathway. The results demonstrated significant decreases in serum concentrations of leukotriene B4 (LTB4) (p < 0.05) and prostaglandin F2α (PGF2α) (p < 0.01) and no significant changes in arachidonic acid (AA) (NS) concentrations after 21 days of gestation in cows. Spearman’s correlation analysis was utilized to investigate the interrelationship between the vaginal microbiota and serum metabolites. In conclusion, the present study demonstrated that biomaterials such as bonactin, Pro-hyp, LTB4, PGF2α in serum metabolites and [Eubacterium]_hallii_group in the vaginal flora of cows could be utilized as potential biomarkers for 21 days of gestation in cows. Full article
(This article belongs to the Section Animal Metabolism)
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18 pages, 2528 KiB  
Article
The Effects of Maternal Nutrient Restriction during Mid to Late Gestation with Realimentation on Fetal Metabolic Profiles in the Liver, Skeletal Muscle, and Blood in Sheep
by Brandon I. Smith, Manuel A. Vásquez-Hidalgo, Xiaomeng Li, Kimberly A. Vonnahme, Anna T. Grazul-Bilska, Kendall C. Swanson, Timothy E. Moore, Sarah A. Reed and Kristen E. Govoni
Metabolites 2024, 14(9), 465; https://doi.org/10.3390/metabo14090465 - 23 Aug 2024
Cited by 1 | Viewed by 1548
Abstract
Poor maternal nutrition during gestation negatively affects offspring growth and metabolism. To evaluate the impact of maternal nutrient restriction and realimentation on metabolism in the fetal liver, skeletal muscle, and circulation, on day 50 of gestation, ewes (n = 48) pregnant with [...] Read more.
Poor maternal nutrition during gestation negatively affects offspring growth and metabolism. To evaluate the impact of maternal nutrient restriction and realimentation on metabolism in the fetal liver, skeletal muscle, and circulation, on day 50 of gestation, ewes (n = 48) pregnant with singletons were fed 100% (CON) or 60% (RES) of requirements until day 90 of gestation, when a subset of ewes (n = 7/treatment) were euthanized, and fetal samples were collected. The remaining ewes were maintained on a current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to an alternative diet (CON-RES, RES-CON; n = 7/treatment). On day 130 of gestation, the remaining ewes were euthanized, and fetal samples were collected. Fetal liver, longissimus dorsi (LD), and blood metabolites were analyzed using LC-MS/MS, and pathway enrichment analysis was conducted using MetaboAnalyst. Then, 600, 518, and 524 metabolites were identified in the liver, LD, and blood, respectively, including 345 metabolites that were present in all three. Nutrient restriction was associated with changes in amino acid, carbohydrate, lipid, and transulfuration/methionine metabolic pathways, some of which were alleviated by realimentation. Fetal age also affected metabolite abundance. The differential abundance of metabolites involved in amino acid, methionine, betaine, and bile acid metabolism could impact fetal epigenetic regulation, protein synthesis, lipid metabolism, and signaling associated with glucose and lipid metabolism. Full article
(This article belongs to the Special Issue Unlocking the Mysteries of Muscle Metabolism in the Animal Sciences)
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14 pages, 2082 KiB  
Article
Untargeted Blood Lipidomics Analysis in Critically Ill Pediatric Patients with Ventilator-Associated Pneumonia: A Pilot Study
by Christina Virgiliou, Olga Begou, Argyro Ftergioti, Maria Simitsopoulou, Maria Sdougka, Emmanuel Roilides, Georgios Theodoridis, Helen Gika and Elias Iosifidis
Metabolites 2024, 14(9), 466; https://doi.org/10.3390/metabo14090466 - 23 Aug 2024
Viewed by 1296
Abstract
This study aims to explore the diagnostic potential of blood lipid profiles in suspected ventilator-associated pneumonia (VAP). Early detection of VAP remains challenging for clinicians due to subjective clinical criteria and the limited effectiveness of current diagnostic tests. Blood samples from 20 patients, [...] Read more.
This study aims to explore the diagnostic potential of blood lipid profiles in suspected ventilator-associated pneumonia (VAP). Early detection of VAP remains challenging for clinicians due to subjective clinical criteria and the limited effectiveness of current diagnostic tests. Blood samples from 20 patients, with ages between 6 months and 15 years, were collected at days 1, 3, 6, and 12, and an untargeted lipidomics analysis was performed using a Ultra high Pressure Liquid Chromatography hyphenated with High Resolution Mass Spectrometry UPLC-HRMS (TIMS-TOF/MS) platform. Patients were stratified based on modified pediatric clinical pulmonary index score (mCPIS) into high (mCPIS ≥ 6, n = 12) and low (mCPIS < 6, n = 8) VAP suspicion groups. With the untargeted lipid profiling, we were able to identify 144 lipid species from different lipid groups such as glycerophospholipids, glycerolipids, and sphingolipids, in the blood of children with VAP. Multivariate and univariate statistical analyses revealed a distinct distribution of blood lipid profiles between the studied groups, indicating the potential utility of lipid biomarkers in discriminating VAP presence. Additionally, specific lipids were associated with pharyngeal culture results, notably the presence of Klebsiella pneumoniae and Staphylococcus aureus, underscoring the importance of lipid profiling in identifying the microbial etiology of VAP. Full article
(This article belongs to the Special Issue Metabolomics: An Emerging Potential Approach to Study Critical Illnesses, 2nd Edition)
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20 pages, 590 KiB  
Article
Metabolite Predictors of Breast and Colorectal Cancer Risk in the Women’s Health Initiative
by Sandi L. Navarro, Brian D. Williamson, Ying Huang, G. A. Nagana Gowda, Daniel Raftery, Lesley F. Tinker, Cheng Zheng, Shirley A. A. Beresford, Hayley Purcell, Danijel Djukovic, Haiwei Gu, Howard D. Strickler, Fred K. Tabung, Ross L. Prentice, Marian L. Neuhouser and Johanna W. Lampe
Metabolites 2024, 14(8), 463; https://doi.org/10.3390/metabo14080463 - 20 Aug 2024
Cited by 4 | Viewed by 2149
Abstract
Metabolomics has been used extensively to capture the exposome. We investigated whether prospectively measured metabolites provided predictive power beyond well-established risk factors among 758 women with adjudicated cancers [n = 577 breast (BC) and n = 181 colorectal (CRC)] and n = [...] Read more.
Metabolomics has been used extensively to capture the exposome. We investigated whether prospectively measured metabolites provided predictive power beyond well-established risk factors among 758 women with adjudicated cancers [n = 577 breast (BC) and n = 181 colorectal (CRC)] and n = 758 controls with available specimens (collected mean 7.2 years prior to diagnosis) in the Women’s Health Initiative Bone Mineral Density subcohort. Fasting samples were analyzed by LC-MS/MS and lipidomics in serum, plus GC-MS and NMR in 24 h urine. For feature selection, we applied LASSO regression and Super Learner algorithms. Prediction models were subsequently derived using logistic regression and Super Learner procedures, with performance assessed using cross-validation (CV). For BC, metabolites did not increase predictive performance over established risk factors (CV-AUCs~0.57). For CRC, prediction increased with the addition of metabolites (median CV-AUC across platforms increased from ~0.54 to ~0.60). Metabolites related to energy metabolism: adenosine, 2-hydroxyglutarate, N-acetyl-glycine, taurine, threonine, LPC (FA20:3), acetate, and glycerate; protein metabolism: histidine, leucic acid, isoleucine, N-acetyl-glutamate, allantoin, N-acetyl-neuraminate, hydroxyproline, and uracil; and dietary/microbial metabolites: myo-inositol, trimethylamine-N-oxide, and 7-methylguanine, consistently contributed to CRC prediction. Energy metabolism may play a key role in the development of CRC and may be evident prior to disease development. Full article
(This article belongs to the Special Issue Metabolomics-Based Biomarkers for Nutrition and Health)
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12 pages, 1894 KiB  
Article
Alterations in Choline Metabolism in Non-Obese Individuals with Insulin Resistance and Type 2 Diabetes Mellitus
by Haya Al-Sulaiti, Najeha Anwardeen, Sara S. Bashraheel, Khaled Naja and Mohamed A. Elrayess
Metabolites 2024, 14(8), 457; https://doi.org/10.3390/metabo14080457 - 18 Aug 2024
Cited by 2 | Viewed by 1717
Abstract
The prevalence of non-obese individuals with insulin resistance (IR) and type 2 diabetes (T2D) is increasing worldwide. This study investigates the metabolic signature of phospholipid-associated metabolites in non-obese individuals with IR and T2D, aiming to identify potential biomarkers for these metabolic disorders. The [...] Read more.
The prevalence of non-obese individuals with insulin resistance (IR) and type 2 diabetes (T2D) is increasing worldwide. This study investigates the metabolic signature of phospholipid-associated metabolites in non-obese individuals with IR and T2D, aiming to identify potential biomarkers for these metabolic disorders. The study cohort included non-obese individuals from the Qatar Biobank categorized into three groups: insulin sensitive, insulin resistant, and patients with T2D. Each group comprised 236 participants, totaling 708 individuals. Metabolomic profiling was conducted using high-resolution mass spectrometry, and statistical analyses were performed to identify metabolites associated with the progression from IS to IR and T2D. The study observed significant alterations in specific phospholipid metabolites across the IS, IR, and T2D groups. Choline phosphate, glycerophosphoethanolamine, choline, glycerophosphorylcholine (GPC), and trimethylamine N-oxide showed significant changes correlated with disease progression. A distinct metabolic signature in non-obese individuals with IR and T2D was characterized by shifts in choline metabolism, including decreased levels of choline and trimethylamine N-oxide and increased levels of phosphatidylcholines, phosphatidylethanolamines, and their degradation products. These findings suggest that alterations in choline metabolism may play a critical role in the development of glucose intolerance and insulin resistance. Targeting choline metabolism could offer potential therapeutic strategies for treating T2D. Further research is needed to validate these biomarkers and understand their functional significance in the pathogenesis of IR and T2D in non-obese populations. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Metabolomics in Health and Disease: Targeted Analysis)
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15 pages, 985 KiB  
Article
Local and Systemic Micro-Rheological Changes during Intestinal Anastomosis Operation: A Metabolic Dependence in an Experimental Model
by Adam Varga, Adam Attila Matrai, Barbara Bedocs-Barath, Laszlo Adam Fazekas, Felipe Salignac Brasil, Aashna Mehta, Erzsebet Vanyolos, Adam Deak, Tamas Lesznyak, Katalin Peto and Norbert Nemeth
Metabolites 2024, 14(8), 458; https://doi.org/10.3390/metabo14080458 - 18 Aug 2024
Viewed by 1299
Abstract
Hemorheological factors may show arterio-venous differences. Alterations in acid-base and metabolic parameters may also influence these factors. However, little is known about changes in micro-rheological parameters during abdominal surgery, influencing splanchnic circulation. In anesthetized pigs, the external jugular vein, femoral artery and vein [...] Read more.
Hemorheological factors may show arterio-venous differences. Alterations in acid-base and metabolic parameters may also influence these factors. However, little is known about changes in micro-rheological parameters during abdominal surgery, influencing splanchnic circulation. In anesthetized pigs, the external jugular vein, femoral artery and vein were cannulated unilaterally, and paramedian laparotomy was performed. In the anastomosis group, after resecting a bowel segment, end-to-end jejuno-jejunostomy was completed. Blood samples (from cannulas and by puncturing the portal vein) were taken before and after the intervention. Hematological, acid-base and blood gas parameters, metabolites, red blood cell (RBC) deformability and aggregation were determined. The highest hematocrit was found in portal blood, increasing further by the end of operation. A significant pH decrease was seen, and portal blood showed the highest lactate and creatinine concentration. The highest RBC aggregation values were found in arterial, the lowest in renal venous blood. The RBC aggregation increased with higher lactate concentration and lower pH. Osmotic gradient deformability declined, with the lowest values in portal and renal venous samples. In conclusion, micro-rheological parameters showed arterio-venous and porto-renal venous differences, influenced by oxygenation level, pH and lactate concentration. The intestinal anastomosis operation caused an immediate micro-rheological deterioration with portal venous dominancy in this experiment. Full article
(This article belongs to the Special Issue Metabolic Biomarkers and Nutrition in Degenerative Conditions and Gastrointestinal Cancer Surgery)
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16 pages, 3811 KiB  
Article
Comparison of Growth and Metabolomic Profiles of Two Afforestation Cypress Species Cupressus chengiana and Platycladus orientalis Grown at Minjiang Valley in Southwest China
by Zhengqiao Liao, Lijun Zhu, Lei Liu, Jürgen Kreuzwieser, Christiane Werner and Baoguo Du
Metabolites 2024, 14(8), 453; https://doi.org/10.3390/metabo14080453 - 17 Aug 2024
Cited by 1 | Viewed by 1027
Abstract
In recent years, afforestation has been conducted in China’s hot and dry valleys. However, there is still a paucity of knowledge regarding the performance of tree species in these semi-arid regions, particularly with regard to interspecies differences. The present study compares the growth [...] Read more.
In recent years, afforestation has been conducted in China’s hot and dry valleys. However, there is still a paucity of knowledge regarding the performance of tree species in these semi-arid regions, particularly with regard to interspecies differences. The present study compares the growth and metabolome characteristics of two widely used cypress species, namely Cupressus chengiana and Platycladus orientalis, grown at two sites with distinct climate conditions in the hot and dry Minjiang Valley in southwestern China. The findings indicate that C. chengiana trees exhibit superior growth rates compared to P. orientalis trees at both study sites. In comparison to P. orientalis trees, C. chengiana trees demonstrated a greater tendency to close their stomata in order to prevent water loss at the hotter and drier site, Llianghekou (LHK). Additionally, C. chengiana trees exhibited significantly lower hydrogen peroxide levels than P. orientalis trees, either due to lower production and/or higher scavenging of reactive oxygen species. C. chengiana trees accumulated soluble sugars as well as sugar derivatives, particularly those involved in sucrose and galactose metabolisms under stressful conditions. The species-specific differences were also reflected in metabolites involved in the tricarboxylic acid cycle, nitrogen, and secondary metabolisms. The metabolome profiles of the two species appeared to be influenced by the prevailing climatic conditions. It appeared that the trees at the drier and hotter site, LHK, were capable of efficient nitrogen uptake from the soil despite the low soil nitrogen concentration. This study is the first to compare the growth performance and metabolic profiles of two widely used tree species with high resistance to adverse conditions. In addition to the species-specific differences and adaptations to different sites, the present study also provides insights into potential management strategies to alleviate abiotic stress, particularly with regard to nitrogen nutrients, in the context of climate change. Full article
(This article belongs to the Special Issue Metabolic Responses of Plants to Abiotic Stress)
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14 pages, 2236 KiB  
Article
Characterizing Growth-Retarded Japanese Eels (Anguilla japonica): Insights into Metabolic and Appetite Regulation
by Xiangbiao Zeng, Jingwei Liu, Yiwen Chen, Huan Han, Yanhe Liu, Bin Xie, Tianwei Jiang, Chris Kong-Chu Wong, Kang Li and Liping Liu
Metabolites 2024, 14(8), 432; https://doi.org/10.3390/metabo14080432 - 5 Aug 2024
Viewed by 2006
Abstract
During field surveys and culture procedures, large growth disparities in Anguilla japonica have been observed. However, the potential causes are unknown. This study explored differences in digestive ability, metabolic levels, and transcriptomic profiles of appetite-related genes between growth-retarded eel (GRE) and normal-growing eel [...] Read more.
During field surveys and culture procedures, large growth disparities in Anguilla japonica have been observed. However, the potential causes are unknown. This study explored differences in digestive ability, metabolic levels, and transcriptomic profiles of appetite-related genes between growth-retarded eel (GRE) and normal-growing eel (NGE) under the same rearing conditions. The results showed that growth hormone (gh) mRNA expression in GREs was considerably lower than NGEs. The levels of total protein (TP), total cholesterol (T-CHO), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood ammonia (BA), blood urea nitrogen (BUN), and alkaline phosphatase (ALP) in GREs were significantly lower than in NGEs. Conversely, levels of glucose (GLU), alanine aminotransferase (ALT), and aspartate transaminase (AST) were higher in GREs. The activities of SOD, CAT, and T-AOC levels were also significantly lower in GREs, as were the activities of glucose-related enzymes including hexokinase (HK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PASE). Additionally, orexigenic genes (npy and ghrelin) were dramatically downregulated, whereas anorexigenic genes (crh and pyy) were significantly upregulated in GREs. These findings suggested that variances in growth hormone, metabolic activities, and appetite level could be associated with the different growth rates of A. japonica. The present research not only revealed the characteristics of the growth, metabolism, and appetite of GREs but also offered new perspectives into the substantial growth discrepancies in A. japonica, providing novel ideas for enhancing fish growth. Full article
(This article belongs to the Special Issue Nutrition, Metabolism and Physiology in Aquatic Animals)
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25 pages, 7059 KiB  
Article
Propionic Acidemia, Methylmalonic Acidemia, and Cobalamin C Deficiency: Comparison of Untargeted Metabolomic Profiles
by Anna Sidorina, Giulio Catesini, Elisa Sacchetti, Cristiano Rizzo and Carlo Dionisi-Vici
Metabolites 2024, 14(8), 428; https://doi.org/10.3390/metabo14080428 - 2 Aug 2024
Cited by 3 | Viewed by 1895
Abstract
Methylmalonic acidemia (MMA), propionic acidemia (PA), and cobalamin C deficiency (cblC) share a defect in propionic acid metabolism. In addition, cblC is also involved in the process of homocysteine remethylation. These three diseases produce various phenotypes and complex downstream metabolic effects. In this [...] Read more.
Methylmalonic acidemia (MMA), propionic acidemia (PA), and cobalamin C deficiency (cblC) share a defect in propionic acid metabolism. In addition, cblC is also involved in the process of homocysteine remethylation. These three diseases produce various phenotypes and complex downstream metabolic effects. In this study, we used an untargeted metabolomics approach to investigate the biochemical differences and the possible connections among the pathophysiology of each disease. The significantly changed metabolites in the untargeted urine metabolomic profiles of 21 patients (seven MMA, seven PA, seven cblC) were identified through statistical analysis (p < 0.05; log2FC > |1|) and then used for annotation. Annotated features were associated with different metabolic pathways potentially involved in the disease’s development. Comparative statistics showed markedly different metabolomic profiles between MMA, PA, and cblC, highlighting the characteristic species for each disease. The most affected pathways were related to the metabolism of organic acids (all diseases), amino acids (all diseases), and glycine and its conjugates (in PA); the transsulfuration pathway; oxidative processes; and neurosteroid hormones (in cblC). The untargeted metabolomics study highlighted the presence of significant differences between the three diseases, pointing to the most relevant contrast in the cblC profile compared to MMA and PA. Some new biomarkers were proposed for PA, while novel data regarding the alterations of steroid hormone profiles and biomarkers of oxidative stress were obtained for cblC disease. The elevation of neurosteroids in cblC may indicate a potential connection with the development of ocular and neuronal deterioration. Full article
(This article belongs to the Special Issue New Advancements and Challenges in Clinical Metabolomics for Inborn Errors of Metabolism and Rare Diseases)
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11 pages, 4526 KiB  
Review
Metabolic Pathways in Hydrocephalus: Profiling with Proteomics and Advanced Imaging
by Laura May Davis and Misun Hwang
Metabolites 2024, 14(8), 412; https://doi.org/10.3390/metabo14080412 - 27 Jul 2024
Cited by 1 | Viewed by 1359
Abstract
Hemorrhagic hydrocephalus is a common pathology in neonates with high mortality and morbidity. Current imaging approaches fail to capture the mechanisms behind its pathogenesis. Here, we discuss the processes underlying this pathology, the metabolic dysfunction that occurs as a result, and the ways [...] Read more.
Hemorrhagic hydrocephalus is a common pathology in neonates with high mortality and morbidity. Current imaging approaches fail to capture the mechanisms behind its pathogenesis. Here, we discuss the processes underlying this pathology, the metabolic dysfunction that occurs as a result, and the ways in which these metabolic changes inform novel methods of clinical imaging. The imaging advances described allow earlier detection of the cellular and metabolic changes, leading to better outcomes for affected neonates. Full article
(This article belongs to the Special Issue Neurometabolic Monitoring and Imaging in Pediatric Critical Care)
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12 pages, 1732 KiB  
Article
Metabolic Plasticity of Glioblastoma Cells in Response to DHODH Inhibitor BAY2402234 Treatment
by Ayenachew Bezawork-Geleta, Diane Moujalled, David P. De Souza, Vinod K. Narayana, James Dimou, Rodney Luwor and Matthew J. Watt
Metabolites 2024, 14(8), 413; https://doi.org/10.3390/metabo14080413 - 27 Jul 2024
Cited by 1 | Viewed by 1470
Abstract
Glioblastoma (IDH-wildtype) represents a formidable challenge in oncology, lacking effective chemotherapeutic or biological interventions. The metabolic reprogramming of cancer cells is a hallmark of tumor progression and drug resistance, yet the role of metabolic reprogramming in glioblastoma during drug treatment remains poorly understood. [...] Read more.
Glioblastoma (IDH-wildtype) represents a formidable challenge in oncology, lacking effective chemotherapeutic or biological interventions. The metabolic reprogramming of cancer cells is a hallmark of tumor progression and drug resistance, yet the role of metabolic reprogramming in glioblastoma during drug treatment remains poorly understood. The dihydroorotate dehydrogenase (DHODH) inhibitor BAY2402234 is a blood–brain barrier penetrant drug showing efficiency in in vivo models of many brain cancers. In this study, we investigated the effect of BAY2402234 in regulating the metabolic phenotype of EGFRWT and EGFRvIII patient-derived glioblastoma cell lines. Our findings reveal the selective cytotoxicity of BAY2402234 toward EGFRWT glioblastoma subtypes with minimal effect on EGFRvIII patient cells. At sublethal doses, BAY2402234 induces triglyceride synthesis at the expense of membrane lipid synthesis and fatty acid oxidation in EGFRWT glioblastoma cells, while these effects are not observed in EGFRvIII glioblastoma cells. Furthermore, BAY2402234 reduced the abundance of signaling lipid species in EGFRWT glioblastoma. This study elucidates genetic mutation-specific metabolic plasticity and efficacy in glioblastoma cells in response to drug treatment, offering insights into therapeutic avenues for precision medicine approaches. Full article
(This article belongs to the Section Lipid Metabolism)
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18 pages, 7899 KiB  
Article
Metabolomic Profiling of Adipose Tissue in Type 2 Diabetes: Associations with Obesity and Insulin Resistance
by Argyri Mathioudaki, Giovanni Fanni, Jan W. Eriksson and Maria J. Pereira
Metabolites 2024, 14(8), 411; https://doi.org/10.3390/metabo14080411 - 26 Jul 2024
Viewed by 1782
Abstract
The global prevalence of Type 2 Diabetes (T2D) poses significant public health challenges due to its associated severe complications. Insulin resistance is central to T2D pathophysiology, particularly affecting adipose tissue function. This cross-sectional observational study investigates metabolic alterations in subcutaneous adipose tissue (SAT) [...] Read more.
The global prevalence of Type 2 Diabetes (T2D) poses significant public health challenges due to its associated severe complications. Insulin resistance is central to T2D pathophysiology, particularly affecting adipose tissue function. This cross-sectional observational study investigates metabolic alterations in subcutaneous adipose tissue (SAT) associated with T2D to identify potential therapeutic targets. We conducted a comprehensive metabolomic analysis of SAT from 40 participants (20 T2D, 20 ND-T2D), matched for sex, age, and BMI (Body Mass Index). Metabolite quantification was performed using GC/MS and LC/MS/MS platforms. Correlation analyses were conducted to explore associations between metabolites and clinical parameters. We identified 378 metabolites, including significant elevations in TCA cycle (tricarboxylic acid cycle) intermediates, branched-chain amino acids (BCAAs), and carbohydrates, and a significant reduction in the nucleotide-related metabolites in T2D subjects compared to those without T2D. Obesity exacerbated these alterations, particularly in amino acid metabolism. Adipocyte size negatively correlated with BCAAs, while adipocyte glucose uptake positively correlated with unsaturated fatty acids and glycerophospholipids. Our findings reveal distinct metabolic dysregulation in adipose tissue in T2D, particularly in energy metabolism, suggesting potential therapeutic targets for improving insulin sensitivity and metabolic health. Future studies should validate these findings in larger cohorts and explore underlying mechanisms to develop targeted interventions. Full article
(This article belongs to the Special Issue Metabolism in Diabetes Progression and Diabetic Complications)
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19 pages, 4642 KiB  
Article
Photosynthetic Activities, Phytohormones, and Secondary Metabolites Induction in Plants by Prevailing Compost Residue
by Lord Abbey, Samuel Kwaku Asiedu, Sparsha Chada, Raphael Ofoe, Peter Ofori Amoako, Stella Owusu-Nketia, Nivethika Ajeethan, Anagha Pradeep Kumar and Efoo Bawa Nutsukpo
Metabolites 2024, 14(8), 400; https://doi.org/10.3390/metabo14080400 - 24 Jul 2024
Viewed by 1425
Abstract
Compost residue enriches soil health with the potential to enhance plant metabolism and hormonal balance, but has not yet been studied. A study was performed to determine how prevailing compost residue induces tomato (Solanum lycopersicum ‘Scotia’) plant morpho-physiology, phytohormones, and secondary metabolites. [...] Read more.
Compost residue enriches soil health with the potential to enhance plant metabolism and hormonal balance, but has not yet been studied. A study was performed to determine how prevailing compost residue induces tomato (Solanum lycopersicum ‘Scotia’) plant morpho-physiology, phytohormones, and secondary metabolites. Plants were grown in soils with a previous history of annual (AN) and biennial (BI) compost amendments. The controls were soil without compost (C) amendment and municipal solid waste compost (MSWC) alone. The MSWC- and AN-plants had similar and significantly (p < 0.05) highest growth and photosynthetic activities compared to the BI- or C-plants. Total phenolics and lipid peroxidase activity were significantly (p < 0.001) high in BI-plants, while hydrogen peroxide and antioxidant capacity were significantly (p < 0.001) high in AN-plants. MSWC-plants recorded the highest cis-abscisic acid, followed by AN-, and then BI- and C-plants. Cis-zeatin, trans-zeatin, and isopentenyladenine ribosides were detected in the MSWC- and AN-plants but not in the BI- or C-plants. Furthermore, gibberellins GA53, GA19, and GA8 were high in the MSWC-plants, but only GA8 was detected in the AN plants and none in the others. Besides, MSWC plants exhibited the highest content of 1-aminocyclopropane-1-carboxylic acid. Conjugated salicylic acid was highest in the BI-plants, while jasmonic acid-isoleucine was highest in MSWC-plants and C plants. In conclusion, prevailing compost chemical residues upregulate plant growth, phytohormones, and metabolic compounds that can potentially increase plant growth and abiotic stress defense. Future work should investigate the flow of these compounds in plants under abiotic stress. Full article
(This article belongs to the Special Issue Plant Biotic and Abiotic Stress Responses and Tolerance: Phytohormonal and Metabolic Insights)
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