Journal Description
Metabolites
Metabolites
is an international, peer-reviewed, open access journal of metabolism and metabolomics, published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Biochemistry & Molecular Biology) / CiteScore - Q2 (Endocrinology, Diabetes and Metabolism)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 13.2 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.1 (2022);
5-Year Impact Factor:
4.5 (2022)
Latest Articles
Application of the Hydrophilic Interaction Liquid Chromatography (HILIC-MS) Novel Protocol to Study the Metabolic Heterogeneity of Glioblastoma Cells
Metabolites 2024, 14(6), 297; https://doi.org/10.3390/metabo14060297 (registering DOI) - 23 May 2024
Abstract
►
Show Figures
Glioblastoma is a highly malignant brain tumor consisting of a heterogeneous cellular population. The transformed metabolism of glioblastoma cells supports their growth and division on the background of their milieu. One might hypothesize that the transformed metabolism of a primary glioblastoma could be
[...] Read more.
Glioblastoma is a highly malignant brain tumor consisting of a heterogeneous cellular population. The transformed metabolism of glioblastoma cells supports their growth and division on the background of their milieu. One might hypothesize that the transformed metabolism of a primary glioblastoma could be well adapted to limitations in the variety and number of substrates imported into the brain parenchyma and present it their microenvironment. Additionally, the phenotypic heterogeneity of cancer cells could promote the variations among their metabolic capabilities regarding the utilization of available substrates and release of metabolic intermediates. With the aim to identify the putative metabolic footprint of different types of glioblastoma cells, we exploited the possibility for separation of polar and ionic molecules present in culture media or cell lysates by hydrophilic interaction liquid chromatography (HILIC). The mass spectrometry (MS) was then used to identify and quantify the eluted compounds. The introduced method allows the detection and quantification of more than 150 polar and ionic metabolites in a single run, which may be present either in culture media or cell lysates and provide data for polaromic studies within metabolomics. The method was applied to analyze the culture media and cell lysates derived from two types of glioblastoma cells, T98G and U118. The analysis revealed that even both types of glioblastoma cells share several common metabolic aspects, and they also exhibit differences in their metabolic capability. This finding agrees with the hypothesis about metabolic heterogeneity of glioblastoma cells. Furthermore, the combination of both analytical methods, HILIC-MS, provides a valuable tool for metabolomic studies based on the simultaneous identification and quantification of a wide range of polar and ionic metabolites—polaromics.
Full article
Open AccessReview
Can Daily Dietary Choices Have a Cardioprotective Effect? Food Compounds in the Prevention and Treatment of Cardiometabolic Diseases
by
Elżbieta Szczepańska, Barbara Janota, Marika Wlazło and Magdalena Gacal
Metabolites 2024, 14(6), 296; https://doi.org/10.3390/metabo14060296 (registering DOI) - 23 May 2024
Abstract
Cardiovascular diseases accompanying metabolic syndrome comprise one of the leading causes of death worldwide. The medical community undertakes attempts to improve treatment options and minimize cardiovascular diseases’ numerous consequences and exacerbations. In parallel with pharmacotherapies provided by physicians, nutritionists are developing strategies for
[...] Read more.
Cardiovascular diseases accompanying metabolic syndrome comprise one of the leading causes of death worldwide. The medical community undertakes attempts to improve treatment options and minimize cardiovascular diseases’ numerous consequences and exacerbations. In parallel with pharmacotherapies provided by physicians, nutritionists are developing strategies for diet therapy and prevention based on lifestyle changes, with high success rates. Consumption of specified food compounds included in various products with proven protective properties can be helpful in this regard. Due to the wide possibilities of diet in metabolic health promotion, it seems necessary to systematize information about the metabolically protective and cardioprotective properties of fiber, probiotic bacteria, plant sterols, folic acid, vitamins B12, C, and E, PUFAs, lycopene, polyphenols, arginine, CoQ10, and allicin. The aim of this review was to present the food compounds with potential use in cardiometabolic prevention and diet therapy based on the latest available literature.
Full article
(This article belongs to the Special Issue Impact of Food and Bioactive Compounds on Metabolic Diseases)
►▼
Show Figures
Figure 1
Open AccessArticle
Metabolites Associated with Polygenic Risk of Breast Cancer
by
Elizabeth Samuels, Jaclyn Parks, Jessica Chu, Treena McDonald, John Spinelli, Rachel A. Murphy and Parveen Bhatti
Metabolites 2024, 14(6), 295; https://doi.org/10.3390/metabo14060295 - 23 May 2024
Abstract
While hundreds of germline genetic variants have been associated with breast cancer risk, the mechanisms underlying the impacts of most of these variants on breast cancer remain uncertain. Metabolomics may offer valuable insights into the mechanisms underlying genetic risks of breast cancer. Among
[...] Read more.
While hundreds of germline genetic variants have been associated with breast cancer risk, the mechanisms underlying the impacts of most of these variants on breast cancer remain uncertain. Metabolomics may offer valuable insights into the mechanisms underlying genetic risks of breast cancer. Among 143 cancer-free female participants, we used linear regression analyses to explore associations between the genetic risk of breast cancer, as determined by a previously developed polygenic risk score (PRS) that included 266 single-nucleotide polymorphisms (SNPs), and 223 measures of metabolites obtained from blood samples using nuclear magnetic resonance (NMR). A false discovery rate of 10% was applied to account for multiple comparisons. PRS was statistically significantly associated with 45 metabolite measures. These were primarily measures of very low-density lipoproteins (VLDLs) and high-density lipoproteins (HDLs), including triglycerides, cholesterol, and phospholipids. For example, the strongest effect was observed with the percent ratio of medium VLDL triglycerides to total lipids (0.53 unit increase in mean-standardized ln-transformed percent ratio per unit increase in PRS; q = 0.1). While larger-scale studies are needed to confirm these results, this exploratory study presents biologically plausible findings that are consistent with previously reported associations between lipids and breast cancer risk. If confirmed, these lipids could be targeted for lifestyle and pharmaceutical interventions among women at increased genetic risk of breast cancer.
Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
►▼
Show Figures
Figure 1
Open AccessArticle
Genetic Evidence for Causal Relationships between Plasma Eicosanoid Levels and Cardiovascular Disease
by
Xukun Bi, Yiran Wang, Yangjun Lin, Meihui Wang and Xiaoting Li
Metabolites 2024, 14(6), 294; https://doi.org/10.3390/metabo14060294 - 23 May 2024
Abstract
Cardiovascular diseases are the most common causes of mortality and disability worldwide. Eicosanoids are a group of bioactive metabolites that are mainly oxidized by arachidonic acid. Eicosanoids play a diverse role in cardiovascular diseases, with some exerting beneficial effects while others have detrimental
[...] Read more.
Cardiovascular diseases are the most common causes of mortality and disability worldwide. Eicosanoids are a group of bioactive metabolites that are mainly oxidized by arachidonic acid. Eicosanoids play a diverse role in cardiovascular diseases, with some exerting beneficial effects while others have detrimental consequences. However, a causal relationship between eicosanoid levels and cardiovascular disease remains unclear. Six single nucleotide polymorphisms (SNPs) with strong associations with plasma eicosanoid levels were selected. Summary-level data for cardiovascular disease were obtained from publicly available genome-wide association studies. A two-sample MR analysis identified that plasma eicosanoid levels were inversely correlated with unstable angina pectoris (OR 1.06; 95% CI 1–1.12; p = 0.04), myocardial infarction (OR 1.05; 95% CI 1.02–1.09; p = 0.005), ischemia stroke (OR 1.05; 95% CI 1–1.11; p = 0.047), transient ischemic attack (OR 1.03; 95% CI 1–1.07; p = 0.042), heart failure (OR 1.03; 95% CI 1.01–1.05; p = 0.011), and pulmonary embolism (OR 1.08; 95% CI 1.02–1.14; p = 1.69 × 10−6). In conclusion, our data strongly suggest a genetic causal link between high plasma eicosanoid levels and an increased cardiovascular disease risk. This study provides genetic evidence for treating cardiovascular diseases.
Full article
(This article belongs to the Special Issue Nutrition and Metabolism in Human Diseases 2nd Edition)
►▼
Show Figures
Figure 1
Open AccessCorrection
Correction: Fadil et al. Isotope Ratio Outlier Analysis (IROA) for HPLC–TOFMS-Based Metabolomics of Human Urine. Metabolites 2022, 12, 741
by
Fadi Fadil, Claudia Samol, Raffaela S. Berger, Fabian Kellermeier, Wolfram Gronwald, Peter J. Oefner and Katja Dettmer
Metabolites 2024, 14(6), 293; https://doi.org/10.3390/metabo14060293 - 23 May 2024
Abstract
It was pointed out to us that we had not followed exactly the IROA TruQuant IQQ Workflow Kit protocol in the experimental part of our work [...]
Full article
Open AccessArticle
Metabolomics Profiling of Stages of Coronary Artery Disease Progression
by
Gulsen Guliz Anlar, Najeha Anwardeen, Sarah Al Ashmar, Shona Pedersen, Mohamed A. Elrayess and Asad Zeidan
Metabolites 2024, 14(6), 292; https://doi.org/10.3390/metabo14060292 - 22 May 2024
Abstract
Coronary artery disease (CAD) and atherosclerosis pose significant global health challenges, with intricate molecular changes influencing disease progression. Hypercholesterolemia (HC), hypertension (HT), and diabetes are key contributors to CAD development. Metabolomics, with its comprehensive analysis of metabolites, offers a unique perspective on cardiovascular
[...] Read more.
Coronary artery disease (CAD) and atherosclerosis pose significant global health challenges, with intricate molecular changes influencing disease progression. Hypercholesterolemia (HC), hypertension (HT), and diabetes are key contributors to CAD development. Metabolomics, with its comprehensive analysis of metabolites, offers a unique perspective on cardiovascular diseases. This study leveraged metabolomics profiling to investigate the progression of CAD, focusing on the interplay of hypercholesterolemia, hypertension, and diabetes. We performed a metabolomic analysis on 221 participants from four different groups: (I) healthy individuals, (II) individuals with hypercholesterolemia (HC), (III) individuals with both HC and hypertension (HT) or diabetes, and (IV) patients with self-reported coronary artery disease (CAD). Utilizing data from the Qatar Biobank, we combined clinical information, metabolomic profiling, and statistical analyses to identify key metabolites associated with CAD risk. Our data identified distinct metabolite profiles across the study groups, indicating changes in carbohydrate and lipid metabolism linked to CAD risk. Specifically, levels of mannitol/sorbitol, mannose, glucose, and ribitol increased, while pregnenediol sulfate, oleoylcarnitine, and quinolinate decreased with higher CAD risk. These findings suggest a significant role of sugar, steroid, and fatty acid metabolism in CAD progression and point to the need for further research on the correlation between quinolinate levels and CAD risk, potentially guiding targeted treatments for atherosclerosis. This study provides novel insights into the metabolomic changes associated with CAD progression, emphasizing the potential of metabolites as predictive biomarkers.
Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
►▼
Show Figures
Figure 1
Open AccessArticle
Molecular Networking-Based Metabolome, In Vitro Antidiabetic and Anti-Inflammatory Effects of Breonadia salicina (Vahl) Hepper & J.R.I. Wood
by
Dorcas Tlhapi, Isaiah Ramaite, Chinedu Anokwuru and Teunis van Ree
Metabolites 2024, 14(6), 291; https://doi.org/10.3390/metabo14060291 - 21 May 2024
Abstract
Breonadia salicina (Vahl) Hepper & J.R.I. Wood is widely distributed throughout Africa. It is used ethnobotanically to treat various diseases. However, the metabolic profile of the Breonadia species is not well characterized and the metabolites that are responsible for the bioactivity of this
[...] Read more.
Breonadia salicina (Vahl) Hepper & J.R.I. Wood is widely distributed throughout Africa. It is used ethnobotanically to treat various diseases. However, the metabolic profile of the Breonadia species is not well characterized and the metabolites that are responsible for the bioactivity of this plant remain unknown. Therefore, there is a need to determine the phytochemical and bioactivity profile to identify metabolites that contribute to the antidiabetic, anti-inflammatory and antiproliferation activity, including the genotoxicity and cytotoxic effects, of Breonadia salicina. The study is aimed at exploring the metabolomic profile antidiabetic, anti-inflammatory and antiproliferation activity, as well as the genotoxicity and cytotoxicity effects, of constituents of B. salicina. The compounds in the B. salicina extract were analyzed by ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS), and the resultant data were further analyzed using a molecular networking approach. The crude stem bark and root extracts showed the highest antidiabetic activity against α-amylase at the lowest test concentration of 62.5 µg/mL, with 74.53 ± 0.74% and 79.1 ± 1.5% inhibition, respectively. However, the crude stem bark and root extracts showed the highest antidiabetic activity against α-glucosidase at the lowest test concentration of 31.3 µg/mL, with 98.20 ± 0.15% and 97.98 ± 0.22% inhibition, respectively. The crude methanol leaf extract showed a decrease in the nitrite concentration at the highest concentration of 200 µg/mL, with cell viability of 90.34 ± 2.21%, thus showing anti-inflammatory activity. No samples showed significant cytotoxic effects at a concentration of 10 µg/mL against HeLa cells. Furthermore, a molecular network of Breonadia species using UPLC-QTOF-MS with negative mode electrospray ionization showed the presence of organic oxygen compounds, lipids, benzenoids, phenylpropanoids and polyketides. These compound classes were differentially distributed in the three different plant parts, indicating the chemical differences between the stem bark, root and leaf extracts of B. salicina. Therefore, the identified compounds may contribute to the antidiabetic and anti-inflammatory activity of Breonadia salicina. The stem bark, root and leaf extracts of B. salicina yielded thirteen compounds identified for the first time in this plant, offering a promising avenue for the discovery of new lead drugs for the treatment of diabetes and inflammation. The use of molecular networking produced a detailed phytochemical overview of this Breonadia species. The results reported in this study show the importance of searching for bioactive compounds from Breonadia salicina and provide new insights into the phytochemical characterization and bioactivity of different plant parts of Breonadia salicina.
Full article
(This article belongs to the Section Plant Metabolism)
►▼
Show Figures
Graphical abstract
Open AccessArticle
Accurate Prediction of 1H NMR Chemical Shifts of Small Molecules Using Machine Learning
by
Tanvir Sajed, Zinat Sayeeda, Brian L. Lee, Mark Berjanskii, Fei Wang, Vasuk Gautam and David S. Wishart
Metabolites 2024, 14(5), 290; https://doi.org/10.3390/metabo14050290 - 19 May 2024
Abstract
NMR is widely considered the gold standard for organic compound structure determination. As such, NMR is routinely used in organic compound identification, drug metabolite characterization, natural product discovery, and the deconvolution of metabolite mixtures in biofluids (metabolomics and exposomics). In many cases, compound
[...] Read more.
NMR is widely considered the gold standard for organic compound structure determination. As such, NMR is routinely used in organic compound identification, drug metabolite characterization, natural product discovery, and the deconvolution of metabolite mixtures in biofluids (metabolomics and exposomics). In many cases, compound identification by NMR is achieved by matching measured NMR spectra to experimentally collected NMR spectral reference libraries. Unfortunately, the number of available experimental NMR reference spectra, especially for metabolomics, medical diagnostics, or drug-related studies, is quite small. This experimental gap could be filled by predicting NMR chemical shifts for known compounds using computational methods such as machine learning (ML). Here, we describe how a deep learning algorithm that is trained on a high-quality, “solvent-aware” experimental dataset can be used to predict 1H chemical shifts more accurately than any other known method. The new program, called PROSPRE (PROton Shift PREdictor) can accurately (mean absolute error of <0.10 ppm) predict 1H chemical shifts in water (at neutral pH), chloroform, dimethyl sulfoxide, and methanol from a user-submitted chemical structure. PROSPRE (pronounced “prosper”) has also been used to predict 1H chemical shifts for >600,000 molecules in many popular metabolomic, drug, and natural product databases.
Full article
(This article belongs to the Special Issue Metabolomics and Machine Learning for Improved Diagnostics and as a Tool to Accelerate Drug Development)
►▼
Show Figures
Figure 1
Open AccessArticle
Long-Term Consumption of Purified Water Altered Amino Acid, Fatty Acid and Energy Metabolism in Livers of Rats
by
Jia Wang, Zhiqun Qiu, Hui Zeng, Yao Tan, Yujing Huang, Jiaohua Luo and Weiqun Shu
Metabolites 2024, 14(5), 289; https://doi.org/10.3390/metabo14050289 - 19 May 2024
Abstract
The consumption of low-mineral water has been increasing worldwide. Drinking low-mineral water is associated with cardiovascular disease, osteopenia, and certain neurodegenerative diseases. However, the specific mechanism remains unclear. The liver metabolic alterations in rats induced by drinking purified water for 3 months were
[...] Read more.
The consumption of low-mineral water has been increasing worldwide. Drinking low-mineral water is associated with cardiovascular disease, osteopenia, and certain neurodegenerative diseases. However, the specific mechanism remains unclear. The liver metabolic alterations in rats induced by drinking purified water for 3 months were investigated with a metabolomics-based strategy. Compared with the tap water group, 74 metabolites were significantly changed in the purified water group (6 increased and 68 decreased), including 29 amino acids, 11 carbohydrates, 10 fatty acids, 7 short chain fatty acids (SCFAs), and 17 other biomolecules. Eight metabolic pathways were significantly changed, namely aminoacyl–tRNA biosynthesis; nitrogen metabolism; alanine, aspartate and glutamate metabolism; arginine and proline metabolism; histidine metabolism; biosynthesis of unsaturated fatty acids; butanoate metabolism; and glycine, serine and threonine metabolism. These changes suggested that consumption of purified water induced negative nitrogen balance, reduced expression of some polyunsaturated fatty acids and SCFAs, and disturbed energy metabolism in rats. These metabolic disturbances may contribute to low-mineral-water-associated health risks. The health risk of consuming low-mineral water requires attention.
Full article
(This article belongs to the Section Animal Metabolism)
►▼
Show Figures
Figure 1
Open AccessArticle
Adipose Tissue Insulin Resistance in South Asian and Nordic Women after Gestational Diabetes Mellitus
by
Ahalya Anita Suntharalingam Kvist, Archana Sharma, Christine Sommer, Elisabeth Qvigstad, Hanne Løvdal Gulseth, Stina Therese Sollid, Ingrid Nermoen, Naveed Sattar, Jason Gill, Tone Møller Tannæs, Kåre Inge Birkeland and Sindre Lee-Ødegård
Metabolites 2024, 14(5), 288; https://doi.org/10.3390/metabo14050288 - 18 May 2024
Abstract
South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This
[...] Read more.
South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This study aimed to assess markers of adipose tissue (AT) IR and liver fat in SA and Nordic women post-GDM. A total of 179 SA and 108 Nordic women in Norway underwent oral glucose tolerance tests 1–3 years post-GDM. We measured metabolic markers and calculated the AT IR index and non-alcoholic fatty liver disease liver fat (NAFLD-LFS) scores. Results showed that normoglycaemic SAs had less non-esterified fatty acid (NEFA) suppression during the test, resembling prediabetes/T2D responses, and higher levels of plasma fetuin-A, CRP, and IL-6 but lower adiponectin, indicating AT inflammation. Furthermore, normoglycaemic SAs had higher NAFLD-LFS scores, lower insulin clearance, and higher peripheral insulin than Nordics, indicating increased AT IR, inflammation, and liver fat in SAs. Higher liver fat markers significantly contributed to the ethnic disparities in glucose metabolism, suggesting a key area for intervention to reduce T2D risk post-GDM in SAs.
Full article
(This article belongs to the Special Issue Glucose Metabolism in Pregnancy)
►▼
Show Figures
Graphical abstract
Open AccessReview
The Role of Exerkines in Obesity-Induced Disruption of Mitochondrial Homeostasis in Thermogenic Fat
by
Hui Shao, Huijie Zhang and Dandan Jia
Metabolites 2024, 14(5), 287; https://doi.org/10.3390/metabo14050287 - 17 May 2024
Abstract
There is a notable correlation between mitochondrial homeostasis and metabolic disruption. In this review, we report that obesity-induced disruption of mitochondrial homeostasis adversely affects lipid metabolism, adipocyte differentiation, oxidative capacity, inflammation, insulin sensitivity, and thermogenesis in thermogenic fat. Elevating mitochondrial homeostasis in thermogenic
[...] Read more.
There is a notable correlation between mitochondrial homeostasis and metabolic disruption. In this review, we report that obesity-induced disruption of mitochondrial homeostasis adversely affects lipid metabolism, adipocyte differentiation, oxidative capacity, inflammation, insulin sensitivity, and thermogenesis in thermogenic fat. Elevating mitochondrial homeostasis in thermogenic fat emerges as a promising avenue for developing treatments for metabolic diseases, including enhanced mitochondrial function, mitophagy, mitochondrial uncoupling, and mitochondrial biogenesis. The exerkines (e.g., myokines, adipokines, batokines) released during exercise have the potential to ameliorate mitochondrial homeostasis, improve glucose and lipid metabolism, and stimulate fat browning and thermogenesis as a defense against obesity-associated metabolic diseases. This comprehensive review focuses on the manifold benefits of exercise-induced exerkines, particularly emphasizing their influence on mitochondrial homeostasis and fat thermogenesis in the context of metabolic disorders associated with obesity.
Full article
(This article belongs to the Special Issue Exploring Pathological Mechanisms in Obesity, Diabetes, and Metabolic Syndrome)
►▼
Show Figures
Figure 1
Open AccessArticle
Targeted Analysis of Plasma Polar Metabolites in Postmenopausal Depression
by
Maria Fernanda Naufel, Amanda Paula Pedroso, Adriana Pereira de Souza, Valter Tadeu Boldarine, Lila Missae Oyama, Edson Guimarães Lo Turco, Helena Hachul, Eliane Beraldi Ribeiro and Mônica Marques Telles
Metabolites 2024, 14(5), 286; https://doi.org/10.3390/metabo14050286 - 16 May 2024
Abstract
Depression will be the disease with the highest incidence worldwide by 2030. Data indicate that postmenopausal women have a higher incidence of mood disorders, and this high vulnerability seems to be related to hormonal changes and weight gain. Although research evaluating the profile
[...] Read more.
Depression will be the disease with the highest incidence worldwide by 2030. Data indicate that postmenopausal women have a higher incidence of mood disorders, and this high vulnerability seems to be related to hormonal changes and weight gain. Although research evaluating the profile of metabolites in mood disorders is advancing, further research, maintaining consistent methodology, is necessary to reach a consensus. Therefore, the objective of the present study was to carry out an exploratory analysis of the plasma polar metabolites of pre- and postmenopausal women to explore whether the profile is affected by depression. The plasma analysis of 50 polar metabolites was carried out in a total of 67 postmenopausal women, aged between 50 and 65 years, either without depression (n = 25) or with depression symptoms (n = 42), which had spontaneous onset of menopause and were not in use of hormone replacement therapy, insulin, or antidepressants; and in 42 healthy premenopausal women (21 without depression and 21 with depression symptoms), aged between 40 and 50 years and who were not in use of contraceptives, insulin, or antidepressants. Ten metabolites were significantly affected by depression symptoms postmenopause, including adenosine (FDR = 3.778 × 10−14), guanosine (FDR = 3.001 × 10−14), proline (FDR = 1.430 × 10−6), citrulline (FDR = 0.0001), lysine (FDR = 0.0004), and carnitine (FDR = 0.0331), which were down-regulated, and dimethylglycine (FDR = 0.0022), glutathione (FDR = 0.0048), creatine (FDR = 0.0286), and methionine (FDR = 0.0484) that were up-regulated. In premenopausal women with depression, oxidized glutathione (FDR = 0.0137) was down-regulated, and dimethylglycine (FDR = 0.0406) and 4-hydroxyproline (FDR = 0.0433) were up-regulated. The present study provided new data concerning the consequences of depression on plasma polar metabolites before and after the establishment of menopause. The results demonstrated that the postmenopausal condition presented more alterations than the premenopausal period and may indicate future measures to treat the disturbances involved in both menopause and depression.
Full article
(This article belongs to the Special Issue Metabolomics Meets Neuropsychiatry)
►▼
Show Figures
Figure 1
Open AccessArticle
Changes in Metabolite Profiles of Chinese Soy Sauce at Different Time Durations of Fermentation Studied by 1H-NMR-Based Metabolomics
by
Jalal Uddin, Samra Yasmin, Ghulam Mustafa Kamal, Mufarreh Asmari, Muhammad Saqib and Heyu Chen
Metabolites 2024, 14(5), 285; https://doi.org/10.3390/metabo14050285 - 15 May 2024
Abstract
Fermentation parameters, especially the duration, are important in imparting a peculiar taste and flavor to soy sauce. The main purpose of this research was to monitor metabolic changes occurring during the various time intervals of the fermentation process. NMR-based metabolomics was used to
[...] Read more.
Fermentation parameters, especially the duration, are important in imparting a peculiar taste and flavor to soy sauce. The main purpose of this research was to monitor metabolic changes occurring during the various time intervals of the fermentation process. NMR-based metabolomics was used to monitor the compositional changes in soy sauce during fermentation. The 1H-NMR spectra of the soy sauce samples taken from the fermentation tanks at 0 to 8 months were analyzed using 1H-NMR spectroscopy, and the obtained spectra were analyzed by multivariate statistical analysis. The Principal Component Analysis (PCA) and Partial Least Square Discriminate analysis (PLSDA) revealed the separation of samples fermented for various time durations under identical conditions. Key metabolites shown by corresponding loading plots exhibited variations in amino acids (lysine, threonine, isoleucine, etc.), acetate, glucose, fructose, sucrose, ethanol, glycerol, and others. The levels of ethanol in soy sauce increased with longer fermentation durations, which can be influenced by both natural fermentation and the intentional addition of ethanol as a preservative. The study shows that the variation in metabolite can be very efficiently monitored using 1H-NMR-based metabolomics, thus suggestion to optimize the time duration to get the soy sauce product with the desired taste and flavor.
Full article
(This article belongs to the Special Issue Application of Metabolomics in Food Fermentation)
►▼
Show Figures
Figure 1
Open AccessArticle
Desorption Electrospray Ionization Mass Spectrometry Imaging Techniques Depict a Reprogramming of Energy and Purine Metabolism in the Core Brain Regions of Chronic Social Defeat Stress Mice
by
Yulong Song, Fan Xiao, Jiye Aa and Guangji Wang
Metabolites 2024, 14(5), 284; https://doi.org/10.3390/metabo14050284 - 15 May 2024
Abstract
Depression is associated with pathological changes and metabolic abnormalities in multiple brain regions. The simultaneous comprehensive and in situ detection of endogenous molecules in all brain regions is essential for a comprehensive understanding of depression pathology, which is described in this paper. A
[...] Read more.
Depression is associated with pathological changes and metabolic abnormalities in multiple brain regions. The simultaneous comprehensive and in situ detection of endogenous molecules in all brain regions is essential for a comprehensive understanding of depression pathology, which is described in this paper. A method based on desorption electrospray ionization mass spectrometry imaging (DESI-MSI) technology was developed to classify mouse brain regions using characteristic lipid molecules and to detect the metabolites in mouse brain tissue samples simultaneously. The results showed that characteristic lipid molecules can be used to clearly distinguish each subdivision of the mouse brain, and the accuracy of this method is higher than that of the conventional staining method. The cerebellar cortex, medial prefrontal cortex, hippocampus, striatum, nucleus accumbens-core, and nucleus accumbens-shell exhibited the most significant differences in the chronic social defeat stress model. An analysis of metabolic pathways revealed that 13 kinds of molecules related to energy metabolism and purine metabolism exhibited significant changes. A DESI-MSI method was developed for the detection of pathological brain sections. We found, for the first time, that there are characteristic changes in the energy metabolism in the cortex and purine metabolism in the striatum, which is highly important for obtaining a deeper and more comprehensive understanding of the pathology of depression and discovering regulatory targets.
Full article
(This article belongs to the Special Issue Mass Spectrometry Imaging: Theory, Methods and Applications in Biochemical and Pharmaceutical Research)
►▼
Show Figures
Figure 1
Open AccessReview
Deleterious Effects of Heat Stress on the Tomato, Its Innate Responses, and Potential Preventive Strategies in the Realm of Emerging Technologies
by
Qaisar Khan, Yixi Wang, Gengshou Xia, Hui Yang, Zhengrong Luo and Yan Zhang
Metabolites 2024, 14(5), 283; https://doi.org/10.3390/metabo14050283 - 15 May 2024
Abstract
The tomato is a fruit vegetable rich in nutritional and medicinal value grown in greenhouses and fields worldwide. It is severely sensitive to heat stress, which frequently occurs with rising global warming. Predictions indicate a 0.2 °C increase in average surface temperatures per
[...] Read more.
The tomato is a fruit vegetable rich in nutritional and medicinal value grown in greenhouses and fields worldwide. It is severely sensitive to heat stress, which frequently occurs with rising global warming. Predictions indicate a 0.2 °C increase in average surface temperatures per decade for the next three decades, which underlines the threat of austere heat stress in the future. Previous studies have reported that heat stress adversely affects tomato growth, limits nutrient availability, hammers photosynthesis, disrupts reproduction, denatures proteins, upsets signaling pathways, and damages cell membranes. The overproduction of reactive oxygen species in response to heat stress is toxic to tomato plants. The negative consequences of heat stress on the tomato have been the focus of much investigation, resulting in the emergence of several therapeutic interventions. However, a considerable distance remains to be covered to develop tomato varieties that are tolerant to current heat stress and durable in the perspective of increasing global warming. This current review provides a critical analysis of the heat stress consequences on the tomato in the context of global warming, its innate response to heat stress, and the elucidation of domains characterized by a scarcity of knowledge, along with potential avenues for enhancing sustainable tolerance against heat stress through the involvement of diverse advanced technologies. The particular mechanism underlying thermotolerance remains indeterminate and requires further elucidatory investigation. The precise roles and interplay of signaling pathways in response to heat stress remain unresolved. The etiology of tomato plants’ physiological and molecular responses against heat stress remains unexplained. Utilizing modern functional genomics techniques, including transcriptomics, proteomics, and metabolomics, can assist in identifying potential candidate proteins, metabolites, genes, gene networks, and signaling pathways contributing to tomato stress tolerance. Improving tomato tolerance against heat stress urges a comprehensive and combined strategy including modern techniques, the latest apparatuses, speedy breeding, physiology, and molecular markers to regulate their physiological, molecular, and biochemical reactions.
Full article
(This article belongs to the Special Issue Metabolomics and Plant Defence)
►▼
Show Figures
Figure 1
Open AccessArticle
Overweight, Obesity, Hypertriglyceridemia, and Insulin Resistance Are Positively Associated with High Serum Copper Levels in Mexican Adults
by
Armando Ramírez-Cruz, María Judith Rios-Lugo, Jacqueline Soto-Sánchez, Cuauhtémoc Arturo Juárez-Pérez, Alejandro Cabello-López, Carmina Jiménez-Ramírez, Consuelo Chang-Rueda, Miguel Cruz, Héctor Hernández-Mendoza and Miguel Vazquez-Moreno
Metabolites 2024, 14(5), 282; https://doi.org/10.3390/metabo14050282 - 14 May 2024
Abstract
Recently, the role of trace elements in the pathophysiology of obesity, insulin resistance (IR), and metabolic diseases has been explored. In this cross-sectional study, we aimed to assess the association of overweight, obesity, and cardiometabolic traits with serum copper (Cu) levels in 346
[...] Read more.
Recently, the role of trace elements in the pathophysiology of obesity, insulin resistance (IR), and metabolic diseases has been explored. In this cross-sectional study, we aimed to assess the association of overweight, obesity, and cardiometabolic traits with serum copper (Cu) levels in 346 Mexican adults. Serum Cu level was measured by inductively coupled plasma mass spectrometry (ICP-MS). Anthropometrical data were collected, and biochemical parameters were measured. The triglyceride-glucose (TyG) index was used as a surrogate marker to evaluate IR. Overweight and obesity status was positively associated with the serum Cu level (β = 19.434 ± 7.309, p = 0.008). Serum Cu level was observed to have a positive association with serum triglycerides level (β = 0.160 ± 0.045, p < 0.001) and TyG (β = 0.001 ± 0.001, p < 0.001). Additionally, high serum Cu level was positively associated with overweight and obesity status (odds ratio [OR] = 1.9, 95% confidence interval [95% CI] 1.1–3.4, p = 0.014), hypertriglyceridemia (OR = 3.0, 95% CI 1.7–5.3, p < 0.001), and IR (OR = 2.6, 95% CI 1.4–4.6, p = 0.001). In conclusion, our results suggest that overweight, obesity, hypertriglyceridemia, and IR are positively associated with serum Cu levels in Mexican adults.
Full article
(This article belongs to the Special Issue Trace Metal Element Metabolism in Biological Systems)
►▼
Show Figures
Figure 1
Open AccessArticle
Volatile Organic Compounds in Cellular Headspace after Hyperbaric Oxygen Exposure: An In Vitro Pilot Study
by
Feiko J. M. de Jong, Thijs A. Lilien, Dominic W. Fenn, Thijs T. Wingelaar, Pieter-Jan A. M. van Ooij, Anke H. Maitland-van der Zee, Markus W. Hollmann, Rob A. van Hulst and Paul Brinkman
Metabolites 2024, 14(5), 281; https://doi.org/10.3390/metabo14050281 - 13 May 2024
Abstract
Volatile organic compounds (VOCs) might be associated with pulmonary oxygen toxicity (POT). This pilot study aims to identify VOCs linked to oxidative stress employing an in vitro model of alveolar basal epithelial cells exposed to hyperbaric and hyperoxic conditions. In addition, the feasibility
[...] Read more.
Volatile organic compounds (VOCs) might be associated with pulmonary oxygen toxicity (POT). This pilot study aims to identify VOCs linked to oxidative stress employing an in vitro model of alveolar basal epithelial cells exposed to hyperbaric and hyperoxic conditions. In addition, the feasibility of this in vitro model for POT biomarker research was evaluated. The hyperbaric exposure protocol, similar to the U.S. Navy Treatment Table 6, was conducted on human alveolar basal epithelial cells, and the headspace VOCs were analyzed using gas chromatography–mass spectrometry. Three compounds (nonane [p = 0.005], octanal [p = 0.009], and decane [p = 0.018]), of which nonane and decane were also identified in a previous in vivo study with similar hyperbaric exposure, varied significantly between the intervention group which was exposed to 100% oxygen and the control group which was exposed to compressed air. VOC signal intensities were lower in the intervention group, but cellular stress markers (IL8 and LDH) confirmed increased stress and injury in the intervention group. Despite the observed reductions in compound expression, the model holds promise for POT biomarker exploration, emphasizing the need for further investigation into the complex relationship between VOCs and oxidative stress.
Full article
(This article belongs to the Section Environmental Metabolomics)
►▼
Show Figures
Figure 1
Open AccessArticle
Olaris Global Panel (OGP): A Highly Accurate and Reproducible Triple Quadrupole Mass Spectrometry-Based Metabolomics Method for Clinical Biomarker Discovery
by
Masoumeh Dorrani, Jifang Zhao, Nihel Bekhti, Alessia Trimigno, Sangil Min, Jongwon Ha, Ahram Han, Elizabeth O’Day and Jurre J. Kamphorst
Metabolites 2024, 14(5), 280; https://doi.org/10.3390/metabo14050280 - 11 May 2024
Abstract
Mass spectrometry (MS)-based clinical metabolomics is very promising for the discovery of new biomarkers and diagnostics. However, poor data accuracy and reproducibility limit its true potential, especially when performing data analysis across multiple sample sets. While high-resolution mass spectrometry has gained considerable popularity
[...] Read more.
Mass spectrometry (MS)-based clinical metabolomics is very promising for the discovery of new biomarkers and diagnostics. However, poor data accuracy and reproducibility limit its true potential, especially when performing data analysis across multiple sample sets. While high-resolution mass spectrometry has gained considerable popularity for discovery metabolomics, triple quadrupole (QqQ) instruments offer several benefits for the measurement of known metabolites in clinical samples. These benefits include high sensitivity and a wide dynamic range. Here, we present the Olaris Global Panel (OGP), a HILIC LC-QqQ MS method for the comprehensive analysis of ~250 metabolites from all major metabolic pathways in clinical samples. For the development of this method, multiple HILIC columns and mobile phase conditions were compared, the robustness of the leading LC method assessed, and MS acquisition settings optimized for optimal data quality. Next, the effect of U-13C metabolite yeast extract spike-ins was assessed based on data accuracy and precision. The use of these U-13C-metabolites as internal standards improved the goodness of fit to a linear calibration curve from r2 < 0.75 for raw data to >0.90 for most metabolites across the entire clinical concentration range of urine samples. Median within-batch CVs for all metabolite ratios to internal standards were consistently lower than 7% and less than 10% across batches that were acquired over a six-month period. Finally, the robustness of the OGP method, and its ability to identify biomarkers, was confirmed using a large sample set.
Full article
(This article belongs to the Special Issue Metabolomics and Machine Learning for Improved Diagnostics and as a Tool to Accelerate Drug Development)
►▼
Show Figures
Figure 1
Open AccessArticle
Mass Spectrometric Analysis of Purine Intermediary Metabolism Indicates Cyanide Induces Purine Catabolism in Rabbits
by
Jordan Morningstar, Jangwoen Lee, Sari Mahon, Matthew Brenner and Anjali K. Nath
Metabolites 2024, 14(5), 279; https://doi.org/10.3390/metabo14050279 - 10 May 2024
Abstract
Purines are the building blocks of DNA/RNA, energy substrates, and cofactors. Purine metabolites, including ATP, GTP, NADH, and coenzyme A, are essential molecules in diverse biological processes such as energy metabolism, signal transduction, and enzyme activity. When purine levels increase, excess purines are
[...] Read more.
Purines are the building blocks of DNA/RNA, energy substrates, and cofactors. Purine metabolites, including ATP, GTP, NADH, and coenzyme A, are essential molecules in diverse biological processes such as energy metabolism, signal transduction, and enzyme activity. When purine levels increase, excess purines are either recycled to synthesize purine metabolites or catabolized to the end product uric acid. Purine catabolism increases during states of low oxygen tension (hypoxia and ischemia), but this metabolic pathway is incompletely understood in the context of histotoxic hypoxia (i.e., inhibition of oxygen utilization despite normal oxygen tension). In rabbits exposed to cyanide—a classical histotoxic hypoxia agent—we demonstrated significant increases in several concordant metabolites in the purine catabolic pathway (including plasma levels of uric acid, xanthosine, xanthine, hypoxanthine, and inosine) via mass spectrometry-based metabolite profiling. Pharmacological inhibition of the purine catabolic pathway with oxypurinol mitigated the deleterious effects of cyanide on skeletal muscle cytochrome c oxidase redox state, measured by non-invasive diffuse optical spectroscopy. Finally, plasma uric acid levels correlated strongly with those of lactic acid, an established clinical biomarker of cyanide exposure, in addition to a tissue biomarker of cyanide exposure (skeletal muscle cytochrome c oxidase redox state). Cumulatively, these findings not only shed light on the in vivo role(s) of cyanide but also have implications in the field of medical countermeasure (MCM) development.
Full article
(This article belongs to the Special Issue Preclinical and Clinical Application of Metabolomics in Medicine)
►▼
Show Figures
Figure 1
Open AccessArticle
A Chemical Structure and Machine Learning Approach to Assess the Potential Bioactivity of Endogenous Metabolites and Their Association with Early Childhood Systemic Inflammation
by
Mario Lovrić, Tingting Wang, Mads Rønnow Staffe, Iva Šunić, Kristina Časni, Jessica Lasky-Su, Bo Chawes and Morten Arendt Rasmussen
Metabolites 2024, 14(5), 278; https://doi.org/10.3390/metabo14050278 - 10 May 2024
Abstract
Metabolomics has gained much attention due to its potential to reveal molecular disease mechanisms and present viable biomarkers. This work uses a panel of untargeted serum metabolomes from 602 children from the COPSAC2010 mother–child cohort. The annotated part of the metabolome consists of
[...] Read more.
Metabolomics has gained much attention due to its potential to reveal molecular disease mechanisms and present viable biomarkers. This work uses a panel of untargeted serum metabolomes from 602 children from the COPSAC2010 mother–child cohort. The annotated part of the metabolome consists of 517 chemical compounds curated using automated procedures. We created a filtering method for the quantified metabolites using predicted quantitative structure–bioactivity relationships for the Tox21 database on nuclear receptors and stress response in cell lines. The metabolites measured in the children’s serums are predicted to affect specific targeted models, known for their significance in inflammation, immune function, and health outcomes. The targets from Tox21 have been used as targets with quantitative structure–activity relationships (QSARs). They were trained for ~7000 structures, saved as models, and then applied to the annotated metabolites to predict their potential bioactivities. The models were selected based on strict accuracy criteria surpassing random effects. After application, 52 metabolites showed potential bioactivity based on structural similarity with known active compounds from the Tox21 set. The filtered compounds were subsequently used and weighted by their bioactive potential to show an association with early childhood hs-CRP levels at six months in a linear model supporting a physiological adverse effect on systemic low-grade inflammation.
Full article
(This article belongs to the Special Issue Machine Learning Applications in Metabolomics Analysis)
►▼
Show Figures
Figure 1
Journal Menu
► ▼ Journal Menu-
- Metabolites Home
- Aims & Scope
- Editorial Board
- Reviewer Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Editor’s Choice Articles
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Conferences
- Editorial Office
Journal Browser
► ▼ Journal BrowserHighly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Analytica, Biomolecules, Metabolites, Molecules, Separations
Advances in Separation Methods for Metabolomics and Lipidomics
Topic Editors: Eduardo Sommella, Giulia Mazzoccanti, Emanuela SalviatiDeadline: 31 May 2024
Topic in
BioChem, Biomedicines, Biomolecules, IJMS, Metabolites, Molecules
Natural Products in Prevention and Therapy of Metabolic Syndrome
Topic Editors: Jianbo Wan, Ligen LinDeadline: 30 June 2024
Topic in
Biomedicines, JCM, Membranes, Metabolites, Reports
Nephrology and Dialysis: From Bench to Bedside
Topic Editors: Eiichi Sato, Tsukasa NakamuraDeadline: 31 July 2024
Topic in
Analytica, Metabolites, Separations, Toxins, Molecules
Application of Chromatography for Point of Care Diagnosis of Noncommunicable Diseases
Topic Editors: Chiranjit Ghosh, Liqin Chen, Keshava Balakrishna, Chiranjay MukhopadhyayDeadline: 31 August 2024
Conferences
Special Issues
Special Issue in
Metabolites
Mineral and Energy Metabolism of Mammals during Pregnancy
Guest Editors: Wellison Jarles Da Silva Diniz, Priyanka BanerjeeDeadline: 25 May 2024
Special Issue in
Metabolites
Neurometabolic Monitoring and Imaging in Pediatric Critical Care
Guest Editor: Tiffany S. KoDeadline: 1 June 2024
Special Issue in
Metabolites
Immunoregulatory Metabolites with Clinical Relevance
Guest Editors: Johanna M. Gostner, Bohuslav Melichar, Dietmar FuchsDeadline: 15 June 2024
Special Issue in
Metabolites
Open-Source Software in Metabolomics
Guest Editor: Seongho KimDeadline: 25 June 2024
Topical Collections
Topical Collection in
Metabolites
Metabolic Effects of Animal Growth Promoters
Collection Editor: Chi Chen
Topical Collection in
Metabolites
Feature Papers in Assessing Environmental Health and Function
Collection Editor: David J. Beale
Topical Collection in
Metabolites
Advances in Metabolomics
Collection Editors: Leonardo Tenori, Edoardo Saccenti