Metabolites

22 pages, 6496 KiB

Open AccessArticle

Comparison of Adiposomal Lipids between Obese and Non-Obese Individuals

by Mohamed Hussein, Imaduddin Mirza, Mohammed Morsy, Amro Mostafa, Chandra Hassan, Mario Masrur, Francesco M. Bianco, Subbaiah Papasani, Irena Levitan and Abeer M. Mahmoud

Metabolites 2024, 14(8), 464; https://doi.org/10.3390/metabo14080464 - 21 Aug 2024

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Abstract

Our recent findings revealed that human adipose tissues (AT)-derived extracellular vesicles (adiposomes) vary in cargo among obese and lean individuals. The main objective of this study was to investigate the adiposomal lipid profiles and their correlation with cardiometabolic risk factors. AT samples were [...] Read more.

Our recent findings revealed that human adipose tissues (AT)-derived extracellular vesicles (adiposomes) vary in cargo among obese and lean individuals. The main objective of this study was to investigate the adiposomal lipid profiles and their correlation with cardiometabolic risk factors. AT samples were collected from obese subjects and lean controls and analyzed for their characteristics and lipid content. In addition, we measured the correlation between adiposomal lipid profiles and body composition, glucose and lipid metabolic profiles, brachial artery vasoreactivity, AT arteriolar flow-induced dilation, and circulating markers such as IL-6, C-reactive protein, and nitric oxide (NO). Compared to lean controls, adiposomes isolated from obese subjects were higher in number after normalization to AT volume. The two major lipid classes differentially expressed were lysophosphatidylcholine/phosphatidylcholine (LPC/PC) and ceramides (Cer). All lipids in the LPC/PC class were several-fold lower in adiposomes from obese subjects compared to lean controls, on top of which were PC 18:2, PC 18:1, and PC 36:3. Most ceramides were markedly upregulated in the obese group, especially Cer d37:0, Cer d18:0, and Cer d39:0. Regression analyses revealed associations between adiposomal lipid profiles and several cardiometabolic risk factors such as body mass index (BMI), fat percentage, insulin resistance, arteriolar and brachial artery vasoreactivity, NO bioavailability, and high-density lipoproteins (HDL-C). We conclude that the ability of adiposomes from obese subjects to disrupt cardiometabolic function could be partly attributed to the dysregulated lipid cargo. Full article

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20 pages, 590 KiB

Open AccessEditor’s ChoiceArticle

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

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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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10 pages, 1560 KiB

Open AccessArticle

Analysis of Serum Exosome Metabolites Identifies Potential Biomarkers for Human Hepatocellular Carcinoma

by Tingting Zhao, Yan Liang, Xiaolan Zhen, Hong Wang, Li Song, Didi Xing and Hui Li

Metabolites 2024, 14(8), 462; https://doi.org/10.3390/metabo14080462 - 20 Aug 2024

Viewed by 1334

Abstract

Currently, the clinical cure rate for primary liver cancer remains low. Effective screening and early diagnosis of hepatocellular carcinoma (HCC) remain clinical challenges. Exosomes are intimately associated with tumor development and their contents have the potential to serve as highly sensitive tumor-specific markers. [...] Read more.

Currently, the clinical cure rate for primary liver cancer remains low. Effective screening and early diagnosis of hepatocellular carcinoma (HCC) remain clinical challenges. Exosomes are intimately associated with tumor development and their contents have the potential to serve as highly sensitive tumor-specific markers. A comprehensive untargeted metabolomics study was conducted using exosome samples extracted from the serum of 48 subjects (36 HCC patients and 12 healthy controls) via a commercial kit. An ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) strategy was used to identify the metabolic compounds. A total of 18 differential metabolites were identified using the non-targeted metabolomics approach of UPLC-QTOF-MS/MS. Pathway analysis revealed significant alterations in the arachidonic acid metabolism, linoleic acid metabolism, and unsaturated fatty acid metabolism pathways. ROC analysis indicated that three metabolites with AUC values exceeding 0.900 were selected as potential biomarkers: caprylic acid and linoleic acid were upregulated in the HCC group, whereas pentadecanoic acid was downregulated. Linoleic acid, caprylic acid, and pentadecanoic acid are potential biomarkers for diagnosing HCC. The significant alterations in these three metabolic pathways offer new insights into the mechanisms underlying HCC formation and progression. Full article

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13 pages, 1858 KiB

Open AccessArticle

Challenges in Lipidomics Biomarker Identification: Avoiding the Pitfalls and Improving Reproducibility

by Johanna von Gerichten, Kyle Saunders, Melanie J. Bailey, Lee A. Gethings, Anthony Onoja, Nophar Geifman and Matt Spick

Metabolites 2024, 14(8), 461; https://doi.org/10.3390/metabo14080461 - 19 Aug 2024

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Abstract

Identification of features with high levels of confidence in liquid chromatography–mass spectrometry (LC–MS) lipidomics research is an essential part of biomarker discovery, but existing software platforms can give inconsistent results, even from identical spectral data. This poses a clear challenge for reproducibility in [...] Read more.

Identification of features with high levels of confidence in liquid chromatography–mass spectrometry (LC–MS) lipidomics research is an essential part of biomarker discovery, but existing software platforms can give inconsistent results, even from identical spectral data. This poses a clear challenge for reproducibility in biomarker identification. In this work, we illustrate the reproducibility gap for two open-access lipidomics platforms, MS DIAL and Lipostar, finding just 14.0% identification agreement when analyzing identical LC–MS spectra using default settings. Whilst the software platforms performed more consistently using fragmentation data, agreement was still only 36.1% for MS² spectra. This highlights the critical importance of validation across positive and negative LC–MS modes, as well as the manual curation of spectra and lipidomics software outputs, in order to reduce identification errors caused by closely related lipids and co-elution issues. This curation process can be supplemented by data-driven outlier detection in assessing spectral outputs, which is demonstrated here using a novel machine learning approach based on support vector machine regression combined with leave-one-out cross-validation. These steps are essential to reduce the frequency of false positive identifications and close the reproducibility gap, including between software platforms, which, for downstream users such as bioinformaticians and clinicians, can be an underappreciated source of biomarker identification errors. Full article

(This article belongs to the Special Issue Challenges and Opportunities in Application of Mass Spectrometry for Metabolomics and Lipidomics)

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13 pages, 631 KiB

Open AccessArticle

Estimating Dietary Protein and Sodium Intake with Sodium Removal in Peritoneal Dialysis Patients

by Ana Bontić, Aleksandra Kezić, Jelena Pavlović, Marko Baralić, Selena Gajić, Kristina Petrovic, Vidna Karadžić Ristanović, Olga Petrović, Vera Stjepanović, Sanja Stanković and Milan Radović

Metabolites 2024, 14(8), 460; https://doi.org/10.3390/metabo14080460 - 19 Aug 2024

Viewed by 963

Abstract

An increase in dietary protein intake (DPI) carries a risk with respect to increased sodium intake, which further leads to the development of cardiovascular morbidity in peritoneal dialysis (PD) patients. Dialytic (DSR) and urinary sodium removal (USR) are potential indicators of sodium intake. [...] Read more.

An increase in dietary protein intake (DPI) carries a risk with respect to increased sodium intake, which further leads to the development of cardiovascular morbidity in peritoneal dialysis (PD) patients. Dialytic (DSR) and urinary sodium removal (USR) are potential indicators of sodium intake. In this single-center cross-sectional study with 60 prevalent PD patients, we analyze the correlation of DPI with sodium intake and the association between residual renal function (RRF) and comorbidity grade, expressed as the Davies score with sodium removal and protein metabolism indices such as normalized protein catabolic rate (nPCR) and lean body mass (LBM). The value of RRF < 2 mL/min/1.73 m² is significantly associated with lower USR (p = 0.000) and lower %LBM (p < 0.001). The greatest USR is detected in patients with low Davies comorbidity grade (p = 0.018). Compared to patients with DPI < 0.8 g/kg/day, patients with DPI > 0.8 g/kg/day have a greater sodium intake (3.69 ± 0.71 vs. 2.94 ± 0.86; p < 0.018) and a greater nPCR (p < 0.001). Protein intake is significantly correlated with sodium intake (p = 0.041), but not with total sodium removal (TSR). A strong correlation is observed between sodium intake and TSR (p = 0.000), although single TSR values are not the same as the corresponding sodium intake values. An increasing protein intake implies the necessity to determine both sodium intake and sodium removal. Preservation of RRF has a beneficial role not just in sodium removal, but also in the increase of LBM. Full article

(This article belongs to the Special Issue Impact of Macronutrients on Metabolism)

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20 pages, 14281 KiB

Open AccessArticle

Effects of Different Drying Methods on Amino Acid Metabolite Content and Quality of Ophiocordyceps sinensis by LC-MS/MS Combined with Multivariate Statistical Methods

by Mengjun Xiao, Tao Wang, Chuyu Tang, Min He, Yuling Li and Xiuzhang Li

Metabolites 2024, 14(8), 459; https://doi.org/10.3390/metabo14080459 - 18 Aug 2024

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Abstract

Ophiocordyceps sinensis, a medicinal fungus utilized in traditional Chinese medicine, exhibits a range of biological activities and pharmacological functions. In this study, we determined the amino acid composition of 94 amino acids in Ophiocordyceps sinensis using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Fresh [...] Read more.

Ophiocordyceps sinensis, a medicinal fungus utilized in traditional Chinese medicine, exhibits a range of biological activities and pharmacological functions. In this study, we determined the amino acid composition of 94 amino acids in Ophiocordyceps sinensis using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Fresh samples of Ophiocordyceps sinensis were analyzed under three different drying methods: vacuum freeze drying (DG), oven drying (HG), and air drying (YG). This investigation aims to assess the effects of these drying methods on the content and quality of amino acid metabolites in Ophiocordyceps sinensis. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed for sample classification and the identification of differentially accumulated metabolites (DAMs). The results revealed the detection of 79 amino acid metabolites, which included elevated levels of oxidized L-glutamic acid, L-glutamic acid, and glutathione. Differential amino acid metabolites that met the criteria of fold change (|FC|) ≥ 2, p-value (p) ≤ 0.5, and variable importance in projection (VIP) ≥ 1 were analyzed. Significant differences in 48 amino acid metabolites between the groups were primarily related to protein synthesis. According to the KEGG analysis, all three comparison samples exhibited significant enrichment in several pathways. These pathways included the interaction of neuroactive ligands with receptors, the metabolism of cysteine and methionine, and the biosynthesis of plant hormones. The variations in amino acid metabolite levels observed across the three drying methods may be attributed to the degradation of proteins or amino acid metabolites, influenced by several factors, including temperature, enzyme activity, and moisture content. Additionally, Maillard and oxidative reactions involving substances such as amino acids, sugars, and oxygen may also play a significant role. This study demonstrates that various drying methods significantly influence the amino acid metabolite content of Ophiocordyceps sinensis. Therefore, the selection of drying methods should be tailored to meet specific requirements. This research provides important insights into the metabolite composition of Ophiocordyceps sinensis under different drying techniques, thereby contributing to a more comprehensive understanding of its nutritional and therapeutic properties. Full article

(This article belongs to the Section Plant Metabolism)

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15 pages, 985 KiB

Open AccessEditor’s ChoiceArticle

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

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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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12 pages, 1894 KiB

Open AccessEditor’s ChoiceArticle

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

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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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19 pages, 1699 KiB

Open AccessArticle

ATP, the ³¹P Spectral Modulus, and Metabolism

by Jack V. Greiner and Thomas Glonek

Metabolites 2024, 14(8), 456; https://doi.org/10.3390/metabo14080456 - 18 Aug 2024

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Abstract

Adenosine triphosphate (ATP) has a high intracellular millimolar concentration (ca. 2.4 mM) throughout the phylogenetic spectrum of eukaryotes, archaea, and prokaryotes. In addition, the function of ATP as a hydrotrope in the prevention of protein aggregation and maintenance of protein solubilization [...] Read more.

Adenosine triphosphate (ATP) has a high intracellular millimolar concentration (ca. 2.4 mM) throughout the phylogenetic spectrum of eukaryotes, archaea, and prokaryotes. In addition, the function of ATP as a hydrotrope in the prevention of protein aggregation and maintenance of protein solubilization is essential to cellular, tissue, and organ homeostasis. The ³¹P spectral modulus (PSM) is a measure of the health status of cell, tissue, and organ systems, as well as of ATP, and it is based on in vivo ³¹P nuclear magnetic resonance (³¹P NMR) spectra. The PSM is calculated by dividing the area of the ³¹P NMR integral curve representing the high-energy phosphates by that of the low-energy phosphates. Unlike the difficulties encountered in measuring organophosphates such as ATP or any other phosphorylated metabolites in a conventional ³¹P NMR spectrum or in processed tissue samples, in vivo PSM measurements are possible with NMR surface-coil technology. The PSM does not rely on the resolution of individual metabolite signals but uses the total area derived from each of the NMR integral curves of the above-described spectral regions. Calculation is based on a simple ratio of the high- and low-energy phosphate bands, which are conveniently arranged in the high- and low-field portions of the ³¹P NMR spectrum. In practice, there is essentially no signal overlap between these two regions, with the dividing point being ca. −3 δ. ATP is the principal contributor to the maintenance of an elevated PSM that is typically observed in healthy systems. The purpose of this study is to demonstrate that (1) in general, the higher the metabolic activity, the higher the ³¹P spectral modulus, and (2) the modulus calculation does not require highly resolved ³¹P spectral signals and thus can even be used with reduced signal-to-noise spectra such as those detected as a result of in vivo analyses or those that may be obtained during a clinical MRI examination. With increasing metabolic stress or maturation of metabolic disease in cells, tissues, or organ systems, the PSM index declines; alternatively, with decreasing stress or resolution of disease states, the PSM increases. The PSM can serve to monitor normal homeostasis as a diagnostic tool and may be used to monitor disease processes with and without interventional treatment. Full article

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10 pages, 1912 KiB

Open AccessArticle

Metabolomic Prediction of Cadmium Nephrotoxicity in the Snail Helix aspersa maxima

by Aude Devalckeneer, Marion Bouviez, Amandine Gautier and Jean-Marie Colet

Metabolites 2024, 14(8), 455; https://doi.org/10.3390/metabo14080455 - 17 Aug 2024

Viewed by 678

Abstract

The decontamination of polluted soils is a major socioeconomic issue in many industrialized countries. In situ remediation approaches are nowadays preferred to ex situ techniques, but they require among others the use of bioindicators, which are sensitive to the progressive depollution on health [...] Read more.

The decontamination of polluted soils is a major socioeconomic issue in many industrialized countries. In situ remediation approaches are nowadays preferred to ex situ techniques, but they require among others the use of bioindicators, which are sensitive to the progressive depollution on health effects. Animal species have been mainly used so far to monitor aquatic and air pollution. Current research focuses on the development of living indicators of soil pollution. In this study, the garden snail Helix aspersa maxima was acutely exposed to cadmium, one major soil contaminant causing severe health effects, including nephrotoxicity. Kidney and hemolymph were sampled and analyzed by a ¹H-NMR-based metabonomic approach. Shortly after Cd exposure, numerous metabolic changes occurred in the hemolymph and kidney extracts. Altogether, they were indicative of a switch in energy sources from the Krebs cycle towards b-oxidation and the utilization of stored galactogen polysaccharides. Then, the activation of antioxidant defenses in the renal cells was suggested by the alteration in some precursors of glutathione synthesis, such as glutamate, and by the release of the antioxidant anserin. Cell membrane damage was evidenced by the increased levels of some osmolytes, betaine and putrescine, as well as by a membrane repair mechanism involving choline. Finally, the development of metabolic acidosis was suggested by the elevation in 3-HMG in the hemolymph, and the more pronounced lysine levels were consistent with acute excretion troubles. Cd-induced renal damage was objectified by the increased level of riboflavin, a recognized biomarker of nephrotoxicity. Full article

(This article belongs to the Special Issue Advances in Ecotoxicology and Metabolism)

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23 pages, 2408 KiB

Open AccessArticle

Validation of the Chemical and Biological Steps Required Implementing an Advanced Multi-Omics Approach for Assessing the Fate and Impact of Contaminants in Lagoon Sediments

by Anouar Mejait, Aurélie Fildier, Barbara Giroud, Gaëlle Daniele, Laure Wiest, Delphine Raviglione, Jules Kotarba, Eve Toulza, Triana Ramirez, Alexia Lanseman, Camille Clerissi, Emmanuelle Vulliet, Christophe Calvayrac and Marie-Virginie Salvia

Metabolites 2024, 14(8), 454; https://doi.org/10.3390/metabo14080454 - 17 Aug 2024

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Abstract

The increasing use of chemicals requires a better understanding of their presence and dynamics in the environment, as well as their impact on ecosystems. The aim of this study was to validate the first steps of an innovative multi-omics approach based on metabolomics [...] Read more.

The increasing use of chemicals requires a better understanding of their presence and dynamics in the environment, as well as their impact on ecosystems. The aim of this study was to validate the first steps of an innovative multi-omics approach based on metabolomics and 16S metabarcoding data for analyses of the fate and impact of contaminants in Mediterranean lagoons. Semi-targeted analytical procedures for water and sediment matrices were implemented to assess chemical contamination of the lagoon: forty-six compounds were detected, 28 of which could be quantified in water (between 0.09 and 47.4 ng/L) and sediment (between 0.008 and 26.3 ng/g) samples using the UHPLC-MS/MS instrument. In addition, a non-targeted approach (UHPLC-HRMS) using four different sample preparation protocols based on solid/liquid extractions or an automated pressurized fluid extraction system (EDGE^®) was carried out to determine the protocol with the best metabolome coverage, efficiency and reproducibility. Solid/liquid extraction using the solvent mixture acetonitrile/methanol (50/50) was evaluated as the best protocol. Microbial diversity in lagoon sediment was also measured after DNA extraction using five commercial extraction kits. Our study showed that the DNeasy PowerSoil Pro Qiagen kit (Promega, USA) was the most suitable for assessing microbial diversity in fresh sediment. Full article

(This article belongs to the Special Issue Metabolomics: A Promising Tool for Environmental Sciences?)

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17 pages, 3811 KiB

Open AccessEditor’s ChoiceArticle

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 617

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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13 pages, 7570 KiB

Open AccessArticle

Bile Acid Metabolism Analysis Provides Insights into Vascular Endothelial Injury in Salt-Sensitive Hypertensive Rats

by Baihan Zeng, Xile Peng, Li Chen, Jiao Liu and Lina Xia

Metabolites 2024, 14(8), 452; https://doi.org/10.3390/metabo14080452 - 16 Aug 2024

Cited by 1 | Viewed by 948

Abstract

As an unhealthy dietary habit, a high-salt diet can affect the body’s endocrine system and metabolic processes. As one of the most important metabolites, bile acids can prevent atherosclerosis and reduce the risk of developing cardiovascular diseases. Therefore, in the present study, we [...] Read more.

As an unhealthy dietary habit, a high-salt diet can affect the body’s endocrine system and metabolic processes. As one of the most important metabolites, bile acids can prevent atherosclerosis and reduce the risk of developing cardiovascular diseases. Therefore, in the present study, we aimed to reveal the bile acid metabolism changes in salt-sensitive hypertension-induced vascular endothelial injury. The model was established using a high-salt diet, and the success of this procedure was confirmed by detecting the levels of the blood pressure, vascular regulatory factors, and inflammatory factors. An evaluation of the histological sections of arterial blood vessels and kidneys confirmed the pathological processes in these tissues of experimental rats. Bile acid metabolism analysis was performed to identify differential bile acids between the low-salt diet group and the high-salt diet group. The results indicated that the high-salt diet led to a significant increase in blood pressure and the levels of endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α). The high-salt diet causes disorders in bile acid metabolism. The levels of four differential bile acids (glycocholic acid, taurolithocholic acid, tauroursodeoxycholic acid, and glycolithocholic acid) significantly increased in the high-salt group. Further correlation analysis indicated that the levels of ET-1 and TNF-α were positively correlated with these differential bile acid levels. This study provides new evidence for salt-sensitive cardiovascular diseases and metabolic changes caused by a high-salt diet in rats. Full article

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17 pages, 6281 KiB

Open AccessArticle

Bile Acid Composition and Transcriptome Analysis of the Liver and Small Intestine in Different Species

by Dongming Qi, Tingting Zheng, Maosen Yang, Zhiying Huang, Tao Wang, Qiang Wang and Binlong Chen

Metabolites 2024, 14(8), 451; https://doi.org/10.3390/metabo14080451 - 15 Aug 2024

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Abstract

Bile, a crucial fluid produced continuously by the liver, plays an essential role in digestion within the small intestine. Beyond its primary function in lipid digestion, bile also acts as a pathway for the elimination of various endogenous and exogenous substances. There have [...] Read more.

Bile, a crucial fluid produced continuously by the liver, plays an essential role in digestion within the small intestine. Beyond its primary function in lipid digestion, bile also acts as a pathway for the elimination of various endogenous and exogenous substances. There have been limited studies focusing on interspecies differences. This study offers a comprehensive analysis of bile acid (BA) composition and its correlation with gene expression patterns across six different species, including mammals and poultry, through combining Liquid Chromatography-Mass Spectrometry (LC-MS) and transcriptome sequencing. The BA profiles revealed distinct metabolite clusters: D-glucuronic acid (GLCA) and glycochenodeoxycholic acid (GCDCA) were predominant in mammals, while taurolithocholic acid (TLCA) and T-alpha-MCA were prevalent in poultry, highlighting species-specific BA compositions. Differentially abundant metabolites, particularly GDCA, glycohyodeoxycholic acid (GHDCA) and taurodeoxycholic acid (TDCA) showed significant variations across species, with pigs showing the highest BA content. Transcriptome analysis of the liver and small intestine tissues of 56 cDNA libraries across the six species revealed distinct mRNA expression patterns. These patterns clustered samples into broad categories based on tissue type and phylogenetic relationships. Furthermore, the correlation between gene expression and BA content was examined, identifying the top 20 genes with significant associations. These genes potentially serve as biomarkers for BA regulation. Full article

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16 pages, 1249 KiB

Open AccessArticle

Alterations in Vagal Tone Are Associated with Changes in the Gut Microbiota of Adults with Anxiety and Depression Symptoms: Analysis of Fecal Metabolite Profiles

by Laura Pasqualette, Tatiana Kelly da Silva Fidalgo, Liana Bastos Freitas-Fernandes, Gabriela Guerra Leal Souza, Luís Aureliano Imbiriba, Leandro Araujo Lobo, Eliane Volchan, Regina Maria Cavalcanti Pilotto Domingues, Ana Paula Valente and Karla Rodrigues Miranda

Metabolites 2024, 14(8), 450; https://doi.org/10.3390/metabo14080450 - 15 Aug 2024

Viewed by 1131

Abstract

Accumulating evidence suggests that interactions between the brain and gut microbiota significantly impact brain function and mental health. In the present study, we aimed to investigate whether young, healthy adults without psychiatric diagnoses exhibit differences in metabolic stool and microbiota profiles based on [...] Read more.

Accumulating evidence suggests that interactions between the brain and gut microbiota significantly impact brain function and mental health. In the present study, we aimed to investigate whether young, healthy adults without psychiatric diagnoses exhibit differences in metabolic stool and microbiota profiles based on depression/anxiety scores and heart rate variability (HRV) parameters. Untargeted nuclear magnetic resonance-based metabolomics was used to identify fecal metabolic profiles. Results were subjected to multivariate analysis through principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), and the metabolites were identified through VIP score. Metabolites separating asymptomatic and symptomatic groups were acetate, valine, and glutamate, followed by sugar regions, glutamine, acetone, valerate, and acetoacetate. The main metabolites identified in high vagal tone (HVT) and low vagal tone (LVT) groups were acetate, valerate, and glutamate, followed by propionate and butyrate. In addition to the metabolites identified by the PLS-DA test, significant differences in aspartate, sarcosine, malate, and methionine were observed between the groups. Levels of acetoacetate were higher in both symptomatic and LVT groups. Valerate levels were significantly increased in the symptomatic group, while isovalerate, propionate, glutamate, and acetone levels were significantly increased in the LVT group. Furthermore, distinct abundance between groups was only confirmed for the Firmicutes phylum. Differences between participants with high and low vagal tone suggest that certain metabolites are involved in communication between the vagus nerve and the brain. Full article

(This article belongs to the Special Issue Novel Approaches for Metabolomics in Drugs and Biomarkers Discovery)

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11 pages, 1632 KiB

Open AccessArticle

Tolerance Mechanisms and Removal Efficiency of Chlorella pyrenoidosa in Treating 3-Fluorophenol Pollution

by Min Li, Zhenfang Shang, Yonglan Ma, Huijun Zhao, Zhijing Ni, Zhaojun Wei and Xiu Zhang

Metabolites 2024, 14(8), 449; https://doi.org/10.3390/metabo14080449 - 15 Aug 2024

Viewed by 1394

Abstract

This study investigates the growth tolerance mechanisms of Chlorella pyrenoidosa to 3-fluorophenol and its removal efficiency by algal cells. Our results indicate that C. pyrenoidosa can tolerate up to 100 mg/L of 3-fluorophenol, exhibiting a significant hormesis effect characterized by initial inhibition followed [...] Read more.

This study investigates the growth tolerance mechanisms of Chlorella pyrenoidosa to 3-fluorophenol and its removal efficiency by algal cells. Our results indicate that C. pyrenoidosa can tolerate up to 100 mg/L of 3-fluorophenol, exhibiting a significant hormesis effect characterized by initial inhibition followed by promotion of growth. In C. pyrenoidosa cells, the activities of superoxide dismutase (SOD) and catalase (CAT), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), were higher than or comparable to the control group. Metabolic analysis revealed that the 3-fluorophenol treatment activated pathways, such as glycerol phospholipid metabolism, autophagy, glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis, and phenylpropanoid biosynthesis, contributed to the stabilization of cell membrane structures and enhanced cell repair capacity. After 240 h of treatment, over 50% of 3-fluorophenol was removed by algal cells, primarily through adsorption. Thus, C. pyrenoidosa shows potential as an effective biosorbent for the bioremediation of 3-fluorophenol. Full article

(This article belongs to the Special Issue New Insights in Plant Metabolism and Chemodiversity)

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16 pages, 2285 KiB

Open AccessArticle

Hyperpolarized Magnetic Resonance Imaging, Nuclear Magnetic Resonance Metabolomics, and Artificial Intelligence to Interrogate the Metabolic Evolution of Glioblastoma

by Kang Lin Hsieh, Qing Chen, Travis C. Salzillo, Jian Zhang, Xiaoqian Jiang, Pratip K. Bhattacharya and Shyan Shams

Metabolites 2024, 14(8), 448; https://doi.org/10.3390/metabo14080448 - 14 Aug 2024

Viewed by 1038

Abstract

Glioblastoma (GBM) is a malignant Grade VI cancer type with a median survival duration of only 8–16 months. Earlier detection of GBM could enable more effective treatment. Hyperpolarized magnetic resonance spectroscopy (HPMRS) could detect GBM earlier than conventional anatomical MRI in glioblastoma murine [...] Read more.

Glioblastoma (GBM) is a malignant Grade VI cancer type with a median survival duration of only 8–16 months. Earlier detection of GBM could enable more effective treatment. Hyperpolarized magnetic resonance spectroscopy (HPMRS) could detect GBM earlier than conventional anatomical MRI in glioblastoma murine models. We further investigated whether artificial intelligence (A.I.) could detect GBM earlier than HPMRS. We developed a deep learning model that combines multiple modalities of cancer data to predict tumor progression, assess treatment effects, and to reconstruct in vivo metabolomic information from ex vivo data. Our model can detect GBM progression two weeks earlier than conventional MRIs and a week earlier than HPMRS alone. Our model accurately predicted in vivo biomarkers from HPMRS, and the results inferred biological relevance. Additionally, the model showed potential for examining treatment effects. Our model successfully detected tumor progression two weeks earlier than conventional MRIs and accurately predicted in vivo biomarkers using ex vivo information such as conventional MRIs, HPMRS, and tumor size data. The accuracy of these predictions is consistent with biological relevance. Full article

(This article belongs to the Special Issue Insights into Metabolism, Diagnostics and Therapeutics of Cancer and Tumor Microenvironment by NMR Spectroscopy)

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17 pages, 2813 KiB

Open AccessArticle

Cardiometabolic and Cellular Adaptations to Multiple vs. Single Daily HIIT Sessions in Wistar Rats: Impact of Short-Term Detraining

by Liliane Vanessa Costa-Pereira, Bruno Ferreira Mendes, Caíque Olegário Diniz Magalhães, Cíntia Maria Rodrigues, Júllia Alves de Andrade, Ramona Ramalho Souza de Pereira, Elizabethe Adriana Esteves, Ricardo Cardoso Cassilhas, Eric Francelino Andrade, Fernando Gripp, Flávio Castro de Magalhães, Kinulpe Honorato Sampaio, Alex Cleber Improta-Caria, Fabiano Trigueiro Amorim and Marco Fabrício Dias-Peixoto

Metabolites 2024, 14(8), 447; https://doi.org/10.3390/metabo14080447 - 14 Aug 2024

Viewed by 925

Abstract

Multiple short daily bouts of HIIT are more effective than single daily sessions in improving cardiometabolic and cellular adaptations in rats. We hypothesize that a short period of detraining is sufficient to abolish the superior adaptive responses to multiple versus single daily sessions [...] Read more.

Multiple short daily bouts of HIIT are more effective than single daily sessions in improving cardiometabolic and cellular adaptations in rats. We hypothesize that a short period of detraining is sufficient to abolish the superior adaptive responses to multiple versus single daily sessions of HIIT in rats. Male rats were divided into untrained, 1xHIIT, and 3xHIIT groups. Over eight weeks, the 1xHIIT group performed 115 min single daily sessions of HIIT, while the 3xHIIT group performed three 5 min sessions with 4 h intervals. After training, both groups remained sedentary for four weeks (detraining). Resting oxygen consumption (VO2), body composition, glucose/insulin tolerance, and blood pressure were recorded. After euthanasia, cardiac function/histology and gastrocnemius mitochondrial density were analyzed. After training, both 1xHIIT and 3xHIIT protocols induced similar improvements in VO2, maximal oxygen uptake (VO2max), cardiac function/hypertrophy, and gastrocnemius mitochondrial density. These effects were maintained even after detraining. Only the 3xHIIT protocol improved insulin sensitivity. After detraining, this effect was abolished. After training, both 1xHIIT and 3xHIIT protocols reduced adiposity. After detraining, the adiposity increased in both groups, with a more pronounced increase in the 3xHIIT rats. A four-week detraining period abolishes the superior adaptive responses to multiple versus single daily HIIT sessions in rats. Full article

(This article belongs to the Special Issue Molecular Mechanisms in Cancer, Cardiovascular and Metabolic Diseases: Potential Therapies and Treatments)

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25 pages, 14348 KiB

Open AccessArticle

Fufang Muji Granules Ameliorate Liver Fibrosis by Reducing Oxidative Stress and Inflammation, Inhibiting Apoptosis, and Modulating Overall Metabolism

by Lei Men, Zhihong Gu, Enhua Wang, Jiwen Li, Zhongyu Li, Keke Li, Chunbin Li and Xiaojie Gong

Metabolites 2024, 14(8), 446; https://doi.org/10.3390/metabo14080446 - 11 Aug 2024

Viewed by 1073

Abstract

Fufang Muji granules (FMGs) are a prominent modern prescription Chinese patent formulation derived from the Muji decoction. Utilized in clinical practice for nearly four decades, FMGs have demonstrated efficacy in treating liver diseases. However, the precise mechanism of action remains unclear. This study [...] Read more.

Fufang Muji granules (FMGs) are a prominent modern prescription Chinese patent formulation derived from the Muji decoction. Utilized in clinical practice for nearly four decades, FMGs have demonstrated efficacy in treating liver diseases. However, the precise mechanism of action remains unclear. This study investigates the hepatoprotective effects of FMGs against liver fibrosis in rats based on untargeted metabolomics and elucidates their underlying mechanisms. A comprehensive model of liver fibrosis was established with 30% CCl₄ (2 mL/kg) injected intraperitoneally, and a fat and sugar diet combined with high temperatures and humidity. Rats were orally administered FMGs (3.12 g/kg/d) once daily for six weeks. FMG administration resulted in improved liver fibrosis and attenuated hepatic oxidative stress and apoptosis. Furthermore, FMGs inhibited hepatic stellate cell activation and modulated transforming growth factor β1/Smad signaling. Additionally, FMG treatment influenced the expression levels of interleukin-6, interleukin-1β, and tumour necrosis factor alpha in the injured liver. Metabolic pathways involving taurine and hypotaurine metabolism, as well as primary bile acid biosynthesis, were identified as mechanisms of action for FMGs. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and quantitative analysis also revealed that FMGs regulated taurine and hypotaurine metabolism and bile acid metabolism. These findings provide a valuable understanding of the role of FMGs in liver fibrosis management. Full article

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13 pages, 5376 KiB

Open AccessArticle

An Exploratory Study on the Rapid Detection of Volatile Organic Compounds in Gardenia Fruit Using the Heracles NEO Ultra-Fast Gas Phase Electronic Nose

by Wenjing Cai, Wei Zhou, Jiayao Liu, Jing Wang, Ding Kuang, Jian Wang, Qing Long and Dan Huang

Metabolites 2024, 14(8), 445; https://doi.org/10.3390/metabo14080445 - 11 Aug 2024

Viewed by 748

Abstract

Gardenia fruit is a popular functional food and raw material for natural pigments. It comes from a wide range of sources, and different products sharing the same name are very common. Volatile organic compounds (VOCs) are important factors that affect the flavor and [...] Read more.

Gardenia fruit is a popular functional food and raw material for natural pigments. It comes from a wide range of sources, and different products sharing the same name are very common. Volatile organic compounds (VOCs) are important factors that affect the flavor and quality of gardenia fruit. This study used the Heracles NEO ultra-fast gas phase electronic nose with advanced odor analysis performance and high sensitivity to analyze six batches of gardenia fruit from different sources. This study analyzed the VOCs to find a way to quickly identify gardenia fruit. The results show that this method can accurately distinguish the odor characteristics of various gardenia fruit samples. The VOCs in gardenia fruit are mainly organic acid esters, ketones, and aldehyde compounds. By combining principal component analysis (PCA) and discriminant factor analysis (DFA), this study found that the hexanal content varied the most in different gardenia fruit samples. The VOCs allowed for the fruit samples to be grouped into two main categories. One fruit sample was quite different from the fruits of other origins. The results provide theoretical support for feasibility of rapid identification and quality control of gardenia fruit and related products in the future. Full article

(This article belongs to the Special Issue Metabolomic Technology in Quality and Safety of Agricultural Products and Foods)

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10 pages, 933 KiB

Open AccessArticle

Association Between Indole-3-Pyruvic Acid and Change in Fat-Free Mass Relative to Weight Loss in Patients Undergoing Sleeve Gastrectomy

by Eunhye Seo, Yeongkeun Kwon and Sungsoo Park

Metabolites 2024, 14(8), 444; https://doi.org/10.3390/metabo14080444 - 11 Aug 2024

Viewed by 678

Abstract

Sleeve gastrectomy typically leads to weight loss, including a reduction in fat-free mass (FFM). Studies have shown significant FFM loss within 1 year after the procedure but with individual variations. This study aimed to assess whether preoperative amino acid metabolite levels can predict [...] Read more.

Sleeve gastrectomy typically leads to weight loss, including a reduction in fat-free mass (FFM). Studies have shown significant FFM loss within 1 year after the procedure but with individual variations. This study aimed to assess whether preoperative amino acid metabolite levels can predict FFM changes following sleeve gastrectomy. This study involved 42 patients. Body weight, fat mass (FM), and FFM were measured preoperatively and 3, 6, and 12 months postoperatively. All participants experienced weight loss, FM reduction, and FFM decrease for up to 3 months after surgery. However, the following distinct groups emerged from 3 to 6 months postoperatively: one showed FFM gain relative to weight loss, whereas the other exhibited continued FFM reduction relative to weight loss. This trend persisted for up to 12 months postoperatively and became more pronounced. The group with FFM gain had lower preoperative BMI and higher levels of indole-3-pyruvic acid (IPyA). Logistic regression and ROC curve analyses confirmed IPyA’s ability to predict FFM gain between 3 and 6 months after sleeve gastrectomy, with a useful cutoff value of 20.205. Preoperative IPyA levels were associated with FFM gain relative to weight loss in the 3 to 6 months following sleeve gastrectomy. These findings suggest that IPyA may be a potential predictor for FFM changes during this period. Full article

(This article belongs to the Special Issue Metabolic Effects of Foregut Surgery in the Management of Obesity and Diabetes)

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15 pages, 2334 KiB

Open AccessArticle

A Comparative Study on the Muscle and Gut Microbiota of Opsariichthys bidens from Rice Field and Pond Culture Breeding Modes

by Fan Zhou, Weichao Bu, Hongjie Fan, Shuirong Guo, Ming Qi, Gaohua Yao, Yijiang Bei, Yuanfei Huang, Shicheng Zhu, Xueyan Ding and Xingwei Xiang

Metabolites 2024, 14(8), 443; https://doi.org/10.3390/metabo14080443 - 9 Aug 2024

Viewed by 1096

Abstract

To investigate difference in the quality of the different parts (back, tail muscles, and fish skin) of Opsariichthys bidens from pond and rice field cultures, a comparative study was conducted in terms of nutritional composition, volatile flavor profiles and gut microbiota. In detail, [...] Read more.

To investigate difference in the quality of the different parts (back, tail muscles, and fish skin) of Opsariichthys bidens from pond and rice field cultures, a comparative study was conducted in terms of nutritional composition, volatile flavor profiles and gut microbiota. In detail, the texture, free amino acids, fatty acids were further assessed. The results suggested that the moisture content, crude protein and crude fat content in the skin of O. bidens are higher than those in the back and tail muscles, regardless of breeding modes. The fish cultured in the rice field had a higher protein content than those from the pond culture, while the fat content of the rice field-cultured fish was significantly low compared to the fish from the pond culture, especially in the back and tail parts. A total of 43 volatile components were detected by Gas Chromatography–Mass Spectrometry (GC-MS), with a maximum of 18 types of aldehydes and the highest concentration being nonanal. Compared to pond cultures, the fish from the rice field cultures showed more abundant flavor composition and odor-active compounds. The total content of DHA (Docosahexaenoic Acid) and EPA (Eicosapentaenoic Acid) in the rice field-cultured fish was higher than that of the pond group, while no significant disparity in amino acid composition was observed (p > 0.05). Comparative and clustering analyses of gut microbiota revealed notable discrepancies in the gut microbiota of O. bidens from two aquaculture systems. However, an inherent correlation between the gut microbiome and meat quality would be further emphasized in further studies. This study can offer a theoretical reference for the development of high-quality aquatic products by selecting the appropriate aquaculture models. Full article

(This article belongs to the Special Issue Metabolism and Nutrition in Fish)

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17 pages, 5609 KiB

Open AccessArticle

Effects of a High Trans Fatty Acid Diet on Kidney-, Liver-, and Heart-Associated Diseases in a Rabbit Model

by Hammad Ismail, Zaryab Mubashar, Hajra Khan, Zeenat Naveed, Erum Dilshad, Muhammad Zeeshan Bhatti, Sadaf Anwaar, Samreen Saleem, Sabba Mehmood, Abdur Rahman, Umer Rashid, Dalia Fouad, Michel De Waard and Gaber El-Saber Batiha

Metabolites 2024, 14(8), 442; https://doi.org/10.3390/metabo14080442 - 8 Aug 2024

Viewed by 1199

Abstract

Trans fatty acids are specific unsaturated fats found in processed foods that undergo hydrogenation, leading to hepatic disorders such as metabolic-associated fatty liver disease (MAFLD) and conditions like CVD and CKD. The effects of different food samples containing trans fatty acids (elaidic and [...] Read more.

Trans fatty acids are specific unsaturated fats found in processed foods that undergo hydrogenation, leading to hepatic disorders such as metabolic-associated fatty liver disease (MAFLD) and conditions like CVD and CKD. The effects of different food samples containing trans fatty acids (elaidic and oleic acid) on the liver, heart, and kidney through antioxidant enzyme activity were investigated in animal models. Liver function tests (ALT, ALP, AST, and LDH), heart biomarker levels (CPK, TC, HDL, LDL, and triglycerides), and kidney biomarker levels (serum creatinine, blood urea nitrogen, and serum uric acid) were examined in serum of rabbits and the histopathology of liver tissues. Results showed that these biomarkers were more elevated in the Mujahid Ghee group than in the normal control, oleic acid, and Kausar Ghee groups. The concentration of antioxidant markers such as peroxidase, glutathione, catalase, thiobarbituric acid reactive substances, and superoxide dismutase were lower in the Mujahid Ghee group. HPLC showed that Mujahid Ghee had the highest quantified value of elaidic acid among all selected samples. Overall, this study demonstrated that elaidic acid in its purest form aggravated MAFLD in rabbit livers and provoked CVK and CVD. Full article

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15 pages, 4457 KiB

Open AccessArticle

Content Determination and Chemical Clustering Analysis of Tanshinone and Salvianolic Acid in Salvia spp.

by Feiyan Wang, Yufeng Bao, Furui Yang, Lu Yuan, Xinchun Han, Yanbo Huang, Yukun Wei, Lei Zhang, Zongqi Yang and Dongfeng Yang

Metabolites 2024, 14(8), 441; https://doi.org/10.3390/metabo14080441 - 8 Aug 2024

Viewed by 882

Abstract

Salvia miltiorrhiza is one of the famous traditional Chinese medicines for treating cardiovascular and cerebrovascular diseases. Tanshinone and phenolic acids are the main active compounds of Salvia miltiorrhiza, whereas the distribution patterns of the two kinds of components are still unclear among [...] Read more.

Salvia miltiorrhiza is one of the famous traditional Chinese medicines for treating cardiovascular and cerebrovascular diseases. Tanshinone and phenolic acids are the main active compounds of Salvia miltiorrhiza, whereas the distribution patterns of the two kinds of components are still unclear among Salvia spp. In this work, high-performance liquid chromatography was applied to analyze the distribution patterns of major components in the roots and leaves of 58 Salvia spp. The results showed that the distribution patterns of tanshinone and phenolic acids in Salvia spp. varied significantly. Phenolic acid components such as rosmarinus acid, caffeic acid, and danshensu are widely distributed in the roots and leaves, and phenolic acids in the leaves of Salvia spp. are generally higher than that in roots. Tanshinones are mainly detected in the roots of Salvia przewalskii, Salvia trijuga, Salvia castanea, and Salvia yunnanensis. The content of major components of the different species varied significantly. The content of phenolic acids in most Salvia spp. generally followed the pattern of salvianolic acid B > rosmarinic acid > danshensu > caffeic acid both in the roots and leaves. Tanshinone IIA and cryptotanshinone were the main lipophilic components of Salvia spp. distributed in southwest China. A correlation between the distribution pattern of tanshinone and the genetic relationship of species was indicated in the work. This research systematically reveals the distribution patterns of tanshinone and phenolic acids in Salvia spp., providing a theoretical basis for the development and utilization of medicinal resources of Salvia. Full article

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23 pages, 5065 KiB

Open AccessArticle

Adenosine Triphosphate and Adenylate Energy Charge in Ready-to-Eat Food

by Georgii Konoplev, Alar Sünter, Artur I. Kuznetsov, Piret Raudsepp, Tõnu Püssa, Lauri Toom, Linda Rusalepp, Dea Anton, Oksana V. Stepanova, Daniil Lyalin, Liubov Abramova, Andrey Kozin, Oksana S. Stepanova, Aleksandr Frorip and Mati Roasto

Metabolites 2024, 14(8), 440; https://doi.org/10.3390/metabo14080440 - 7 Aug 2024

Viewed by 835

Abstract

It is commonly accepted that dietary nucleotides should be considered as essential nutrients originating mainly but not exclusively from meat and fish dishes. Most research in food science related to nutrition nucleotides is focused on raw products, while the effects of thermal processing [...] Read more.

It is commonly accepted that dietary nucleotides should be considered as essential nutrients originating mainly but not exclusively from meat and fish dishes. Most research in food science related to nutrition nucleotides is focused on raw products, while the effects of thermal processing of ready-to-eat food on nucleotide content are largely overlooked by the scientific community. The aim of this study is to investigate the impact of thermal processing and cold storage on the content of dietary nucleotides in freshly prepared and canned ready-to-eat meat and fish food. The concentrations of ATP, ADP, AMP, IMP, Ino, and Hx were determined using NMR, HPLC, FPMLC, and ATP bioluminescence analytical techniques; freshness indices K and K₁ and adenylate energy charge (AEC) values were estimated to assess the freshness status and confirm a newly unveiled phenomenon of the reappearance of adenylate nucleotides. It was found that in freshly prepared at 65 °C ≤ T ≤ +100 °C and canned food, the concentration of free nucleotides was in the range of 0.001–0.01 µmol/mL and remained unchanged for a long time during cold storage; the correct distribution of mole fractions of adenylates corresponding to 0 < AEC < 0.5 was observed compared to 0.2 < AEC < 1.0 in the original raw samples, with either a high or low content of residual adenylates. It could be assumed that heating at nonenzymatic temperatures T > 65 °C can rupture cell membranes and release residual intracell nucleotides in quite a meaningful concentration. These findings may lead to a conceptual change in the views on food preparation processes, taking into account the phenomenon of the free adenylates renaissance and AEC bioenergetics. Full article

(This article belongs to the Special Issue Metabolomic Technology in Quality and Safety of Agricultural Products and Foods)

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16 pages, 2315 KiB

Open AccessArticle

Potential Use of Common Administration of Emulsion for Parenteral Nutrition and Vinpocetine: Compatibility Study and Prospect

by Szymon Tomczak, Kornelia Kaszuba, Jagoda Szkudlarek, Ludwika Piwowarczyk and Anna Jelińska

Metabolites 2024, 14(8), 439; https://doi.org/10.3390/metabo14080439 - 7 Aug 2024

Viewed by 787

Abstract

Vinpocetine (VP) is distributed after oral and intravenous administration, and its uptake in the thalamus, basal ganglia, and visual cortex. Due to poor bioavailability (~7%) and marked first-pass effect (~75%), including a short half-life (2–3 h), oral administration of VP is limited. It [...] Read more.

Vinpocetine (VP) is distributed after oral and intravenous administration, and its uptake in the thalamus, basal ganglia, and visual cortex. Due to poor bioavailability (~7%) and marked first-pass effect (~75%), including a short half-life (2–3 h), oral administration of VP is limited. It requires frequent administration of the drug to obtain a therapeutic effect. Attempts to overcome these difficulties include the use of new drug delivery systems and/or alternative routes of drug administration. One possibility is the common administration of lipid emulsion and drug using the same catheter. However, this procedure is not recommended due to potential interaction and lack of safety data. For this purpose, we checked the compatibility of VP solutions with eight commercially available parenteral nutrition admixtures, i.e., Lipoflex special, Omegaflex special, Lipoflex peri, Omegaflex peri, Kabiven, SmofKabiven, Kabiven Peripheral, and Olimel Peri N4E. Coadministration is only possible if the stability of the drug and the lipid emulsion is confirmed. The available data are scarce and only concern the incompatibility of VP with ibuprofen. Compatibility tests were carried out in simulated administration through a Y-site connector using clinical flow rates. The stability of the drug and lipid emulsion was assessed by visual inspection and measurement of pH, osmolality, particle size as mean droplet diameter (MDD) and percentage of lipids residing in globules larger than 5 µm (PFAT5), zeta potential, polydispersity index, and lipid-free parenteral nutrition admixture(PNA) turbidity. The results of the compatibility of VP with eight commercial PN admixtures showed that all lipid emulsions show different signs of destabilization. In the studied samples, particles larger than 1000 nm, a significant increase in MDD, zeta potential, and loss of homogeneity visible as an increase in the polydispersity index were observed. Most of the samples had PFAT5 above the USP limit (0.05%). Taking into account the obtained data, VP should not be administered with the studied lipid emulsions for parenteral nutrition. Full article

(This article belongs to the Special Issue Drug Metabolism and New Drug Development for Cancers)

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17 pages, 1310 KiB

Open AccessReview

The Application of Metabolomics in Hyperlipidemia: Insights into Biomarker Discovery and Treatment Efficacy Assessment

by Mohammad Alwahsh, Rahaf Alejel, Aya Hasan, Haneen Abuzaid and Tariq Al-Qirim

Metabolites 2024, 14(8), 438; https://doi.org/10.3390/metabo14080438 - 6 Aug 2024

Viewed by 1029

Abstract

Hyperlipidemia is a lipid metabolism disorder that refers to increased levels of total triglycerides (TGs), cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) and decreased levels of high-density lipoprotein-cholesterol (HDL-C). It is a major public health issue with increased prevalence and incidence worldwide. The ability [...] Read more.

Hyperlipidemia is a lipid metabolism disorder that refers to increased levels of total triglycerides (TGs), cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) and decreased levels of high-density lipoprotein-cholesterol (HDL-C). It is a major public health issue with increased prevalence and incidence worldwide. The ability to identify individuals at risk of this disorder before symptoms manifest will facilitate timely intervention and management to avert potential complications. This can be achieved by employing metabolomics as an early detection method for the diagnostic biomarkers of hyperlipidemia. Metabolomics is an analytical approach used to detect and quantify metabolites. This provides the ability to explain the metabolic processes involved in the development and progression of certain diseases. In recent years, interest in the use of metabolomics to identify disease biomarkers has increased, and several biomarkers have been discovered, such as docosahexaenoic acid, glycocholic acid, citric acid, betaine, and carnitine. This review discusses the primary metabolic alterations in the context of hyperlipidemia. Furthermore, we provide an overview of recent studies on the application of metabolomics to the assessment of the efficacy of traditional herbal products and common lipid-lowering medications. Full article

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11 pages, 875 KiB

Open AccessArticle

Branched-Chain Amino Acids, Alanine, and Thyroid Function: A Cross-Sectional, Nuclear Magnetic Resonance (NMR)-Based Approach from ELSA-Brasil

by Carolina Castro Porto Silva Janovsky, Vandrize Meneghini, William Tebar, Joao Roberto Maciel Martins, José Augusto Sgarbi, Patrícia de Fatima dos Santos Teixeira, Steven R. Jones, Michael J. Blaha, Peter P. Toth, Paulo A. Lotufo, Marcio S. Bittencourt, Raul D. Santos, Itamar S. Santos, Layal Chaker and Isabela M. Bensenor

Metabolites 2024, 14(8), 437; https://doi.org/10.3390/metabo14080437 - 6 Aug 2024

Viewed by 1072

Abstract

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs—leucine, isoleucine, and valine) and of alanine [...] Read more.

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs—leucine, isoleucine, and valine) and of alanine in the general population. We utilized data from the São Paulo research center of ELSA-Brasil, a longitudinal population-based cohort study. Thyroid parameters included thyroid stimulating hormone (TSH), free T4 and free T3 levels, and the FT4:FT3 ratio. BCAAs and alanine were analyzed on a fully automated NMR platform. The current analysis included euthyroid participants and participants with subclinical hyperthyroidism and hypothyroidism. We used Pearson’s coefficient to quantify the correlation between thyroid-related parameters and amino acids. Linear regression models were performed to analyze whether thyroid parameters were associated with BCAAs and alanine levels. We included 4098 participants (51.3 ± 9.0 years old, 51.5% women) in this study. In the most adjusted model, higher levels of TSH were associated with higher levels of alanine, FT4 levels were inversely associated with isoleucine levels, FT3 levels were statistically significant and positively associated with valine and leucine, and the T3:T4 ratio was positively associated with all amino acids. We observed that subclinical hypothyroidism was positively associated with isoleucine and alanine levels in all models, even after full adjustment. Our findings highlight the association of subclinical hypothyroidism and thyroid-related parameters (including TSH, free T4, free T3, and FT4:FT3 ratio) with BCAAs and alanine. Further studies are needed to explore the mechanisms underlying this association. These insights contribute to our understanding of the influence of thyroid-related parameters on BCAA and alanine metabolism. Full article

(This article belongs to the Special Issue Metabolites and Thyroid)

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13 pages, 532 KiB

Open AccessArticle

Investigating the Link between Intermediate Metabolism, Sexual Dimorphism, and Cardiac Autonomic Dysfunction in Patients with Type 1 Diabetes

by María Rosa Insenser, Lía Nattero-Chávez, Manuel Luque-Ramírez, Sara de Lope Quiñones, Alejandra Quintero-Tobar, Sara Samino, Núria Amigó, Beatriz Dorado Avendaño, Tom Fiers and Héctor F. Escobar-Morreale

Metabolites 2024, 14(8), 436; https://doi.org/10.3390/metabo14080436 - 6 Aug 2024

Viewed by 1028

Abstract

Sexual dimorphism influences cardiovascular outcomes in type 1 diabetes (T1D), with women facing a higher relative risk of macrovascular events compared to men, especially after menopause. This study hypothesizes that abnormalities in intermediate metabolism may be associated with cardiac autonomic neuropathy (CAN) in [...] Read more.

Sexual dimorphism influences cardiovascular outcomes in type 1 diabetes (T1D), with women facing a higher relative risk of macrovascular events compared to men, especially after menopause. This study hypothesizes that abnormalities in intermediate metabolism may be associated with cardiac autonomic neuropathy (CAN) in T1D. We aim to assess low molecular weight metabolites (LMWM) as markers of CAN in T1D, considering the effects of sexual dimorphism and age. In this cross-sectional study, we included 323 subjects with T1D (147 women and 176 men), with a mean age of 41 ± 13 years. A total of 44 women and 41 men were over 50 years old. CAN was assessed using Ewing’s tests, and serum metabolites were analyzed by proton nuclear magnetic resonance spectroscopy (¹H-NMR). Patients with CAN had lower levels of valine, isoleucine, and threonine, and higher levels of lactate, compared to those without CAN. These differences persisted after adjusting for BMI and estimated glucose disposal rate (eGDR). In a logistic regression model (R² = 0.178, p < 0.001), the main determinants of CAN included isoleucine [Exp(β) = 0.972 (95% CI 0.952; 0.003)], age [Exp(β) = 1.031 (95% CI 1.010; 1.053)], A_1c [Exp(β) = 1.361 (95% CI 1.058; 1.752)], and microangiopathy [Exp(β) = 2.560 (95% CI 1.372; 4.778)]. Sex influenced LMWM profiles, with over half of the metabolites differing between men and women. However, no interactions were found between CAN and sex, or between sex, age, and CAN, on metabolomics profiles. Our findings suggest an association between CAN and LMWM levels in T1D. The sexual dimorphism observed in amino acid metabolites was unaffected by the presence of CAN. Full article

(This article belongs to the Special Issue Advances in Metabolomics and Multi-omics Integration)

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Open AccessArticle

Metabolic and Oxidative Stress Management Heterogeneity in a Panel of Breast Cancer Cell Lines

by Paola Maycotte, Fabiola Lilí Sarmiento-Salinas, Alin García-Miranda, Cesar Ivan Ovando-Ovando, Diana Xochiquetzal Robledo-Cadena, Luz Hernández-Esquivel, Ricardo Jasso-Chávez and Alvaro Marín-Hernández

Metabolites 2024, 14(8), 435; https://doi.org/10.3390/metabo14080435 - 6 Aug 2024

Viewed by 1660

Abstract

Metabolic alterations are recognized as one of the hallmarks of cancer. Among these, alterations in mitochondrial function have been associated with an enhanced production of Reactive Oxygen Species (ROS), which activate ROS-regulated cancer cell signaling pathways. Breast cancer is the main cancer-related cause [...] Read more.

Metabolic alterations are recognized as one of the hallmarks of cancer. Among these, alterations in mitochondrial function have been associated with an enhanced production of Reactive Oxygen Species (ROS), which activate ROS-regulated cancer cell signaling pathways. Breast cancer is the main cancer-related cause of death for women globally. It is a heterogeneous disease with subtypes characterized by specific molecular features and patient outcomes. With the purpose of identifying differences in energy metabolism and the oxidative stress management system in non-tumorigenic, estrogen receptor positive (ER+) and triple negative (TN) breast cancer cells, we evaluated ROS production, protein enzyme levels and activities and profiled energy metabolism. We found differences in energetic metabolism and ROS management systems between non-tumorigenic and cancer cells and between ER+ and TN breast cancer cells. Our results indicate a dependence on glycolysis despite different glycolytic ATP levels in all cancer cell lines tested. In addition, our data show that high levels of ROS in TN cells are a result of limited antioxidant capacity in the NADPH producing and GSH systems, mitochondrial dysfunction and non-mitochondrial ROS production, making them more sensitive to GSH synthesis inhibitors. Our data suggest that metabolic and antioxidant profiling of breast cancer will provide important targets for metabolic inhibitors or antioxidant treatments for breast cancer therapy. Full article

(This article belongs to the Special Issue Reactive Oxygen Species and Energy Metabolic Alterations in Health and Disease)

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Metabolites, Volume 14, Issue 8 (August 2024) – 67 articles

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