Metabolites

17 pages, 3018 KiB

Open AccessArticle

Disturbances in Muscle Energy Metabolism in Patients with Amyotrophic Lateral Sclerosis

by Petra Parvanovova, Petra Hnilicova, Martin Kolisek, Zuzana Tatarkova, Erika Halasova, Egon Kurca, Simona Holubcikova, Monika Turcanova Koprusakova and Eva Baranovicova

Metabolites 2024, 14(7), 356; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14070356 - 23 Jun 2024

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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle atrophy and spasticity. It leads to death, mostly due to respiratory failure. Within the pathophysiology of the disease, muscle energy metabolism seems to be an important part. In our study, we used blood plasma from 25 patients with ALS diagnosed by definitive El Escorial criteria according to ALSFR-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) criteria and 25 age and sex-matched subjects. Aside from standard clinical biochemical parameters, we used the NMR (nuclear magnetic resonance) metabolomics approach to determine relative plasma levels of metabolites. We observed a decrease in total protein level in blood; however, despite accelerated skeletal muscle catabolism characteristic for ALS patients, we did not detect changes in plasma levels of essential amino acids. When focused on alterations in energy metabolism within muscle, compromised creatine uptake was accompanied by decreased plasma creatinine. We did not observe changes in plasma levels of BCAAs (branched chain amino acids; leucine, isoleucine, valine); however, the observed decrease in plasma levels of all three BCKAs (branched chain alpha-keto acids derived from BCAAs) suggests enhanced utilization of BCKAs as energy substrate. Glutamine, found to be increased in blood plasma in ALS patients, besides serving for ammonia detoxification, could also be considered a potential TCA (tricarboxylic acid) cycle contributor in times of decreased pyruvate utilization. When analyzing the data by using a cross-validated Random Forest algorithm, it finished with an AUC of 0.92, oob error of 8%, and an MCC (Matthew’s correlation coefficient) of 0.84 when relative plasma levels of metabolites were used as input variables. Although the discriminatory power of the system used was promising, additional features are needed to create a robust discriminatory model. Full article

(This article belongs to the Special Issue Metabolomics in Neurodegenerative Diseases)

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23 pages, 1088 KiB

Open AccessReview

The Cellular Stability Hypothesis: Evidence of Ferroptosis and Accelerated Aging-Associated Diseases as Newly Identified Nutritional Pentadecanoic Acid (C15:0) Deficiency Syndrome

by Stephanie Venn-Watson

Metabolites 2024, 14(7), 355; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14070355 - 23 Jun 2024

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Abstract

Ferroptosis is a newly discovered form of cell death caused by the peroxidation of fragile fatty acids in cell membranes, which combines with iron to increase reactive oxygen species and disable mitochondria. Ferroptosis has been linked to aging-related conditions, including type 2 diabetes, [...] Read more.

Ferroptosis is a newly discovered form of cell death caused by the peroxidation of fragile fatty acids in cell membranes, which combines with iron to increase reactive oxygen species and disable mitochondria. Ferroptosis has been linked to aging-related conditions, including type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). Pentadecanoic acid (C15:0), an odd-chain saturated fat, is an essential fatty acid with the primary roles of stabilizing cell membranes and repairing mitochondrial function. By doing so, C15:0 reverses the underpinnings of ferroptosis. Under the proposed “Cellular Stability Hypothesis”, evidence is provided to show that cell membranes optimally need >0.4% to 0.64% C15:0 to support long-term health and longevity. A pathophysiology of a newly identified nutritional C15:0 deficiency syndrome (“Cellular Fragility Syndrome”) is provided that demonstrates how C15:0 deficiencies (≤0.2% total circulating fatty acids) can increase susceptibilities to ferroptosis, dysmetabolic iron overload syndrome, type 2 diabetes, cardiovascular disease, and NAFLD. Further, evidence is provided that C15:0 supplementation can reverse the described C15:0 deficiency syndrome, including the key components of ferroptosis. Given the declining dietary intake of C15:0, especially among younger generations, there is a need for extensive studies to understand the potential breadth of Cellular Fragility Syndrome across populations. Full article

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

10 pages, 4124 KiB

Open AccessArticle

Microwave Radiation Caused Dynamic Metabolic Fluctuations in the Mammalian Hippocampus

by Yu Xin, Shu-Ting Guan, Ke Ren, Hui Wang, Ji Dong, Hao-Yu Wang, Jing Zhang, Xin-Ping Xu, Bin-Wei Yao, Li Zhao, Chang-Xiu Shi and Rui-Yun Peng

Metabolites 2024, 14(7), 354; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14070354 - 23 Jun 2024

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Abstract

To investigate the dynamic changes in hippocampal metabolism after microwave radiation using liquid chromatography in tandem with mass spectrometry/mass spectrometry (LC‒MS/MS) and to identify potential biomarkers. Wistar rats were randomly assigned to a sham group and a microwave radiation group. The rats in [...] Read more.

To investigate the dynamic changes in hippocampal metabolism after microwave radiation using liquid chromatography in tandem with mass spectrometry/mass spectrometry (LC‒MS/MS) and to identify potential biomarkers. Wistar rats were randomly assigned to a sham group and a microwave radiation group. The rats in the microwave radiation group were exposed to 2.856 GHz for 15 min for three times, with 5 min intervals. The rats in the sham group were not exposed. Transmission electron microscope revealed blurring of the synaptic cleft and postsynaptic dense thickening in hippocampal neurons after microwave radiation. Metabolomic analysis revealed 38, 24, and 39 differentially abundant metabolites at 3, 7, and 14 days after radiation, respectively, and the abundance of 9 metabolites, such as argininosuccinic acid, was continuously decreased. After microwave radiation, the abundance of metabolites such as argininosuccinic acid was successively decreased, indicating that these metabolites could be potential biomarkers for hippocampal tissue injury. Full article

(This article belongs to the Section Animal Metabolism)

32 pages, 4651 KiB

Open AccessArticle

Changes in Plasma Free Amino Acid Profile in Endurance Athletes over a 9-Month Training Cycle

by Krzysztof Kusy, Monika Ciekot-Sołtysiak, Jan Matysiak, Agnieszka Klupczyńska-Gabryszak, Szymon Plewa, Ewa Anna Zarębska, Zenon J. Kokot, Paweł Dereziński and Jacek Zieliński

Metabolites 2024, 14(7), 353; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14070353 - 23 Jun 2024

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Abstract

We aimed to evaluate long-term changes in proteinogenic and non-proteinogenic plasma free amino acids (PFAA). Eleven male endurance triathletes participated in a 9-month study. Blood was collected at rest, immediately after exhaustive exercise, and during 30-min recovery, in four consecutive training phases: transition, [...] Read more.

We aimed to evaluate long-term changes in proteinogenic and non-proteinogenic plasma free amino acids (PFAA). Eleven male endurance triathletes participated in a 9-month study. Blood was collected at rest, immediately after exhaustive exercise, and during 30-min recovery, in four consecutive training phases: transition, general, specific, and competition. Twenty proteinogenic and 22 non-proteinogenic PFAAs were assayed using the LC-ESI-MS/MS technique. The structured training modified the patterns of exercise-induced PFAA response, with the competition phase being the most distinct from the others. Branched-chain amino acids (p = 0.002; η² = 0.216), phenylalanine (p = 0.015; η² = 0.153), methionine (p = 0.002; η² = 0.206), and lysine (p = 0.006; η² = 0.196) declined more rapidly between rest and exhaustion in the competition phase. Glutamine (p = 0.008; η² = 0.255), glutamate (p = 0.006; η² = 0.265), tyrosine (p = 0.001; η² = 0.195), cystine (p = 0.042; η² = 0.183), and serine (p < 0.001; η² = 0.346) levels were reduced in the competition phase. Arginine (p = 0.046; η² = 0.138) and aspartate (p = 0.011; η² = 0.171) levels were highest during exercise in the transition phase. During the competition phase, α-aminoadipic acid (p = 0.023; η² = 0.145), β-aminoisobutyric acid (p = 0.007; η² = 0.167), β-alanine (p < 0.001; η² = 0.473), and sarcosine (p = 0.017; η² = 0.150) levels increased, whereas phosphoethanolamine (p = 0.037; η² = 0.189) and taurine (p = 0.008; η² = 0.251) concentrations decreased. Overtraining indicators were not elevated. The altered PFAA profile suggests adaptations within energy metabolic pathways such as the tricarboxylic acid cycle, oxidative phosphorylation, ammonia neutralization, the purine nucleotide cycle, and buffering of intracellular H⁺ ions. The changes seem to reflect normal adaptations. Full article

(This article belongs to the Special Issue Metabolomic Advances in Promoting Exercise-Induced Metabolic Changes)

35 pages, 1389 KiB

Open AccessReview

Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies

by Chiara Sanluca, Paolo Spagnolo, Romina Mancinelli, Maria Ilenia De Bartolo, Marina Fava, Mauro Maccarrone, Simone Carotti, Eugenio Gaudio, Alessandro Leuti and Giorgio Vivacqua

Metabolites 2024, 14(7), 352; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14070352 - 22 Jun 2024

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Abstract

The present review provides a comprehensive examination of the intricate dynamics between α-synuclein, a protein crucially involved in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease and multiple system atrophy, and endogenously-produced bioactive lipids, which play a pivotal role in neuroinflammation and [...] Read more.

The present review provides a comprehensive examination of the intricate dynamics between α-synuclein, a protein crucially involved in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease and multiple system atrophy, and endogenously-produced bioactive lipids, which play a pivotal role in neuroinflammation and neurodegeneration. The interaction of α-synuclein with bioactive lipids is emerging as a critical factor in the development and progression of neurodegenerative and neuroinflammatory diseases, offering new insights into disease mechanisms and novel perspectives in the identification of potential biomarkers and therapeutic targets. We delve into the molecular pathways through which α-synuclein interacts with biological membranes and bioactive lipids, influencing the aggregation of α-synuclein and triggering neuroinflammatory responses, highlighting the potential of bioactive lipids as biomarkers for early disease detection and progression monitoring. Moreover, we explore innovative therapeutic strategies aimed at modulating the interaction between α-synuclein and bioactive lipids, including the development of small molecules and nutritional interventions. Finally, the review addresses the significance of the gut-to-brain axis in mediating the effects of bioactive lipids on α-synuclein pathology and discusses the role of altered gut lipid metabolism and microbiota composition in neuroinflammation and neurodegeneration. The present review aims to underscore the potential of targeting α-synuclein-lipid interactions as a multifaceted approach for the detection and treatment of neurodegenerative and neuroinflammatory diseases. Full article

(This article belongs to the Special Issue Bioactive Lipids in Neuroinflammatory Diseases)

21 pages, 6974 KiB

Open AccessArticle

Integrated Microbiome-Metabolomics Analysis Reveals the Potential Mechanism of Dandelion Root Polysaccharides to Ameliorate Ulcerative Colitis

by Shengkun Yan and Rong Dong

Metabolites 2024, 14(7), 351; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14070351 - 22 Jun 2024

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Abstract

In the conducted research, a murine model for ulcerative colitis (UC) was established utilizing dextran sodium sulfate (DSS) to investigate the therapeutic potential of dandelion root polysaccharide extracts on this disease. This study employed an analysis of gut microbiota composition and serum metabolomics [...] Read more.

In the conducted research, a murine model for ulcerative colitis (UC) was established utilizing dextran sodium sulfate (DSS) to investigate the therapeutic potential of dandelion root polysaccharide extracts on this disease. This study employed an analysis of gut microbiota composition and serum metabolomics to understand the biochemical effects of these polysaccharides. Sequencing of the 16S ribosomal DNA component indicated an increased presence of Bacteroides in the DSS-treated model group, contrasting with a significant enhancement in Faecalibaculum populations in mice treated with dandelion root polysaccharides (DPs). This shift suggests a pivotal role of DPs in elevating fecal N-butyric acid levels—a crucial factor in the maintenance of gut microbiota equilibrium. Through metabolomic profiling of serum, this research identified distinct metabolic changes across the control, DSS model, and DP treatment groups, highlighting four major differential metabolites: (2S)-2-amino-3-[[(2R)-2-butanoyloxy-3-propanoyloxypropoxy]-hydroxyphosphoryl]oxypropanoic acid; (1R,8S,9S)-3,4-dihydroxy-8-methoxy-11,11-dimethyl-5-propan-2-yl-16-oxatetracyclo [7.5.2.01,10.02,7]hexadeca-2,4,6-trien-15-one; Aspartylasparagine; and Nap-Phe-OH. These metabolites are implicated in mitigating oxidative stress, suggesting that DPs facilitate a protective mechanism for the intestinal lining through various biochemical pathways. Additionally, a notable correlation was established between the altered gut microbiota and the serum metabolomic profiles, underscoring the intricate interplay between these two biological systems in the context of UC. This study’s outcomes illustrate that UC induces significant alterations in both gut microbiota and metabolic signatures, whereas dandelion root polysaccharides exhibit a profound ameliorative effect on these disruptions. This investigation underscores the therapeutic promise of dandelion root polysaccharides in the management of UC by modulating gut microbiota and metabolic pathways. Full article

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17 pages, 4804 KiB

Open AccessArticle

The Application of Resveratrol Derivatives in Oral Cells Reduces the Oxidative Stress Induced by Glucocorticoids

by Emira D’Amico, Chiara Cinquini, Morena Petrini, Antonio Barone, Giovanna Iezzi, Simonetta D’Ercole, Barbara De Filippis and Tania Vanessa Pierfelice

Metabolites 2024, 14(7), 350; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14070350 - 22 Jun 2024

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Abstract

Oxidative stress and high levels of reactive oxygen species (ROS) are linked to various age-related diseases and chronic conditions, including damage to oral tissues. Dexamethasone (DEX), a widely used glucocorticoid in dentistry, can have side effects like increased ROS production and delayed wound [...] Read more.

Oxidative stress and high levels of reactive oxygen species (ROS) are linked to various age-related diseases and chronic conditions, including damage to oral tissues. Dexamethasone (DEX), a widely used glucocorticoid in dentistry, can have side effects like increased ROS production and delayed wound healing. Resveratrol (RSV) is known for its antioxidant properties, but its limited bioavailability hinders its clinical use. This study investigated the potential of two RSV derivatives (1d and 1h) to address these limitations. The antioxidant abilities of 1d and 1h (5 μM) against DEX-induced oxidative stress (200 μM) were evaluated in human gingival fibroblasts (hGFs) and osteoblasts (hOBs). The effects of these compounds on cell viability, morphology, ROS levels, SOD activity, gene expression, and collagen production were evaluated. RSV derivatives, under DEX-induced oxidative stress condition, improved cell growth at 72 h (191.70 ± 10.92% for 1d+DEX and 184.80 ± 13.87% for 1h+DEX), morphology, and SOD activity (77.33 ± 3.35 OD for 1d+DEX; 76.87 ± 3.59 OD for 1h+DEX at 1 h), while reducing ROS levels (2417.33 ± 345.49 RFU for 1d+DEX and 1843.00 ± 98.53 RFU at 4 h), especially in hOBs. The co-treatment of RSV or derivatives with DEX restored the expression of genes that were downregulated by DEX, such as HO-1 (1.76 ± 0.05 for 1d+DEX and 1.79 ± 0.01 for 1h+DEX), CAT (0.97 ± 0.06 for 1d+DEX and 0.99 ± 0.03 for 1h+DEX), NRF2 (1.62 ± 0.04 for 1d+DEX and 1.91 ± 0.05 for 1h+DEX), SOD1 (1.63 ± 0.15 for 1d+DEX and 1.69 ± 0.04 for 1h+DEX). In addition, 1d and 1h preserved collagen production (111.79 ± 1.56 for 1d+DEX and 122.27 ± 1.56 for 1h+DEX). In conclusion, this study suggests that the RSV derivatives 1d and 1h hold promise as potential antioxidant agents to counteract DEX-induced oxidative stress. These findings contribute to the development of novel therapeutic strategies for managing oxidative stress-related oral conditions. Full article

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20 pages, 2420 KiB

Open AccessArticle

Metabolomics Analysis of Rabbit Plasma after Ocular Exposure to Vapors of Sulfur Mustard

by Jihéne Bouhlel, Fanny Caffin, Fanny Gros-Désormeaux, Thierry Douki, Jean-François Benoist, Florence A. Castelli, Emeline Chu-Van, Christophe Piérard, Christophe Junot and François Fenaille

Metabolites 2024, 14(7), 349; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14070349 - 21 Jun 2024

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Abstract

Sulfur mustard (SM) is a highly potent alkylating vesicant agent and remains a relevant threat to both civilians and military personnel. The eyes are the most sensitive organ after airborne SM exposure, causing ocular injuries with no antidote or specific therapeutics available. In [...] Read more.

Sulfur mustard (SM) is a highly potent alkylating vesicant agent and remains a relevant threat to both civilians and military personnel. The eyes are the most sensitive organ after airborne SM exposure, causing ocular injuries with no antidote or specific therapeutics available. In order to identify relevant biomarkers and to obtain a deeper understanding of the underlying biochemical events, we performed an untargeted metabolomics analysis using liquid chromatography coupled to high-resolution mass spectrometry of plasma samples from New Zealand white rabbits ocularly exposed to vapors of SM. Metabolic profiles (332 unique metabolites) from SM-exposed (n = 16) and unexposed rabbits (n = 8) were compared at different time intervals from 1 to 28 days. The observed time-dependent changes in metabolic profiles highlighted the profound dysregulation of the sulfur amino acids, the phenylalanine, the tyrosine and tryptophan pathway, and the polyamine and purine biosynthesis, which could reflect antioxidant and anti-inflammatory activities. Taurine and 3,4-dihydroxy-phenylalanine (Dopa) seem to be specifically related to SM exposure and correspond well with the different phases of ocular damage, while the dysregulation of adenosine, polyamines, and acylcarnitines might be related to ocular neovascularization. Additionally, neither cysteine, N-acetylcysteine, or guanine SM adducts were detected in the plasma of exposed rabbits at any time point. Overall, our study provides an unprecedented view of the plasma metabolic changes post-SM ocular exposure, which may open up the development of potential new treatment strategies. Full article

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

19 pages, 1774 KiB

Open AccessReview

Bile Acids in Pancreatic Carcinogenesis

by Bharti Sharma, Kate Twelker, Cecilia Nguyen, Scott Ellis, Navin D. Bhatia, Zachary Kuschner, Andrew Agriantonis, George Agriantonis, Monique Arnold, Jasmine Dave, Juan Mestre, Zahra Shafaee, Shalini Arora, Hima Ghanta and Jennifer Whittington

Metabolites 2024, 14(7), 348; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14070348 - 21 Jun 2024

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Abstract

Pancreatic cancer (PC) is a dangerous digestive tract tumor that is becoming increasingly common and fatal. The most common form of PC is pancreatic ductal adenocarcinoma (PDAC). Bile acids (BAs) are closely linked to the growth and progression of PC. They can change [...] Read more.

Pancreatic cancer (PC) is a dangerous digestive tract tumor that is becoming increasingly common and fatal. The most common form of PC is pancreatic ductal adenocarcinoma (PDAC). Bile acids (BAs) are closely linked to the growth and progression of PC. They can change the intestinal flora, increasing intestinal permeability and allowing gut microbes to enter the bloodstream, leading to chronic inflammation. High dietary lipids can increase BA secretion into the duodenum and fecal BA levels. BAs can cause genetic mutations, mitochondrial dysfunction, abnormal activation of intracellular trypsin, cytoskeletal damage, activation of NF-κB, acute pancreatitis, cell injury, and cell necrosis. They can act on different types of pancreatic cells and receptors, altering Ca²⁺ and iron levels, and related signals. Elevated levels of Ca²⁺ and iron are associated with cell necrosis and ferroptosis. Bile reflux into the pancreatic ducts can speed up the kinetics of epithelial cells, promoting the development of pancreatic intraductal papillary carcinoma. BAs can cause the enormous secretion of Glucagon-like peptide-1 (GLP-1), leading to the proliferation of pancreatic β-cells. Using Glucagon-like peptide-1 receptor agonist (GLP-1RA) increases the risk of pancreatitis and PC. Therefore, our objective was to explore various studies and thoroughly examine the role of BAs in PC. Full article

(This article belongs to the Special Issue Metabolic Cancer Therapy: Targeting Tumor Metabolism for Innovative Adjuvant Treatment)

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20 pages, 1188 KiB

Open AccessReview

Effects of the Menstrual Cycle and Hormonal Contraceptive Use on Metabolic Outcomes, Strength Performance, and Recovery: A Narrative Review

by Hannah E. Cabre, Lacey M. Gould, Leanne M. Redman and Abbie E. Smith-Ryan

Metabolites 2024, 14(7), 347; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14070347 - 21 Jun 2024

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Abstract

The effects of female sex hormones on optimal performance have been increasingly recognized as an important consideration in exercise and sport science research. This narrative review explores the findings of studies evaluating the effects of menstrual cycle phase in eumenorrheic women and the [...] Read more.

The effects of female sex hormones on optimal performance have been increasingly recognized as an important consideration in exercise and sport science research. This narrative review explores the findings of studies evaluating the effects of menstrual cycle phase in eumenorrheic women and the use of hormonal contraception (oral contraceptives and hormonal intrauterine devices) on metabolism, muscular strength, and recovery in active females. Ovarian hormones are known to influence metabolism because estrogen is a master regulator of bioenergetics. Importantly, the menstrual cycle may impact protein synthesis, impacting skeletal muscle quality and strength. Studies investigating muscular strength in eumenorrheic women report equivocal findings between the follicular phase and luteal phase with no differences compared to oral contraceptive users. Studies examining recovery measures (using biomarkers, blood lactate, and blood flow) do not report clear or consistent effects of the impact of the menstrual cycle or hormonal contraception use on recovery. Overall, the current literature may be limited by the evaluation of only one menstrual cycle and the use of group means for statistical significance. Hence, to optimize training and performance in females, regardless of hormonal contraception use, there is a need for future research to quantify the intra-individual impact of the menstrual cycle phases and hormonal contraceptive use in active females. Full article

(This article belongs to the Special Issue Sports: Nutrition and Metabolism in Relation to Athletes’ Health and Performance)

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Metabolites, Volume 14, Issue 7 (July 2024) – 10 articles

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