PubMed

Metabolites. 2024 Aug 5;14(8):433. doi: 10.3390/metabo14080433.ABSTRACT(1) Objective: The aim of this study was to observe the lipid-lowering effects of blood flow restriction training (BFR) combined with moderate-intensity continuous training (MICT) in obese college students by observing lipid-lowering hormones and untargeted metabolomics. (2) Methods: In this study, 14 obese college students were convened into three groups-MICT, MICT+BFR, and high-intensity interval training (HIIT)-for a crossover experiment. Blood was drawn before and after exercise for the analysis of lipolytic agents and untargeted metabolomics. The study used a paired t-test and ANOVA for statistical analyses. (3) Results: The lipolytic agent results showed that MICT+BFR was superior to the other two groups in terms of two agents (p = 0.000 and p = 0.003), namely, GH and IL-6 (difference between before and after testing: 10,986.51 ± 5601.84 and 2.42 ± 2.49, respectively), and HIIT was superior to the other two groups in terms of one agent (p = 0.000), i.e., EPI (22.81 ± 16.12). No advantage was observed for MICT. The metabolomics results showed that, compared to MICT, MICT+BFR was associated with the upregulated expression of xanthine, succinate, lactate, N-lactoylphenylalanine, citrate, ureido acid, and myristic acid after exercise, with the possibility of the involvement of the citric acid cycle, alanine, aspartic acid, glutamate metabolism, butyric acid metabolism, and the histidylate metabolism pathway. (4) Conclusions: The superior lipid-lowering effect of MICT+BFR over MICT in a group of obese college students may be due to the stronger activation of GH and IL-6 agents, with the citric acid cycle and alanine, aspartate, and glutamate metabolic pathways being associated with this type of exercise.PMID:39195529 | DOI:10.3390/metabo14080433

Metabolites. 2024 Aug 3;14(8):430. doi: 10.3390/metabo14080430.ABSTRACTMetabolomics, the study of small-molecule metabolites within biological systems, has become a potent instrument for understanding cellular processes. Despite its profound insights into health, disease, and drug development, identifying the protein partners for metabolites, especially dietary phytochemicals, remains challenging. In the present study, we introduced an innovative in silico, structure-based target prediction approach to efficiently predict protein targets for metabolites. We analyzed 27 blood serum metabolites from nutrition intervention studies' blueberry-rich diets, known for their health benefits, yet with elusive mechanisms of action. Our findings reveal that blueberry-derived metabolites predominantly interact with Carbonic Anhydrase (CA) family proteins, which are crucial in acid-base regulation, respiration, fluid balance, bone metabolism, neurotransmission, and specific aspects of cellular metabolism. Molecular docking showed that these metabolites bind to a common pocket on CA proteins, with binding energies ranging from -5.0 kcal/mol to -9.0 kcal/mol. Further molecular dynamics (MD) simulations confirmed the stable binding of metabolites near the Zn binding site, consistent with known compound interactions. These results highlight the potential health benefits of blueberry metabolites through interaction with CA proteins.PMID:39195526 | DOI:10.3390/metabo14080430

Metabolites. 2024 Aug 2;14(8):428. doi: 10.3390/metabo14080428.ABSTRACTMethylmalonic acidemia (MMA), propionic acidemia (PA), and cobalamin C deficiency (cblC) share a defect in propionic acid metabolism. In addition, cblC is also involved in the process of homocysteine remethylation. These three diseases produce various phenotypes and complex downstream metabolic effects. In this study, we used an untargeted metabolomics approach to investigate the biochemical differences and the possible connections among the pathophysiology of each disease. The significantly changed metabolites in the untargeted urine metabolomic profiles of 21 patients (seven MMA, seven PA, seven cblC) were identified through statistical analysis (p < 0.05; log2FC > |1|) and then used for annotation. Annotated features were associated with different metabolic pathways potentially involved in the disease's development. Comparative statistics showed markedly different metabolomic profiles between MMA, PA, and cblC, highlighting the characteristic species for each disease. The most affected pathways were related to the metabolism of organic acids (all diseases), amino acids (all diseases), and glycine and its conjugates (in PA); the transsulfuration pathway; oxidative processes; and neurosteroid hormones (in cblC). The untargeted metabolomics study highlighted the presence of significant differences between the three diseases, pointing to the most relevant contrast in the cblC profile compared to MMA and PA. Some new biomarkers were proposed for PA, while novel data regarding the alterations of steroid hormone profiles and biomarkers of oxidative stress were obtained for cblC disease. The elevation of neurosteroids in cblC may indicate a potential connection with the development of ocular and neuronal deterioration.PMID:39195524 | DOI:10.3390/metabo14080428

Metabolites. 2024 Aug 1;14(8):426. doi: 10.3390/metabo14080426.ABSTRACTCommon wheat (Triticum aestivum L.) is one of the most valuable cereal crops worldwide. This study examined leaf extracts of 30 accessions of T. aestivum and its subspecies using 48 h maceration with methanol by GC-MS and GCxGC-MS. The plants were grown from seeds of the wheat genetics collection of the Wheat Genetics Sector of the Institute of Cytology and Genetics, SB RAS. The analysis revealed 263 components of epicuticular waxes, including linear and branched alkanes, aliphatic alcohols, aldehydes, ketones, β-diketones, carboxylic acids and their derivatives, mono- and diterpenes, phytosterols, and tocopherols. Hierarchical cluster analysis and principal component analysis were used to identify and visualize the differences between the leaf extracts of different wheat cultivars. Three clusters were identified, with the leading components being (1) octacosan-1-ol, (2) esters of saturated and unsaturated alcohols, and (3) fatty acid alkylamides, which were found for the first time in plant extracts. The results highlight the importance of metabolic studies in understanding the adaptive mechanisms and increasing wheat resistance to stress factors. These are crucial for breeding new-generation cultivars with improved traits.PMID:39195522 | DOI:10.3390/metabo14080426

Metabolites. 2024 Jul 31;14(8):423. doi: 10.3390/metabo14080423.ABSTRACTNeurodegenerative retinal diseases such as glaucoma, diabetic retinopathy, Leber's hereditary optic neuropathy (LHON), and dominant optic atrophy (DOA) are marked by progressive death of retinal ganglion cells (RGC). This decline is promoted by structural and functional mitochondrial deficits, including electron transport chain (ETC) impairments, increased oxidative stress, and reduced energy (ATP) production. These cellular mechanisms associated with progressive optic nerve atrophy have been similarly observed in familial dysautonomia (FD) patients, who experience gradual loss of visual acuity due to the degeneration of RGCs, which is thought to be caused by a breakdown of mitochondrial structures, and a disruption in ETC function. Retinal metabolism plays a crucial role in meeting the elevated energetic demands of this tissue, and recent characterizations of FD patients' serum and stool metabolomes have indicated alterations in central metabolic processes and potential systemic deficits of taurine, a small molecule essential for retina and overall eye health. The present study sought to elucidate metabolic alterations that contribute to the progressive degeneration of RGCs observed in FD. Additionally, a critical subpopulation of retinal interneurons, the dopaminergic amacrine cells, mediate the integration and modulation of visual information in a time-dependent manner to RGCs. As these cells have been associated with RGC loss in the neurodegenerative disease Parkinson's, which shares hallmarks with FD, a targeted analysis of the dopaminergic amacrine cells and their product, dopamine, was also undertaken. One dimensional (1D) proton (1H) nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and retinal histology methods were employed to characterize retinae from the retina-specific Elp1 conditional knockout (CKO) FD mouse model (Pax6-Cre; Elp1LoxP/LoxP). Metabolite alterations correlated temporally with progressive RGC degeneration and were associated with reduced mitochondrial function, alterations in ATP production through the Cahill and mini-Krebs cycles, and phospholipid metabolism. Dopaminergic amacrine cell populations were reduced at timepoints P30-P90, and dopamine levels were 25-35% lower in CKO retinae compared to control retinae at P60. Overall, this study has expanded upon our current understanding of retina pathology in FD. This knowledge may apply to other retinal diseases that share hallmark features with FD and may help guide new avenues for novel non-invasive therapeutics to mitigate the progressive optic neuropathy in FD.PMID:39195519 | DOI:10.3390/metabo14080423

Metabolites. 2024 Jul 30;14(8):419. doi: 10.3390/metabo14080419.ABSTRACTThe presence and localization of plant metabolites are indicative of physiological processes, e.g., under biotic and abiotic stress conditions. Further, the chemical composition of plant parts is related to their quality as food or for medicinal applications. Mass spectrometry imaging (MSI) has become a popular analytical technique for exploring and visualizing the spatial distribution of plant molecules within a tissue. This review provides a summary of mass spectrometry methods used for mapping and identifying metabolites in plant tissues. We present the benefits and the disadvantages of both vacuum and ambient ionization methods, considering direct and indirect approaches. Finally, we discuss the current limitations in annotating and identifying molecules and perspectives for future investigations.PMID:39195515 | DOI:10.3390/metabo14080419

Metabolites. 2024 Jul 27;14(8):415. doi: 10.3390/metabo14080415.ABSTRACTTo investigate the metabolomic mechanisms by which changes in cardiorespiratory fitness (CRF) levels affect metabolic syndrome (MetS) risk factors and to provide a theoretical basis for the improvement of body metabolism via CRF in people with MetS risk factors, a comparative blood metabolomics study of individuals with varying levels of CRF and varying degrees of risk factors for MetS was conducted.METHODS: Ninety subjects between the ages of 40 and 45 were enrolled, and they were categorized into low-MetS (LM ≤ two items) and high MetS (HM > three items) groups, as well as low- and high-CRF (LC, HC) and LCLM, LCLM, LCHM, and HCHM groups. Plasma was taken from the early morning abdominal venous blood. LC-MS was conducted using untargeted metabolomics technology, and the data were statistically and graphically evaluated using SPSS26.0 and R language.RESULTS: (1) There were eight common differential metabolites in the HC vs. LC group as follows: methionine (↓), γ-aminobutyric acid (↑), 2-oxoglutatic acid (↑), arginine (↑), serine (↑), cis-aconitic acid (↑), glutamine (↓), and valine (↓); the HM vs. LM group are contrast. (2) In the HCHM vs. LCLM group, trends were observed in 2-oxoglutatic acid (↑), arginine (↑), serine (↑), cis-aconitic acid (↑), glutamine (↓), and valine (↓). (3) CRF and MetS risk factors jointly affect biological metabolic pathways such as arginine biosynthesis, TCA cycle, cysteine and methionine metabolism, glycine, serine, and threonine metabolism, arginine and proline metabolism, and alanine, aspartate, and glutamate metabolism.CONCLUSION: The eight common differential metabolites can serve as potential biomarkers for distinguishing individuals with different CRF levels and varying degrees of MetS risk factors. Increasing CRF levels may potentially mitigate MetS risk factors, as higher CRF levels are associated with reduced MetS risk.PMID:39195511 | DOI:10.3390/metabo14080415

Metabolites. 2024 Jul 27;14(8):414. doi: 10.3390/metabo14080414.ABSTRACTThe environment is an important factor affecting the composition and abundance of metabolites in O. sinensis, which indirectly determines its edible function and medicinal potential. This study integrated metabolomics and redundancy analysis (RDA) to analyze the metabolite profile characteristics and key environmental factors influencing O. sinensis in various production areas. A total of 700 differentially accumulated metabolites (DAMs) were identified, primarily comprising lipids, organic acids, and organoheterocyclic compounds. Results from hierarchical cluster analysis and KEGG indicated distinct accumulation patterns of these DAMs in O. sinensis from different regions, with enrichment in pathways such as tryptophan metabolism and glycerophospholipid metabolism. Environmental factors like annual mean precipitation, pH, temperature, and altitude were found to significantly influence metabolite composition, particularly lipids, organic acids, and nucleosides. Overall, this study highlights the impact of environmental factors on metabolite diversity in O. sinensis and sheds light on the evolutionary processes shaping its metabolic landscape.PMID:39195510 | DOI:10.3390/metabo14080414

Metabolites. 2024 Jul 27;14(8):413. doi: 10.3390/metabo14080413.ABSTRACTGlioblastoma (IDH-wildtype) represents a formidable challenge in oncology, lacking effective chemotherapeutic or biological interventions. The metabolic reprogramming of cancer cells is a hallmark of tumor progression and drug resistance, yet the role of metabolic reprogramming in glioblastoma during drug treatment remains poorly understood. The dihydroorotate dehydrogenase (DHODH) inhibitor BAY2402234 is a blood-brain barrier penetrant drug showing efficiency in in vivo models of many brain cancers. In this study, we investigated the effect of BAY2402234 in regulating the metabolic phenotype of EGFRWT and EGFRvIII patient-derived glioblastoma cell lines. Our findings reveal the selective cytotoxicity of BAY2402234 toward EGFRWT glioblastoma subtypes with minimal effect on EGFRvIII patient cells. At sublethal doses, BAY2402234 induces triglyceride synthesis at the expense of membrane lipid synthesis and fatty acid oxidation in EGFRWT glioblastoma cells, while these effects are not observed in EGFRvIII glioblastoma cells. Furthermore, BAY2402234 reduced the abundance of signaling lipid species in EGFRWT glioblastoma. This study elucidates genetic mutation-specific metabolic plasticity and efficacy in glioblastoma cells in response to drug treatment, offering insights into therapeutic avenues for precision medicine approaches.PMID:39195509 | DOI:10.3390/metabo14080413

Metabolites. 2024 Jul 26;14(8):411. doi: 10.3390/metabo14080411.ABSTRACTThe global prevalence of Type 2 Diabetes (T2D) poses significant public health challenges due to its associated severe complications. Insulin resistance is central to T2D pathophysiology, particularly affecting adipose tissue function. This cross-sectional observational study investigates metabolic alterations in subcutaneous adipose tissue (SAT) associated with T2D to identify potential therapeutic targets. We conducted a comprehensive metabolomic analysis of SAT from 40 participants (20 T2D, 20 ND-T2D), matched for sex, age, and BMI (Body Mass Index). Metabolite quantification was performed using GC/MS and LC/MS/MS platforms. Correlation analyses were conducted to explore associations between metabolites and clinical parameters. We identified 378 metabolites, including significant elevations in TCA cycle (tricarboxylic acid cycle) intermediates, branched-chain amino acids (BCAAs), and carbohydrates, and a significant reduction in the nucleotide-related metabolites in T2D subjects compared to those without T2D. Obesity exacerbated these alterations, particularly in amino acid metabolism. Adipocyte size negatively correlated with BCAAs, while adipocyte glucose uptake positively correlated with unsaturated fatty acids and glycerophospholipids. Our findings reveal distinct metabolic dysregulation in adipose tissue in T2D, particularly in energy metabolism, suggesting potential therapeutic targets for improving insulin sensitivity and metabolic health. Future studies should validate these findings in larger cohorts and explore underlying mechanisms to develop targeted interventions.PMID:39195507 | DOI:10.3390/metabo14080411

Metabolites. 2024 Jul 26;14(8):409. doi: 10.3390/metabo14080409.ABSTRACTDrynaria roosii Nakaike, a fern widely distributed in China and some countries in Southeast Asia, is a commonly used herbal medicine in tonic diets and Chinese patented medicine. The metabolites of its dried rhizomes are easily affected by the epiphytic pattern, whether on rock tunnels (RTs) or tree trunks (TTs). The current research focused on rhizomes from these two patterns, RTs and TTs (further divided into subclasses TA, TB, TC, and TD, based on trunk differences) and conducted a widely targeted metabolomics analysis. A total of 1435 components were identified across 13 categories, with flavonoids, amino acids, and their derivative, lipids, identified as the main components. They accounted for 19.96%, 12.07%, and 12.14% of all metabolites, respectively. The top five flavonoids in TB were eriodicty-ol-7-O-(6″-acetyl)glucoside, quercetin-3-O-sophoroside (baimaside), dihydrochar-cone-4'-O-glucoside, morin, and hesperetin-7-O-glucoside, with relative contents 76.10, 24.20, 17.02, 15.84, and 14.64 times higher than in RTs. Principal component analysis revealed that samples with different epiphytic patterns clustered into five groups. The RT patterns revealed unique metabolites that were not detected in the other four epiphytic species (TA, TB, TC, and TD), including 16 authenticated metabolites: 1 alkaloid, 1 amino acid derivative, 7 flavonoids, 2 lignans, 1 lipid, 1 alcohol, 1 aldehyde, and 2 phenolic acids. These differences in epiphytic patterns considerably affected the accumulation of both primary and secondary metabolites. The comparison of diversity between RTs and TTs can guide the selection of a cultivation substance and the grading of collective rhizomes in the wild. This comprehensive analysis of D. roosii rhizome metabolites also offers fundamental insights for identifying active components and understanding the mechanisms underlying their potential pharmacological activities.PMID:39195505 | DOI:10.3390/metabo14080409

Metabolites. 2024 Jul 26;14(8):408. doi: 10.3390/metabo14080408.ABSTRACTMetabolic health is tightly regulated by neuro-hormonal control, and systemic metabolic dysfunction may arise from altered function of the hypothalamic-anterior pituitary axis (HAPA). Ancient experimental observations of hypothalamic obesity (HO) and liver cirrhosis occurring among animals subjected to hypothalamic injury can now be explained using the more recent concepts of lipotoxicity and metabolic dysfunction-associated steatotic liver disease (MASLD). Lipotoxicity, the range of abnormalities resulting from the harmful effects of fatty acids accumulated in organs outside of adipose tissue, is the common pathogenic factor underlying closely related conditions like hypothalamic syndrome, HO, and MASLD. The hormonal deficits and the array of metabolic and metabolomic disturbances that occur in cases of HO are discussed, along with the cellular and molecular mechanisms that lead, within the MASLD spectrum, from uncomplicated steatotic liver disease to steatohepatitis and cirrhosis. Emphasis is placed on knowledge gaps and how they can be addressed through novel studies. Future investigations should adopt precision medicine approaches by precisely defining the hormonal imbalances and metabolic dysfunctions involved in each individual patient with HO, thus paving the way for tailored management of MASLD that develops in the context of altered HAPA.PMID:39195504 | DOI:10.3390/metabo14080408

Metabolites. 2024 Jul 25;14(8):406. doi: 10.3390/metabo14080406.ABSTRACTTo analyze the potential mechanisms of growth differences in spotted seabass (Lateolabrax maculatus) fed a low-phosphorus diet, a total of 150 spotted seabass with an initial body weight of 4.49 ± 0.01 g were used (50 fish per tank) and fed a low-phosphorus diet for eight weeks. At the end of the experiment, five of the heaviest and five of the lightest fish were selected from each tank as fast-growing spotted seabass (FG) and slow-growing spotted seabass (SG), respectively, and their livers were analyzed by metabolomics and transcriptomics. The hepatic antioxidant capacity of the FG fed a low-phosphorus diet was significantly higher than that of the SG. A total of 431 differentially expressed genes (DEGs) were determined in the two groups, and most of the DEGs were involved in metabolism-related pathways such as steroid biosynthesis, glycolysis/gluconeogenesis, and protein digestion and absorption. Substance transport-related regulators and transporters were predominantly up-regulated. Furthermore, a large number of metabolites in the liver of FG were significantly up-regulated, especially amino acids, decanoyl-L-carnitine and dehydroepiandrosterone. The integration analysis of differential metabolites and genes further revealed that the interaction between protein digestion and absorption, as well as phenylalanine metabolism pathways were significantly increased in the liver of FG compared to those of the SG. In general, FG fed a low-phosphorus diet induced an enhancement in hepatic immune response, substance transport, and amino acid metabolism. This study provides new information on genetic mechanisms and regulatory pathways underlying differential growth rate and provides a basis for the foundation of efficient utilization of low-phosphorus diets and selective breeding programs for spotted seabass.PMID:39195503 | DOI:10.3390/metabo14080406

Metabolites. 2024 Jul 25;14(8):407. doi: 10.3390/metabo14080407.ABSTRACTFever is one of the most common clinical conditions and is characterized by pyrogenic infection, malignancy, inflammation, and tissue damage, among others. Ellagic acid (EA) can inhibit the expression of related proteins on the pathway by blocking the nuclear factor kappa-B(NF-κB) signaling pathway, inhibit the levels of pro-inflammatory factors interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), increase the level of anti-inflammatory factor IL-10, and effectively alleviate inflammatory symptoms. In addition, EA can also reduce the levels of malondialdehyde(MDA) and nitric oxide(NO) in the body, increase the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase(CAT), scavenge oxidative free radicals, inhibit lipid oxidation, and achieve antipyretic and anti-inflammatory effects. The purpose of this study was to establish the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, prostaglandin E2(PGE2), and cyclic adenosine monophosphate(cAMP), and clarify the mechanism of the cyclooxidase-2(COX-2)/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism. Compared to lipopolysaccharide (LPS)- treated animals, subsequent administration of EA significantly lowered the LPS-induced rectal temperature increase (p < 0.05 or p < 0.01), significantly increased serum SOD and GSH levels (p < 0.05 or p < 0.01), and significantly decreased serum MDA, IL-1β, IL-6, and TNF-α levels (p < 0.05 or p < 0.01). In addition, compared to LPS-treated animals, subsequent administration of EA significantly decreased cerebrospinal fluid cAMP and PGE2 levels (p < 0.05 or p < 0.01), significantly decreased cAMP, significantly increased 5-HT levels (p < 0.05 or p < 0.01), and significantly down-regulated p-NF-κB p65 and COX-2 protein levels in the hypothalamus. Subsequent gas chromatography mass spectrometry(GC-MS) metabolite analysis indicated that 12 differential metabolites were detected in serum isolated 4 h after LPS treatment, and 10 differential metabolites were detected in serum collected 7 h after LPS treatment. Next, Pearson correlation analysis was used to systematically characterize the relationship between the identified metabolites and TNF-α, IL-6, MDA, SOD, PGE2, and cAMP. The levels of propionic acid, pyridine, and L-valine were up-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α and increased the activity of GSH. The levels of inositol, urea, and 2-monopalmitin were down-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α, increased the activity of SOD and GSH, reduced the inflammatory response, and alleviated the oxidative stress state. Combined with the results of the metabolic pathway analysis, we suggest that the pathways of the galactose metabolism, synthesis and degradation of ketone bodies, as well as ascorbic acid and aldehyde acid metabolism are closely related to the antipyretic and anti-inflammatory effects of EA. Our study established the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, PGE2, and cAMP, and clarified the mechanism of the COX-2/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism.PMID:39195502 | DOI:10.3390/metabo14080407

Metabolites. 2024 Jul 25;14(8):405. doi: 10.3390/metabo14080405.ABSTRACTMetabolic perturbation has been associated with depression. An untargeted metabolomics approach using liquid chromatography-high resolution mass spectrometry was employed to detect and measure the rat serum metabolic changes following chronic social isolation (CSIS), an animal model of depression, and effective antidepressant fluoxetine (Flx) treatment. Univariate and multivariate statistics were used for metabolic data analysis and differentially expressed metabolites (DEMs) determination. Potential markers and predictive metabolites of CSIS-induced depressive-like behavior and Flx efficacy in CSIS were evaluated by the receiver operating characteristic (ROC) curve, and machine learning (ML) algorithms, such as support vector machine with linear kernel (SVM-LK) and random forest (RF). Upregulated choline following CSIS may represent a potential marker of depressive-like behavior. Succinate, stachydrine, guanidinoacetate, kynurenic acid, and 7-methylguanine were revealed as potential markers of effective Flx treatment in CSIS rats. RF yielded better accuracy than SVM-LK (98.50% vs. 85.70%, respectively) in predicting Flx efficacy in CSIS vs. CSIS, however, it performed almost identically in classifying CSIS vs. control (75.83% and 75%, respectively). Obtained DEMs combined with ROC curve and ML algorithms provide a research strategy for assessing potential markers or predictive metabolites for the designation or classification of stress-induced depressive phenotype and mode of drug action.PMID:39195501 | DOI:10.3390/metabo14080405

Metabolites. 2024 Jul 24;14(8):401. doi: 10.3390/metabo14080401.ABSTRACTAs obesity develops, metabolic changes increase the risk of non-communicable diseases such as type 2 diabetes (T2D). Weight loss is crucial for improving health in T2D and cardiometabolic conditions. However, weight loss rates vary between individuals, even with identical diets or energy restrictions, highlighting the need to identify markers or predictors of weight loss success to enhance intervention outcomes. Using nuclear magnetic resonance (NMR) spectroscopy-based metabolomics, we investigated the change in serum polar metabolites in 28 women with overweight or obesity and prediabetes who completed an 8-week low-energy diet (LED) as part of the PREVIEW (PREVention of diabetes through lifestyle intervention and population studies in Europe and around the World) clinical trial. We aimed to characterize the metabolic shift in substrate oxidation under fixed energy intake (~4 MJ/day) and its relation to weight loss success. Nine of the thirty-four serum metabolites identified significantly changed during the LED phase: 3-hydroxybutyrate, O-acetylcarnitine, 2-hydroxybutyrate, mannose, dimethyl sulfone and isobutyrate increased, whilst choline, creatine and tyrosine decreased. These results confirmed a shift towards lipid oxidation, but no metabolites predicted the response to the LED-induced weight loss. Further studies in larger populations are required to validate these metabolites as biomarkers of diet exposure.PMID:39195497 | DOI:10.3390/metabo14080401

Mar Drugs. 2024 Aug 22;22(8):377. doi: 10.3390/md22080377.ABSTRACTIn this study, we aimed to explore the hypoglycemic effects of a hydrolysate on Takifugu bimaculatus skin (TBSH). The effect of the dipeptidyl peptidase-IV (DPP-IV) inhibitory activities from different TBSH fractions was investigated on basic indexes, gut hormones, blood lipid indexes, viscera, and the gut microbiota and its metabolites in rats with type 2 diabetes mellitus (T2DM). The results showed that the <1 kDa peptide fraction from TBSH (TBP) exhibited a more potent DPP-IV inhibitory effect (IC50 = 0.45 ± 0.01 mg/mL). T2DM rats were induced with streptozocin, followed by the administration of TBP. The 200 mg/kg TBP mitigated weight loss, lowered fasting blood glucose levels, and increased insulin secretion by 20.47%, 25.23%, and 34.55%, respectively, rectified irregular hormonal fluctuations, lipid metabolism, and tissue injuries, and effectively remedied gut microbiota imbalance. In conclusion, TBP exerts a hypoglycemic effect in rats with T2DM. This study offers the potential to develop nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus. It will provide information for developing nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus.PMID:39195493 | DOI:10.3390/md22080377

Cells. 2024 Aug 13;13(16):1345. doi: 10.3390/cells13161345.ABSTRACTCurrently, there is a growing focus on aging and age-related diseases. The processes of aging are based on cell senescence, which results in changes in intercellular communications and pathological alterations in tissues. In the present study, we investigate the influence of senescent mesenchymal stem cells (MSCs) on endothelial cells (ECs). In order to induce senescence in MSCs, we employed a method of stress-induced senescence utilizing mitomycin C (MmC). Subsequent experiments involved the interaction of ECs with MSCs in a coculture or the treatment of ECs with the secretome of senescent MSCs. After 48 h, we assessed the EC state. Our findings revealed that direct interaction led to a decrease in EC proliferation and migratory activity of the coculture. Furthermore, there was an increase in the activity of the lysosomal compartment, as well as an upregulation of the genes P21, IL6, IL8, ITGA1, and ITGB1. Treatment of ECs with the "senescent" secretome resulted in less pronounced effects, although a decrease in proliferation and an increase in ICAM-1 expression were observed. The maintenance of high levels of typical "senescent" cytokines and growth factors after 48 h suggests that the addition of the "senescent" secretome may have a prolonged effect on the cells. It is noteworthy that in samples treated with the "senescent" secretome, the level of PDGF-AA was higher, which may explain some of the pro-regenerative effects of senescent cells. Therefore, the detected changes may underlie both the negative and positive effects of senescence. The findings provide insight into the effects of cell senescence in vitro, where many of the organism's regulatory mechanisms are absent.PMID:39195236 | DOI:10.3390/cells13161345

Cells. 2024 Aug 11;13(16):1333. doi: 10.3390/cells13161333.ABSTRACTBoth experimental and clinical liver fibrosis leave a metabolic footprint that can be uncovered and defined using metabolomic approaches. Metabolomics combines pattern recognition algorithms with analytical chemistry, in particular, 1H and 13C nuclear magnetic resonance spectroscopy (NMR), gas chromatography-mass spectrometry (GC-MS) and various liquid chromatography-mass spectrometry (LC-MS) platforms. The analysis of liver fibrosis by each of these methodologies is reviewed separately. Surprisingly, there was little general agreement between studies within each of these three groups and also between groups. The metabolomic footprint determined by NMR (two or more hits between studies) comprised elevated lactate, acetate, choline, 3-hydroxybutyrate, glucose, histidine, methionine, glutamine, phenylalanine, tyrosine and citrate. For GC-MS, succinate, fumarate, malate, ascorbate, glutamate, glycine, serine and, in agreement with NMR, glutamine, phenylalanine, tyrosine and citrate were delineated. For LC-MS, only β-muricholic acid, tryptophan, acylcarnitine, p-cresol, valine and, in agreement with NMR, phosphocholine were identified. The metabolomic footprint of liver fibrosis was upregulated as regards glutamine, phenylalanine, tyrosine, citrate and phosphocholine. Several investigators employed traditional Chinese medicine (TCM) treatments to reverse experimental liver fibrosis, and a commentary is given on the chemical constituents that may possess fibrolytic activity. It is proposed that molecular docking procedures using these TCM constituents may lead to novel therapies for liver fibrosis affecting at least one-in-twenty persons globally, for which there is currently no pharmaceutical cure. This in-depth review summarizes the relevant literature on metabolomics and its implications in addressing the clinical problem of liver fibrosis, cirrhosis and its sequelae.PMID:39195223 | DOI:10.3390/cells13161333

J Fungi (Basel). 2024 Aug 5;10(8):551. doi: 10.3390/jof10080551.ABSTRACTThis study aimed to investigate the efficiency of the secondary metabolites (SMs) produced by a co-culture of Trichoderma harzianum TW21990 and Burkholderia vietnamiensis B418 in the control of Colletotrichum siamense CM9. A fermentation filtrate of B418 + TW21990 co-culture (BT21) produced a notable increase in the inhibition rate of CM9 compared to those of TW21990 and B418 monocultures, which reached 91.40% and 80.46% on PDA plates and strawberry leaves, respectively. The BT21 fermentation broth exhibited high control efficiency on strawberry root rot of 68.95% in a pot experiment, which was higher than that in the monocultures and fluazinam treatment. In addition, BT21 treatment promoted strawberry root development, improved antioxidative enzyme activities in the leaves and roots, and enhanced the total chlorophyll content of the strawberry leaves. UHPLC-MS/MS analysis of fermentation filtrates was performed to elucidate SM variations, revealing 478 and 795 metabolites in BT21 co-culture in positive and negative ion modes, respectively. The metabolomic profiles suggested abundant SMs with antagonistic capabilities and growth-promoting effects: 3-(propan-2-yl)-octahydropyrrolo [1,2-a]pyrazine-1,4-dione (cyclo(L-Pro-L-Val)), 3-[(4-hydroxyphenyl)methyl]-octahydropyrrolo[1,2-a]pyrazine-1,4-dione (cyclo(L-Pro-L-Tyr)), 3-indoleacetic acid (IAA), 2-hydroxycinnamic acid, 4-aminobutyric acid (GABA), bafilomycin B1, and DL-indole-3-lactic acid (ILA) were significantly enhanced in the co-culture. Overall, this study demonstrates that a co-culture strategy is efficient for inducing bioactive SMs in T. harzianum and B. vietnamiensis, which could be exploited as a novel approach for developing biocontrol consortia.PMID:39194877 | DOI:10.3390/jof10080551