PubMed

Metabolites. 2024 Aug 16;14(8):452. doi: 10.3390/metabo14080452.ABSTRACTAs 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.PMID:39195548 | DOI:10.3390/metabo14080452

Metabolites. 2024 Aug 15;14(8):450. doi: 10.3390/metabo14080450.ABSTRACTAccumulating 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.PMID:39195546 | DOI:10.3390/metabo14080450

Metabolites. 2024 Aug 14;14(8):448. doi: 10.3390/metabo14080448.ABSTRACTGlioblastoma (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.PMID:39195544 | DOI:10.3390/metabo14080448

Metabolites. 2024 Aug 11;14(8):446. doi: 10.3390/metabo14080446.ABSTRACTFufang 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.PMID:39195542 | DOI:10.3390/metabo14080446

Metabolites. 2024 Aug 6;14(8):438. doi: 10.3390/metabo14080438.ABSTRACTHyperlipidemia 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.PMID:39195534 | DOI:10.3390/metabo14080438

Metabolites. 2024 Aug 6;14(8):436. doi: 10.3390/metabo14080436.ABSTRACTSexual 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)], A1c [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.PMID:39195532 | DOI:10.3390/metabo14080436

Metabolites. 2024 Aug 6;14(8):434. doi: 10.3390/metabo14080434.ABSTRACTThe popularity of e-cigarettes (vaping) has soared, creating a public health crisis among teens and young adults. Chronic vaping can induce gut inflammation and reduce intestinal barrier function through the production of the proinflammatory molecule hydrogen sulfide (H2S). This is particularly concerning for people with HIV (PWH) as they already face impaired immune function and are at a higher risk for metabolic dysregulation, diabetes, and chronic liver disease. Furthermore, PWH experience unhealthy behaviors, making it crucial to understand the systemic metabolic dysregulation and pathophysiological mechanisms associated with vaping in this population. Here, we employed liquid chromatography-mass spectrometry (LC-MS)-based metabolomics to investigate the upper respiratory, circulation, and gut metabolic profiles of PWH who vape (n = 7) and smoke combustible tobacco/marijuana (n = 6) compared to control participants who did not vape or smoke (n = 10). This hypothesis-generating exploratory study revealed systemic alterations in purine, neurotransmitter, and vitamin B metabolisms and tissue-specific changes in inflammatory pathways and cryptic sulfur cycling associated with vaping and combustible tobacco/marijuana smoking in PWH. In addition, this study provides the first link between microbial-derived metabolite 2,3-dihydroxypropane-1-sulfonate (DHPS) and vaping/smoking (tobacco and marijuana)-induced metabolic dyshomeostasis in the gut. These findings highlight the importance of identifying the full biological and clinical significance of the physiological changes and risks associated with vaping.PMID:39195530 | DOI:10.3390/metabo14080434

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