Search Results (103)

Chiang Mai, Thailand, experiences seasonal fine particulate matter (PM_2.5) pollution associated with metabolic diseases, but the underlying mechanisms remain unclear. This prospective observational study compared plasma metabolomes of 25 healthy adults in Samoeng District, a highly affected area, between low and high PM_2.5 exposure seasons using proton nuclear magnetic resonance (¹H-NMR) spectroscopy. Twenty-six metabolites differentiating haze and non-haze seasons were identified using PLS-DA (VIP > 1.5). During the haze season, 11 were elevated, whereas 15 were decreased. Among the elevated metabolites, the top five—maleylacetoacetic acid, deoxyribose 5-phosphate, betaine, 3-hydroxyanthranilic acid, and 1-methyladenosine—were associated with inflammation, increased reactive oxygen species, nitric oxide inhibition, and altered amino acid metabolism. The top five decreased metabolites—deoxyguanosine, D-arabitol, glycerophosphocholine, ophthalmic acid, and oxaloacetic acid—were involved in several metabolic pathways, particularly those involved in energy metabolism. A total of 56 metabolic pathways were altered by high PM_2.5 exposure, including pathways related to amino acids, lipids, sugars, nucleotides, vitamins, and energy metabolism. High PM_2.5 exposure disrupts metabolites and pathways, inducing inflammation, oxidative stress, impaired lipid/energy metabolism, insulin resistance, and high blood pressure. These alterations may increase the risk of metabolic and cardiovascular diseases, with dysregulated metabolites serving as potential biomarkers. These findings highlight the molecular impact of air pollution in affected populations and may support preventive strategies and public health policy development in affected regions. Further studies are needed to clarify these findings. Full article

Background: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on serum metabolomics in obese type 2 diabetic (T2DM) mice. Methods: Four-week-old male C57BL/6 mice were fed a high-fat diet and intraperitoneally injected with streptozotocin (35 mg/kg) to establish an obese T2DM model. Mice were randomized into control, T2DM and T2DM+Ang-(1-7) groups (n = 6). Body weight and blood glucose were recorded weekly. At 10 weeks, blood glucose, serum inflammatory factors, lipid profiles, and pancreatic β-cell insulin secretion were detected; serum metabolite alterations were analyzed via untargeted metabolomics. Results: 1. Ang-(1-7) intervention decreased blood glucose (p < 0.05) and CRP levels (p < 0.01), and alleviated dyslipidemia (p < 0.05 or p < 0.01), as well as β-cell morphology and insulin expression in obese T2DM mice. 2. Non-targeted metabolomics analysis suggested that Ang-(1-7) may alleviate abnormal amino acid metabolic pathways by regulating levels of metabolites such as L-valine, L-proline, L-histidine, and glutamic acid. This intervention also tended to reduce multiple lipid metabolites, including Omega-3 Arachidonic Acid Ethyl Ester, phosphatidylcholine, and glycerophosphocholine, thereby participating in the modulation of lipid metabolism balance. KEGG enrichment analysis further indicated that Ang-(1-7) was involved in the regulation of protein digestion and the absorption pathway, as well as the HIF-1 signaling pathway related to oxidative stress, bile acid metabolism pathway, and other signaling pathways, and improving the insulin secretion pathway, pyrimidine metabolism, and TCA cycle energy metabolism pathway. Conclusions: Ang-(1-7) may partially improve metabolic disturbances in obese T2DM mice, which is potentially associated with the modulation of multiple metabolic processes, including amino acid metabolism, lipid metabolism, insulin secretion, and TCA cycle energy metabolism. Full article

Glycerophosphocholine (GPC) is a well-known choline-containing compound commonly found in nature and has demonstrated potential therapeutic effects in aging-related conditions, such as neurodegenerative disorders, skeletal muscle performance, and eye disorders. Despite being widely used as a supplement, the mechanism by which GPC is absorbed and metabolized in the digestive system remains elusive. Furthermore, growing evidence suggests that high intake of choline-containing compounds, including GPC, is linked with trimethylamine N-oxide (TMAO) production, a metabolite associated with atherosclerosis progression. However, there has been an inconsistency that is not commonly discussed, and thus, the adverse effect of TMAO remains debatable. These warrant a better understanding of the physiological significance and metabolism of GPC in the body and how it is linked to TMAO and its potential risk. Through a comprehensive literature search, this narrative review aims to fill these gaps by providing a summary of the physiological significance and supplementation evidence of GPC. Further, the review also highlights the absorption mechanisms and relationship of GPC with intestinal microbiota and its relationship with TMAO production. Lastly, this review addresses and discusses the challenge of GPC supplementation and provides a brief view on future perspectives on GPC as a bioactive compound. Full article

Environmental temperature-induced metabolic changes in dams can be reflected by alterations in metabolomic and fatty acid profiles in colostrum. The colostrum from 13 Black Bengal (BB) dams was collected on the day of parturition at two consecutive parities during the hot conditions (HCs) of summer or rainy seasons and the cold conditions (CCs) of winter. The metabolomic and fatty acid profiles were analyzed using nuclear magnetic resonance (NMR) and gas chromatography–mass spectrometry, respectively. The results showed significantly higher sarcosine, tyrosine, citrate, succinate, galactose, acetylglucosamine, carnitine, choline, glycerophosphocholine, and trimethylamine N-oxide during CCs than HCs; potential discriminant metabolites according to VIP scores were sarcosine, succinate, and choline. Colostrum from CCs had significantly lower levels of saturated fatty acids (SFAs), including butyric acid (C4:0), myristic acid (C14:0), and pentadecanoic acid (C15:0), but higher omega-9 monounsaturated fatty acids (MUFAs), especially oleic acid (C18:1n9c), elaidic acid (C18:1n9t), and eicosenoic acid (C20:1n9), than in HC. Linoleic acid (C18:2n6c) and the omega 6/omega 3 PUFA ratio were higher during CCs than HCs. It is concluded that a metabolic shift for nutrient utilization occurs, from glucose during HCs toward fat during CCs, which may not be due to the diet but rather neurohumoral alterations occurring during temperature adaptation. Full article

Membrane lipid remodeling plays a pivotal role in regulating plant growth, reproductive development, and adaptive responses to environmental stress. However, several lipid-modifying enzymes remain uncharacterized in Arabidopsis thaliana. Here, we provide the first comprehensive in silico functional characterization of the unannotated gene AT5G35460, integrating domain architecture, AlphaFold-supported structural validation, and phylogenetic, expression, and regulatory analyses. Domain architecture and conserved DUF2838 signatures, together with transmembrane topology and validation using AlphaFold-predicted structural data, support its identity as a glycerophosphocholine acyltransferase (GPCAT1). Phylogenetic reconstruction showed that GPCAT1 clustered closely with its orthologs of major angiosperms, suggesting deep evolutionary preservation. Expression profiling revealed over a tenfold higher transcript abundance in mature pollen, detected 6–8 times more than during leaf senescence, indicating strong developmental control. Co-expression network analysis revealed links to the lipid metabolism genes (CDS2, LACS8, and SBH1) as well as factors involved in response to stress, indicating that AT5G35460 may act at the level of phosphatidylcholine remodeling, membrane resistance and stress response. Analysis of the promoter sequences showed AACTAAA, ABRE and G-box elements (pollen-specific, ABA-responsive and stress-inducible motif respectively), suggesting appropriate transcriptional regulation consistent with its expression profile. As a whole, the findings revealed that AT5G35460 is an unexplored membrane-localized acyltransferase involved in lipid maintenance during reproductive development and environmental responses. This study serves as a basis for subsequent functional characterization and identifies AT5G35460 as a potential target for modifying pollen viability, senescence kinetics and stress tolerance in plants. Full article

Background/Objectives: This pilot study aimed to evaluate the metabolic profiles in plasma and cerebrospinal fluid (CSF) of 14 patients with acute lymphoblastic leukemia (ALL) and plasma of a control group, using proton magnetic resonance spectroscopy (¹H NMR). Methods: Multivariate analysis, including orthogonal partial least-squares discriminant analysis (OPLS-DA), was used to analyze the metabolome composition. Results: Significant differences in plasma metabolic profiles were found between the ALL and control groups. We detected elevated levels of formate, citrate, and glycerophosphocholine (GPC), along with decreased concentrations of glutamine and myo-inositol. The OPLS-DA model showed stability, with R²Y = 69.7% and Q² = 45.15%. Additionally, we observed differences in chemical shifts for leucine, myo-inositol, alanine, phenylalanine, and valine between CSF and plasma in patients with ALL. Conclusions: Our findings suggest that metabolomic analysis with ¹H NMR is a promising tool for identifying potential molecular biomarkers and for deepening our understanding of metabolic reprogramming in pediatric ALL. The observed metabolic differences highlight the potential involvement of the central nervous system in the disease’s pathophysiology. Full article

Glycerophosphocholine (GPC) and glycerophosphoinositol (GPI) are phospholipid metabolites generated by phospholipase-mediated deacylation. In budding yeast, they enter cells via the Git1 permease; in fission yeast, the homolog is Tgp1. This study investigates why GPC is toxic to asp1-STF mutants, where Tgp1 is upregulated due to loss of Asp1 pyrophosphatase, resulting in elevated inositol pyrophosphate 1,5-IP₈. We show that S. pombe Tgp1 specifically transports GPC, explaining why GPC, but not GPI, impairs growth. Increased GPC uptake slows doubling time but does not reduce viability. Toxicity is relieved by deletion of Gde1, a phosphodiesterase that hydrolyzes GPC to choline and glycerol-3-phosphate. Mutations in either the Gde1 active site or SPX domain also suppress toxicity, and radiolabeling confirms both domains are required for enzymatic activity. GPC is toxic in cells vastly overexpressing Tgp1 even without elevated IP₈, but Gde1 loss does not suppress this effect. Similarly, in S. cerevisiae overexpressing the Candida albicans Git3 transporter, GPC provision causes toxicity independent of Gde1. Loss of Gpc1, the acyltransferase converting GPC to lysophosphatidylcholine, does not alter toxicity in either yeast. These findings highlight a conserved process by which GPC regulates growth and reveal a role for IP₈ in modulating this process. Full article

Rheumatoid arthritis involves chronic synovitis and immune-metabolic dysregulation, highlighting a need for multi-target therapies that jointly modulate metabolism and inflammation. We developed glycyrrhiza protein–paeoniflorin self-assembled nanoparticles (GP-PF NPs) and investigated their anti-arthritic mechanism in adjuvant-induced arthritis (AIA) mice, using UHPLC-Orbitrap-MS-based metabolomics. Male C57BL/6 mice (n = 42) were assigned to the control, model, GP-PF NPs, paeoniflorin, glycyrrhiza protein, physical mixture, and celecoxib groups. All groups except controls received complete Freund’s adjuvant, and treatments were given intraperitoneally for 10 days. GP-PF NPs produced the greatest reduction in paw thickness versus the model (p < 0.0001) and outperformed all other active treatments, which was consistent with the improved histopathology. UHPLC-Orbitrap-MS detected 473 serum metabolites, and the model group showed 59 significant changes versus the control. GP-PF NPs significantly modulated 108 metabolites and yielded robust OPLS-DA separation from the model (R²Y = 0.98; Q² = 0.742). Venn and pathway analyses identified 43 NP-specific metabolites enriched in glycerophospholipid metabolism, including glycerophosphocholine, 1-oleylglycerophosphocholine, PE (16:0/16:0), phosphocholine, and sphingosine-1-phosphate. These metabolites were selectively normalized toward control levels by GP-PF NPs. qPCR further showed that GP-PF NPs significantly reduced synovial PI3K, AKT, mTOR, NLRP3, Caspase-1, and GSDMD mRNA overexpression (all p < 0.001 vs. model). Correlation analysis indicated significant associations between key serum lipids and synovial genes (e.g., PI3K positively correlated with several metabolites, r = 0.71–0.82; mTOR negatively correlated with sphinganine 1-phosphate and glycerophosphocholine, r = −0.65 and −0.54). These data suggest that GP-PF NPs ameliorate AIA and are associated with the normalization of glycerophospholipid-related metabolic perturbations and reduced synovial mRNA expression of the PI3K/AKT/mTOR-NLRP3 pathway, supporting their potential as a metabolism-inflammation preclinical oriented anti-arthritic nanomedicine. Full article

Background/Objectives: This study aimed to explore the association between maternal gut microbiota and metabolic profiles in the first trimester and the subsequent risk of gestational diabetes mellitus (GDM), as well as to characterize association patterns linking gut microbiota, serum metabolites, and metabolic traits. Methods: A nested case–control study was conducted among women with GDM (n = 47) and those without GDM (n = 94). Metagenomic sequencing was applied to analyze fecal microbiota, and liquid chromatography–mass spectrometry (LC–MS) was used for non-targeted plasma metabolomics. Differential microbiota and metabolites between groups were identified, and correlation analyses were conducted to assess their associations with clinical indicators. Results: Women who later developed GDM showed lower alpha diversity and higher beta diversity. Eleven differential species were identified, with Collinsella aerofaciens and Clostridium bartlettii enriched in GDM, while nine species such as Alistipes putredinis and Bacteroidales bacterium ph8 were enriched in controls. Sixty-four plasma metabolites differed between groups, including increased glycerol-3-phosphate, aromatic amino acids, and glycerophosphocholine, and decreased cysteine, tryptophan, niacinamide, and stearic acid. Correlation analyses revealed significant relationships between Alistipes putredinis, Eubacterium eligens, and Bacteroidales bacterium ph8 with metabolic and clinical indicators (e.g., TG, TC, LDL). Conclusions: In this nested case–control study, women who later developed GDM exhibited reduced gut microbial diversity and altered metabolic profiles during the first trimester of pregnancy. Several microbial taxa and microbiota–metabolite associations were observed in relation to subsequent GDM status, highlighting early-pregnancy microbial and metabolic features that may be relevant to GDM-related metabolic changes. Full article

Background/Objectives: The impact of choline on congenital heart defects (CHDs) in humans remains unclear. This study aimed to investigate the associations between maternal dietary intakes of choline and choline derivatives during pregnancy and CHD. Methods: This case–control study included 474 cases and 948 controls from hospitals in Northwest China. Pregnant women admitted for delivery were enrolled and completed a validated food frequency questionnaire to assess their dietary intake during pregnancy. A standardized questionnaire was also administered to collect additional pregnancy-related information. Mixed logistic regression models were used to estimate ORs (95%CIs) for CHD in association with choline intake. Results: Higher intakes of total choline, phosphatidylcholine, sphingomyelin, glycerophosphocholine, and phosphocholine in pregnancy were associated with reduced risks of total CHD, ventricular septal defects, and atrial septal defects, with all trend tests showing statistical significance (all p < 0.05). The ORs (95%CIs) of total CHD, comparing the highest with the lowest tertiles of intake, were 0.38 (0.24–0.61) for total choline, 0.51 (0.38–0.70) for phosphatidylcholine, 0.37 (0.26–0.51) for sphingomyelin, 0.34 (0.21–0.53) for glycerophosphocholine, and 0.53 (0.34–0.82) for phosphocholine. The inverse associations remained unchanged according to maternal age, work, education, parity, passive smoking, anemia, medication use, or folate/iron supplements use in pregnancy; however, these associations appeared to be more pronounced among pregnant women in urban areas. Conclusions: Higher maternal intake of dietary choline during pregnancy may be associated with a lower risk of CHD. Promoting choline intake in pregnant women could serve as a potential strategy for the primary prevention of fetal CHD in China. Full article

In modern bioinformatics, the analysis of high-dimensional data (genomic, metabolomic, etc.) remains a critical challenge due to the “curse of dimensionality,” where feature redundancy reduces classification efficiency and model interpretability. This study introduces a novel method, AIMarkerFinder (v0.1.0), for analyzing metabolomic data to identify key biomarkers. The method is based on a denoising autoencoder with an attention mechanism (DAE), enabling the extraction of informative features and the elimination of redundancy. Experiments on glioblastoma and adjacent tissue metabolomic data demonstrated that AIMarkerFinder reduces dimensionality from 446 to 4 key features while improving classification accuracy. Using the selected metabolites (Malonyl-CoA, Glycerophosphocholine, SM(d18:1/22:0 OH), GC(18:1/24:1)), the Random Forest and Kolmogorov–Arnold Networks (KAN) models achieved accuracies of 0.904 and 0.937, respectively. The analytical formulas derived by the KAN provide model interpretability, which is critical for biomedical research. The proposed approach is applicable to genomics, transcriptomics, proteomics, and the study of exogenous factors on biological processes. The study’s results open new prospects for personalized medicine and early disease diagnosis. Full article

Background/Objectives: Pre-analytical variation is a major challenge in metabolomics, yet most stability studies have focused on healthy volunteers and have overlooked the impact of disease and medication. To address this gap, we conducted a pilot study in systemic lupus erythematosus (SLE) to assess serum metabolite stability under delayed centrifugation. Methods: Peripheral blood from 10 SLE patients and 5 healthy controls (HC) was stored at room temperature for 1–24 h before processing and analyzed by untargeted LC-MS-based metabolomics. This design enabled direct evaluation of the effect of pre-analytical delay within the context of clinical heterogeneity. Results: Principal component trajectories showed reproducible temporal shifts in HC but dispersed patterns in SLE, indicating disease- and treatment-related influences. Linear mixed-effects models identified metabolites with condition-specific kinetics, including glucose, choline, glycerophosphocholine, and pyroglutamic acid. Mycophenolate intake was further associated with distinct AMP dynamics. Conclusions: These findings demonstrate that both disease state and medication reshape apparent metabolite stability, highlighting the need for strictly controlled sample handling and well-characterized clinical cohorts in metabolomics studies. Full article

Sour soup, a traditional fermented specialty from Northeast China, is renowned for its distinctive aroma and various health benefits. Here, we report the probiotic properties of Lactiplantibacillus plantarum Z45—a strain isolated from sour soup broth—along with its fermentative potential in sour soup production. This strain is suitable for food fermentation due to its absence of biogenic amine production and non-hemolytic activity. It exhibited strong tolerance to simulated gastrointestinal conditions and demonstrated high adherence capability to Caco-2 cells. Additionally, the strain displayed antioxidant and antimicrobial activities. Whole-genome sequencing revealed that Z45 carries no virulence or antibiotic resistance genes. It also harbors multiple carbohydrate-active enzymes and a complete folate biosynthesis pathway, alongside genes associated with stress response, antioxidant activity, and adhesion. Subsequently, Z45 was employed as a starter culture for sour soup fermentation, and its effects on the physicochemical and sensory properties of the product were evaluated. The results indicated that fermentation with Z45 did not alter the physicochemical properties of sour soup but significantly enhanced its sensory attributes. Compared to spontaneous fermentation, Z45-fermented sour soup showed reduced levels of harmful biogenic amines, improved flavor and overall sensory quality, notable enrichment of Lactobacillus and Oscillospirales in the microbial community, and upregulation of beneficial metabolites such as flavonoids and glycerophosphocholine. In summary, Lactiplantibacillus plantarum Z45 is safe, demonstrates probiotic potential, and holds promise for improving the quality and functional properties of fermented foods. Full article

Background/Objectives: The prebiotic effect of resistant potato starch (RPS) has been demonstrated, but the role of this nutrient in choline metabolism and the production of microbially modified choline-derived toxins is unknown. Methods: We performed post hoc analysis comparing changes in choline and related metabolites in serum from baseline to the week 4 time point in a human clinical trial evaluating daily consumption of 3.5 g RPS versus a placebo. Results: Choline levels increased in the RPS consuming group, while levels of trimethylamine decreased and levels of the cardiovascular toxin trimethylamine oxide were unaffected by RPS consumption. Increases in choline were positively correlated with increases in Akkermansia in the gut. Oxidation of choline to betaine was unaffected by RPS, as was acetylcholine metabolism. Levels of various saturated even acyl chain and hydroxylated acyl chain sphingomyelins were increased in RPS consuming participants, and levels of phospholipid degradation products phosphocholine and glycerophosphocholine were decreased. Conclusions: These data suggest that RPS enhances choline absorption without increasing TMAO and stimulates the incorporation of choline into sphingomyelins containing saturated even acyl chains and hydroxylated acyl chains. Future studies assessing the physiological consequences, such as cognitive or neurological benefits, of enhanced choline absorption and sphingomyelin levels in people consuming RPS are warranted. Full article

Objective: Vitamin D deficiency (VDD) is common in pregnancy and may affect lipid metabolism. The underlying mechanisms are multifactorial, but most evidence so far comes from non-pregnant populations. This study aims to identify metabolites and metabolic patterns associated with VDD in early pregnancy and to evaluate their relationships with maternal lipid profiles. Methods: A nested case–control research was carried out in the Zhoushan Pregnant Women Cohort (ZPWC). Cases were defined as women with VDD (25(OH)D < 20 ng/mL), and controls (≥20 ng/mL) were matched 1:1 using propensity scores based on age, pre-pregnancy BMI, gestational week, and calendar year at blood sampling. The untargeted metabolomics of first-trimester maternal plasma were measured. Metabolic profiles were analyzed using partial least squares-discriminant analysis (PLS-DA). Principal component analysis (PCA) was applied to visualize group separation, and metabolite set enrichment analysis (MSEA) was performed to reveal biologically relevant metabolic patterns. Associations between VDD-related metabolite components in early pregnancy and lipid levels in mid-pregnancy were assessed using linear regression models. Results: 44 cases and 44 controls were selected for the study. There were 60 metabolites identified as being connected to VDD. Among these, 26 metabolites, primarily glycerophospholipids and fatty acyls, exhibited decreased levels in the VDD group. In contrast, 34 metabolites showed increased levels, mainly comprising benzene derivatives, carboxylic acids, and organooxygen compounds. PCA based on these metabolites explained 52.8% of the total variance (R²X = 0.528) across the first six principal components (PC1: 16.4%, PC2: 10.6%, PC3: 9.2%, PC4: 6.3%, PC5: 5.7%, PC6: 4.6%). PC2, dominated by lineolic acids and derivatives, was negatively associated with total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) (all p < 0.01). PC3, dominated by glycerophosphocholines, was negatively associated with TC, TG, and high-density lipoprotein cholesterol (HDL-C) (all p < 0.05). MSEA revealed significant enrichment of the pantothenate and CoA biosynthesis pathway after multiple testing correction (FDR < 0.05). Conclusions: This study reveals distinct metabolic alterations linked to VDD and suggests potential mechanisms underlying its association with maternal lipid metabolism in early pregnancy. Full article