Search Results (7,011)

Background/Objectives: The Mediterranean diet is widely recognized for its cardiovascular and metabolic benefits, including weight reduction; however, the metabolic mechanisms underlying these effects remain incompletely understood. This study investigated whether changes in circulating polyamines are associated with metabolic improvements following a Mediterranean diet intervention, particularly in breast cancer survivors. Methods: This exploratory secondary analysis used stored paired serum samples from a previously reported 8-week controlled intervention conducted in three groups: Group A (breast cancer survivors following a Mediterranean diet alone, n = 21), Group B (breast cancer survivors following a Mediterranean diet combined with naltrexone/bupropion, n = 23), and Group C (non-cancer participants receiving the combined intervention, n = 28). Paired polyamine data were available for 16, 9, and 16 participants, respectively. Breast cancer survivors were randomized to Groups A and B, whereas Group C was enrolled as a non-randomized active comparison group. Serum metabolic profiles were analyzed using liquid chromatography–mass spectrometry-based untargeted metabolomics, and nine polyamines were quantified using targeted analysis. An exploratory indirect-effect analysis examined associations between changes in serum polyamines and clinical outcomes, including body composition and lipid parameters. Results: Body weight, fat mass, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) decreased significantly within all three groups after the 8-week intervention (median changes: −1.9 to −2.8 kg, −1.9 to −2.8 kg, and −0.3 to −0.7, respectively). LDL cholesterol decreased significantly only within the two groups receiving naltrexone/bupropion (median changes: −20.6 and −10.1 mg/dL). However, between-group differences in these changes were not statistically significant. N-acetylspermine increased nominally in all groups (p < 0.01), whereas spermine increased only in the Mediterranean diet alone group (p = 0.015). Conclusions: Mediterranean diet-related metabolic improvements were accompanied by changes in circulating polyamines. Spermine and N-acetylspermine may represent candidate metabolic response markers associated with nutritional and pharmacological interventions in breast cancer survivorship. Full article

Background: Visceral adipose tissue (VAT) is a key determinant of cardiometabolic risk, yet its underlying molecular mechanisms remain incompletely characterized. Metabolomics offers an opportunity to identify circulating biomarkers that capture VAT-related biology beyond conventional clinical measures. Methods: We conducted a cross-sectional analysis of 2526 participants from the Qatar Biobank using untargeted serum metabolomics profiling. VAT was quantified using DXA-derived estimates and analyzed both as a continuous variable and by comparing individuals in the highest quartile to the remainder quartiles. Associations between metabolites and VAT were assessed using multivariate partial least squares discriminant analysis and adjusted linear regression models controlling for age, sex, and BMI, with Bonferroni correction for multiple testing. Results: Continuous VAT was associated with 106 metabolites, while the Q4 versus Q1–Q3 contrast identified 23 metabolites, with overlapping metabolites defining a robust core VAT signature. Higher VAT was characterized by coordinated elevation of branched-chain amino acids and their keto/hydroxy acid derivatives, glutamate, and central carbon intermediates, consistent with impaired mitochondrial oxidative decarboxylation. We further identified 4-hydroxyglutamate as a novel collagen-derived metabolite positively associated with VAT, suggesting a potential link between extracellular matrix remodeling and glutamate-centered metabolism. Additionally, greater VAT was associated with lower concentrations of glycine and glycine conjugates and reduced levels of unsaturated sphingomyelins and plasmalogens. Conclusions: These findings provide potential mechanistic insights into VAT-related metabolic dysfunction and identify candidate circulating biomarkers that may enable non-invasive assessment of visceral fat-associated cardiometabolic risk. Longitudinal and mechanistic studies are warranted to establish causality and clinical utility. Full article

Alzheimer’s disease (AD) is a common age-related neurodegenerative disorder with extremely low drug development success rates, making nutritional intervention a promising strategy. Cerebral energy metabolism dysfunction is a core pathological feature of AD. Odd-chain fatty acids (OCFAs) can generate propionyl-CoA via β-oxidation to replenish the impaired tricarboxylic acid (TCA) cycle. This study characterized the lipid composition of OCFAs-enriched algal oil by UPC²-Q-TOF-MS, evaluated its neuroprotective effects on Caenorhabditis elegans (C. elegans) models with AD, Parkinson’s disease (PD), and Huntington’s disease (HD), and explored the metabolic mechanism of its key component pentadecanoic acid (C15:0) using untargeted metabolomics. Results showed that triglycerides (TAGs) represented the predominant lipid class, accounting for 97.3% of the total lipid content in the algal oil. Among all the identified TAG molecular species, TAGs containing C15:0/C17:0 accounted for more than 90%. OCFAs-enriched algal oil exhibited disease-selective neuroprotection. It significantly improved locomotor function in AD nematodes, moderately ameliorated PD-related deficits, whereas showed no efficacy in HD nematodes. Metabolomics revealed that C15:0 produced propionyl-CoA to rescue TCA cycle dysfunction and energy deficits, upregulated membrane phospholipids to repair membrane integrity, and reduced abnormal metabolites to restore metabolic homeostasis. KEGG analysis confirmed that C15:0 globally regulated core metabolic pathways including amino acid, cofactor, nucleotide, and carbon metabolism. OCFAs-enriched algal oil exerted selective anti-AD effects by repairing energy metabolism, remodeling membrane phospholipids, and restoring metabolic homeostasis, providing a novel nutritional candidate for AD intervention. Full article

Metabolic health extends beyond BMI: some obese individuals remain metabolically resilient, while many normal-weight individuals exhibit hidden dysfunction. In Qatar, where obesity and metabolic disorders are widespread, understanding these divergent phenotypes is clinically paramount. This study maps the circulating metabolites and biological pathways associated with metabolic dysfunction. Clinical data from 6000 adults in the Qatar Biobank were used to determine obesity prevalence and classify metabolic health status among individuals with normal-weight and obese individuals. Comprehensive statistical analyses were conducted to determine associations between metabolic phenotypes and clinical parameters. Untargeted plasma metabolomics were performed in a subset of participants. Differential metabolite expression and pathway enrichment analyses were conducted to identify the distinct metabolic signatures underlying metabolic health. Mean age ranged from 30.9 ± 11.3 years in metabolically healthy normal-weight (MHNW) individuals to 46.0 ± 10.9 years in metabolically unhealthy obese (MUHO) individuals, with females predominating in the MHO group (65.2%). MUHO participants had higher rates of diabetes (21%), hypertension (34.7%), and insulin resistance (96.8%). Elevated C-peptide, uric acid, ferritin, and inflammatory markers were positively associated with metabolic unhealthiness, particularly in obese females, whereas estradiol and free thyroxine showed protective associations. Metabolomic profiling revealed distinct lipid and amino acid signatures differentiating MHO, MUHO, and MHNW phenotypes, with pathway analysis highlighting disruptions in lipid metabolism, amino acid pathways, and membrane transport. Metabolic heterogeneity in obesity reflects differences in coordinated biochemical regulation rather than adiposity alone. Identified metabolite signatures and ratios may serve as biomarkers of metabolic resilience and early risk stratification. Full article

Grape seeds are a major by-product of grape processing and a rich source of polyphenolic compounds, yet their value remains underutilized. In this study, 12 lactic acid bacteria (LAB) strains were evaluated in a grape seed-based fermentation system to compare their tolerance, metabolic performance, and ability to promote polyphenol release. Among them, Lactiplantibacillus plantarum FBL002 showed the best overall performance. The strain maintained strong viability and metabolic activity at 5% grape seed concentration and released polyphenols more effectively than the other tested strains. The resulting fermentation broth also showed pronounced intracellular antioxidant activity. To clarify the basis of this phenotype, we further combined metabolomic, genomic, and transcriptomic analyses. Fermentation caused substantial shifts in phenolic metabolites, characterized by a decrease in glycosylated forms and an increase in more bioactive aglycones. Genome annotation revealed an enrichment of β-glucosidase-related genes in FBL002, and transcriptomic analysis showed that these genes were markedly upregulated during fermentation. This pattern was closely associated with the enhanced release of polyphenols. Together, these findings identify β-glucosidase as a key driver of grape seed polyphenol biotransformation by FBL002 and support the sustainable, high-value use of grape seeds in functional foods and cosmetic applications. Full article

This study aimed to identify candidate molecular pathways mediating dopaminergic dysfunction induced by PFAS mixture exposure, with a focus on the TM/5-HT signaling axis and calcium-linked lipid metabolites, and to explore potential gut-brain axis involvement. Adult mice were exposed to a PFAS mixture. Behavioral tests assessed spatial memory, spontaneous activity, and motor coordination. Histopathological and ultrastructural analyses examined neuronal atrophy, mitochondrial damage, α-synuclein (α-syn), and tyrosine hydroxylase (TH). Transcriptomics, metabolomics, and gut microbiota profiling (16S rRNA sequencing) were performed, followed by integrated multi-omics and correlation analyses. PFAS exposure was associated with PD-relevant motor and cognitive impairments, including impaired spatial memory, reduced spontaneous activity, and motor coordination deficits. Neuronal atrophy, mitochondrial structural damage, upregulation of α-syn, and downregulation of TH were observed. Transcriptomics identified 315 differentially expressed genes (DEGs) enriched in ciliary movement, neuroactive ligand-receptor interactions, and serotonergic synapses. Metabolomics identified 130 differentially abundant metabolites involved in arachidonic acid metabolism and serotonergic synapses. Integrated analysis highlighted correlative changes in the TM/5-HT signaling pathway. Phosphatidylinositol PI(16:0/20:2(11Z,14Z)) showed a strong positive correlation with Dbh gene expression, suggesting a candidate association between Dbh expression and phosphatidylinositol alterations. Gut microbiota analysis revealed compositional alterations (e.g., Muribaculaceae, Ileibacterium) and predicted functional shifts (e.g., tryptophan metabolism–related modules) were observed; these findings are exploratory. This study identifies multi-omics signatures associated with PFAS mixture-induced dopaminergic dysfunction in mice. The TM/5-HT pathway emerges as a candidate molecular axis requiring further investigation. Gut microbiota alterations suggest a potential peripheral component, but causality and gut-brain axis involvement remain hypothetical and need direct experimental validation. Full article

Tributyrin, a short-chain fatty acid derivative, has been shown to hold potential in improving intestinal health in livestock and poultry. However, its multidimensional effects on the health of meat pigeons, particularly during the young pigeon stage, remain unclear. This study aimed to investigate the comprehensive effects of dietary tributyrin supplementation on the growth, health status, intestinal function, and metabolic profile of young pigeons. A total of 100 healthy 29-day-old White King pigeons, with half male and half female, were randomly divided into a control group (fed a basal diet) and a treatment group (fed a basal diet supplemented with 1500 mg/kg tributyrin) for a 35-day trial. The results showed that compared with the control group, young pigeons in the treatment group had significantly reduced serum triglyceride levels, alanine aminotransferase activity, and concentrations of pro-inflammatory cytokines (TNF-α, IL-6), along with significantly increased levels of high-density lipoprotein, immunoglobulin G, total antioxidant capacity, and glutathione peroxidase activity. Concurrently, the villus height-to-crypt depth ratio in the jejunum and ileum was significantly elevated, indicating improved intestinal morphological structure. Untargeted metabolomics analysis further revealed significant changes in the relative abundances of 13 key differential metabolites (e.g., L-carnitine, pyridoxamine, indoleacetic acid) in the small intestinal contents of the treatment group. These metabolites were mainly enriched in metabolic pathways such as 2-oxoCarboxylic acid metabolism, tryptophan metabolism, and vitamin B6 metabolism. In conclusion, dietary supplementation with 1500 mg/kg tributyrin can exert multifaceted beneficial effects on young pigeon health by improving lipid metabolism, enhancing immune and antioxidant functions, optimizing intestinal structure, and regulating the local metabolic network. This study provides a theoretical basis for the application of tributyrin as a functional additive in the green and healthy production of meat pigeons. Full article

This study investigated the effects of dietary nano-antimicrobial peptides (NAP) on the microbial communities and metabolic profiles in Tibetan sheep. Using 16S rRNA gene high-throughput sequencing and non-targeted metabolomics, the contents of the small intestine, rumen, and rectum were systematically analyzed in a control group (Group A) and a NAP-supplemented group (Group B). Multi-omics integration methods, including O2PLS and Pearson correlation analysis, were employed to explore the association between microbial communities and metabolites. Alpha and beta diversity analyses revealed significant differences (p < 0.05) in the microbial community structure of the small intestine between the two groups. In contrast, the rumen and rectal microbiota remained relatively stable, indicating that the regulatory effects of NAP on the intestinal microecology are site-specific. In the small intestine, NAP altered the composition of dominant functional microbiota and the abundance of taxa related to energy metabolism. Metabolomic analysis identified significant shifts in metabolic profiles, specifically within the bile acid, fatty acid, and phospholipid pathways (p < 0.05). Group A exhibited baseline steady-state characteristics (e.g., cholic acids and phospholipids), whereas Group B showed activation of unsaturated fatty acids and related metabolites. Multi-omics integration revealed a stable systematic association between intestinal microbial genera and metabolites. Specifically, bile acid and prostaglandin metabolites were negatively correlated with Firmicutes-related taxa. These findings suggest that NAP supplementation may contribute to maintaining host energy metabolism and intestinal homeostasis by regulating intestinal microecology. Full article

Prunus salicina var. cordata cv. ‘Younai’ is a characteristic stone fruit germplasm resource of Fujian Province, yet its core flavor components remain unclear. This study aimed to comprehensively characterize the flavor chemistry of Younai by determining the contents of sugar–acid components and volatile compounds, combined with untargeted metabolomics analysis. Results showed that fructose was the predominant sweet component, while malic acid was the dominant organic acid in Younai. (Z)-3-Hexen-1-ol, 1-Hexanol and (Z)-3-Hexen-1-yl acetate were screened as potential key aroma-active compounds based on odor activity values, and γ-Decalactone plus Linalool further enriched the fruit aroma hierarchy. Untargeted metabolomics identified 26 saccharides and 21 organic acids in the fruits. Additionally, Younai fruit metabolites were dominated by polyphenols, with flavonols and phenolic acids as the core polyphenol subclasses. This study provides a chemically grounded baseline characterization of Younai flavor. The screened potential aroma-active compounds and metabolite profiles provide a foundation for future sensory validation studies and the development of quality evaluation criteria. Full article

Ulcerative colitis (UC) is characterized by barrier disruption, microbiota dysbiosis, fibrosis, and impaired autophagy. We investigated the effects of Rhamnocitrin (Rha) in dextran sulfate sodium (DSS)-induced chronic UC mice using histological analysis, molecular assays, and multiomics profiling. Rha alleviated weight loss and colon shortening; improved mucus secretion and tight junction protein expression; suppressed NLRP3 inflammasome activation; activated autophagy via AMPK activation and consequent Akt/mTOR inhibition; and attenuated colonic fibrosis. Multiomics analysis integrating 16S rRNA sequencing, metagenomics, and metabolomics revealed that Rha remodels the gut microbiota and is associated with elevated levels of beneficial metabolites, including butyrate in the colon, glutamate and γ-aminobutyric acid in the liver, and α-linolenic acid in the serum. Correlation analysis revealed close associations between microbiota and metabolite alterations, and improved barrier integrity, reduced inflammation, and attenuated fibrosis. These findings suggest that Rha ameliorates chronic UC by modulating autophagy, microbiota composition, and host metabolism across the gut–liver axis. Full article

Soil salinity is a major environmental constraint limiting plant productivity and modulating secondary metabolism. Triterpenoid saponins play crucial roles in plant stress adaptation, yet their biosynthetic regulation in Cyclocarya paliurus under salt stress remains poorly understood. This research integrated transcriptomic and metabolomic analyses to investigate triterpenoid saponin metabolism in C. paliurus leaves at four NaCl concentrations and two sampling times. Salt stress altered ion homeostasis, suppressed growth, and induced distinct triterpenoid saponins accumulation patterns, with cyclocaric acid B and oleanolic acid showing significant increases. Weighted gene co-expression network analysis identified two modules significantly correlated with triterpenoid saponin accumulation and highlighted transcription factors including WRKY18, bHLH121, ERF4, and ERF1 as regulators of key biosynthetic genes (DXS, SQS, and HMGR). Molecular docking further validated these regulatory interactions, demonstrating that bHLH35, MYC2, ERF113, and MED26B form stable complexes with target gene promoters through extensive hydrogen-bond networks. These findings elucidate the regulatory framework of triterpenoid saponin metabolism under salinity and provide a foundation for molecular breeding and cultivation of C. paliurus in saline regions. Full article

Feed additives play a crucial role in boosting livestock immunity, but their underlying molecular mechanisms are often incompletely understood. This study used integrated proteomics and metabolomics to systematically investigate the immunomodulatory effects of dietary fermented onion (FO) on the spleen of Liangshan Black Sheep. Results showed that FO supplementation significantly improved systemic antioxidant capacity and immune function, indicated by a higher spleen index and increased serum concentrations of SOD, MCP-1, and IL-2 (p < 0.05). Multi-omics profiling of spleen tissues identified 169 differentially expressed proteins and 168 differential metabolites. Integrated pathway enrichment revealed calcium signaling and purine metabolism as potential core regulatory hubs for the observed immunomodulation. This molecular remodeling correlated with key molecules including protein F2R and metabolites adenosine and hypoxanthine, which may form a coordinated regulatory network. Overall, our findings suggest potential pathways linking dietary FO supplementation to enhanced splenic immune function in Liangshan Black Sheep, likely via synergistic regulation of specific signaling pathways. This work supports FO as a promising functional feed additive and provides a molecular framework for developing novel immunomodulatory strategies in livestock production. Full article

The seed oil of Prinsepia utilis is a traditional food-medicine homology used by the Naxi people in Yunnan Province of the Himalayan region. This study explored the potential applications of food-medicine homology in health and wellness. Using untargeted metabolomics, we compared the metabolite profiles of the subcritical extraction method (edible oil as crude oil) (CO) and its improved processing method (medicinal oil as refined oil) (RO) extracted from P. utilis seeds by UPLC–QTOF MS/MS and evaluated their in vivo and in vitro activities. We screened 14 discriminatory metabolites and performed their tentative annotation, including fatty acids, terpenoids, steroids, and quinones. Furthermore, we quantified 12 bioactive compounds in CO samples via targeted chromatographic analysis, which support the promising food-medicine homology applications of the oil. RO exhibited potent antioxidant activity (DPPH radical scavenging rate of 79.7%, representing 65.7% increase over CO), with an ABTS⁺ radical scavenging rate of 95.8% (77.1% improvement over CO). The hyaluronidase inhibition rate for RO was 43.4%, whilst that for CO was 30.8%; the elastase inhibition rate for RO was 69.8%, whilst that for CO was 59.8%, and promoted zebrafish fin regeneration by 15% at 3% concentration. Our results validated the seed oil of P. utilis as a traditional food and its antioxidants, anti-aging, demonstrating that the CO processing method is able to meet with medicine and food homology in health, and the RO processing method may satisfy skin care function. These findings highlight the potential applications of P. utilis seed oil for food-medicine homology in health and wellness properties. Full article

Selenium (Se) is an important micronutrient that is required in very small amounts and plays a significant role in enhancing plant growth, stress resistance, and fruit quality. In this study, we investigated the effects of different sodium selenite concentrations (CK, 0 mg/L; Se1, 0.50 mg/L; Se2, 1.00 mg/L, Se3, 2.00; and Se4, 3.00 mg/L) on the growth, nutrient absorption, antioxidant capacity, and leaf metabolome of blueberry (Vaccinium corymbosum L. ‘Brigitta’) in hydroponic culture. Our results showed that moderate Se concentration (1.00 mg/L, Se2) had noticeable enhancements in key traits like taller plants, thicker stems, a greater number of leaves, and stem fresh weight, with increases of 60.23%, 61.90%, 36.05%, and 87.97%, respectively, compared to the CK. In addition, the appropriate application of Se fertilizer (1.0 mg/L, Se2) can enhance the absorption of macronutrients by plants, with the total contents of nitrogen (N), phosphorus (P), and potassium (K) increasing by 48.11%, 15.85%, and 14.25%, respectively, compared to CK. In comparison to CK, the content and accumulation of total Se rose dramatically under the Se4 treatment, showing increases of 2300% and 2514%. The contents of chlorophyll and antioxidant enzyme activities were maximized at Se2, while excessive Se (Se4) led to oxidative damage, as indicated by elevated MDA, H₂O₂, and O₂⁻ levels. Moreover, metabolomic analysis revealed that moderate Se concentration (Se2) significantly altered metabolic pathways related to aminoacyl-tRNA biosynthesis, arachidonic acid metabolism, and ABC transporters, with downregulation of key metabolites in sugar and organic acid metabolism (e.g., α-D-glucose-6-phosphate, L-lactic acid, maleic acid). In contrast, high Se concentration (Se4) disrupted these pathways and promoted volatile compound accumulation. These findings demonstrate that moderate Se application enhances blueberry growth and quality by regulating nutrient uptake, antioxidant defense, and primary metabolism, whereas excessive Se induces metabolic imbalance and oxidative stress. Overall, moderate Se fertilizer (1.00 mg/L) can significantly enhance the growth and quality of blueberries, while excessive selenium may have adverse effects. Full article

Water stress is a major abiotic constraint limiting the growth and productivity of alfalfa (Medicago sativa L.). To elucidate the adaptive mechanisms and identify key drought-tolerance genes, physiological measurements were integrated with multi-omics analyses of cultivar ‘Tamu 1’ under three water treatments: waterlogging (100% field water capacity), normal irrigation (80% FWC), and drought (light: 60% FWC, moderate: 40% FWC, severe: 20% FWC). Water stress markedly inhibited plant growth, induced oxidative stress, and reduced the photosynthetic capacity. Compared with waterlogging stress (DAMs: n = 71; DEGs: n = 313), drought stress resulted in a substantially greater number of differentially accumulated metabolites (DAMs, n = 1504) and differentially expressed genes (DEGs, n = 8006). Weighted gene co-expression network analysis (WGCNA) identified six key modules and ten hub genes associated with stress responses. Integrated transcriptomic and metabolomic analyses further revealed four major responsive pathways: starch and sucrose metabolism, phenylpropanoid and flavonoid metabolism, glutathione metabolism, and zeatin biosynthesis. Based on integrative criteria, including differential expression (|log₂FC| ≥ 1, adjusted p < 0.05), WGCNA modules significantly associated with drought-related traits (R² > 0.6), as well as functional annotation and protein–protein interaction (PPI) network topology, 28 candidate genes associated with drought tolerance were identified, of which six were further validated by quantitative real-time PCR (qRT-PCR). These findings highlight key metabolic pathways and regulatory modules underlying alfalfa responses to water stress and provide valuable candidate gene resources for improving drought tolerance. Full article