Search Results (207)

The global obesity epidemic and associated metabolic disorders present urgent public health challenges. This study employed a multi-omics approach (lipidomics, metabolomics, and gut microbiome analysis) to investigate how Bletilla striata polysaccharides (BSPs) and composite polysaccharides modulate liver lipid metabolism and gut microbiota in high-fat diet (HFD)-induced obese mice. HFD elevated hepatic phosphatidylcholines, cholesteryl esters (CEs), and acylcarnitines (CARs), alongside increased cecal choline and trimethylamine. BSP interventions reduced hepatic CEs, free fatty acids (FAs), CARs, and cecal sarcosine while restoring gut microbial diversity. Notably, BSP enriched beneficial genera, including Jeotgalicoccus and Atopostipes, and the network analysis revealed negative correlations between these genera and hepatic triglycerides (TGs), implicating the gut–liver axis in lipid metabolism regulation. These findings elucidate the anti-obesity mechanisms of polysaccharides through gut microbiota remodeling and cross-tissue metabolic interactions, providing a foundation for leveraging plant polysaccharides in developing safer, effective obesity therapies. Full article

Breast cancer (BC) is a neoplasm characterized by high heterogeneity and is influenced by intrinsic molecular subtypes and clinical stage, aspects that remain underexplored in the Colombian population. This study aimed to characterize metabolic alterations associated with subtypes and disease progression in a group of newly diagnosed, treatment-naive Colombian women using an untargeted metabolomics approach. To improve metabolite coverage, samples were analyzed using LC-QTOF-MS and GC-QTOF-MS, along with amino acid profiling. The Luminal B subtype exhibited elevated levels of long-chain acylcarnitines and higher free fatty acid concentrations than the other subtypes. It also presented elevated levels of carbohydrates and essential glycolytic intermediates, suggesting that this subtype may adopt a hybrid metabolic phenotype characterized by increased glycolytic flux as well as enhanced fatty acid catabolism. Tumor, Node, and Metastasis (TNM) staging analysis revealed progressive metabolic reprogramming of BC. In advanced stages, a sustained increase in phosphatidylcholines and a decrease in lysophosphatidylcholines were observed, reflecting lipid alterations associated with key roles in tumor progression. In early stages (I-II), plasma metabolites with high discriminatory power were identified, such as glutamic acid, ribose, and glycerol, which are associated with dysfunctions in energy and carbohydrate metabolism. These results highlight metabolomics as a promising tool for the early diagnosis, clinical follow-up, and molecular characterization of BC. Full article

Background: Exposure to per- and polyfluoroalkyl substances (PFAS, including 7H-Perfluoro-4-methyl-3,6-dioxaoctanesulfonic acid (PFESA-BP2), perfluorooctanoic acid (PFOA), and hexafluoropropylene oxide (GenX), has been associated with liver dysfunction. While previous research has characterized PFAS-induced hepatic lipid alterations, their downstream effects on energy metabolism remain unclear. This study investigates metabolic alterations in the liver following PFAS exposure to identify mechanisms leading to hepatoxicity. Methods: We analyzed RNA sequencing datasets of mouse liver tissues exposed to PFAS to identify metabolic pathways influenced by the chemical toxicant. We integrated the transcriptome data with a mouse genome-scale metabolic model to perform in silico flux analysis and investigated reactions and genes associated with lipid and energy metabolism. Results: PFESA-BP2 exposure caused dose- and sex-dependent changes, including upregulation of fatty acid metabolism, β-oxidation, and cholesterol biosynthesis. On the contrary, triglycerides, sphingolipids, and glycerophospholipids metabolism were suppressed. Simulations from the integrated genome-scale metabolic models confirmed increased flux for mevalonate and lanosterol metabolism, supporting potential cholesterol accumulation. GenX and PFOA triggered strong PPARα-dependent responses, especially in β-oxidation and lipolysis, which were attenuated in PPARα^−/− mice. Mitochondrial fatty acid transport and acylcarnitine turnover were also disrupted, suggesting impaired mitochondrial dysfunction. Additional PFAS effects included perturbations in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and blood–brain barrier (BBB) function, pointing to broader systemic toxicity. Conclusions: Our findings highlight key metabolic signatures and suggest PFAS-mediated disruption of hepatic and possibly neurological functions. This study underscores the utility of genome-scale metabolic modeling as a powerful tool to interpret transcriptomic data and predict systemic metabolic outcomes of toxicant exposure. Full article

Burnout syndrome is characterized mainly by three criteria (emotional exhaustion, depersonalization, and low personal accomplishment), and further exacerbated by night shift work, with profound implications for individual and societal well-being. The Maslach Burnout Inventory survey applied to 97 medical care professionals (with day and night work) revealed different scores for these criteria. Blood metabolic profiles were obtained by UHPLC-QTOF-ESI⁺-MS untargeted metabolomics and multivariate statistics using the Metaboanalyst 6.0 platform. The Partial Least Squares Discrimination scores and VIP values, Random Forest graphs, and Heatmaps, based on 99 identified metabolites, were complemented with Biomarker Analysis (AUC ranking) and Pathway Analysis of metabolic networks. The data obtained reflected the biochemical implications of night shift work and correlated with each criterion’s burnout scores. Four main metabolic pathways with important consequences in burnout were affected, namely lipid metabolism, especially steroid hormone synthesis and cortisol, the energetic mitochondrial metabolism involving acylated carnitines, fatty acids, and phospholipids as well polar metabolites’ metabolism, e.g., catecholamines (noradrenaline, acetyl serotonin), and some amino acids (tryptophan, tyrosine, aspartate, arginine, valine, lysine). These metabolic profiles suggest potential strategies for managing burnout levels in healthcare professionals, based on validated criteria, including night shift work management. Full article

Background/Objectives: Autism Spectrum Disorder (ASD) etiology is complex, involving genetics and environmental factors, and associated with impaired energy metabolism. Mitochondrial fatty acid oxidation (mFAO) is instrumental to energy production through the oxidation of acylcarnitines (ACs). We performed a comprehensive investigation of blood AC profiles in a pediatric ASD cohort, aiming to define ASD subgroups based on AC profiles and link these profiles to key clinical features and comorbidities using a phenotype-first approach. Methods: Blood levels of 31 ACs (μmol/L) collected from 102 ASD patients and 117 healthy controls (HCs) were evaluated via tandem mass spectrometry. The percentile distribution of blood AC levels in HC samples was computed to define the normal reference range (RR) and identify values corresponding to the 10th and 90th percentiles. Cognitive levels, emotional–behavioral disturbances and the severity of ASD symptoms (Autism Diagnostic Observation Schedule-Calibrated Severity Score ADOS-CSS) were assessed. Clinical correlates of ASD groups based on AC profiles were evaluated. Results: Three ASD subgroups were identified based on the percentile distribution of AC levels: group A (ACs < 10th percentile), group B (ACs 10th–90th percentile) and group C (ACs > 90th percentile) (abnormal AC number ≥ 3). Out of the thirty-one analyzed ACs in DBSs, fifteen (48.4%) were significantly different when comparing ASD group A to ASD group C. There was a significant difference in the severity of autism symptoms (ADOS CSS) related to the repetitive and restricted behaviors domain (CSS RRB) among the different groups (χ²(2) = 6.26; p = 0.044). The post hoc Dunn’s test with Bonferroni correction showed that ADOS-CSS RRB was significantly higher in ASD group A compared to ASD group B (p = 0.013). AC C14 was more frequently decreased (<10th pc) in patients with more severe symptoms (p = 0.006); C10:1 tended to be more frequently increased (>90th pc) in patients with lower clinical severity (p = 0.052). Conclusions: This study highlights differences across blood AC levels in children with ASD and conveys novel information on clinical severity in ASD patients with abnormal blood AC profiles. Thus, examining metabolic profiles may provide helpful insights to understand the variability of ASD symptoms. Full article

Hypertensive disorders of pregnancy are associated with a higher risk of later cardiovascular disease, but the mechanistic links are unknown. We recruited two groups of women, one during pregnancy and another at least two years after delivery, including both cases (with a hypertensive disorder of pregnancy) and controls (with a normotensive pregnancy). We measured metabolites using liquid chromatography–mass spectroscopy and applied machine learning to identify metabolomic signatures at three time points: antepartum, postpartum, and mid-life. The mean ages of the pregnancy cohort (58 cases, 46 controls) and the mid-life group (71 cases, 74 controls) were 33.8 and 40.8 years, respectively. The levels of 157 metabolites differed significantly between the cases and the controls antepartum, including 19 acylcarnitines, 12 gonadal steroids, 11 glycerophospholipids, nine fatty acids, six vitamin D metabolites, and four corticosteroids. The machine learning model developed using all antepartum metabolite levels discriminated well between the cases and the controls antepartum (c-index = 0.96), postpartum (c-index = 0.63), and in mid-life (c-index = 0.60). Levels of 10,20-dihydroxyeicosanoic acid best distinguished the cases from the controls both antepartum and postpartum. These data suggest that the pattern of differences in metabolites found antepartum continues to distinguish women who had a hypertensive disorder of pregnancy from women with a normotensive pregnancy for years after delivery. Full article

This study investigated the potential of dietary garlic skin supplementation to enhance meat quality in black goats, addressing the growing demand for natural feed additives in sustainable livestock production. Twelve 4-month-old Youzhou black goats were randomly assigned to a control group (FR, basal diet) or an experimental group (NR, 16% garlic skin supplementation) for 90 days. Meat quality parameters, amino acid and fatty acid profiles, and metabolomic pathways were systematically analyzed. The NR group demonstrated significantly reduced backfat thickness (p < 0.05), increased eye muscle area (p < 0.05), higher pH at 0 h post-slaughter (p < 0.05), and improved meat color (L* and a* values at 24 h, p < 0.05) compared to FR. Cooking loss was significantly lower in NR (p < 0.05), alongside elevated arginine and n-3 PUFA (α-linolenic acid, EPA, DHA) levels (p < 0.01) and a favorable n-6/n-3 ratio. Metabolomics identified 1970 differentially abundant metabolites, with key enrichments in propionate metabolism, oxidative phosphorylation, and amino acid pathways, notably linking acylcarnitines to color stability and water retention. These findings indicated that garlic skin improved meat quality through coordinated regulation of lipid metabolism, antioxidant enhancement, and mitochondrial optimization. The study provided foundational evidence for utilizing garlic byproducts as functional feed additives to improve nutritional and sensory attributes in goat meat, supporting sustainable meat production strategies. Full article

The analysis of blood metabolites may help identify individuals at risk of having COPD and offer insights into its underlying pathophysiology. This study aimed to identify COPD-related metabolic alterations and generate a biological signature potentially useful for screening purposes. Plasma metabolomic profiles from 91 COPD patients and 91 controls were obtained using complementary semi-targeted and untargeted LC-MS approaches. Univariate analysis identified metabolites with significant differences between groups, and enrichment analysis highlighted the most affected metabolic pathways. Multivariate analysis, including ROC curve assessment and machine learning algorithms, was applied to assess the discriminatory capacity of selected metabolites. After adjustment for major potential confounders, 56 metabolites showed significant differences between COPD patients and controls. The enrichment analysis revealed that COPD-associated metabolic alterations primarily involved lipid metabolism (especially fatty acids and acylcarnitines), followed by amino acid pathways and xenobiotics. A panel of 10 metabolites, mostly related to lipid metabolism, demonstrated high discriminatory performance for COPD (ROC-AUC: 0.916; 90.1% sensitivity and 89% specificity). These findings may contribute to improving screening strategies and a better understanding of COPD-related metabolic changes. However, our findings remain exploratory and should be interpreted with caution, needing further validation and mechanistic studies. Full article

Background: Very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is caused by biallelic pathogenic variants in ACADVL (acyl-CoA dehydrogenase very-long-chain), leading to impaired fatty acid oxidation and the accumulation of long-chain acylcarnitine. We report a single case of a two-year-old girl, whose neonatal metabolic screening revealed an acylcarnitine profile suggestive of VLCADD, with residual enzymatic activity of 19.8%. Methods: We performed ACADVL whole-gene sequencing. We then carried out an in silico analysis of the potential effects of the variants with dedicated tools, assessing splicing, RNA structure, RNA binding factors, and protein structure. We also conducted gene expression analysis. Results: Genetic testing identified her as compound heterozygous for the pathogenic ACADVL variant (NM_000018.3):c.848T>C, inherited from her mother, and for the two paternal variants, c.-64T>C in the basal promoter and c.957G>A, a synonymous substitution in exon 10. Gene expression analysis revealed reduced ACADVL mRNA levels in the proband’s blood cells but without abnormal isoform production. A decreased expression of the paternal allele carrying the 957A was also observed. Despite this significant reduction in mRNA levels, the underlying mechanism remains unclear. Conclusions: Although currently healthy, due to the VLCAD residual activity within the range associated with the mild form of the disease, the child might be at potential risk for metabolic decompensation or late-onset VLCADD. Our results indicated an allelic imbalance in mRNA expression and c.957G>A is identified as a hypomorphic allele. This suggests that deep ACADVL sequencing is a valuable tool for correlating genetic variants with enzymatic activity levels. Full article

The detection of elevated long-chain acylcarnitine levels, particularly C14:1 and the C14:1/C2 ratio, during neonatal screening may indicate very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), although similar findings can result from postnatal starvation. We investigated the relationship between false-positive results, postnatal weight loss, and subsequent growth. Additionally, we explored potential diagnostic markers of postnatal starvation. The following neonates from Oita Prefecture (April 2014–March 2024) were included in this study: patients identified as false-positive for VLCADD (n = 19), patients with VLCADD (n = 3), and children negative in mass screening who completed their 3-year-old health check-up (n = 30). The false-positive group exhibited significant weight loss at blood sampling for neonatal screening. An acylcarnitine analysis showed significant increases in various short- to long-chain fatty acids in the false-positive group, likely owing to enhanced fatty acid catabolism via β-oxidation. Elevation of a broad range of fatty acids and reduced amino acid levels seemed to be associated with significant weight loss at blood sampling. Full article

Background: The presence and concentration of lipids in serum of dairy cows have significant implications for both animal health and productivity and are potential biomarkers for several common diseases. However, information on serum lipid composition is rather fragmented, and lipid remodelling during the transition period is only partially understood. Methods: Using a combination of reversed-phase liquid chromatography-mass spectrometry (RP-LC-MS), hydrophilic interaction-mass spectrometry (HILIC-MS), and lipid annotation software, we performed a comprehensive identification and quantification of serum of dairy cows in pasture-based Holstein-Friesian cows. The lipid remodelling induced by negative energy balance was investigated by comparing the levels of all identified lipids between the fresh lactation (5–14 days in milk, DIM) and full lactation (65–80 DIM) stages. Results: We identified 535 lipid molecular species belonging to 19 classes. The most abundant lipid class was cholesteryl ester (CE), followed by phosphatidylcholine (PC), sphingomyelin (SM), and free fatty acid (FFA), whereas the least abundant lipids included phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylglycerol (PG), acylcarnitine (AcylCar), ceramide (Cer), glucosylceramide (GluCer), and lactosylceramide (LacCer). Conclusions: A remarkable increase in most lipids and a dramatic decrease in FFAs, AcylCar, and DHA-containing species were observed at the full lactation compared to fresh lactation stage. Several serum lipid biomarkers for detecting negative energy balance in cows were also identified. Full article

Burnout syndrome, which significantly impacts both individual and societal quality of life, is primarily characterized by three key criteria: depersonalization, emotional exhaustion, and low personal accomplishment, all linked to work-related stress. Purpose: Comparative evaluation of urine metabolite patterns that may discriminate the burnout levels and the effects of night shifts on healthcare professionals. The Maslach Burnout Inventory survey was administered to 64 physicians and nurses working day and night shifts, with scores for each criterion recorded. Methods: Urine samples were collected, and metabolomic patterns were analyzed using UHPLC-QTOF-ESI+-MS technology. This analysis employed both untargeted and semi-targeted metabolomics, coupled with multivariate and ANOVA statistics, utilizing the online Metaboanalyst 6.0 platform. Partial Least Squares Discriminant Analysis (PLSDA) was performed, along with VIP values, Random Forest graphs, and heatmaps based on 79 identified metabolites. These were further complemented by biomarker analysis (AUC ranking) and pathway analysis of metabolic networks. Results: The findings highlighted the biochemical effects of night shifts and their correlation with burnout scores from each dimension. Conclusions: This study demonstrated the involvement of three major metabolic pathways in diagnosing burnout: lipid metabolism, particularly related to steroid hormones (cortisol, cortisone, and androsterone metabolites); energetic metabolism, involving long-chain acylated carnitines as transporters of free fatty acids, which play a role in burnout control; and a third pathway affecting catecholamine metabolism (neurotransmitters derived from tyrosine, such as dopamine, adrenaline, and noradrenaline), as well as tryptophan metabolism (serotonin and melatonin metabolites) and amino acid metabolism (including aspartate, arginine, and valine). Full article

The present study aimed to investigate the effects of exogenous carnitine treatments on maize seed germination by stimulating lipid metabolism and regulating the mitochondrial respiratory pathway. Maize seeds were grown as control, 5, 7.5, and 10 μM carnitine treatment groups in a germination chamber at 25 °C under dark conditions for 5 d. It was determined that carnitine treatments increased the germination rate (GR), germination index (GI), germination potential (GP), vigor index (VI), root and hypocotyl length, fresh weight (FW), and content of total soluble protein but decreased the total carbohydrate content. It was also found that it increased the activities of α-amylase, isocitrate lyase (ICL), and malate synthase (MS) enzymes, which are critical in the germination process, and upregulated the expression of ICL and MS genes. To clarify the potential of carnitine treatments to promote the participation of lipids in respiration in roots and hypocotyls, lipase, carnitine acyltransferases (CATI and CATII), and citrate synthase (CS) enzyme activities were examined, and significant increases in these activities were detected. It was also found that gene levels of respiratory enzymes cytochrome oxidase (COX), pyruvate dehydrogenase (PDH), and Atp synthase, lipase, and CS proteins were upregulated by carnitine treatment. In support of the enzyme and gene change findings, significant changes were determined in fatty acid contents, free carnitine, and long-chain acylcarnitine levels in seeds, roots, and hypocotyls depending on carnitine application. In roots and hypocotyls, carnitine treatments significantly increased glutamine synthase (GS) and glutamate dehydrogenase (NADH-GDH) activities and gene expression levels, which are closely related to the tricarboxylic acid cycle (TCA). It was also noted that all proteins analyzed at the gene expression level were upregulated by carnitine applications in seeds. In addition, significant increases were recorded in antioxidant enzyme ascorbate peroxidase (APX) and superoxide dismutase (SOD) activities and total ascorbate (AsA) and glutathione (GSH) contents in roots and hypocotyls, while decreases were determined in guaiacol peroxidase (GPX) and catalase activities. Significant changes were recorded in all parameters examined, especially with 7.5 µM carnitine application. The findings suggest that carnitine may promote the transport of fatty acids to mitochondrial respiration by accelerating lipid catabolism in five-day-old maize and contribute to seed germination and growth and development processes by activating other metabolic pathways associated with respiration in this process. Full article

Background/Objectives: Millions of new diagnoses of breast cancer are made each year, with many cases having poor prognoses and limited treatment options, particularly for some subtypes such as triple-negative breast cancer. Resveratrol, a naturally occurring polyphenol, has demonstrated many anticancer properties in breast cancer studies. However, the mechanism of action of this compound remains elusive, although prior evidence suggests that this compound may work through altering cancer cell metabolism. Our objective for the current study was to perform untargeted metabolomics analysis on resveratrol-treated breast cancer cells to identify key metabolic targets of this compound. Methods: MCF-7 and MDA-MB-231 breast cancer cells were treated with varying doses of resveratrol and extracted for mass spectrometry-based untargeted metabolomics. Data preprocessing and filtering of metabolomics data from MCF-7 samples yielded 4751 peaks, with 312 peaks matched to an in-house standards library and 3459 peaks matched to public databases. Results: Pathway analysis in MetaboAnalyst identified significant (p < 0.05) metabolic pathways affected by resveratrol treatment, particularly those involving steroid, fatty acid, amino acid, and nucleotide metabolism. Evaluation of standard-matched peaks revealed acylcarnitines as a major target of resveratrol treatment, with long-chain acylcarnitines exhibiting a 2–5-fold increase in MCF-7 cells and a 5–13-fold increase in MDA-MB-231 cells when comparing the 100 µM treated cells to vehicle-treated cells (p < 0.05, VIP > 1). Notably, doses below 10 µM showed an opposite effect, possibly indicating a biphasic effect of resveratrol due to a switch from anti-oxidant to pro-oxidant effects as dose levels increase. Conclusions: These findings suggest that resveratrol induces mitochondrial metabolic reprogramming in breast cancer cells in a dose-dependent manner. The biphasic response indicates a potential optimal dosage for therapeutic effectiveness. Further research is warranted to explore the mechanisms underlying these metabolic alterations and their implications for precision nutrition strategies in cancer treatment. Full article

Very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is due to a defect in metabolism of long-chain fatty acids. Infants with VLCADD may experience cardiomyopathy, hypoglycemia, or even death; thus, early detection and intervention is crucial. The spectrum of disease and natural variation in newborn metabolism, however, lead to overlap in acylcarnitine values between affected and unaffected individuals, which contributes to the difficulty in identifying true positive cases while minimizing false positive cases. VLCADD was added to the state of Wisconsin’s newborn screening (NBS) panel in 2000. A previous retrospective review of VLCADD screen positive cases identified between 2000 and 2014 resulted in a change to the screening algorithm. Following implementation, a reduction in the percentage of false positive screens from 25.3% to 20.4% was observed between 2015 and 2021. The overall PPV also decreased, from 37.2% to 28%, due to an increase in the number of carriers identified (27.5% of cases in 2000–2014 and 51.8% of cases in 2015–2021). A data review also identified three long-chain acylcarnitine elevations (C14:1, C14:1/C16, and C14:1/C2) that had statistically significant differences in concentrations in true positive populations versus false positive populations. Utilization of the C14:1, C14:1/C16, and C14:1/C2 values in newborn screening may provide clearer distinction between true positive and carrier populations and additionally increase the PPV of this screen. Full article