Search Results (430)

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

Sudden cardiac death (SCD) is a major public health concern, being a leading cause of death worldwide. SCD is particularly alarming for individuals with apparently good health, as it often occurs without preceding warning signs. Unfortunately, traditional autopsy methods frequently fail to identify the precise cause of death in these cases, highlighting the need for advanced techniques to elucidate underlying mechanisms. Recent advances in molecular biology over the past few years, particularly in proteomics, transcriptomics, and metabolomics techniques, have led to an expanded understanding of gene expression, protein activity, and metabolic changes, offering valuable insights into fatal cardiac events. Combining multi-omics methods with bioinformatics and machine learning algorithms significantly enhances our ability to uncover the processes behind lethal cardiac dysfunctions by identifying new useful biomarkers (like cardiac myosin-binding protein C, acylcarnitines, or microRNAs) to reveal molecular pathways linked to SCD. This narrative review summarizes the role of multi-omics approaches in forensic diagnosis by exploring current applications in unexplained cases and the benefits of integrating merged techniques in otherwise negative autopsies. We also discuss the potential for developing personalized and preventive forensic medicine, the technical limitations of currently available methods, and the ethical considerations arising from these advancements. 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

Psychiatric disorders, particularly schizophrenia (SCZ), bipolar disorder (BD), and schizoaffective disorder (SAD), present significant diagnostic challenges. Current diagnostic methods rely on clinical observation and self-reported symptoms, leading to under-diagnosis and delayed treatment. To address this gap, we applied mass spectrometry-based metabolomic profiling and targeted analysis of inflammatory proteins to plasma samples from patients versus controls, aiming to uncover disease-related molecular patterns and enhance our understanding of the underlying pathophysiology of these complex disorders. This study included 26 patients with BD, 34 with SCZ, 16 with SAD, and age- and sex-matched controls. All diagnoses were established according to DSM-5 criteria. Unsupervised analysis shows a clear separation between controls and patients, indicating distinct metabolic and inflammatory profiles. However, the lack of clear differentiation among the three disease subgroups suggests shared biological profiles across these psychiatric disorders. Biomolecules driving this separation between controls and patients includes decreased levels of proinflammatory cytokines, amino acids, and glycerophospholipids, and increased levels of acylcarnitines. This study represents a step towards addressing the limitations of current diagnostic approaches to severe psychiatric disorders, which rely heavily on clinical symptoms, by using omics approaches to refine their diagnosis and treatment. 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

Bipolar disorder (BD) and schizophrenia (SCH) are results of the complex interactions between genetic and environmental factors, and the underlying pathophysiology is not yet completely understood. The current diagnostic criteria for psychiatric diagnosis are based purely on clinical phenomenology and they are limited to psychiatrist judgment after a standardized clinical interview, with no precise biomarkers used to discriminate between the disorders. Besides gaps in the understanding and diagnosis of these diseases, there is also a need for personalized and precise approaches to patients through customized medical treatment and reliable monitoring of treatment response. To fulfill existing gaps, the establishment of disorder biomarker sets is a necessary step. LC-MS lipidomic blood sample analysis is one of the ongoing omics approaches. In the last ten years, several studies have identified alterations in lipid metabolism associated with BD and SCH, and this review summarizes current knowledge on their lipidomic patterns, which is essential for identifying lipid biomarkers. Currently, findings indicate decreases in plasmalogens and acyl-carnitines, along with increases in certain triacylglycerol species, shared by both conditions. In contrast, serum LC-MS lipidomic profiles of sphingolipids including ceramides could be unique to BD, indicating the need for further investigation in future studies. Full article

Background: Endometrial cancer is among the most prevalent gynecological malignancies, with increasing mortality primarily due to initially advanced disease with lymph node metastasis or tumor recurrence. Current risk stratification models show limited accuracy, highlighting the need for more accurate biomarkers. This study aimed to identify metabolic compounds that can serve as predictors of recurrence risk and lymph node status in endometrial cancer. Methods: Targeted metabolomic profiling of preoperative serum samples from 123 patients with endometrial cancer, stratified into high- or low-risk and lymph node-positive or -negative groups, was conducted using the AbsoluteIDQ p180 Kit and high-performance liquid chromatography–mass spectrometry. Results: Analysis revealed significant differences in metabolites related to lipid and amino acid metabolism between groups. High-risk and lymph node-positive patients presented significantly lower concentrations of phosphatidylcholines, lysophosphatidylcholines, medium-chain acylcarnitines, and specific amino acids such as alanine, histidine, and tryptophan compared to low-risk and lymph node-negative patients. Receiver operating characteristic curve analyses highlighted the diagnostic potential of these metabolites, particularly alanine and taurine, in distinguishing patient groups. Conclusions: The findings indicate complex metabolic reprogramming associated with aggressive endometrial cancer phenotypes, involving enhanced lipid utilization and amino acid metabolism alterations, potentially supporting tumor proliferation and metastatic progression. Thus, targeted metabolomic serum profiling might be a powerful tool for improving risk assessment, enabling more personalized therapeutic approaches and management strategies in endometrial cancer. Full article

Background/Objectives: Insomnia has been widely associated with cognitive impairment (CI). However, the relationship between the two entities (insomnia and CI) is poorly understood. In this context, adults with insomnia show metabolic changes, including alterations in the catabolism of branched-chain amino acids, glycerophospholipids, and glutathione and glutamate biosynthesis. Nevertheless, aging itself induces metabolic changes that may be amplified by chronic diseases that compromise the health of the elderly. Therefore, in the present study we aim to characterise metabolomic profiles of insomnia and CI alone in order to address a significant gap in current research regarding the pathways through which insomnia may lead to CI in older persons. Methods: In this study we perform a targeted metabolomics analysis (UPLC-MS) on 80 serum samples from the Cohort of Obesity, Sarcopenia, and Frailty of Older Mexican Adults (COSFOMA); these samples were classified into four groups (control, insomnia, CI, and insomnia + CI). Results: Our results show that insomnia increases the concentration of acylcarnitines (C10, C8, C14, C12:1, C18:1 and C18) as compared to CI group, while older persons with CI show a decrease the concentration of the acylcarnitines C16, C10 and C8. Finally, individuals with both conditions (insomnia + CI) show that only the concentration of the acylcarnitine C16 decreases compared to controls. Conclusions: Taken together, our results shed light on the relevance of insomnia on lipid metabolism in older persons. Full article

Background: Newborns are referred primary carnitine deficiency (PCD) when a low free carnitine (C0) concentration (<10 μmol/L) is detected, leading to high false-positive referrals. To improve the follow-up protocol for PCD, various acylcarnitines and the summations were comprehensively evaluated in the present study. Methods: A retrospective study was performed using samples due to low C0 concentration. Data were available for 72 patients with genetically confirmed PCD, whereafter C0 with the selected sum of (butyrylcarnitine (C4) + isovalerylcarnitine (C5)) was validated in an additional cohort study including about 80,000 samples. Results: In the discovery study, C4, acetylcarnitine (C2) and C5 exhibited significant discriminant power in distinguishing PCDs from NoPCDs. The area under the ROC curve (AUC) was 99.792% (C4), 98.715% (C2) and 98.620% (C5). The excellent performances in sensitivity, specificity, negative predictive value, positive predictive value (PPV) and accuracy indexes suggested that C4, C2 and C5 would be ideal auxiliary indicators in improving the diagnostic performance of C0 for PCD. Multivariate ROC curve-based exploratory analysis showed that C5, C4 and C2 were the most top-ranked features in differentiating PCDs from NoPCDs. AUC for C4 + C5 was the highest with a cutoff required for 100% sensitivity at 0.181 μmol/L. In the validation cohort, adding C4 + C5 in the NBS program could elevate PPV from 0.75% to 1.54%. Conclusions: Our work revealed that C4 + C5 summation should be used as the auxiliary quantization indicator to reduce false-positive results for PCD. Full article

Background: Food allergy (FA) is associated with dietary habits, antibiotic use, living environment, and delivery method. Pregnancy and lactation represent critical periods for neonatal immune system development. Methods: This study investigated the relationship between maternal dietary habits and FA risk in offspring. Pregnant C57BL/6J mice (8-week-old males and females) were fed either a high-fat diet (HFD) or HFD supplemented with fermented apple juice (FAJ) during pregnancy and lactation. Offspring were nursed by their respective dams until weaning at 21 days postpartum, followed by ovalbumin (OVA) sensitization. Lipid profiles, acylcarnitines, immunological, and histopathological analyses were performed. Gut microbiota composition and serum markers were also assessed. Results: The findings indicated that maternal HFD had a negative impact on OVA-sensitized offspring mice. Early-life FAJ intervention modulated gut microbiota alterations and alleviated maternal HFD-worsened allergic symptoms through Th1/Th2 and Th17/Treg immunity balance and intestinal barrier repair. Maternal serum triglyceride and total cholesterol levels, along with gut microbiota profiles, significantly influenced offspring gut microbiota composition. Moreover, reduced short-chain and medium-chain acylcarnitines in offspring may be associated with increased allergy risk. Conclusions: Maternal HFD during pregnancy and lactation disrupted gut microbiota balance and exacerbated offspring FA susceptibility. These findings provide a scientific foundation for developing early-life FA prevention strategies. 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

Background/Objectives: Hexaraphane, also known as 6-methylsulfinylhexyl isothiocyanate, derived from wasabi (Eutrema japonicum), increases heme oxygenase-1 (HO-1) and aldehyde dehydrogenase 2 (ALDH2) mRNA expression by activating nuclear factor erythroid 2-related factor 2 (Nrf2) in both HepG2 cells and the mouse liver. Given the presence of a peroxisome proliferator-activated receptor (PPAR) response element (PPRE) in the HO-1 and ALDH2 promoters, the present study aimed to determine the effects of hexaraphane on PPARα-associated genes, age-related weight gain, plasma triglyceride levels, and hepatic senescence. Methods: HepG2 cells were treated with hexaraphane to evaluate PPARα target gene expression and PPRE transcriptional activity. Male C57BL/6J young control, aged control, and aged mice administered with hexaraphane for 16 weeks were assessed for food and water intake, body and tissue weights, plasma parameters, and hepatic PPARα-related gene expression. Results: Hexaraphane increased HO-1 mRNA expression levels in HepG2 cells, which was inhibited by GW6471, a PPARα antagonist. It elevated PPRE transcriptional activity and increased carnitine palmitoyltransferase 1A (CPT1A) mRNA expression levels, indicating PPARα activation. In aged mice, hexaraphane intake reduced body weight gain by decreasing the adipose tissue weight. Increased CPT1A expression levels and a tendency toward increased acyl-CoA oxidase 1 (ACOX1) expression levels in the liver of aged mice administered hexaraphane were associated with reduced plasma triglyceride levels and body weight gain. Increased hepatic Sirt1 expression levels in aged mice administered hexaraphane was associated with lower plasma triglyceride levels. Increased hepatic PPARα mRNA expression levels in aged mice administered hexaraphane suggest a positive feedback loop between PPARα and Sirt1. The expression levels of hepatic p21 mRNA, a senescence marker regulated by Sirt1, were upregulated in aged mice but suppressed by hexaraphane intake. Conclusions: Hexaraphane may prevent age-related body weight gain, elevated plasma triglyceride levels, and hepatic senescence by activating PPARα, potentially contributing to longevity. Full article