Search Results (1,278)

Galacto-oligosaccharides (GOSs) are well-recognized for their beneficial effects on intestinal health, yet their regulatory impacts on the metabolic dynamics of other intestinal metabolites remain elusive. In this study, 24 male C57BL/6 mice were assigned to three groups: control (CON), low-dose GOS (L-GOS; 500 mg/kg body weight), and high-dose GOS (H-GOS; 800 mg/kg body weight). Following a 4-week intervention, the cecal contents were analyzed to characterize the bacterial community structure and metabolic profiles. Results indicated that GOS supplementation significantly increased the ACE and Chao1 indices of cecal bacteria. Specifically, L-GOS led to notable enrichment of the [Eubacterium] brachy group, Coriobacteriaceae UCG-002, Faecalimonas, and the [Eubacterium] siraeum group, whereas H-GOS significantly increased the abundance of Clostridium, Ruminiclostridium, Thomasclavelia, Adlercreutzia, and Faecalimonas. Metabolomic profiling revealed that L-GOS profoundly reduced levels of phosphatidylethanolamine, phosphatidylcholine and their downstream metabolites, while inhibiting the conversion of sphingolipids to ceramides. The changes in phospholipid derivatives imply enhanced intestinal epithelial integrity, supporting intestinal homeostasis. GOS intervention also decreased phenylacetic acid content. L-GOS increased the 4-hydroxyphenylpyruvic acid content, whereas H-GOS reduced 4-hydroxyphenyllactic acid levels. Notably, H-GOS significantly up-regulated the production of indole-3-acetic acid, a tryptophan-derived microbial metabolite with multiple biological activities. Collectively, these findings provide insights and potential targets for future research on GOS application in intestinal health interventions. Full article

Mitochondrial dysfunction profoundly alters cellular metabolism, yet its systems-level consequences remain incompletely characterized. Here, we present a comprehensive untargeted metabolomics analysis of respiratory-deficient (ρ⁰) and competent (ρ⁺) Saccharomyces cerevisiae prototrophic cells using ultra-high-performance liquid chromatography coupled to Orbitrap Fusion™ Tribrid™ high-resolution mass spectrometry. By integrating hydrophilic interaction and reversed-phase chromatography in both ionization modes, we detected ~7000 features per chromatographic condition, of which ~12% were structurally annotated through MSⁿ fragmentation and in silico spectral matching. Principal component analysis revealed distinct metabolic signatures between ρ⁰ and ρ⁺ cells, with ~73% of total variance explained by the first two components. Volcano plot and hierarchical clustering analyses identified a marked accumulation of phosphate-containing metabolites, sphingolipids, ceramides, and fatty acid residues in ρ⁰ cells, whereas amino acids, excluding arginine, cysteine, and aromatics, were enriched in ρ⁺ cells. Notably, branched-chain amino acid depletion in ρ⁰ cells correlated with impaired growth and mitochondrial stress. Pathway enrichment analysis, supported by transcriptomic integration, prompted us to further investigate reprogramming of polyamine biosynthesis and aromatic amino acid metabolism. Calibration curves constructed from certified standards validated the accuracy of the LC–MS platform and reinforced annotation confidence. Our findings demonstrate that advanced untargeted metabolomics, coupled with MS³ fragmentation and multi-omics integration, enables high-resolution mapping of metabolic reconfiguration under mitochondrial dysfunction, offering mechanistic insights into mitochondrial retrograde signaling and adaptation. Full article

Broccoli (Brassica oleracea L. var. italica) is prone to rapid yellowing when stored at ambient temperature after harvest due to membrane damage. Here, freshly harvested broccoli florets were stored in a static magnetic field (5 mT) at 20 °C. The current results demonstrated that a static magnetic field lowered postharvest yellowing (chlorophyll breakdown), water loss, and oxidative stress. An integrated transcriptome and metabolome analysis suggested that static magnetic field-mediated alleviation of postharvest yellowing and senescence of broccoli florets involved the following factors: (1) downregulating the expression of genes related to organ senescence; (2) delaying the breakdown of chlorophylls through preventing the upregulation of chlorophyll degradation-related genes and the increase in oxidative stress; (3) alleviating cellular energy imbalance by upregulated fatty acid oxidation (as indicated by decreased free fatty acids) to reduce water loss and oxidative stress and to maintain membrane integrity; (4) increasing the abundances of lysophospholipids and sphingolipids and preventing the decrease in phosphatidylcholine abundance to lower water loss and oxidative stress, inhibit ethylene production, delay chlorophyll degradation, and keep membrane integrity; (5) reducing water loss via increasing cutin, suberin, and wax biosynthesis and stomatal closure brought about by upregulated expression of phospholipase D genes; and (6) preventing the increase in malondialdehyde (MDA) content, electrolyte leakage, and weight loss rate. To conclude, this work provided some novel data elucidating the underlying mechanism by which a static magnetic field delayed postharvest yellowing and senescence of broccoli florets. A static magnetic field could retard postharvest deterioration of broccoli florets, thereby providing a clean and non-thermal method for their green preservation. Full article

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is characterized by dysregulated apoptosis and metabolic reprogramming, including alterations in lipid metabolism. However, the plasma lipidome of newly diagnosed, treatment-naïve CLL patients remains insufficiently characterized. This study aimed to define disease-specific plasma lipidomic alterations, identify discriminatory lipid species, and investigate associated metabolic pathways. Methods: The study cohort consisted of 41 participants (median age 75 years, range: 40–86), including 30 newly diagnosed, treatment-naïve CLL patients (median age 75 years, range: 40–86) and 11 age- and sex-matched healthy controls (median age 75 years, range: 41–85). Targeted lipidomic profiling was performed on plasma samples using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Data processing was conducted in R using LipidSigR. Statistical analyses employed the Wilcoxon–Mann–Whitney test with Benjamini–Hochberg correction. To address data dimensionality, Boruta machine learning and pathway enrichment analyses were applied. Gene–lipid associations were further explored using GATOm, followed by Metascape analysis to identify enriched biological processes. Results: A total of 124 lipid species from five major classes (phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, ether-linked phosphatidylcholines, and acylcarnitines) were quantified. CLL patients exhibited significant enrichment of acylcarnitines, saturated phosphatidylcholines, and sphingolipids compared with controls. Principal component analysis showed partial separation by disease status. Machine learning identified carnitines and ether-linked phospholipids as key discriminators. Integrated gene–lipid analyses revealed significant enrichment of lipid metabolism-related pathways, particularly glycerolipid and phosphatidylcholine metabolism, as well as lipid catabolism, ether lipid metabolism, and fatty acid metabolism. Conclusions: Treatment-naïve CLL patients display distinct plasma lipidomic signatures indicative of disease-specific metabolic reprogramming. Integrated lipidomic and predictive pathway analyses suggest disruptions in lipid metabolic pathways and highlight carnitines and ether-linked phospholipids as biological markers warranting further investigation as potential CLL biomarkers. Full article

Influenza is a persistent public health concern worldwide. The elucidation of influenza A virus (IAV)–host interactions and the identification of host factors that regulate IAV infection would be beneficial for combating and treating the disease. Ceramides, comprising a host sphingolipid family, have been shown to regulate virus infections. However, the effect of IAV on individual ceramides remains unknown. This study aimed to investigate the changes in ceramide species during the infection of human lung epithelial A549 cells and human primary tracheal epithelial cells with IAV. We established a method utilizing UHPLC-MS analysis to measure individual ceramides (C14- to C26-ceramide). The results indicate that two main ceramide species, C16- and C24-ceramide, constitute approximately 80% of the ceramide population in human respiratory epithelial cells. Following IAV infection, these ceramides were found to undergo a shift in abundance, with a reduction in C16-ceramide and an increase in C24-ceramide, under various infection conditions. Primarily, IAV infection led to an increase in multiple long-chain ceramides. These findings could provide details for understanding how the ceramide system is disrupted during influenza virus infection and to further support the ongoing efforts to understand influenza–host interactions. Full article

Sphingolipids (SL) are essential structural and bioactive components of cell membranes, remarkably involved in inflammatory signaling and membrane dynamics. Dysregulation of SL metabolism contributes to pathological inflammation and cellular stress. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (FXT), are known inhibitors of acid sphingomyelinase (aSMase), although their impact on macrophage SL remodeling and inflammatory responses remains unclear. Here, we investigated the modulation of FXT on SL species composition and inflammatory activation in THP-1-derived macrophages stimulated with inactivated SARS-CoV-2 particles, which is a model of viral-induced inflammation. Sphingolipidomic profiling revealed that FXT pre-treatment markedly reduced ceramide (Cer) species while increasing sphingomyelin (SM) and sphingosine-1-phosphate (S1P) levels, consistent with inhibition of the aSMase-Cer axis. These changes were accompanied by attenuation of proinflammatory components, including interleucin (IL)-6, IL-1β, and matrix metalloproteinase (MMP)-9, indicating that SL remodeling correlates with reduced macrophage activation. Despite pronounced alterations in membrane lipid composition, the quantification of extracellular vesicles (EVs) released by FXT-treated macrophages remained unchanged, however the EVs size distribution was smaller compared to non-treated cells. Altogether, our findings demonstrate that FXT reshapes SL metabolism and lipid membrane composition, thereby diminishing macrophage activation without affecting EVs biogenesis. This study emphasizes the immunometabolic role of SL on membrane reprogramming as a mechanism by which pharmacological aSMase inhibition modulates viral inflammation responses. Full article

In addition to binding to and regulating over 400 different proteins, calmodulin (CaM) also binds to lipids. Binding occurs to the prenylated tails of various small GTPases, to specific lipids in biological membranes and to free lipids in the cytoplasm. Here, CaM binding to Rac1, RalA, and KRAS4b is covered, emphasizing its importance in protein translocation from the cell membrane to the cytosol and its resultant impact on cell signaling. Binding phosphatidylserine and phosphatidylethanolamine in membranes not only leads to the tethering of CaM, but also to the disruption of lipid bilayers. Binding to sphingolipids also occurs, an event that acts as a competitive inhibitor of CaM function. The mechanism through which CaM binds to lipids is also examined. In total, the current state of affairs regarding calcium-dependent CaM–lipid binding is reviewed, including potential therapeutic uses, setting the stage for future work on this important biological event. Full article

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide, yet only a fraction of smokers develops the disease, suggesting protective mechanisms in resilient individuals. Identifying airway-localized molecular signatures may improve our understanding of disease pathomechanisms and support hypothesis generation for biomarker research. In this pilot study, induced sputum from smokers with COPD (n = 28) and smokers without COPD (n = 16; Global Initiative for Chronic Obstructive Lung Disease (GOLD)-defined pre-COPD) was analyzed by untargeted proteomics, metabolomics, and lipidomics. After quality control, 1180 proteins, 187 metabolites, and 1234 lipids were retained. Analyses included univariate models with false discovery rate adjustment and multivariate analyses (PCA, PLS-DA), followed by pathway enrichment and protein interaction network analysis. While few features remained significant after FDR correction, consistent cross-omics patterns were observed. COPD was characterized by ↑ glutathione, creatine, and L-arginine; ↓ CCDC88A and ↑ STAT3 and SYDE2; and broad lipid remodeling involving phosphatidylcholines, sphingolipids, and eicosanoids. Network analysis highlighted STAT3 as a highly connected node linking COPD-related genes. These findings suggest that the multi-omic profiling of induced sputum can capture coherent airway-localized molecular signatures such as oxidative stress, cytoskeletal remodeling, and Rho-family GTPase signaling. However, the results should be interpreted as exploratory and require validation in functional studies. Full article

Hot air drying is widely used in edible mushroom processing, but often leads to quality changes, including browning and flavor changes. This study focused on Phallus impudicus (P. impudicus), combining dynamic monitoring of browning-related indicators with lipidomics technology to systematically investigate the mechanism by which lipid changes influence quality during hot air drying. The results showed that drying significantly altered lipid metabolism. Encompassing 28 subclasses, five major lipid categories were identified: glycerophospholipids (GP), glycolipids (GL), sphingolipids (SP), isoprenylglycolipids (PR), and fatty acids (FA). From among these, the total content of GP remained the highest and increased significantly after drying, whereas the contents of GL and FA decreased markedly. Hydrolysis of structural lipids led to the collapse of cellular structure, and the levels of hydrolyzed lipids phosphatidic acid (PA), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and lysophosphatidic acid (LPA) increased significantly after drying, which may adversely affect long-term storage. Furthermore, increased lipid unsaturation intensified browning, and lipid oxidation also promoted the formation of volatile flavor compounds. Overall, this lipidomic research demonstrated that hot air drying determines the final quality and flavor profile of dried P. impudicus through coordinated mechanisms involving membrane lipid oxidation, structural membrane damage, browning, and flavor generation. These findings provided a new insight into the mechanism of quality changes and a theoretical basis for quality improvement and process regulation for dried edible mushroom products. Full article

Probiotics are widely consumed as health-promoting agents, with probiotic supplements (PS) and yogurt (YG) representing formulated products and fermented foods, respectively. Despite their broad consumption, systematic comparisons of their biochemical characteristics remain limited. In this study, integrated untargeted and targeted metabolomics approaches were applied to compare the comprehensive metabolite profiles of PS and YG. PS exhibited relatively higher levels of amino acids, dicarboxylic acids, and lysophospholipids, along with short-chain fatty acids such as acetate and propionate, and amino acid-derived bioactive metabolites, including γ-aminobutyric acid, branched-chain hydroxy acids, indole derivatives, and γ-glutamylpeptides. In contrast, YG showed higher relative abundances of carbohydrates, acylcarnitines, sphingolipids, and bioactive metabolites such as butyrate, creatine, carnitine, and orotic acid. Based on these metabolomic differences, 27 PS-specific and 17 YG-specific marker metabolites were identified. To explore their functional relevance, in vitro antioxidant and antiglycation activities were evaluated. PS exhibited significantly higher antioxidant and antiglycation activities than YG, which were positively correlated with amino acids and indole derivatives. Indole-3-acrylic acid, indole-3-acetic acid, and indole-3-propionic acid showed antiglycation activity and were identified as PS-specific bioactive marker metabolites. These findings reveal the distinct biochemical characteristics of PS and YG and highlight potential bioactive candidate metabolites that may contribute to their functional differences. Full article

Vibrio alginolyticus is an important antibiotic-resistant pathogen in aquaculture that can cause mortality in a wide range of aquatic animals and infect humans. It is urgently necessary to discover and develop effective antibiotic alternatives. Citral, a key antibacterial component of lemongrass oil, can be used as a food flavoring and additive. Although the antimicrobial activity and antibiofilm effect of citral against V. alginolyticus have been noted in our previous study, the potential lipidome influence of citral remains unclear. Accordingly, a non-targeted lipidomics approach was employed to investigate citral-induced lipidome disturbances and reveal potential regulated targets of citral against V. alginolyticus. We found that the citral exposure triggered substantial lipidome alterations (i.e., composition, contents, and structure) in V. alginolyticus. Specifically, the content of most phospholipids (e.g., phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidylserines (PSs), phosphatidylinositols (PIs), and phosphatidylglycerols (PGs)) decreased with the increase in citral concentration, while ceramides (Cers) and lysophospholipids (LPLs) (e.g., lyso-PAs, lyso-PCs, lyso-PEs, and lyso-PGs) showed concentration-dependent accumulation under citral treatment. Notably, the critical lipid remodeling in response to citral exposure mainly involved the phospholipid and sphingolipid metabolic pathways. Collectively, our study reveals the bacterial lipidome response to citral exposure and highlights pivotal metabolic pathways, potentially offering a novel perspective for future investigations into lipid-centric antibacterial targets. Full article

Mechanosensitive ion channels (MSCs) are fundamental transducers that convert mechanical forces into electrochemical signals, enabling cells to regulate processes such as Ca²⁺ homeostasis, migration, proliferation, and adhesion. Located in both plasma and organellar membranes, MSCs, including Piezos, TRPs, K2Ps, MscL, and MscS families exhibit diverse ion selectivity, gating mechanisms and physiological roles. Emerging evidence demonstrates that lipids are dynamic regulators of MSC activation, sensitivity, and kinetics. Endogenous membrane lipids such as cholesterol, phospholipids, sphingolipids and fatty acids modulate MSC behavior by altering bilayer tension, curvature, stiffness and protein–lipid interactions. Exogenous lipids, including dietary fatty acids and lipid-derived metabolites, influence MSCs by modifying membrane physical properties or engaging specific lipid-binding sites on channel proteins. These interactions shape fundamental biological processes and contribute to disease mechanisms in cardiovascular dysfunction, neurological disorders, metabolic disease, and cancer. Despite significant progress, the molecular principles by which lipids regulate MSC conformational transitions and force sensing remain incompletely defined. This review synthesizes current knowledge on endogenous and exogenous lipid modulation of MSCs, integrating structural, computational and electrophysiological insights to highlight emerging therapeutic opportunities targeting lipid–mechanotransduction interfaces. Full article

Aromatase inhibitors (AIs) are the standard adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer; however, their effects on lipid metabolism remain incompletely characterized. In this study, we investigated AI-associated alterations in the plasma lipidome using mass spectrometry-based lipidomics. Plasma samples were collected from 30 patients prior to AI initiation and 29 patients receiving non-steroidal AI therapy for at least 24 months. Ultra-high-performance liquid chromatography–tandem mass spectrometry identified and relatively quantified 649 lipid species across 23 lipid classes and subclasses. Lipidomic analysis revealed significant differences in specific lipid species. Several phosphatidylcholine, sphingomyelin, and lysophosphatidylethanolamine species were significantly more abundant in patient plasma prior to AI therapy, whereas higher levels of selected ceramides, hexosylceramides, phosphatidylinositol (PI 16:0_16:0), and a polyunsaturated diacylglycerol species were observed in patients receiving AI therapy. Multivariate analyses revealed patient group separation, and a Naive Bayes classification model based on lipid-class levels achieved an area under the curve of 0.79. Additionally, lipid network and hierarchical clustering analyses identified systematic lipid-class trends. Protein–protein interaction network analysis based on lipidomic profiles highlighted enzymes associated with sphingolipid metabolism pathways. These findings demonstrate that long-term AI therapy is associated with specific alterations in the plasma lipidome, consistent with estrogen-deprivation-related metabolic differences. Targeted lipidomic profiling may provide mechanistic insights into therapy-associated metabolic effects and support future efforts to optimize long-term management of breast cancer survivors. Full article

Background/Objectives: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants that accumulate in humans through everyday exposure pathways, raising concern about long-term metabolic health effects in exposed populations. This study aimed to characterize PFAS-associated serum metabolic alterations in a Flemish population residing within a 3 km radius of a PFAS production facility using untargeted metabolomics and lipidomics. Methods: A cohort of 82 adults was stratified into high-exposure (n = 41, median total PFAS = 162.0 ng/mL) and low-exposure (n = 41, median total PFAS = 7.2 ng/mL) groups. Serum metabolic profiling was performed using four liquid chromatography–high-resolution mass spectrometry (LC-HRMS)-based platforms. Univariate and multivariate statistics were conducted to identify metabolites that were differentially expressed between both exposure groups. Results: The analysis revealed 38 altered metabolites. Overall, high PFAS exposure was characterized by upregulation of phosphatidylglycerols (PG), phosphatidylinositols, phosphatidylethanolamines (PE), and triacylglycerols (TG) and downregulation of sphingomyelins, with differential regulation of ceramides, hexosylceramides (HexCer), and phosphatidylcholines. Glycerophospholipid metabolism as well as sphingolipid metabolism pathways were identified as perturbed. Seven lipids and one amino acid showed weak-to-strong correlations (|r|= 0.23–0.61) with PFAS levels. A panel of five metabolites was selected to explore whether they collectively form a potential metabolic signature associated with PFAS exposure. This panel, including L-aspartic acid, PG 18:0_18:2, HexCer (d18:1/14:0), PE 16:0_18:3, and TG 16:0_20:5_22:6, showed moderate discrimination between residents with high and low PFAS levels (area under the curve, AUC = 0.753). Conclusions: This study identifies coordinated lipid metabolic changes associated with PFAS exposure and highlights a small, exploratory metabolite panel that may provide complementary insight into the biological effects of PFAS. Full article

Mutations in leucine-rich repeat kinase 2 (LRRK2) are among the most common genetic causes of Parkinson’s disease (PD), yet substantial heterogeneity exists among pathogenic variants. How mutations in distinct functional domains of LRRK2 differentially perturb cellular homeostasis remains incompletely understood. Here, we compared two pathogenic LRRK2 mutations—G2019S in the kinase domain and I1371V in the GTPase domain—across multiple cellular models, including SH-SY5Y and U87 cells, and healthy human iPSC-derived floor plate cells. We demonstrate that the I1371V mutation induces markedly more severe cellular dysfunction than G2019S. I1371V-expressing cells exhibited elevated LRRK2 autophosphorylation at S1292 and robust hyperphosphorylation of Rab8A and Rab10, indicating enhanced downstream signaling. These alterations impaired sterol trafficking, leading to selective depletion of membrane cholesterol without changes in total cellular cholesterol. Consequently, I1371V cells displayed increased membrane fluidity, disrupted microdomain organization, altered membrane topology, reduced caveolin-1 expression, and impaired dopamine transporter surface expression and dopamine uptake. Lipidomic profiling further revealed a broad disruption of lipid homeostasis, including reductions in cholesteryl esters, sterols, sphingolipids, and glycerophospholipids, whereas G2019S cells showed comparatively modest changes. Pharmacological intervention revealed mutation-specific responses, with the non-selective LRRK2 modulator GW5074 outperforming the kinase-selective inhibitor MLi-2 in restoring Rab8A phosphorylation, membrane integrity, and dopaminergic function. Collectively, these findings identify membrane lipid dysregulation as a central cell biological mechanism in LRRK2-associated PD and underscore the importance of variant-specific therapeutic strategies. Full article