Search Results (30)

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: Insulin resistance is a key driver of metabolic syndrome and related disorders, yet its underlying metabolic alterations remain incompletely understood. The Triglyceride–Glucose (TyG) index is an emerging, accessible marker for insulin resistance, with growing evidence supporting its clinical utility. This study aimed to characterize the metabolic profiles associated with insulin resistance using the TyG index in a large, population-based cohort, and to identify metabolic pathways potentially implicated in insulin resistance. Methods: Here, we conducted a cross-sectional study using data from the Qatar Biobank, including 1255 participants without diabetes classified as insulin-sensitive or insulin-resistant based on TyG index tertiles. Untargeted serum metabolomics profiling was performed using high-resolution mass spectrometry. Our statistical analyses included orthogonal partial least squares discriminate analysis and linear models. Results: Distinct metabolic signatures differentiated insulin-resistant from insulin-sensitive participants. Phosphatidylethanolamines, phosphatidylinositols, and phosphatidylcholines, were strongly associated with insulin resistance, while plasmalogens and sphingomyelins were consistently linked to insulin sensitivity. Conclusions: Lipid-centric pathways emerge as potential biomarkers and therapeutic targets for the early detection and personalized management of insulin resistance and related metabolic disorders. Longitudinal studies are warranted to validate causal relationships. Full article

Background: Plasmalogens (Pls) are phospholipids with a unique structure, abundant in the brain and heart. Due to their chemical instability and analytical difficulties, less information is available compared to other phospholipids. The importance of Pls in several cellular processes is known, one of which is their protective effect against oxidative damage. The physiological role of Pls in human development has not been elucidated. Despite their clinical importance, the quantitative analysis of Pls in children’s plasma has been limited. Methods: This study aims to determine the plasma levels of Pls in prepubertal children using liquid chromatography/tandem mass spectrometry (LC-MS/MS). The plasma samples used were obtained from 9- to 12-year-old girls (n = 156) and boys (n = 178), n = 334 in total, who participated in the Hokkaido study. Results: Ethanolamine plasmalogen (PlsEtn) and choline plasmalogen (PlsCho), both carrying eicosapentaenoic acid, were significantly lower in girls than in boys. In both sexes, the plasmalogen levels for the 12-year-old children were lower than those for the 9-year-old children. PlsCho (16:0/18:2) was lower in the overweight children than in the normal-weight children for both sexes. PlsEtn (18:0/20:4) was the most abundant ethanolamine-type plasmalogen in both sexes. Conclusions: This study is the first report on plasmalogen levels and molecular types in children’s plasma. This study provides the information needed to understand the role of Pls in human developmental processes and may open up new opportunities in the future to control age-related changes in Pls. Full article

Peripheral blood mononuclear cells (PBMCs), including lymphocytes, are important components of the human immune system. These cells contain a diverse array of lipids, primarily glycerophospholipids (GPs) and sphingolipids (SPs), which play essential roles in cellular structure, signaling, and programmed cell death. This study presents a detailed analysis of GP and SP profiles in human PBMC samples using tandem mass spectrometry (MS/MS). Hydrophilic interaction liquid chromatography (HILIC) and electrospray ionization (ESI) coupled with linear ion-trap MS/MS were employed to investigate the diagnostic fragmentation patterns that aided in determining regiochemistry in complex lipid extracts. Specifically, the study explored the fragmentation patterns of various lipid species, including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), their plasmalogen and lyso forms, phosphatidylserines (PSs), phosphatidylinositols (PIs), phosphatidylglycerols (PGs), sphingomyelins (SMs), and dihexosylceramides (Hex₂Cer). Our comprehensive analysis led to the characterization of over 200 distinct lipid species, significantly expanding our understanding of PBMC lipidome complexity. A freely available spreadsheet tool for simulating MS/MS spectra of GPs is provided, enhancing the accessibility and reproducibility of this research. This study advances our knowledge of PBMC lipidomes and establishes a robust analytical framework for future investigations in lipidomics. Full article

Background and aims: Mastitis is one of the main complications during breastfeeding and contributes to the cessation of breastfeeding. However, the etiopathogenesis and diagnosis of mastitis are complex and not yet well defined. We aimed to identify metabolic and lipidic changes in human milk during acute and subacute mastitis in order to detect potential biomarkers of mastitis. Methods: We conducted a pilot case–control study including 14 breastfeeding women with acute mastitis, 32 with subacute mastitis symptoms, and 19 without any mastitis symptoms (control). Milk samples were collected and analyzed by proton nuclear magnetic resonance (H-NMR) for metabolomics analysis. To assess the association between the significant metabolites and lipids and the development of acute and subacute mastitis, multi-adjusted logistic regression models were developed. Results: The NMR-based metabolomics approach was able to identify and quantify a total of 40 metabolites in breast milk samples. After adjusting for confounding variables, acute mastitis was significantly associated with acetate (OR 3.9 IC 1.4–10.8), total cholesterol (OR 14 CI 3.2–62), esterified cholesterol (OR 3.3 CI 1.9–5.8), and sphingomyelin (OR 2.6 CI 1.2–5.8). The other metabolites presented weak association (OR < 2.5). Subacute mastitis was significantly associated with glutamine, lysophosphatidylcholine, phosphatidylcholine, plasmalogen, and total polyunsaturated fatty acids, but only cholesterol showed a strong association (OR > 2.5) with an OR of 2.6 (IC 1.1–6.6). Conclusions: Metabolic alteration in breast milk occurs during a process of both acute and subacute mastitis. Acetate, esterified cholesterol, lysophostidylcholine, and polyunsaturated fatty acids increased in both acute and subacute mastitis. However, according to the multi-adjusted regression logistic models, the candidate biomarkers for acute and subacute mastitis are cholesterol, lysophosphatidylcoholine, phosphatidylcholine, plasmalogen, and polyunsaturated fatty acids. Full article

Parkinson’s-disease (PD) is an incurable, age-related neurodegenerative disease, and its global prevalence of disability and death has increased exponentially. Although motor symptoms are the characteristic manifestations of PD, the clinical spectrum also contains a wide variety of non-motor symptoms, which are the main cause of disability and determinants of the decrease in a patient’s quality of life. Noteworthy in this regard is the stress on the cardiac system that is often observed in the course of PD; however, its effects have not yet been adequately researched. Here, an untargeted metabolomics approach was used to assess changes in cardiac metabolism in the 6-hydroxydopamine model of PD. Beta-sitosterol, campesterol, cholesterol, monoacylglycerol, α-tocopherol, stearic acid, beta-glycerophosphoric acid, o-phosphoethanolamine, myo-inositol-1-phosphate, alanine, valine and allothreonine are the metabolites that significantly discriminate parkinsonian rats from sham counterparts. Upon analysis of the metabolic pathways with the aim of uncovering the main biological pathways involved in concentration patterns of cardiac metabolites, the biosynthesis of both phosphatidylethanolamine and phosphatidylcholine, the glucose-alanine cycle, glutathione metabolism and plasmalogen synthesis most adequately differentiated sham and parkinsonian rats. Our results reveal that both lipid and energy metabolism are particularly involved in changes in cardiac metabolism in PD. These results provide insight into cardiac metabolic signatures in PD and indicate potential targets for further investigation. Full article

Plasmalogens are membrane phospholipids with two fatty acid hydrocarbon chains linked to L-glycerol, one containing a characteristic cis-vinyl ether function and the other one being a polyunsaturated fatty acid (PUFA) residue linked through an acyl function. All double bonds in these structures display the cis geometrical configuration due to desaturase enzymatic activity and they are known to be involved in the peroxidation process, whereas the reactivity through cis-trans double bond isomerization has not yet been identified. Using 1-(1Z-octadecenyl)-2-arachidonoyl-sn-glycero-3-phosphocholine (C18 plasm-20:4 PC) as a representative molecule, we showed that the cis-trans isomerization can occur at both plasmalogen unsaturated moieties, and the product has characteristic analytical signatures useful for omics applications. Using plasmalogen-containing liposomes and red blood cell (RBC) ghosts under biomimetic Fenton-like conditions, in the presence or absence of thiols, peroxidation, and isomerization processes were found to occur with different reaction outcomes due to the particular liposome compositions. These results allow gaining a full scenario of plasmalogen reactivity under free radical conditions. Moreover, clarification of the plasmalogen reactivity under acidic and alkaline conditions was carried out, identifying the best protocol for RBC membrane fatty acid analysis due to their plasmalogen content of 15–20%. These results are important for lipidomic applications and for achieving a full scenario of radical stress in living organisms. Full article

There has been increasing interest in bacterial lipids in recent years due, in part, to their emerging role as molecular signalling molecules. Bacteroides thetaiotaomicron is an important member of the mammalian gut microbiota that has been shown to produce sphingolipids (SP) that pass through the gut epithelial barrier to impact host SP metabolism and signal into host inflammation pathways. B. thetaiotaomicron also produces a novel family of N-acyl amines (called glycine lipids) that are potent ligands of host Toll-like receptor 2 (TLR2). Here, we specifically examine the lipid signatures of four species of gut-associated Bacteroides. In total we identify 170 different lipids, and we report that the range and diversity of Bacteroides lipids is species specific. Multivariate analysis reveals that the differences in the lipid signatures are largely driven by the presence and absence of plasmalogens, glycerophosphoinositols and certain SP. Moreover, we show that, in B. thetaiotaomicron, mutations altering either SP or glycine lipid biosynthesis result in significant changes in the levels of other lipids, suggesting the existence of a compensatory mechanisms required to maintain the functionality of the bacterial membrane. Full article

Peroxisome biogenesis disorders (due to PEX gene mutations) are associated with symptoms that range in severity and can lead to early childhood death, but a common feature is hearing impairment. In this study, mice carrying Pex3 mutations were found to show normal auditory development followed by an early-onset progressive increase in auditory response thresholds. The only structural defect detected in the cochlea at four weeks old was the disruption of synapses below inner hair cells. A conditional approach was used to establish that Pex3 expression is required locally within the cochlea for normal hearing, rather than hearing loss being due to systemic effects. A lipidomics analysis of the inner ear revealed a local reduction in plasmalogens in the Pex3 mouse mutants, comparable to the systemic plasmalogen reduction reported in human peroxisome biogenesis disorders. Thus, mice with Pex3 mutations may be a useful tool to understand the physiological basis of peroxisome biogenesis disorders. Full article

Male fertility, as manifest by the quantity and progressive motility of spermatozoa, is negatively impacted by obesity, dyslipidaemia and metabolic disease. However, the relative distribution of lipids in spermatozoa and the two compartments which supply lipids for spermatogenesis (seminal fluid and blood serum) has not been studied. We hypothesised that altered availability of lipids in blood serum and seminal fluid may affect the lipid composition and progressive motility of sperm. 60 men of age 35 years (median (range 20–45) and BMI 30.4 kg/m² (24–36.5) under preliminary investigation for subfertility were recruited at an NHS clinic. Men provided samples of serum and semen, subject to strict acceptance criteria, for analysis of spermatozoa count and motility. Blood serum (n = 60), spermatozoa (n = 26) and seminal fluid (n = 60) were frozen for batch lipidomics analysis. Spermatozoa and seminal fluid had comparable lipid composition but showed marked differences with the serum lipidome. Spermatozoa demonstrated high abundance of ceramides, very-long-chain fatty acids (C20-22), and certain phospholipids (sphingomyelins, plasmalogens, phosphatidylethanolamines) with low abundance of phosphatidylcholines, cholesterol and triglycerides. Men with spermatozoa of low progressive motility had evidence of fewer concentration gradients for many lipid species between blood serum and spermatozoa compartments. Spermatozoa are abundant in multiple lipid species which are likely to contribute to key cellular functions. Lipid metabolism shows reduced regulation between compartments in men with spermatozoa with reduced progressive motility. Full article

Background: Transcriptomic and lipidomic dual analyses usually initiate with independent extractive procedures. That entails a difficulty in aligning results from both omics platforms, especially in the case of highly heterogeneous tissues, such as the kidney. Methods: Bligh and Dyer lipid extraction was performed using rat kidney homogenates prepared in PBS or commercially available Tri-reagent used for RNA extraction. Samples were analyzed by ultrahigh performance liquid chromatography-mass spectrometry (UHPLC-MS) lipidomic analysis. Results: Comparison of the lipidome obtained from phosphate-buffered saline (PBS) and Tri-reagent homogenates showed qualitative and quantitative validity of the Tri-reagent homogenate with the exception of ether lipids; the acidic nature of the mix seems to promote the hydrolysis of the ether bond, especially in plasmalogens. We tested several conditions in the sample processing, which allowed to optimize the procedure. Conclusions: Aiming to implement a method that allows the extraction of RNA and lipids from the same tissue homogenate not using external tracers, we here report the use of Tri-reagent homogenates as a suitable starting material for UHPLC-MS lipidomic analysis. Full article

Herein, we present a qualitative and quantitative analysis of the compositions of plasmalogens and phospholipids (PLs) in dried big head shrimp (Solenocera melantho), opossum shrimp (Neomysis awatschensis), mussel (Mytilus galloprovincialis), and sea cucumber (Apostichopus japonicus). We also analyze the fatty acid composition of the extracted lipids, phosphatidyl choline (PtdCho), and plasmalogen choline (PlsCho) from each sample. In big head shrimp, opossum shrimp, and mussel, phosphatidyl choline (PtdCho) was the most abundant PL at 1677.9, 1603, and 1661.6 mg/100 g of dried sample, respectively, whereas the most abundant PL in sea cucumber was PlsCho (206.9 mg/100 g of dried sample). In all four samples, plasmalogen ethanolamine (PlsEtn) was higher than phosphatidyl ethanolamine (PtdEtn). The content (mg/100 g of dried sample) of PlsCho was highest in mussel (379.0), and it was higher in big head shrimp (262.3) and opossum shrimp (245.6) than sea cucumber (206.9). The contents (mg/100 g of dried sample) of PlsEtn were in the order of mussel (675.4) > big head shrimp (629.5) > opossum shrimp (217.9) > sea cucumber (51.5). For analyzing the fatty acids at the sn-2 position of PlsCho, the consecutive treatment with phospholipase A₁, solid phase extraction, thin-layer chromatography (TLC), and GC-FID were applied. The most abundant fatty acid was eicosapentaenoic acid (EPA, C20:5, n-3) in big head shrimp and sea cucumber, palmitoleic acid (C16:1, n-7) in opossum shrimp, and docosadienoic acid (C22:2, n-6) in mussel. Full article

Patients with higher genetic West African ancestry (GWAA) have hypertension (HTN) that is more difficult to treat and have higher rates of cardiovascular diseases (CVD) and differential responses to antihypertensive drugs than those with lower GWAA. The mechanisms underlying these disparities are poorly understood. Using data from 84 ancestry-informative markers in US participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, the GWAA proportion was estimated. Using multivariable linear regression, the baseline levels of 886 metabolites were compared between PEAR participants with GWAA < 45% and those with GWAA ≥ 45% to identify differential metabolites and metabolic clusters. Metabolites with a false discovery rate (FDR) < 0.2 were used to create metabolic clusters, and a cluster analysis was conducted. Differential clusters were then tested for replication in PEAR-2 participants. We identified 353 differential metabolites (FDR < 0.2) between PEAR participants with GWAA < 45% (n = 383) and those with GWAA ≥ 45% (n = 250), which were used to create 24 metabolic clusters. Of those, 13 were significantly different between groups (Bonferroni p < 0.002). Four clusters, plasmalogen and lysoplasmalogen, sphingolipid metabolism and ceramide, cofactors and vitamins, and the urea cycle, were replicated in PEAR-2 (Bonferroni p < 0.0038) and have been previously linked to HTN and CVD. Our findings may give insights into the mechanisms underlying HTN racial disparities. Full article

Plasmalogens (Pls) are glycerophospholipids that play critical roles in the brain. Evidence supports the role of diet and that of the gut microbiota in regulating brain lipids. We investigated the impact of dietary intake of inulin—a soluble fiber used as prebiotic—on the Pl content of the cortex in mice. No global modification in the Pl amounts was observed when evaluated by gas chromatographic analysis of dimethyl acetals (DMAs). However, the analysis of individual molecular species of Pls by liquid chromatography revealed a reduced abundance of major species of ethanolamine Pls (PlsEtn)―PE(P-18:0/22:6) and PE(P-34:1)―in the cortex of mice fed a diet supplemented with inulin. DMA and expression levels of genes (Far-1, Gnpat, Agps, Pla2g6 and Tmem86b) encoding key enzymes of Pl biosynthesis or degradation were not altered in the liver and in the cortex of mice exposed to inulin. In addition, the fatty acid profile and the amount of lyso forms derived from PlsEtn were not modified in the cortex by inulin consumption. To conclude, inulin affects the brain levels of major PlsEtn and further investigation is needed to determine the exact molecular mechanisms involved. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease. Full article