Search Results (365)

Background: High-throughput metabolomics studies have promoted the discovery of candidate biomarkers linked to atherosclerosis (AS). This narrative systematic review summarises metabolomics studies conducted in (1) individuals with subclinical AS (assessed by imaging techniques such as carotid intimal media thickness, IMT, and coronary artery calcium, CAC), (2) patients with established atherosclerotic plaques, and (3) individuals with AS risk factors. Methods: The systematic search was conducted in the PubMed database according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were as follows: (i) publication date between 2009 and 2024; (ii) identification of potential biomarkers for AS in subjects with a diagnosis of AS or with one or more traits characteristic of the disease (i.e., CAC or IMT); (iii) identification of potential AS biomarkers in subjects with atherogenic clinical conditions (i.e., Down’s syndrome, DS, polycystic ovarian syndrome, PCOS, and systemic lupus erythematosus, SLE); (iv) metabolomic studies; and (iv) studies in human samples. Exclusion criteria comprised the following: (i) studies on lipid metabolic diseases unrelated to AS, (ii) “omics” results not derived from metabolomics, (iii) reviews and studies in animal models or cell cultures, and (iv) systematic reviews and meta-analyses. Of 90 eligible studies screened, 24 met the inclusion criteria. Results: Across subclinical and overt AS, consistent disturbances were observed in amino acid, lipid, and carbohydrate metabolism. Altered profiles included branched-chain amino acids (BCAAs), aromatic amino acids (AACs) and derivatives (e.g., kynurenine–tryptophan pathway), bile acids (BAs), androgenic steroids, short-chain fatty acids (FAs)/ketone intermediates (e.g., acetate, 3-hydroxybutyrate, 3-HB), and Krebs cycle intermediates (e.g., citrate). Several metabolites (e.g., glutamine, lactate, 3-HB, phosphatidylcholines, PCs/lysophosphatidylcholines, lyso-PCs) showed reproducible associations with vascular phenotypes (IMT/CAC) and/or clinical AS. Conclusions: The identification of low-weight metabolites altered in both subclinical and overt AS suggests their potential as candidate biomarkers for early AS diagnosis. Given the steady increase in deaths from cardiovascular disease, a manifestation of advanced AS, this finding could have significant clinical relevance. Full article

Somatic cell nuclear transfer (SCNT) or cloning technology is widely used in agriculture and biomedicine. However, the application of this technology is limited by the low developmental competence of cloned embryos or fetuses, which frequently exhibit abnormal development of trophoblast cells or placentas. The purpose of this study was to investigate the possible causes of the erroneous placental development of SCNT-derived pig fetuses. The placental transcriptomic and lipidomic profiles were compared between 30-day-old SCNT- and artificial insemination (AI)-produced pig fetuses. Differentially expressed lipid metabolites between two groups of placentas were selected to test their effects on porcine trophoblast cell activity. The results showed that SCNT placentas exhibit impaired lipid metabolism and function. The level of a metabolite, lysophosphatidylcholine (LPC), in the glycerophospholipid metabolism pathway was substantially increased in SCNT placentas, compared with AI placentas. The elevation in LPC content may lead to impaired placental development in cloned pig fetuses, as LPC inhibited the proliferation and migration of porcine trophoblast cells. This study discovers a main cause of erroneous development of cloned pig fetuses, which will be beneficial for understanding the regulation of SCNT embryo development, as well as developing new methods to improve the efficiency of pig cloning. Full article

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, often diagnosed at late stages due to the limited sensitivity of current screening tools. This study explores whether blood-based lipidomic profiling, combined with explainable artificial intelligence (XAI), can improve early and interpretable detection of HCC. Methods: We analyzed lipidomic data from 219 HCC patients and 219 matched healthy controls using liquid chromatography-mass spectrometry. An Explainable Boosting Machine (EBM) was employed to identify discriminatory lipid biomarkers and was compared against several standard machine learning algorithms. Results: The EBM model achieved superior performance with 87.0% accuracy, 87.7% sensitivity, 86.3% specificity, and an AUC of 91.8%, outperforming other models. Key lipid biomarkers identified included specific phosphatidylcholines (PC 38:2, PC 40:4), sphingomyelins (SM d40:2 B), and lysophosphatidylcholines (LPC 18:2), which exhibited significant alterations in HCC patients and highlighted disruptions in sphingolipid metabolism. Conclusions: Integration of lipidomics with explainable machine learning offers a powerful, transparent approach for HCC biomarker discovery, achieving high diagnostic accuracy while providing biological insights. This strategy holds promise for developing non-invasive, clinically interpretable screening tools to improve early detection of liver cancer. Full article

Background and Objectives: Avian influenza poses a continuous public health threat, particularly to individuals with occupational exposure to poultry such as farm workers, live animal market employees, and processing plant staff. This study aimed to investigate the systemic metabolic effects of such exposure and to identify potential biomarkers for early detection and health risk assessment. Materials and Methods: An untargeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomics approach was applied to analyze serum samples from occupationally exposed individuals and healthy controls. Multivariate statistical analysis, pathway enrichment, and topology analysis were performed to identify significantly altered metabolites and metabolic pathways. The least absolute shrinkage and selection operator (LASSO) algorithm was employed to select key metabolites. Results: Multivariate statistical analysis revealed a clear separation between the exposure group and control, suggesting distinct metabolic profiles between the two populations. Pathway analysis indicated significant alterations in alanine, aspartate, and glutamate metabolism, as well as tryptophan metabolism, which are closely linked to immune regulation, energy metabolism, and host–pathogen interactions. LASSO feature selection and subsequent manual verification identified 17 key metabolites with strong discriminative power. Furthermore, lipidomic profiling revealed a pronounced increase in lysophosphatidylcholine (LPC) levels and a concurrent decrease in phosphatidylcholine (PC) species in exposed individuals. Conclusions: This study reveals metabolic disruptions associated with occupational avian influenza exposure and identifies potential serum biomarkers related to immune and lipid metabolism. These findings provide novel insights into host responses to avian influenza exposure and may support early detection and health risk assessment in high-risk occupational populations. Full article

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder, caused by mutations in the ABCD1 gene. Early diagnosis is critical to manage adrenal insufficiency and cerebral forms of the disease. Since 2021, a pilot newborn screening (NBS) program for X-ALD has been launched in Lombardy, Italy. From September 2021 to June 2025, 138,116 newborns (≥37 weeks’ gestational age) were screened for elevated C26:0-lysophosphatidylcholine (C26:0-LPC) levels using a two-tier algorithm. Genetic testing was performed in non-negative cases. Males found to be ABCD1 variant carriers were enrolled in multidisciplinary follow-up, including neurological, endocrinological, and nutritional assessments. Eleven individuals (six males, five females) carried pathogenic or likely pathogenic ABCD1 variants. Three males were diagnosed with adrenal insufficiency and started hydrocortisone therapy between 1 and 2 years of age. Growth parameters were within normal range overall, but two children showed signs of stunting associated with poor dietary compliance. Additionally, three patients were diagnosed with Zellweger spectrum disorders (ZSDs). No patients affected with Aicardi-Goutières Syndrome were identified. Newborn screening for X-ALD in Italy is feasible and enables early detection and intervention. Biochemical markers and genetic analysis are reliable tools for identifying affected males and female carriers. Multidisciplinary management is essential to address medical and psychosocial challenges during follow-up. Full article

Empagliflozin is a sodium–glucose co-transporter inhibitor approved for the treatment of type 2 diabetes mellitus. The aim of this study was the 6-month effect of empagliflozin on serum and liver lipidome in C57BL/6J mice fed on a fast food diet (FFD). Three groups were studied; two of them fed on FFD, one with empagliflozin (EMPA group), and another without empagliflozin (FFD group); the third group fed on a chow diet and served as the control group (CD group). Following untargeted lipidomic analysis, the FFD and EMPA groups displayed largely similar serum lipid profiles, characterized by elevated levels in the majority of identified lipids, compared with the CD group, particularly glycerophospholipids. For instance, phosphatidylcholine (PC) 34:1 and phosphatidylinositol (PI) 38:3 increased in the FFD compared with the CD group (both p < 0.001, fold change 2.4 and 17.6, respectively) with comparable increases observed in the EMPA group. Hepatic lipid profiles varied more significantly between groups. For example, PC 34:1 was increased in the FFD and in the EMPA compared with the CD group (both p < 0.001, fold change 1.7 and 1.6, respectively), whereas PC 32:0 was decreased in the FFD group and in the EMPA group compared with the CD group (both p < 0.001, fold change 0.6 and 0.5, respectively). FFD appears to have a more substantial impact on lipidomic profiles compared with the preventive empagliflozin effect. Notably, the concentration of lysophosphatidylcholine (LPC) 22:6 was significantly reduced in the EMPA compared with the FFD group (p < 0.001, fold change 1.4). Interestingly, several glycerophospholipids, including PC 34:1, PC 35:1, PC 36:3, PC 38:4, PI 34:2 and PI 38:3, increased in both serum and hepatic tissues of the FFD and EMPA groups compared with the CD group. In conclusion, limited differences in the lipidomic profile were observed in the EMPA compared with the FFD group (e.g., LPC 22:6). However, both the EMPA and FFD groups showed distinct lipidomic profiles compared with the CD group. Full article

Lower respiratory tract infections (LRTIs) remain a major cause of global morbidity and mortality, yet accurate pathogen identification and risk stratification continue to pose clinical challenges. Lipidomics—the comprehensive analysis of lipid species within biological systems—has emerged as a promising tool to unravel host–pathogen interactions and reveal novel diagnostic and prognostic biomarkers. This systematic review synthesizes evidence from nine original studies applying mass spectrometry-based lipidomic profiling in human LRTIs, including community-acquired pneumonia (CAP), ventilator-associated pneumonia (VAP), and coronavirus disease 2019 (COVID-19). Across diverse study designs, sample types, and analytical platforms, consistent alterations in lipid metabolism were observed. Perturbations in phospholipid classes, particularly phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs), were frequently associated with disease severity and immune activation. The ratios of PC to LPC and phosphatidylethanolamine (PE) to lysophosphatidylethanolamine (LPE) emerged as markers of inflammatory remodeling. Sphingolipids—including sphingomyelins (SMs) and sphingosine-1-phosphate (S1P)—were identified as key modulators of monocyte and neutrophil activation. Fatty acid–derived lipid mediators such as oxylipins (e.g., 12,13-epoxyoctadecenoic acid and 15-hydroxyeicosatetraenoic acid) and acylcarnitines reflected pathogen-specific immune responses and mitochondrial dysfunction. Several lipid-based classifiers demonstrated superior diagnostic and prognostic performance compared to conventional clinical scores, including the CURB-65 and pneumonia severity index. However, significant heterogeneity in experimental design, lipid identification workflows, and reporting standards limits inter-study comparability. While preliminary findings support the integration of lipidomics into infectious disease research, larger multi-omic and longitudinal studies are required. This review provides the first comprehensive synthesis of lipidomic alterations in human LRTIs and highlights their emerging translational relevance. Full article

N-acetylchitooligosaccharides (NACOS) are functional oligosaccharides derived from shrimp and crab shells that exhibit a variety of biological activities. This study investigates the protective effects of NACOS against acute lung injury (ALI) induced by lipopolysaccharides (LPS) in mice and explores its underlying metabolic regulatory mechanisms. Histopathological analysis showed that NACOS reduced pulmonary inflammation, edema, and disruption of tight junctions in ALI mice. Molecular analysis indicated that NACOS downregulated key inflammatory mediators, including NLRP3, IL-1β, TNF-α, MPO, and GCSF. Using untargeted metabolomics, glycerophospholipid metabolism was identified as the most significantly altered pathway following NACOS pre-treatment. Key regulated metabolites included triacylglycerols, phosphatidylethanolamines, lysophosphatidylcholines, and other glycerophospholipid derivatives. These findings suggest that NACOS exerts preventive effects through two primary mechanisms: the suppression of pro-inflammatory mediators and the modulation of glycerophospholipid metabolism. The identified metabolic alterations may serve as potential biomarkers for the progression of ALI and for monitoring prophylactic interventions. Full article

Background/Objectives: Neonatal respiratory distress syndrome (NRDS) is a heterogenous respiratory illness that mainly affects preterm neonates. It is characterized by insufficient production of pulmonary surfactant and impaired lung compliance. The lysophosphatidylcholine acyltransferase 1 (LPCAT1) enzyme has a crucial function in lipid remodeling through the conversion of lysophosphatidylcholine to phosphatidylcholine, the major component of pulmonary surfactant. In this research, we aimed to investigate the association of the LPCAT1*rs9728 variant with NRDS susceptibility using hereditary analysis and bioinformatic approaches. Methods: The LPCAT1 (rs9728; c.*1668T>C) variant was characterized among 100 preterm neonates with RDS and 100 non-RDS neonates utilizing the TaqMan SNP genotyping assay. Logistic regression analysis was performed to identify the risk factors of respiratory distress syndrome. The functional mechanism of the LPCAT1 gene was elucidated using bioinformatic approaches. Results: The LPCAT1*rs9728 C/C genotype was significantly associated with a 78% reduced risk of NRDS (OR = 0.22, p = 0.027), although the minor C allele did not attain a significant finding (OR = 0.83, p = 0.416). Apgar score and Silverman–Andersen respiratory severity score (RSS) were statistically significant with prematurity classes (p < 0.05). Additionally, gestational age and birth weight were considered independent risk factors in the progression of RDS among preterm neonates. Conclusions: This research exhibited a significant difference between the LPCAT1 (rs9728; c.*1668T>C) variant and reduced risk against the development of RDS among preterm neonates. The rs9728*C/C genotype revealed a significant association with decreased risk of NRDS compared to non-RDS neonates. Full article

Background: Fontan circulation is associated with impaired cardiac output, reduced exercise capacity, and systemic metabolic stress. However, the underlying lipidomic alterations remain poorly defined. Methods: Using targeted mass spectrometry, we analyzed 291 lipid species in fasting plasma samples from 20 adults with Fontan circulation and 20 age- and sex-matched healthy controls. Results: Forty-eight lipids were significantly altered between groups (p < 0.05), including reductions in total lysophosphatidylcholines (LPC) and total ether-linked LPC [LPC(O)] and elevations in total phosphatidylserines (PS). Notably, LPC(O-22:1) and LPC(O-20:0) were decreased, while PS 40:5 was elevated, with several of these species demonstrating strong correlations (|r| > 0.5, p < 0.001) with the stroke index, cardiac index, and VO₂max. These three lipid species also showed excellent capability in discriminating Fontan patients from healthy controls (AUC > 0.78). Correlation network and pathway enrichment analyses revealed tightly coordinated lipid clusters containing LPC/LPC(O), PE, and PS species as central features of dysregulated Fontan metabolism. Conclusions: These exploratory findings highlight coordinated lipid alterations associated with impaired cardiovascular reserve in Fontan patients. While based on unadjusted p-values and therefore being hypothesis-generating, they provide novel insight into the metabolic landscape of Fontan physiology and warrant validation in larger, independent cohorts. Full article

The aim of this study was to improve screening efficiency by establishing reasonable interpretation criteria for the use of flow injection analysis tandem mass spectrometry (FIA-MS/MS) in newborn screening (NBS) for X-linked adrenoleukodystrophy (X-ALD). FIA-MS/MS was employed to analyze very-long-chain acylcarnitines (ACs) and lysophosphatidylcholines (LPCs) and their ratios in dried blood spot (DBS) obtained from five X-ALD patients in the neonatal period (0–7 days old) and 7123 healthy neonate controls. By comparing these results and analyzing receiver operating characteristic (ROC) curves, we identified sensitive indicators for X-ALD screening in newborns. To evaluate the performance of different FIA-MS/MS screening indicators, we simultaneously analyzed 7712 neonatal DBS samples obtained for X-ALD screening using FIA-MS/MS and the established liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantitative detection of C26:0-lysophosphatidylcholine (C26:0-LPC). Furthermore, 84,268 newborn X-ALD screening results were retrospectively analyzed to further evaluate the screening performance of FIA-MS/MS. After the three-step optimization evaluation, the optimized first-tier sensitive screening indicators of FIA-MS/MS were C24:0-AC, C26:0LPC, and C24:0/C22:0-AC. Among the 7712 newborns screened, one case was confirmed to be double-positive. Within separate statistical analyses, based on LC-MS/MS screening alone (positive cutoff > 0.17 µmol/L), only seven cases (0.09%) were initially positive, with a positive predictive value (PPV) of 42.8%, and two additional ABCD1 VUS hemizygous males were detected. Through the retrospective analysis of 84,268 newborns, eight ABCD1 variants (six hemizygous males and two heterozygous females) were ultimately identified. Our study showed that the optimization of first-tier screening performance is particularly important if second-tier screening is not performed. Using LC-MS/MS for second-tier screening for X-ALD can significantly reduce the number of false positives, but the method still misses some false negatives. If it is used as a first-tier assessment, more VUS variant neonates can be detected. Full article

Background/Objectives: Low levels of lysophosphatidylcholine (LPC) in the blood can be used as a diagnostic marker for sepsis. SARS-CoV-2 infection, a more recent cause of sepsis, shares similarities with non-SARS-CoV-2 sepsis but also exhibits distinct features. We have recently shown that plasma cholesteryl ester levels are higher in patients with SARS-CoV-2 infection than in patients without, and this study analysed whether this may extend to differences in LPC, a bioactive constituent of lipoproteins. Methods: The plasma levels of 13 LPC species were measured by flow injection analysis tandem mass spectrometry (FIA-MS/MS) in 157 patients with systemic inflammatory response syndrome (SIRS), sepsis or septic shock. Of these patients, 24 had SARS-CoV-2 infection. Results: Patients with SIRS exhibited higher plasma levels of the minor LPC species LPC 15:0 and 22:4 compared to those with sepsis or septic shock. Five LPC species were also reduced in the plasma of 31 patients with liver cirrhosis; therefore, patients with cirrhosis or SIRS were excluded from subsequent analyses. Compared to 76 non-COVID-19 patients with sepsis or septic shock, SARS-CoV-2 infection in 21 patients was associated with significantly higher plasma levels of ten individual LPC species and total LPC concentration. In patients with sepsis/septic shock, LPC species showed negative correlations with procalcitonin and interleukin-6, and positive correlations with gamma-glutamyltransferase and cholesteryl ester levels. In contrast, no significant associations were observed between LPC levels and C-reactive protein, aminotransferases, or free cholesterol. Conclusions: Differential LPC levels, despite comparable disease severity, may serve as metabolic biomarkers to distinguish SARS-CoV-2 sepsis from other causes of sepsis and inform targeted therapeutic approaches. Full article

This study aimed to investigate the effects of training on cardiac structure and function, as well as plasma metabolite profiles in horses, in order to uncover the molecular regulatory mechanisms and cardiac remodeling under long-term exercise. We hypothesize that long-term standardized training induces physiological cardiac remodeling and differential metabolomic changes in Yili horses, which correlate with improved athletic performance. The study focuses on physiological exercise-induced cardiac remodeling, characterized by increased left ventricular wall thickness and chamber size. A total of 18 Yili horses, a unique Chinese equine breed, were included in the study of equine exercise physiology. Twelve horses underwent six months of standardized training followed by three 1000 m performance tests. Based on final rankings, they were divided into an advanced group (AG, top six horses) and a habitual group (HG, bottom six horses). The remaining six untrained horses served as the untrained group (UG), with only free-range activity. Echocardiographic results revealed significant differences (p < 0.05) between the trained and untrained groups in cardiac parameters such as LVID, LVFW, LVM, AODd, IVSs, HR, EDV, ESV, LADs, LVLD, MVD, PADs, and SV. Further comparison between AG and HG showed significant differences in AODd, EESV, HR, IVSd, LVIDs, LVM, RVDd, and RVDs (p < 0.05). Metabolomic analysis identified 465 differential metabolites between AG and HG, 456 between AG and UG, and 379 between HG and UG, with 106 overlapping metabolites among all three groups. Plasma metabolomics revealed significant negative correlations between specific long-chain lysophosphatidylcholines (LPCs) and cardiac structural parameters (LVIDd, LVFWD, LVIDs, LVLD, MVD, and LADs), whereas LPC (O-18:2) showed an opposite trend. Key metabolites such as 3-hydroxybutanoic acid, carnitine C4:0, carnitine isoC4:0, hippuric acid, and uric acid were significantly lower in AG compared to HG and UG, with uric acid levels negatively correlated with LVID and LVM. Glycerophospholipid metabolism emerged as the core pathway differentiating exercise capacity among all groups. Notably, efferocytosis (vs. HG and UG) and tryptophan metabolism/aromatic amino acid biosynthesis (vs. HG) were specifically enriched in AG. These findings provide a novel theoretical basis and research perspective for optimizing racehorse training strategies and exploring the metabolic regulation of the athletic heart. Full article

Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, is used as a feed additive in aquaculture. However, its effects on muscle quality and lipid metabolism in fish remain understudied. Therefore, three diets supplemented with 0%, 0.01%, and 0.10% GABA were fed to juvenile Acanthopagrus latus (initial weight: 9.96 g) for 9 weeks, followed by analyses of growth performance, muscle quality indices, and hepatic lipid profiles. Fish fed 0.01% GABA showed the highest weight gain rate (p < 0.05). Their muscles exhibited improved muscle texture, higher levels of essential/non-essential and flavor amino acids, and a higher proportion of long-chain polyunsaturated fatty acids (LC-PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), along with triglycerides and cardiolipin enriched in LC-PUFA chains (p < 0.05). Moreover, their livers demonstrated increased levels of triglycerides, phosphatidylethanolamine, and LC-PUFA, along with reduced levels of phosphatidylcholine, lysophosphatidylcholine, lysophosphatidylethanolamine, and phosphatidylserine (p < 0.05). These results suggest that 0.01% GABA supplementation improves growth performance, enhances flesh quality, and optimizes liver lipid profiles in A. latus. Full article

Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy controls. To our knowledge, the correlation between serum LPC species levels and measures of inflammation, as well as their potential as markers for monitoring IBD activity, has not yet been investigated. Methods: Thirteen LPC species, varying in acyl chain length and number of double bonds, were measured in the serum of 16 controls and the serum of 57 patients with IBD. Associations with C-reactive protein (CRP) and fecal calprotectin levels as markers of IBD severity were assessed. Results: Serum levels of LPC species did not differ between the healthy controls and the entire patient cohort. In patients with IBD, serum levels of LPC 16:1, 18:0, 18:3, 20:3, and 20:5, as well as total LPC concentrations, showed inverse correlations with both CRP and fecal calprotectin levels, indicating an association with inflammatory activity. Nine LPC species were significantly reduced in patients with high fecal calprotectin compared to those with low values. LPC species with 22 carbon atoms and 4 to 6 double bonds were not related to disease activity. Stool consistency and gastrointestinal symptoms did not influence serum LPC profiles. Corticosteroid treatment was associated with lower serum LPC 20:3 and 22:5 levels, while mesalazine, anti-TNF, and anti-IL-12/23 therapies had no significant impact on LPC concentrations. There was a strong positive correlation between LPC species containing 15 to 18 carbon atoms and serum cholesterol, triglycerides, and phosphatidylcholine levels. However, there was no correlation with markers of liver disease. Conclusions: Shorter-chain LPC species are reduced in patients with active IBD and reflect underlying hypolipidemia. While these lipid alterations provide insight into IBD-associated metabolic changes, they appear unsuitable as diagnostic or disease monitoring biomarkers. Full article