Glycerophospholipid Profile Research Articles

LPG 18:0 is a general biomarker of asthma and inhibits the differentiation and function of regulatory T-cells.

The diagnosis, severity assessment, and development of therapeutic strategies for asthma are crucial aspects of disease management. Since biomarkers are reliable tools in disease management, we aimed to identify and explore asthma-associated biomarkers and investigate their mechanisms. Lipidomics was used to profile serum glycerophospholipids in asthmatic patients and controls. The absolute concentration of lysophosphatidylglycerol (LPG) 18:0 was quantified in various asthma subtypes. Mouse asthma models were used to confirm its potential as a biomarker and investigate its mechanisms in vivo. The effects of LPG 18:0 on CD4+ T-cell differentiation, proliferation and apoptosis were assessed in vitro by flow cytometry, while mitochondrial dysfunction was evaluated through mitochondrial membrane potential, reactive oxygen species and ATP production measurements. The intracellular mechanism of LPG 18:0 in regulatory T-cells (Tregs) was investigated using small-molecule inhibitors. The serum glycerophospholipid profile varied between asthmatic patients and control group, with LPG 18:0 levels being notably higher in asthmatic patients, correlating with asthma severity and control level. In vivo and in vitro studies revealed that LPG 18:0 impaired naïve CD4+ T-cell differentiation into Tregs and compromised their suppressive function. Further investigation demonstrated that LPG 18:0 treatment reduced the FOXP3 protein level via SIRT1-mediated deacetylation during Treg differentiation. This study identifies that serum levels of LPG 18:0 are generally elevated in asthmatics and serve as a biomarker for asthma. LPG 18:0 impairs Treg function via the NAD+/SIRT1/FOXP3 pathway. Our research reveals the potential of LPG 18:0 as a biomarker for asthma, elucidating its role in asthma diagnosis and treatment.

GDE5/Gpcpd1 activity determines phosphatidylcholine composition in skeletal muscle and regulates contractile force in mice

Glycerophosphocholine (GPC) is an important precursor for intracellular choline supply in phosphatidylcholine (PC) metabolism. GDE5/Gpcpd1 hydrolyzes GPC into choline and glycerol 3-phosphate; this study aimed to elucidate its physiological function in vivo. Heterozygous whole-body GDE5-deficient mice reveal a significant GPC accumulation across tissues, while homozygous whole-body knockout results in embryonic lethality. Skeletal muscle-specific GDE5 deletion (Gde5 skKO) exhibits reduced passive force and improved fatigue resistance in electrically stimulated gastrocnemius muscles in vivo. GDE5 deficiency also results in higher glycolytic metabolites and glycogen levels, and glycerophospholipids alteration, including reduced levels of phospholipids that bind polyunsaturated fatty acids (PUFAs), such as DHA. Interestingly, this PC fatty acid compositional change is similar to that observed in skeletal muscles of denervated and Duchenne muscular dystrophy mouse models. These are accompanied by decrease of GDE5 expression, suggesting a regulatory role of GDE5 activity for glycerophospholipid profiles. Furthermore, a DHA-rich diet enhances contractile force and lowers fatigue resistance, suggesting a functional relationship between PC fatty acid composition and muscle function. Finally, skinned fiber experiments show that GDE5 loss increases the probability of the ryanodine receptor opening and lowers the maximum Ca2+-activated force. Collectively, GDE5 activity plays roles in PC and glucose/glycogen metabolism in skeletal muscle.

Pathogenic variants of sphingomyelin synthase SMS2 disrupt lipid landscapes in the secretory pathway.

Sphingomyelin is a dominant sphingolipid in mammalian cells. Its production in the trans-Golgi traps cholesterol synthesized in the ER to promote formation of a sphingomyelin/sterol gradient along the secretory pathway. This gradient marks a fundamental transition in physical membrane properties that help specify organelle identify and function. We previously identified mutations in sphingomyelin synthase SMS2 that cause osteoporosis and skeletal dysplasia. Here, we show that SMS2 variants linked to the most severe bone phenotypes retain full enzymatic activity but fail to leave the ER owing to a defective autonomous ER export signal. Cells harboring pathogenic SMS2 variants accumulate sphingomyelin in the ER and display a disrupted transbilayer sphingomyelin asymmetry. These aberrant sphingomyelin distributions also occur in patient-derived fibroblasts and are accompanied by imbalances in cholesterol organization, glycerophospholipid profiles, and lipid order in the secretory pathway. We postulate that pathogenic SMS2 variants undermine the capacity of osteogenic cells to uphold nonrandom lipid distributions that are critical for their bone forming activity.

697P Lipid profile as a new diagnostic marker in head and neck cancer

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer and its main etiological factors are smoking, alcohol consumption and HPV infection. OSCC metabolic profile is heterogeneous and related to mutations in several tumor suppressor genes and oncogenes. Patterns have become apparent, such as increased choline metabolism, which indicates active proliferation. Phosphatidylcholine (PC) is a key component of membranes and source of signaling molecules. The project aimed to analyze the glycerophospholipid profile in OSCC patients compared with control samples using mass spectrometry and gene expression techniques to analyze blood, tissue and clinical-pathological characteristics.

Associations of plasma glycerophospholipid profile with modifiable lifestyles and incident diabetes in middle-aged and older Chinese.

Glycerophospholipid (GPL) perturbance was linked to the pathogenesis of diabetes in animal studies but prospective studies in humans are rare, particularly in Asians. We aimed to investigate the associations between plasma GPLs and incident diabetes and to explore effects of lifestyle on the associations in a Chinese population. The study included 1877 community-dwelling Chinese individuals aged 50-70years (751 men and 1126 women), free of diabetes at baseline and followed for 6years. A total of 160 GPL species were quantified in plasma at baseline by using high-throughput targeted lipidomics. Log-Poisson regression was used to assess the associations between GPLs and incidence of diabetes. Over the 6years of follow-up, 499 participants (26.6%) developed diabetes. After multivariable adjustment, eight GPLs were positively associated with incident diabetes (RRper SD 1.13-1.25; all false-discovery rate [FDR]-corrected p < 0.05), including five novel GLPs, namely phosphatidylcholines (PCs; 16:0/18:1, 18:0/16:1, 18:1/20:3), lysophosphatidylcholine (LPC; 20:3) and phosphatidylethanolamine (PE; 16:0/16:1), and three reported GPLs (PCs 16:0/16:1, 16:0/20:3 and 18:0/20:3). In network analysis, a PC-containing module was positively associated with incident diabetes (RRper SD 1.16 [95% CI 1.06, 1.26]; FDR-corrected p< 0.05). Notably, three of the diabetes-associated PCs (16:0/16:1, 16:0/18:1 and 18:0/16:1) and PE (16:0/16:1) were associated not only with fatty acids in the de novo lipogenesis (DNL) pathway, especially 16:1n-7 (Spearman correlation coefficients = 0.35-0.62, p< 0.001), but also with an unhealthy dietary pattern high in refined grains and low in fish, dairy and soy products (|factor loadings| ≥0.2). When stratified by physical activity levels, the associations of the eight GPLs and the PC module with incident diabetes were stronger in participants with lower physical activity (RRper SD 1.24-1.49, FDR-corrected p< 0.05) than in those with the median and higher physical activity levels (RRper SD 1.03-1.12, FDR-corrected p ≥ 0.05; FDR-corrected pinteraction < 0.05). Eight GPLs, especially PCs associated with the DNL pathway, were positively associated with incident diabetes in a cohort of Chinese men and women. The associations were most prominent in participants with a low level of physical activity.

Itraconazole Inhibits Intracellular Cholesterol Trafficking and Decreases Phosphatidylserine Level in Cervical Cancer Cells.

Itraconazole shows anticancer activity in various types of cancer but its underlying mechanism is unclear. We investigated the effect of itraconazole on membrane-associated lipids. To investigate the influences of itraconazole on cholesterol trafficking, cervical cancer CaSki cells were cultured with itraconazole and analyzed by Filipin staining followed by confocal microscopy. Effect on the glycerophospholipid profiles was analyzed by liquid chromatography/mass spectrometry (LC/MS). After itraconazole treatment, Filipin staining revealed cholesterol accumulation in the intracellular compartments, which was similar to the distribution after treatment of U18666A (cholesterol transport inhibitor). LC/MS analysis showed a significant decrease in phosphatidylserine levels and an increase in lysophosphatidylcholine levels in CaSki cells. Itraconazole inhibited cholesterol trafficking and altered the phospholipid composition. Alterations in the cell membrane can potentiate the anticancer activity of itraconazole.

Structure-specific, accurate quantitation of plasmalogen glycerophosphoethanolamine

Changes in plasmalogen glycerophosphoethanolamine (PE-P) composition (structure and abundance) are a key indicator of altered lipid metabolism. Differential changes in the levels of PE-P have been reported in different disease states, including neurodegenerative diseases. Of particular interest, traumatic brain injury (TBI) has resulted in altered expression of glycerophospholipid profiles, including PE-P. To date, most analytical assays assessing PE-P have focused on general lipidomic workflows to evaluate the relative, semi-quantitative abundance of PE-P during disease progression. This approach provides a broad evaluation of PE-P, yet often lacks specificity and sensitivity for individual PE-P structures which is a necessity for robust quantitative data. The present study highlights the development of a targeted, quantitative method using a HILIC separation and selective reaction monitoring mass spectrometry for the confident identification and accurate quantitation of PE-P. Our innovative method incorporates both the sn-1 alkyl vinyl ether and sn-2 acyl chain as product ion transitions, for specific and sensitive quantitation of 100 PE-P structures. Our method also uniquely allowed for the unambiguous assignment and quantitation of di-unsaturated sn-1 PE-P structures, which to date have not been conclusively quantified. Application of this assay to a TBI mouse model resulted in distinct temporal profiles for plasma PE-P up to 28 days post injury. Plasma PE-P were significantly increased 24 h after induced TBI, followed by a gradual reduction to sham concentrations by day 28. Overall, we established a structure-specific, quantitative assay for identification and quantitation of a comprehensive set of PE-P structures with demonstrated relevance to brain injury.

Plasma glycerophospholipid profile, erythrocyte n–3 PUFAs, and metabolic syndrome incidence: a prospective study in Chinese men and women

Animal studies have highlighted critical roles of glycerophospholipid (GP) metabolism in various metabolic syndrome (MetS)-related features such as dyslipidemia, obesity, and insulin resistance. However, human prospective studies of associations between circulating GPs and risks of MetS are scarce. We aimed to investigate whether GPs are associated with incidence of MetS in a well-established cohort. A total of 1243 community-dwelling Chinese aged 50-70 y without MetS at baseline and followed up for 6 y were included in current analyses. A total of 145 plasma GPs were quantified by high-throughput targeted lipidomics. MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. After 6 y, 429 participants developed MetS. Eleven GPs, especially those with long-chain polyunsaturated fatty acids (LCPUFAs) or very-long-chain polyunsaturated fatty acids (VLCPUFAs) at the sn-2 position, including 1 phosphatidylcholine (PC) [PC(18:0/22:6)], 9 phosphatidylethanolamines (PEs) [PE(16:0/22:6), PE(18:0/14:0), PE(18:0/18:1), PE(18:0/18:2), PE(18:0/20:3), PE(18:0/22:5), PE(18:0/22:6), PE(18:1/22:6), and PE(18:2/22:6)], and 1 phosphatidylserine (PS) [PS(18:0/18:0)], were positively associated with incident MetS (RRs: 1.16-1.30 per SD change; Bonferroni-corrected P<0.05). In network analysis, the strongest positive association for MetS incidence was evidenced in a module mainly composed of PEs containing C22:6 and PSs [RR: 1.21; 95% CI: 1.12, 1.31 per SD change; Bonferroni-corrected P<0.05]. This association was more pronounced in participants with lower erythrocyte total n-3 PUFA concentrations [Bonferroni-corrected Pinter(P value for the interaction)<0.05]. Elevated plasma concentrations of GPs, especially PEs with LCPUFAs or VLCPUFAs at the sn-2 position, are associated with higher risk of incident MetS. Future studies are merited to confirm our findings.

LC-ESI-MS/MS Method for the Profiling of Glycerophospholipids and its Application to the Analysis of Tobacco Hairy Roots as Early Indicators of Phenol Pollution

The growing impact of organic and inorganic pollutants on the environment has led to the development of numerous strategies to counteract this effect. Among all, green technologies such as phytoremediation, has won relevance for its low cost as well as being an eco-friendly and sustainable process. In the past years, tobacco hairy roots (HRs) have become a good example of the effectiveness of plants as a tool for removing different pollutants. In this sense, the understanding of the intracellular mechanisms involved in the phytoremediation process has become of great interest. Glycerophospholipids (GLPs) are a key factor on intracellular signaling, given that they can activate different pathways, despite there is not enough information available about their levels and fluctuation under certain stress conditions. The aim of this work was to develop of a new chromatographic method coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) with selected reaction monitoring (SRM) and data dependent scan detection for the evaluation of GLP profile after the exposure to phenol, to get a better understanding of lipids turnover and their effect on signaling pathways. This highly sensitive method allows the identification, separation and quantification in less than a 20 min-run of the eleven most relevant GPL species present in hairy tobacco root extracts after phenol exposure, and is suitable for evaluating small changes in GPL levels.

Serum Glycerophospholipid Profile in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Studies have shown that glycerophospholipids are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study adopted targeted metabolomic analysis to investigate the changes in serum glycerophospholipids in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and their differential expression in patients with different inflammatory subtypes. Patients with AECOPD admitted between January 2015 and December 2017 were enrolled, and their clinical data were collected. The patients’ gender, age, body mass index, and lung function were recorded. Routine blood and induced sputum tests were performed. Liquid chromatography-mass spectrometry was used to detect the serum glycerophospholipid metabolic profiles and to analyze the metabolic profile changes between the acute exacerbation and recovery stages as well as the differences between different inflammatory subtypes. A total of 58 patients were hospitalized for AECOPD, including 49 male patients with a mean age of 74.8 ± 10.0 years. In the metabolic profiles, the expression of lysophosphatidylcholine (LPC) 18:3, lysophosphatidylethanolamine (LPE) 16:1, and phosphatidylinositol (PI) 32:1 was significantly reduced in the acute exacerbation stage compared to the recovery stage (P < 0.05). The three glycerophospholipids were used to plot the receiver operating characteristic curves to predict the acute exacerbation/recovery stage, and the areas under the curves were all above 70%. There were no differential metabolites between the two groups of patients with blood eosinophil percentage (EOS%) ≥2% and <2% at exacerbation. The expression of LPC 18:3, LPE 16:1, and PI 32:1 was significantly reduced in the acute exacerbation stage compared to the recovery stage in the inflammatory subtype with blood EOS <2% (P < 0.05). Abnormalities in the metabolism of glycerophospholipids may be involved in the onset of AECOPD, especially in the non-eosinophilic subtype.

Effects of Dietary Supplementation with EPA-enriched Phosphatidylcholine and Phosphatidylethanolamine on Glycerophospholipid Profile in Cerebral Cortex of SAMP8 Mice fed with High-fat Diet.

The destruction of lipid homeostasis is associated with nervous system diseases such as Alzheimer's disease (AD). It has been reported that dietary EPA-enriched phosphatidylcholine (EPA-PC) and phosphatidylethanolamine (EPA-PE) could improve brain function. However, it was unclear that whether EPA-PC and EPA-PE intervention could change the lipid composition of cerebral cortex in AD mice. All the senescence-accelerated mouse-prone 8 (SAMP8) mice were fed with a high-fat diet for 8 weeks. After another 8 weeks of intervention with EPA-PC and EPA-PE (1%, w/w), the cerebral cortex lipid levels were determined by lipidomics. Results demonstrated that dietary supplementation with EPA-PE and EPA PC for 8 weeks significantly increased the amount of choline plasmalogen (pPC) and Lyso phosphatidylethanolamine (LPE) in the cerebral cortex of SAMP8 mice fed with high fat diet. Meanwhile, administration with EPA-PE and EPA-PC could significantly decrease the level of docosapentaenoic acid (DPA)-containing phosphatidylserine (PS) as well as increase the levels of arachidonic acid (AA)-containing phosphatidylethanolamine and PS in cerebral cortex. EPA-PE and EPA-PC could restore the lipid homeostasis of dementia mice to a certain degree, which might provide a potential novel therapy strategy and direction of dietary intervention in patients with cognitive impairment.

Glycerophospholipid profile alterations are associated with murine muscle-wasting phenotype.

Phospholipids are essential components of cellular membranes and are closely associated with cellular functions, but relationships involving skeletal muscle phospholipid profiles and their physiological phenotypes have remained unclear. We carried out comprehensive phospholipid analyses using liquid chromatography-tandem mass spectrometry to determine the phospholipid profiles of skeletal muscles derived from muscle-wasting mouse models, including denervated and Duchenne muscular dystrophy mouse models (mdx) as well as rescued mdx mice expressing truncated dystrophin. Consistent phosphatidylcholine and phosphatidylethanolamine alterations in skeletal muscles isolated from denervated and mdx mice were observed. Notably, the levels of these phospholipids binding polyunsaturated fatty acids were reduced in denervated and mdx muscles. Moreover, rescuing the mdx pathology by expressing truncated dystrophin led to the restoration of phospholipid profiles. Our findings support the hypothesis that phospholipid profiles of the skeletal muscle may be associated with skeletal muscle function.

Metabolomic Analysis of Serum Glycerophospholipid Levels in Eosinophilic and Neutrophilic Asthma

ObjectiveTo compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. MethodsDemographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ≥ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ≥ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. ResultsThe serum lysophosphatidylglycerol level was significantly higher in the group with ≥ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ≥ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ≥ 71% and the group with sputum neutrophils < 71%. ConclusionSerum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.

Glycerophospholipid Metabolism Alterations in Patients with Type 2 Diabetes Mellitus and Tuberculosis Comorbidity

Type-2 Diabetes (T2D) is a predisposing cause for developing tuberculosis (TB) in low- and middle-income countries. TB-T2D comorbidity worsens clinical control and prognosis of the affected individuals. The underlying metabolic alterations for this infectious-metabolic disease are still largely unknown. Possible mediators of the increased susceptibility to TB in diabetic patients are lipids levels, which are altered in individuals with T2D. To evaluate the modulation of glycerophospholipids in patients with TB-T2D, an untargeted lipidomic approach was developed by means of ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization/quadrupole time-of-flight mass spectrometry (ESI-QToF). In addition, tandem mass spectrometry was performed to determine the identity of the differentially expressed metabolites. We found that TB infected individuals with or without T2D share a common glycerophospholipid profile characterized by a decrease in phosphatidylcholines. A total of 14 glycerophospholipids were differentially deregulated in TB and TB-T2D patients and could potentially be considered biomarkers. It is necessary to further validate these identified lipids as biomarkers, focusing on the anticipate diagnosis for TB development in T2D predisposed individuals.

Changes in the Lipidomic Profile of Aqueous Humor in Open-Angle Glaucoma

To identify and determine differences in lipid profiles of aqueous humor (AH) in patients with open-angle glaucoma (OAG). The lipidomic profile of 10 samples of AH of patients with OAG and 10 controls was analyzed. Patients with a history of anterior segment surgery, anterior segment pathology, or intraocular injections were excluded. Topical ocular medications within the last 6 months were reported. AH was obtained during the first step of nonperforating deep sclerotomy in OAG patients and during refractive lensectomy in controls. Lipidomic ultra-performance liquid chromatography mass spectrometry was used to perform an optimal profiling of glycerolipids, sterol lipids, sphingolipids, and glycerophospholipids. Metabolite extraction was accomplished by fractionating the samples into pools of species with similar physicochemical properties. The levels of 37 of 110 lipids changed in OAG when compared with controls samples. The concentration of most diacylglycerophosphocholines and 1-ether, 2-acylglycerophosphocholines increases in OAG when compared with healthy controls. In addition, 14 sphingomyelins increased significantly, up to 2.75-fold, in OAG. 5 cholesteryl esters are also present at higher levels in OAG when compared with controls. The lipid composition of AH in OAG patients shows differences when compared with healthy individuals. Changes in lipid synthesis may relate to oxidative stress metabolic response in OAG and may play an important role in the pathophysiology of the disease.

Regional changes in CNS and retinal glycerophospholipid profiles with age: a molecular blueprint

We present here a quantitative molecular blueprint of the three major glycerophospholipid (GPL) classes, phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE), in retina and six regions of the brain in C57Bl6 mice at 2, 10, and 26 months of age. We found an age-related increase in molecular species containing saturated and monoenoic FAs and an overall decrease in the longer-chain PUFA molecular species across brain regions, with loss of DHA-containing molecular species as the most consistent and dramatic finding. Although we found very-long-chain PUFAs (VLC-PUFAs) (⩾C28) in PC in the retina, no detectable levels were found in any brain region at any of the ages examined. All brain regions (except hippocampus and retina) showed a significant increase with age in PE plasmalogens. All three retina GPLs had di-PUFA molecular species (predominantly 44:12), which were most abundant in PS (∼30%). In contrast, low levels of di-PUFA GPL (1–2%) were found in all regions of the brain. This study provides a regional and age-related assessment of the brain’s lipidome with a level of detail, inclusion, and quantification that has not heretofore been published.

Quantitative profiling of glycerophospholipids during mouse and human macrophage differentiation using targeted mass spectrometry

Macrophage lipid metabolism plays a pivotal role in innate and adaptive immune responses. Previous studies have shown that this process plays a role in infections and contributes to the pathogenesis of diabetes, atherosclerosis, and other immunometabolic diseases. M1 macrophages, or classically activated macrophages, are key players in the defense against bacterial infections. M2 macrophages, or alternatively activated macrophages, are involved in anti-inflammatory responses. Using the multiple reaction monitoring method, we identified changes in lipid composition during the differentiation of human and murine macrophages. We detected over 300 lipid molecules in mammalian macrophages, and we observed a striking shift in the composition of glycerophospholipids (GLs) from saturated and monounsaturated to polyunsaturated during human macrophage polarization. Moreover, M2 macrophages showed a higher level of lysophospholipids (lysoGLs) than did M1 macrophages. The lysoPI species increased in human and mouse M2 macrophages, suggesting that they may be involved in M2 macrophage polarization and anti-inflammatory processes. Collectively, these results indicate that lipids may play a role in the pro- and anti-inflammatory activities of macrophages and may be markers of the macrophage activation state.

Changes in lipidomic profile of aqueous humour in Fuchs endothelial dystrophy.

To identify and determine differences in lipid profile of aqueous humour (AH) in patients with Fuchs endothelial corneal dystrophy (FECD). Lipidomic profile of eight AH samples of FECD patients and 10 control samples was analysed. Patients with previous history of anterior segment surgery, anterior segment pathology or intraocular injections were excluded. Topical ocular medications within the last 6months were reported. Aqueous humour (AH) was obtained during the first step of Descemet membrane endothelial keratoplasty in FECD patients and during refractive lensectomy in the control group. Lipidomic ultra-performance liquid chromatography mass spectrometry was used to perform an optimal profiling of glycerolipids, sterol lipids, sphingolipids and glycerophospholipids. Metabolite extraction was accomplished by fractionating the samples into pools of species with similar physicochemical properties. The levels of 27 of 110 lipids change significantly in the AH of FECD eyes when compared to control samples. The concentration of most diacylglycerophosphocholines and 1-ether, 2-acylglycerophosphocholines increases in the AH of FECD eyes when compared to healthy controls. In addition, eight sphingomyelins and up to two long-chain highly unsaturated cholesteryl esters present higher levels in FECD samples when compared to controls. The lipid composition of AH in FECD patients differs from that of healthy subjects. Those changes may reflect oxidative stress-related changes in the lipid metabolism of the corneal endothelial cells in FECD.

Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii.

Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03–149.1 (polymyxin-susceptible) and 03–149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.

Dietary Effects on Plasma Glycerophospholipids.

Human milk provides a complex mixture of animal lipids, whereas the fat supply of most modern infant formula is based on vegetable oils. We studied the effects of breast-feeding and of feeding infant formula either without or with dairy goat lipids on the composition of infant plasma glycerophospholipids. Healthy-term infants were randomized double blind to feeding with infant formula based on whole goats' milk (GIF, approximately 60% milk fat and 40% vegetable oils) or a control cows' milk infant formula based on vegetable oils (VIF) from 2 weeks after birth. A reference group of fully breast-fed infants was also followed. At the age 4 months, blood samples were collected and plasma glycerophospholipids were analyzed with liquid chromatography coupled to triple quadrupole mass spectrometry. The group of breast-fed infants showed significantly higher contents of glycerophospholipid species containing sn-2 palmitic acid [PC(16:0/16:0) and PC(18:0/16:0)] and significantly higher contents of glycerophospholipid species containing long-chain polyunsaturated fatty acids than infants in both formula groups. The GIF group demonstrated significantly higher glycerophospholipid species containing myristic acid [LPC(14:0), PC(14:0/18:1), PC(16:0/14:0)] and palmitoleic acid [LPC(16:1), PC(16:0/16:1), and PC(16:1/18:1)] than the VIF group. We conclude that breast-feeding induces marked differences in infant plasma glycerophospholipid profiles compared with formula feeding, whereas the studied different sources of formula fat resulted in limited effects on plasma glycerophospholipids.