Plasma Lipidome Research Articles

Plasma lipidome is dysregulated in Alzheimer\u2019s disease and is associated with disease risk genes

Lipidomics research could provide insights of pathobiological mechanisms in Alzheimer’s disease. This study explores a battery of plasma lipids that can differentiate Alzheimer’s disease (AD) patients from healthy controls and determines whether lipid profiles correlate with genetic risk for AD. AD plasma samples were collected from the Sydney Memory and Ageing Study (MAS) Sydney, Australia (aged range 75–97 years; 51.2% male). Untargeted lipidomics analysis was performed by liquid chromatography coupled–mass spectrometry (LC–MS/MS). We found that several lipid species from nine lipid classes, particularly sphingomyelins (SMs), cholesterol esters (ChEs), phosphatidylcholines (PCs), phosphatidylethanolamines (PIs), phosphatidylinositols (PIs), and triglycerides (TGs) are dysregulated in AD patients and may help discriminate them from healthy controls. However, when the lipid species were grouped together into lipid subgroups, only the DG group was significantly higher in AD. ChEs, SMs, and TGs resulted in good classification accuracy using the Glmnet algorithm (elastic net penalization for the generalized linear model [glm]) with more than 80% AUC. In general, group lipids and the lipid subclasses LPC and PE had less classification accuracy compared to the other subclasses. We also found significant increases in SMs, PIs, and the LPE/PE ratio in human U251 astroglioma cell lines exposed to pathophysiological concentrations of oligomeric Aβ42. This suggests that oligomeric Aβ42 plays a contributory, if not causal role, in mediating changes in lipid profiles in AD that can be detected in the periphery. In addition, we evaluated the association of plasma lipid profiles with AD-related single nucleotide polymorphisms (SNPs) and polygenic risk scores (PRS) of AD. We found that FERMT2 and MS4A6A showed a significantly differential association with lipids in all lipid classes across disease and control groups. ABCA7 had a differential association with more than half of the DG lipids (52.63%) and PI lipids (57.14%), respectively. Additionally, 43.4% of lipids in the SM class were differentially associated with CLU. More than 30% of lipids in ChE, PE, and TG classes had differential associations with separate genes (ChE-PICALM, SLC24A4, and SORL1; PE-CLU and CR1; TG-BINI) between AD and control group. These data may provide renewed insights into the pathobiology of AD and the feasibility of identifying individuals with greater AD risk.

1151-P: Differential Associations between Plasma Lipids and Insulin Resistance in Women with and without Type 1 Diabetes

People with type 1 diabetes (T1D) can have significant insulin resistance (IR), increasing risk for cardiovascular disease and mortality. Associations between circulating lipids and IR have been demonstrated; whether these associations differ in people with and without T1D is not well understood. We analyzed targeted plasma lipidomics in 30 premenopausal women aged 18-45 years (15 with T1D and 15 without diabetes [non-DM]) who underwent a hyperinsulinemic euglycemic clamp to measure glucose infusion rate (GIR). After stratifying by diabetes status, women were classified by tertiles of GIR, and moderated t-tests were used to compare lipids in the least IR vs. most IR tertile. Ceramide (Cer) 18:0, sphingomylelin (SM) 24:3 and SM 18:0 were higher in the most IR tertile in both groups (Table). However, 4 lipids (2 Cer, 1 SM, and 1 dihyrdoceramide [DHCer]) were higher in the most IR tertile in non-DM women, but were not significantly different in women with T1D. Eleven lipids (1 SM, 1 Cer, 1 DHCer, 1 lactosylceramide, and 7 1,2-diacylglycerols) were higher in the most IR tertile in women with T1D, but were not significantly different in non-DM women. Plasma lipid species were differentially associated with IR in women with and without T1D. Future work is needed to validate these findings in a larger sample of women and men, and to understand how these biomarkers relate to IR and lipid metabolism in T1D.View largeDownload slideView largeDownload slide DisclosureL. Pyle: None. T. B. Vigers: None. I. E. Schauer: None. B. C. Bergman: Consultant; Spouse/Partner; AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk. J. K. Snell-bergeon: Stock/Shareholder; Self; GlaxoSmithKline plc.FundingAmerican Diabetes Association (7-13-CD-10 to J.K.S-B.); National Heart, Lung, and Blood Institute (R01HL61753, HL79611, HL113029); JDRF (17-2013-313) University of Colorado Diabetes & Endocrinology Research Center (P30DK57516); National Institutes of Health (M01-RR00051)

A high throughput lipidomics method and its application in atrial fibrillation based on 96-well plate pretreatment and liquid chromatography-mass spectrometry

Successful applications of lipidomics in clinic need study large-scale samples, and the bottlenecks are in throughput and robustness of the lipid analytical method. Here, we report an untargeted lipidomics method by combining high throughput pretreatment in the 96-well plate with ultra-high performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry. The developed method was validated to have satisfactory analytical characteristics in terms of linearity, repeatability and extraction recovery. It can be used to handle 96 samples simultaneously in 25 min and detect 441 lipids in plasma sample. Storage stability investigation on lipid extracts provided an operable procedure for large-scale sample analysis and demonstrated most lipids were stable in autosampler at 10 °C within 36 h and at -80 °C within 72 h after the pretreatment. To prove the usefulness, the method was employed to investigate abnormal plasma lipidome related to atrial fibrillation. A biomarker panel with the area under the curve (AUC) values of 0.831 and 0.745 was achieved in the discovery and external validation sets, respectively. These results showed that the developed method is applicable for large-scale biological sample handling and lipid analysis of plasma.

An exploratory analysis of comparative plasma metabolomic and lipidomic profiling in salt-sensitive and salt-resistant individuals from The Dietary Approaches to Stop Hypertension Sodium Trial.

Objective:This study conducted exploratory metabolomic and lipidomic profiling of plasma samples from the DASH (Dietary Approaches to Stop Hypertension) Sodium Trial to identify unique plasma biomarkers to identify salt-sensitive versus salt-resistant participants.Methods:Utilizing plasma samples from the DASH-Sodium Trial, we conducted untargeted metabolomic and lipidomic profiling on plasma from salt-sensitive and salt-resistant DASH-Sodium Trial participants. Study 1 analyzed plasma from 106 salt-sensitive and 85 salt-resistant participants obtained during screening when participants consumed their regular diet. Study 2 examined paired within-participant plasma samples in 20 salt-sensitive and 20 salt-resistant participants during a high-salt and low-salt dietary intervention. To investigate differences in metabolites or lipidomes that could discriminate between salt-sensitive and salt-resistant participants or the response to a dietary sodium intervention Principal Component Analysis and Orthogonal Partial Least Square Discriminant Analysis was conducted. Differential expression analysis was performed to validate observed variance and to determine the statistical significance.Results:Differential expression analysis between salt-sensitive and salt-resistant participants at screening revealed no difference in plasma metabolites or lipidomes. In contrast, three annotated plasma metabolites, tocopherol alpha, 2-ketoisocaproic acid, and citramalic acid, differed significantly between high-sodium and low-sodium dietary interventions in salt-sensitive participants.Conclusion:In DASH-Sodium Trial participants on a regular diet, plasma metabolomic or lipidomic signatures were not different between salt-sensitive and salt-resistant participants. High-sodium intake was associated with changes in specific circulating metabolites in salt-sensitive participants. Further studies are needed to validate the identified metabolites as potential biomarkers that are associated with the salt sensitivity of blood pressure.

Plasma lipidome profiling of newborns with antenatal exposure to Zika virus.

The 2015-2016 Zika virus (ZIKV) outbreak in Brazil was remarkably linked to the incidence of microcephaly and other deleterious clinical manifestations, including eye abnormalities, in newborns. It is known that ZIKV targets the placenta, triggering an inflammatory profile that may cause placental insufficiency. Transplacental lipid transport is delicately regulated during pregnancy and deficiency on the delivery of lipids such as arachidonic and docosahexaenoic acids may lead to deficits in both brain and retina during fetal development. Here, plasma lipidome profiles of ZIKV exposed microcephalic and normocephalic newborns were compared to non-infected controls. Our results reveal major alterations in circulating lipids from both ZIKV exposed newborns with and without microcephaly relative to controls. In newborns with microcephaly, the plasma concentrations of hydroxyoctadecadienoic acid (HODE), primarily as 13-HODE isomer, derived from linoleic acid were higher as compared to normocephalic ZIKV exposed newborns and controls. Total HODE concentrations were also positively associated with levels of other oxidized lipids and several circulating free fatty acids in newborns, indicating a possible plasma lipidome signature of microcephaly. Moreover, higher concentrations of lysophosphatidylcholine in ZIKV exposed normocephalic newborns relative to controls suggest a potential disruption of polyunsaturated fatty acids transport across the blood-brain barrier of fetuses. The latter data is particularly important given the neurocognitive and neurodevelopmental abnormalities observed in follow-up studies involving children with antenatal ZIKV exposure, but normocephalic at birth. Taken together, our data reveal that plasma lipidome alterations associated with antenatal exposure to ZIKV could contribute to identification and monitoring of the wide spectrum of clinical phenotypes at birth and further, during childhood.

Characterization of the Plasma Lipidome in Dairy Cattle Transitioning from Gestation to Lactation: Identifying Novel Biomarkers of Metabolic Impairment.

The discovery of novel biomarkers for peripartal diseases in dairy cows can improve our understanding of normal and dysfunctional metabolism, and lead to nutritional interventions that improve health and milk production. Our objectives were to characterize the plasma lipidome and identify metabolites associated with common markers of metabolic disease in peripartal dairy cattle. Multiparous Holstein cows (n = 27) were enrolled 30 d prior to expected parturition. Blood and liver samples were routinely collected through to d 14 postpartum. Untargeted lipidomics was performed using quadrupole time-of-flight mass spectrometry. Based on postpartum measures, cows were categorized into low or high total fatty acid area under the curve (total FAAUC; d 1–14 postpartum; 4915 ± 1369 vs. 12,501 ± 2761 (μmol/L × 14 d); n = 18), β-hydroxybutyrate AUC (BHBAAUC; d 1–14 postpartum; 4583 ± 459 vs. 7901 ± 1206 (μmol/L × 14 d); n = 18), or liver lipid content (d 5 and 14 postpartum; 5 ± 1 vs. 12 ± 2% of wet weight; n = 18). Cows displayed decreases in plasma triacylglycerols and monoalkyl-diacylglycerols, and the majority of phospholipids reached a nadir at parturition. Phosphatidylcholines (PC) 32:3, 35:5, and 37:5 were specific for high total FAAUC, PC 31:3, 32:3, 35:5, and 37:5 were specific for high BHBAAUC, and PC 31:2, 31:3, and 32:3 were specific for high liver lipid content. PC 32:3 was specific for elevated total FA, BHBA, and liver lipid content. Lipidomics revealed a dynamic peripartal lipidome remodeling, and lipid markers associated with elevated total FA, BHBA, and liver lipid content. The effectiveness of nutrition to impact these lipid biomarkers for preventing excess lipolysis and fatty liver warrants evaluation.

UPLC-MS/MS-based plasma lipidomics reveal a distinctive signature in systemic lupus erythematosus patients.

Global lipidomics is of considerable utility for exploring altered lipid profiles and unique diagnostic biomarkers in diseases. We aim to apply ultra‐performance liquid chromatography‐tandem mass spectrometry to characterize the lipidomics profile in systemic lupus erythematosus (SLE) patients and explore the underlying pathogenic pathways using the lipidomics approach. Plasma samples from 18 SLE patients, 20 rheumatoid arthritis (RA) patients, and 20 healthy controls (HC) were collected. A total of 467 lipids molecular features were annotated from each sample. Orthogonal partial least square‐discriminant analysis, K‐mean clustering analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated disrupted lipid metabolism in SLE patients, especially in phospholipid, glycerol, and sphingolipid metabolism. The area under curve (AUC) of lipid metabolism biomarkers was better than SLE inflammation markers that ordinarily used in the clinic. Proposed model of monoglyceride (MG) (16:0), MG (18:0), phosphatidylethanolamine (PE) (18:3–16:0), PE (16:0–20:4), and phosphatidylcholine (PC) (O‐16:2–18:3) yielded AUC 1.000 (95% CI, 1.000–1.000), specificity 100% and sensitivity 100% in the diagnosis of SLE from HC. A panel of three lipids molecular PC (18:3‐18:1), PE (20:3–18:0), PE (16:0–20:4) permitted to accurately diagnosis of SLE from RA, with AUC 0.921 (95% CI, 0.828–1.000), 70% specificity, and 100% sensitivity. The plasma lipidomics signatures could serve as an efficient and accurate tool for early diagnosis and provide unprecedented insight into the pathogenesis of SLE.

Mass Spectrometry-Based Lipidomics Reveals Differential Changes in the Accumulated Lipid Classes in Chronic Kidney Disease.

Chronic kidney disease (CKD) is characterized by the progressive loss of functional nephrons. Although cardiovascular disease (CVD) complications and atherosclerosis are the leading causes of morbidity and mortality in CKD, the mechanism by which the progression of CVD accelerates remains unclear. To reveal the molecular mechanisms associated with atherosclerosis linked to CKD, we applied a shotgun lipidomics approach fortified with standard laboratory analytical methods and gas chromatography-mass spectrometry technique on selected lipid components and precursors to analyze the plasma lipidome in CKD and classical CVD patients. The MS-based lipidome profiling revealed the upregulation of triacylglycerols in CKD and downregulation of cholesterol/cholesteryl esters, sphingomyelins, phosphatidylcholines, phosphatidylethanolamines and ceramides as compared to CVD group and controls. We have further observed a decreased abundance of seven fatty acids in CKD with strong inter-correlation. In contrast, the level of glycerol was elevated in CKD in comparison to all analyzed groups. Our results revealed the putative existence of a functional causative link—the low cholesterol level correlated with lower estimated glomerular filtration rate and kidney dysfunction that supports the postulated “reverse epidemiology” theory and suggest that the lipidomic background of atherosclerosis-related to CKD is unique and might be associated with other cellular factors, i.e., inflammation.

Hepatic lipidomic remodeling in severe obesity manifests with steatosis and does not evolve with non-alcoholic steatohepatitis

Obesity often leads to non-alcoholic fatty liver disease (NAFLD), which can progress from simple steatosis (non-alcoholic fatty liver (NAFL)) to non-alcoholic steatohepatitis (NASH). The accumulation of certain lipid subtypes is linked with worsening metabolic and liver disease, however, specific changes during progression from No-NAFL to NAFL then NASH are unresolved. Herein, we characterise the liver, adipose tissue and plasma lipidome of worsening NAFLD in obesity, and evaluate the utility of plasma lipids as biomarkers of NAFLD. Venous blood, liver, visceral and subcutaneous adipose tissue samples were obtained from 181 patients undergoing bariatric surgery. NAFLD severity was assessed histologically. Lipidomic analysis was performed using liquid chromatography-tandem mass spectrometry. The liver lipidome showed substantial changes with increasing steatosis, with increased triacylglycerols, diacylglycerols and sphingolipids including ceramide, dihydroceramide, hexosyl-ceramide and GM3 ganglioside species. These lipid species were also increased in plasma with increasing hepatic steatosis and showed strong correlations with liver lipids. Adipose tissue lipidomes showed no correlation with NAFLD. There were no significant changes in liver lipids with NASH compared to NAFL. The addition of plasma lipid variables to routine markers yielded significant improvements in diagnostic accuracy for NASH (AUROC 0.667 vs. 0.785, p=0.025). Overall, these data provide a detailed description of the lipidomic changes with worsening NAFLD, showing significant changes with steatosis but no additional changes with NASH. Alterations in the liver lipidome are paralleled by similar changes in plasma. Further investigation is warranted into the potential utility of plasma lipids as non-invasive biomarkers of NAFLD in obesity. Non-alcoholic fatty liver disease (NAFLD) is characterised by distinct changes in the liver lipidome with steatosis. The development of non-alcoholic steatohepatitis (NASH) does not result in further changes in the lipidome. Lipids within body fat do not appear to influence the lipid profile of the liver or blood. Changes in liver lipids are paralleled by changes in blood lipids. This has potential to be developed into a non-invasive biomarker for NAFLD. ACTRN12615000875505.

Lipids: biomarkers of healthy aging.

Life expectancy, and longevity have been increasing in recent years. However, this is, in most cases, accompanied by age-related diseases. Thus, it became essential to better understand the mechanisms inherent to aging, and to establish biomarkers that characterize this physiological process. Among all biomolecules, lipids appear to be a good target for the study of these biomarkers. In fact, some lipids have already been associated with age-related diseases. With the development of analytical techniques such as Mass Spectrometry, and Nuclear Magnetic Resonance, Lipidomics has been increasingly used to study pathological, and physiological states of an organism. Thus, the study of serum, and plasma lipidome in centenarians, and elderly individuals without age-related diseases can be a useful tool for the identification of aging biomarkers, and to understand physiological aging, and longevity. This review focus on the importance of lipids as biomarkers of aging, and summarize the changes in the lipidome that have been associated with aging, and longevity.

Plasma Metabolome and Lipidome Associations with Type 2 Diabetes and Diabetic Nephropathy.

We conducted untargeted metabolomics analysis of plasma samples from a cross-sectional case–control study with 30 healthy controls, 30 patients with diabetes mellitus and normal renal function (DM-N), and 30 early diabetic nephropathy (DKD) patients using liquid chromatography-mass spectrometry (LC-MS). We employed two different modes of MS acquisition on a high-resolution MS instrument for identification and semi-quantification, and analyzed data using an advanced multivariate method for prioritizing differentially abundant metabolites. We obtained semi-quantification data for 1088 unique compounds (~55% lipids), excluding compounds that may be either exogenous compounds or treated as medication. Supervised classification analysis over a confounding-free partial correlation network shows that prostaglandins, phospholipids, nucleotides, sugars, and glycans are elevated in the DM-N and DKD patients, whereas glutamine, phenylacetylglutamine, 3-indoxyl sulfate, acetylphenylalanine, xanthine, dimethyluric acid, and asymmetric dimethylarginine are increased in DKD compared to DM-N. The data recapitulate the well-established plasma metabolome changes associated with DM-N and suggest uremic solutes and oxidative stress markers as the compounds indicating early renal function decline in DM patients.

Age and sex are associated with the plasma lipidome: findings from the GOLDN study

BackgroundDeveloping an understanding of the biochemistry of aging in both sexes is critical for managing disease throughout the lifespan. Lipidomic associations with age and sex have been reported, but prior studies are limited by measurements in serum rather than plasma or by participants taking lipid-lowering medications.MethodsOur study included lipidomic data from 980 participants aged 18–87 years old from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN). Participants were off lipid-lowering medications for at least 4 weeks, and signal intensities of 413 known lipid species were measured in plasma. We examined linear age and sex associations with signal intensity of (a) 413 lipid species; (b) 6 lipid classes (glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, fatty acids, and acylcarnitines); and (c) 15 lipid subclasses; as well as with the particle sizes of three lipoproteins.ResultsSignificant age associations were identified in 4 classes, 11 subclasses, 147 species, and particle size of one lipoprotein while significant sex differences were identified in 5 classes, 12 subclasses, 248 species, and particle sizes of two lipoproteins. For many lipid species (n = 97), age-related associations were significantly different between males and females. Age*sex interaction effects were most prevalent among phosphatidylcholines, sphingomyelins, and triglycerides.ConclusionWe identified several lipid species, subclasses, and classes that differ by age and sex; these lipid phenotypes may serve as useful biomarkers for lipid changes and associated cardiovascular risk with aging in the future. Future studies of age-related changes throughout the adult lifespan of both sexes are warranted.Trial registrationClinicalTrials.gov NCT00083369; May 21, 2004.

Aberrations in circulating ceramide levels are associated with poor clinical outcomes across localised and metastatic prostate cancer.

Dysregulated lipid metabolism is associated with more aggressive pathology and poorer prognosis in prostate cancer (PC). The primary aim of the study is to assess the relationship between the plasma lipidome and clinical outcomes in localised and metastatic PC. The secondary aim is to validate a prognostic circulating 3-lipid signature specific to metastatic castration-resistant PC (mCRPC). Comprehensive lipidomic analysis was performed on pre-treatment plasma samples from men with localised PC (N = 389), metastatic hormone-sensitive PC (mHSPC)(N = 44), or mCRPC (validation cohort, N = 137). Clinical outcomes from our previously published mCRPC cohort (N = 159) that was used to derive the prognostic circulating 3-lipid signature, were updated. Associations between circulating lipids and clinical outcomes were examined by Cox regression and latent class analysis. Circulating lipid profiles featuring elevated levels of ceramide species were associated with metastatic relapse in localised PC (HR 5.80, 95% CI 3.04-11.1, P = 1 × 10-6), earlier testosterone suppression failure in mHSPC (HR 3.70, 95% CI 1.37-10.0, P = 0.01), and shorter overall survival in mCRPC (HR 2.54, 95% CI 1.73-3.72, P = 1 × 10-6). The prognostic significance of circulating lipid profiles in localised PC was independent of standard clinicopathological and metabolic factors (P < 0.0002). The 3-lipid signature was verified in the mCRPC validation cohort (HR 2.39, 95% CI 1.63-3.51, P = 1 × 10-5). Elevated circulating ceramide species are associated with poorer clinical outcomes across the natural history of PC. These clinically actionable lipid profiles could be therapeutically targeted in prospective clinical trials to potentially improve PC outcomes.

Lipidomic Perturbations in Cynomolgus Monkeys are Regulated by Thyroid Stimulating Hormone.

Thyroid disease affects an estimated 200 million people worldwide, and is commonly associated with increased blood lipid levels. However, the mechanism by which thyroid-stimulating hormone (TSH) affects lipid profiles is not clear. Twenty-four cynomolgus monkeys were treated with a novel exogenous recombinant human TSH (rhTSH) (SNA001) at 9 μg kg−1, 22 μg kg−1, or 54 μg kg−1, and reference rhTSH (Thyrogen®) at 22 μg kg−1. The primary TSH (SNA001) pharmacokinetic (PK) parameters increased in a dose-dependent manner across the dose range of 9 μg kg−1, 22 μg kg−1, or 54 μg kg−1. Peak triiodothyronine (T3) and thyroxine (T4) levels were reached within 24 h after rhTSH administration, which was delayed by approximately 20 h. In total, 420 lipid species were detected and quantified by ultra-performance liquid chromatography high resolution spectrometry (UPLC-HR-MS)-based lipidomics. Notably, peak levels of lipid accumulation, particularly sphingomyelin (SM) and triglycerides (TG), appeared at 4 and 24 h, which was consistent with the pattern of TSH and T3/T4 levels, respectively. According to weighted correlation network analysis (WGCNA), perturbations of many lipid species were strongly correlated with TSH and T3/T4 levels. TSH and the stimulated T3/T4 levels and lipid profiles following SNA001 administration were comparable to those after administration of the reference rhTSH (Thyrogen®). The plasma lipidome and changes in lipid levels after rhTSH stimulation were associated with TSH and T3/T4 concentrations. T3/T4 and lipid profiles were delayed after TSH stimulation. Such phenomena require further exploration.

Fine particulate matter (PM2.5) inhalation-induced alterations in the plasma lipidome as promoters of vascular inflammation and insulin resistance.

Fine particulate matter (PM2.5) air pollution exposure increases the risk of developing cardiovascular disease (CVD). Although the precise mechanisms by which air pollution exposure increases CVD risk remain uncertain, research indicates that PM2.5-induced endothelial dysfunction contributes to CVD risk. Previous studies demonstrate that concentrated ambient PM2.5 (CAP) exposure induces vascular inflammation and impairs insulin and vascular endothelial growth factor (VEGF) signaling dependent on pulmonary oxidative stress. To assess whether CAP exposure induces these vascular effects via plasmatic factors, we incubated aortas from naïve mice with plasma isolated from mice exposed to HEPA-filtered air or CAP (9 days) and examined vascular inflammation and insulin and VEGF signaling. We found that treatment of naïve aortas with plasma from CAP-exposed mice activates NF-κBα and induces insulin and VEGF resistance, indicating transmission by plasmatic factor(s). To identify putative factors, we exposed lung-specific ecSOD-transgenic (ecSOD-Tg) mice and wild-type (WT) littermates to CAP at concentrations of either ∼60 µg/m3 (CAP60) or ∼100 µg/m3 (CAP100) and measured the abundance of plasma metabolites by mass spectrometry. In WT mice, both CAP concentrations increased levels of fatty acids such as palmitate, myristate, and palmitoleate and decreased numerous phospholipid species; however, these CAP-induced changes in the plasma lipidome were prevented in ecSOD-Tg mice. Consistent with the literature, we found that fatty acids such as palmitate are sufficient to promote endothelial inflammation. Collectively, our findings suggest that PM2.5 exposure, by inducing pulmonary oxidative stress, promotes unique lipidomic changes characterized by high levels of circulating fatty acids, which are sufficient to trigger vascular pathology.NEW & NOTEWORTHY We found that circulating plasma constituents are responsible for air pollution-induced vascular pathologies. Inhalation of fine particulate matter (≤PM2.5) promotes a unique form of dyslipidemia that manifests in a manner dependent upon pulmonary oxidative stress. The air pollution-engendered dyslipidemic phenotype is characterized by elevated free fatty acid species and diminished phospholipid species, which could contribute to vascular inflammation and loss of insulin sensitivity.

Plasma lipidomics profile in pregnancy and gestational diabetes risk: a prospective study in a multiracial/ethnic cohort

IntroductionDisruption of lipid metabolism is implicated in gestational diabetes (GDM). However, prospective studies on lipidomics and GDM risk in race/ethnically diverse populations are sparse. Here, we aimed to (1) identify...

Adverse Effects of Refeeding on the Plasma Lipidome in Young Individuals With Anorexia Nervosa?

Refeeding is the cornerstone of anorexia nervosa (AN) treatment, but little is known regarding the optimal pace and dietary composition or possible adverse effects of current clinical practices. Plasma lipids may be a moderating factor underlying unfavorable refeeding effects in AN, such as an abnormal central body fat distribution. The objective of this study was to analyze the plasma lipidome in the acutely underweight state of AN before and after refeeding. Using high-throughput quantitative mass spectrometry-based shotgun lipidomics, we measured 13 lipid classes and 204 lipid species or subspecies in the plasma of young female patients with acute AN, before (n= 39) and after (n= 23) short-term weight restoration during an intensive inpatient refeeding program (median body mass index [BMI] increase= 26.4%), in comparison to those in healthy control participants (n= 37). Before inpatient treatment, patients with AN exhibited increased concentrations of cholesterol and several other lipid classes. After refeeding, multiple lipid classes including cholesterol and ceramides, as well as certain ceramide species previously associated with obesity or overfeeding, showed increased concentrations, and a pattern of shorter and more saturated triacylgycerides emerged. A machine learning model trained to predict BMI based on the lipidomic profiles revealed a sizable overprediction in patients with AN after weight restoration. The results point toward a profound lipid dysregulation with similarities to obesity and other features of the metabolic syndrome after short-term weight restoration. Thus, this study provides evidence for possible short-term adverse effects of current refeeding practices on the metabolic state and should inspire more research on nutritional interventions in AN.

Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted "Shotgun" Lipidomic Approach Reveals Low-Abundance Plasma Phospholipids and Dynamic Recovery over 8-Day Period, a Single-Center Observational Study.

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.

The effect of gut microbiota on the intestinal lipidome of mice

Gut microbiota significantly influence the plasma and liver lipidome. An interconnecting metabolite is acetate generated after degradation and fermentation of dietary fiber by the gut microbiota, which is metabolized in the liver into longer chain fatty acids and complex lipids reaching the circulation. Whether these systemic changes are accompanied by alternations of the intestinal lipidome is unclear. Therefore, we quantified glycerophospholipids, sphingolipids and sterols in ileum and colon, the two segments containing the highest densities of microbes in the gastrointestinal tract, of germfree and specific pathogen free mice using mass spectrometry-based lipidomics. We found that the presence of gut microbes lowers the free cholesterol content in colon while elevating phosphatidylcholine levels. Further, PUFA-containing phosphatidylcholine and -ethanolamine fractions are increased in ileum and colon of germfree compared to SPF mice. A total fatty acid analysis by GC–MS revealed higher levels of arachidonic and docosahexaenoic acid in the ileum of germfree mice indicating that the gut microbiota inhibits PUFA metabolism in the small intestine.

Dairy-Derived Emulsifiers in Infant Formula Show Marginal Effects on the Plasma Lipid Profile and Brain Structure in Preterm Piglets Relative to Soy Lecithin.

Breastfed infants have higher intestinal lipid absorption and neurodevelopmental outcomes compared to formula-fed infants, which may relate to a different surface layer structure of fat globules in infant formula. This study investigated if dairy-derived emulsifiers increased lipid absorption and neurodevelopment relative to soy lecithin in newborn preterm piglets. Piglets received a formula diet containing soy lecithin (SL) or whey protein concentrate enriched in extracellular vesicles (WPC-A-EV) or phospholipids (WPC-PL) for 19 days. Both WPC-A-EV and WPC-PL emulsions, but not the intact diets, increased in vitro lipolysis compared to SL. The main differences of plasma lipidomics analysis were increased levels of some sphingolipids, and lipid molecules with odd-chain (17:1, 19:1, 19:3) as well as mono- and polyunsaturated fatty acyl chains (16:1, 20:1, 20:3) in the WPC-A-EV and WPC-PL groups and increased 18:2 fatty acyls in the SL group. Indirect monitoring of intestinal triacylglycerol absorption showed no differences between groups. Diffusor tensor imaging measurements of mean diffusivity in the hippocampus were lower for WPC-A-EV and WPC-PL groups compared to SL indicating improved hippocampal maturation. No differences in hippocampal lipid composition or short-term memory were observed between groups. In conclusion, emulsification of fat globules in infant formula with dairy-derived emulsifiers altered the plasma lipid profile and hippocampal tissue diffusivity but had limited effects on other absorptive and learning abilities relative to SL in preterm piglets.