Our objective was to test whether a the plasticity is genetically influenced and b whether it is associated with the presence of type 2 diabetes t2d in the highrisk. It is prepared from whole blood that is collected with anticoagulants 9. Compared with healthy controls, 1 x 1 quehenberger, o. We hypothesized that both the absolute concentration and change in concentration. Wiggins departments of internal medicine and pathology, university of michigan medical school ann arbor, mi 48109 usa received june 1st. In addition to enhancing the current understanding of.
Plasma and serum lipidomics of healthy white adults shows. The materials, including resins used for chromatographic separation, were prewashed in buffer con. Blood samples were collected from all dogs control diet. The lipidome of the yeast saccharomyces cerevisiae has been characterised with an estimated 95% coverage. Metabolism of plasma membrane lipids in mycobacteria and. Pcsk9 inhibition alters the lipidome of plasma and. Sep 01, 2010 the complex plasma lipidome quantified 6 replies there are thousands of lipid species in our bodies that represent 6 categories, but we only usually hear about the subcategories of cholesterol and triglycerides. Alterations in the human plasma lipidome in response to. The human genetic predisposition to obesity is rather low. Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases. Therefore, we measured the plasma lipidome of individuals with ards at two timepoints to determine if changes in the plasma lipidome distinguished survivors from nonsurvivors.
Phospholipids, described in chapter 2, are polar and hydrophilic in the region that contains the phosphate group and nonpolar and hydrophobic throughout the rest. First largescale study of the genetics of human plasma. Changes in the canine plasma lipidome after short and. Validation of lipidomic analysis of human plasma and serum. Apr, 2020 the plasma membrane also called the cell membrane, and indeed all of the membranes surrounding organelles within the cell, are composed primarily of phospholipids and proteins. Polymeric complexes and fragments of albumin in normal human plasma bharati kshirsagar, barry wilson and roger c. Plasma lipidome reveals critical illness and recovery from. In this study, we used metabolomics and lipidomics approaches paired with univariate and multivariate statistical analyses to assess the effects of anticoagulant, temperature, and time on healthy human plasma samples collected to provide guidelines on sample collection, handling, and.
Pcsk9 inhibition alters the lipidome of plasma and lipoprotein fractions. For example, the human plasma lipidome consist of almost 600 distinct molecular species. The first cell lipidome to be published was that of a mouse macrophage in 2010. The human plasma proteome holds the promise of a revolution in disease diagnosis and therapeutic monitoring provided that major challenges in proteomics and related disciplines can be addressed.
Our results indicate that plasma is an optimal matrix for exploring lipid biomarkers because it represents the original properties of an individuals blood sample. Highthroughput quantitative lipidomics analysis of. Plasma and serum levels of most lipid metabolites were reduced by freezethawing. Biochemical analyses reveal that plasma contains over 600 structural forms of lipid molecules. Lipidomics reveals a remarkable diversity of lipids in human plasma. Plasma lipidome reveals critical illness and recovery from human. Methods and results we performed a genomewide association study gwas of 141 lipid species n2,181 individuals, followed by phenomewide scans phewas with 44 clinical endpoints related to cardiometabolic, psychiatric and gastrointestinal. High density lipoprotein hdl, human plas part of medix biochemica group. Lipidomic analysis of human plasma reveals etherlinked. Novel technologies for human blood plasma fractionation.
Associations of the plasma lipidome with mortality in the. Polymeric complexes and fragments of albumin in normal human. Human plasma lipidome variations in active tuberculosis. Robot grabs bag and pulls it across stationary knife 2. Any of a group of organic compounds, including the fats, oils, waxes, sterols, and triglycerides, that are insoluble in water but soluble in nonpolar organic solvents, are oily to the touch, and together with carbohydrates and proteins constitute the principal structural material of living cells. Dennis departments of chemistrybiochemistry and pharmacology school of medicine, university of california, san diego lipid maps glue grant nih u54 gm 69338 perception of the lipidome after the first decade of lipidomics. Two parallel robots work independently to increase pooling rate plasma bag opener designed and built by grifols engineering.
Using shannons entropy, we quantified the plasticity of the human plasma lipidome defined as the extent to which the lipidome departs froma homeostatic equilibrium. A definitive version of this document, which will differ from this version in editorial but not scientific detail, will. From the departments of medicine and pharmacology o. Utilising an imsdiams workflow to characterise and quantify the obesity or diabetes lipidome in human plasma lee a gethings1, johannes pc vissers1, oliver burt1, jose castroperez2, james i langridge1 1 waters corporation, wilmslow, united kingdom, 2 waters corporation, milford, ma, usa. Diversity of lipids in human plasma plasma lipids in the metabolic syndrome obesity and glycerolipids saturated and unsaturated fatty acids in the regulation of energy metabolism free fatty acid signaling and insulin sensitivity fish. The comparison of lipid extraction methods for the lipidomic. Plasma was collected from 15 morbidly obese and control subjects.
Prevention of cvd focuses on controlling or improving the lipid profile of patients at risk. Equine metabolic syndrome ems is similar to human metabolic syndrome, which is associated with abnormal lipidomic profiles. The human plasma proteome is likely to contain most, if not all, human proteins, as well as proteins derived from some viruses, bacteria, and fungi. Camera system automatically detects unsuccessful discharge. Buy high purity high density lipoprotein hdl from human plasma for ivd manufacturing of controls, calibrators and standards in stock. Plasma lipidomic and inflammatory cytokine profiles of horses.
Lipidomics unveils the complexity of the lipidome in. The levels of gm3 and glucer in human plasma were nearly fourfold of that in monkey plasma. Human plasma comprises hundreds of lipid species which differ in chemical structure and function. To understand the genetic influence on cvd, it is imperative to understand i if the human plasma lipidome is itself genetically controlled and ii whether the plasma lipidome and cvd share genetic influences. Smalls from the division of biophysics, department of medicine, boston university school of medicine, boston, massachusetts 02118. Knowledge about the plasma or serum lipidome, s1p and the influence of diets. Core e analysis of neutral lipids from human plasma. Barkley this protocol describes the extraction and direct measurement of cholesterol esters ces and triacylglycerols. The human plasma lipidome this article has no abstract. The results highlight the profound impact of evd on the host lipidome, leading to possible therapies for improving evd survival. The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. We also examined the association of human plasma lipidome with. We investigated the potential genetic redundancy in the human plasma lipidome in mexican americans and the association of these genetically derived phenotypes with common risk factors of cvd. Pdf human plasma lipidome is pleiotropically associated.
Easy, fast, and reproducible quantification of cholesterol. Analyses of cholesterol and triglycerides in plasma derived from nhps can easily be achieved using methods employed in humans. After separating the serum from the cellular components, it is allowed to undergo secondary clotting to ensure removal of all remaining components necessary for the clotting cascade. Structure and interactions of lipids in human plasma low. Whether the wide interindividual variability in the plasma lipidome contributes to the genetic basis of t2d is unknown. Machine learning of human plasma lipidomes for obesity estimation. Human serum samples for research biochemed services.
More diversity of ce species was also found in human plaques compared to plasma, indicating specific lipidome changes in the plaque during atherogenesis. Pdf impact of blood collection tubes and sample handling. Metabolism of plasma membrane lipids in mycobacteria and corynebacteria 123 pim6 species see below is viable, but shows severe plasma membrane abnormalities 36, suggesting that higher order pims may be involved in the maintenance of plasma membrane integrity. Many of the human proteins, introduced by lowlevel tissue leakage, ought to be present at. Lipid profiles of horses with ems compared to controls were characterized, as well as the inflammatory state of these horses. Lipidomics is the largescale study of pathways and networks of cellular lipids in biological systems the word lipidome is used to describe the complete lipid profile within a cell, tissue, organism, or ecosystem and is a subset of the metabolome which also includes the three other major classes of biological molecules. The effect of anticoagulants, temperature, and time on the. The method enables us to chromatographically separate. Lipids were extracted from plasma and analyzed using lcms, and msms to characterize lipid. In addition, more than 40% of ce consisted of ce 18.
A phospholipidomic analysis of all defined human plasma. Changes in clinical plasma markers of lipid metabolism. The effect of anticoagulants, temperature, and time on the human plasma metabolome and lipidome from healthy donors as determined by liquid chromatographymass spectrometry. The plasma lipidome offers a plethora of information on lipids, the metabolism, and biological functions that are currently. Genetic architecture of human plasma lipidome and its link. A phospholipidomic analysis of all defined human plasma lipoproteins. Over 1500 different lipids have been reported in human plasma at the sum composition level. Plasma is not only the primary clinical specimen but also represents the largest and deepest version of the human proteome present in. Tularemia is a highly infectious and contagious disease caused by bacteria francisella tularensis. Structure and interactions of lipids in human plasma low density lipoproteins received for publication, july 2, 1976 richard j. Nov 10, 2011 human plasma comprises nucleic acids, amino acids mostly in the form of proteins, carbohydrates in the form of monosaccharides and disaccharides, and lipids fig. We report association of new genomic loci with lipid species and cvd risk in humans. Comparative plasma lipidome between human and cynomolgus. Background non human primates nhp are now being considered as models for investigating human metabolic diseases including diabetes.
Ppas normal peripheral blood plasma is collected from healthy donors at the same time as the peripheral blood mononuclear cells by apheresis. Several lipidregulating loci in the mouse population harbor genes associated with abnormal lipid metabolism in human gwas. It is notable that some unusual phospholipids have been identified in corynebacteria. Using liquid chromatography tandem mass spectrometry, we profiled the human plasma lipidome of patients that survived and succumbed to evd during the 2014 outbreak in sierra leone. Van slyke from the hospital of the rockefeller institute for medical research, new york, and the biophysical laboratory of the department of pathology. Data characterizing the plasma lipidome of ems horses is lacking. Plasma is devoid of cells and, unlike serum, has not clotted.
Information pertaining to other lipid species in monkey plasma, however, is lacking and requires comprehensive experimental analysis. Labelfree and compoundspecific quantification was validated by comparison against a recent international interlaboratory study on human plasma srm 1950. The comparison of lipid extraction methods for the lipidomic analysis of blood plasma ali awwad, catharine ortori, dave a. A novel lipidomics workflow for improved human plasma. In order to resolve this ambiguity, herein, we describe the incorporation of ozoneinduced dissociation ozid into dataindependent shotgun. Genetic architecture of human plasma lipidome and its. Oct 23, 2017 reliable, costeffective, and goldstandard absolute quantification of nonesterified cholesterol in human plasma is of paramount importance in clinical lipidomics and for the monitoring of metabolic health. Serum lipidome analysis of healthy beagle dogs receiving different. Genetic correlation of the plasma lipidome with type 2. Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases cvds. Cardiovascular disease cvd is the most common cause of death in the united states and is associated with a high economic burden. Shared genetic influences reduce the dimensionality of the human lipidome into clusters that are associated with risk factors of. All procedures were performed with plastic containers or siliconized glassware and in the presence of inhibitors to minimize activation of plasma proteases 8, 20.
The ckd plasma lipidome varies with disease severity and. Many of these are known risk factors for human diseases. Considering that the human plasma lipidome contains at least 600 named and quantifiable lipid species 45 but probably many more 46, our assays captured only a small part of the possible. Partial lipid analysis is now a regular part of every patients blood test and physicians. Methods and results screening of the fasted plasma lipidome was performed by topdown shotgun.
Aim genetic investigation of human plasma lipidome to get insights into lipidrelated disorders beyond traditional lipid measures. Normal human plasma article about normal human plasma by. Genetics of human plasma lipidome and its link to diseases susceptibility. For longterm examination of arhcv2b as a clinical assay positive control, a single large pool of arhcv2bsupplemented normal human plasma was aliquoted into several hundred 100microl samples and stored at 4degreesc. Find, read and cite all the research you need on researchgate.
Yet the number of unique lipids present is surely higher, once isomeric contributions from double bond locations and fatty acyl regiochemistry are considered. Genetics of human plasma lipidome and its link to diseases. Here, we investigated the potential overlap in the genetic basis of the plasma lipidome and t2drelated traits. Human plasma comprises nucleic acids, amino acids mostly in the form of proteins, carbohydrates in the form of monosaccharides and disaccharides, and lipids fig. Human plasma lipidome is pleiotropically associated with. Genetic regulation of plasma lipid species and their. A novel lipidomics workflow for improved human plasma identification and quantification using rplcmsn methods and isotope dilution strategies. Plasticity of the human plasma lipidome is genetically. Pdf the effect of anticoagulants, temperature, and time. Alterations in the human plasma lipidome in response to tularemia vaccination.
Advances in mass spectrometrydriven lipid analysis lipidomics has made it possible to study the patient lipidome to a greater extent than is possible with conventional analytical. We integrated the c lipids in the lcms workflow to enable relative and absolute compoundspecific quantification in yeast and human plasma samples by isotope dilution. Human plasma lipidome has been extensively studied in many pathophysiological contexts with the hope of identifying biomarkers for early diagnostics and. Genetic architecture of human plasma lipidome and its link to. Lipidomics reveals a remarkable diversity of lipids in human. Human plasma lipidome has been extensively studied in many pathophysiological contexts with the hope of identifying biomarkers for early diagnostics and monitoring the progression and treatment of a broad spectrum of diseases. Technical guide for the elaboration and use of monographs on. Lipoproteins, oxidized ldl oxldl, human plasma athens. However, the level of sm was not found to be significantly. Levels for each dog before 0 d and 0 w, respectively and after 3 d and 25 w, respectively treatment with shortterm prednisolone left. We present a highthroughput, nontargeted lipidomics approach using liquid chromatography coupled to highresolution mass spectrometry for quantitative analysis of nonesterified fatty acids. Expanding lipidome coverage using msmsaided untargeted. Core e analysis of neutral lipids from human plasma june 4, 2010 thomas j. Two rollers squeeze frozen plasma block out of plastic.
Plasma lipid definition of plasma lipid by medical dictionary. Plasma is the liquid part of the blood and lymphatic fluid, which makes up about half of its volume. Profiling the human plasma lipidome provides insight into critical illness as well as diseased states. Differential plasma concentrations of circulating lipid species are associated with pathogenesis of type 2 diabetes t2d. To better understand human response to a live, attenuated tularemia vaccine and the biological pathways altered postvaccination, healthy adults were vaccinated and plasma was collected pre and postvaccination for longitudinal lipidomics studies. Here, we compared the performance of three mass spectrometric approaches available for direct detection and quantification of cholesterol in extracts of human plasma. Lipid function and importance in disease are being rediscovered due to modern advancements in chemical analysis. Our study integrates lipidome, genome and phenome to reveal detailed description of genetic regulation of lipid metabolism and its effect on disease risk. Plasma membrane lipid and cholesterol distribution. Specific changes in the lipidome suggested contributions from extracellular vesicles, viremia, liver dysfunction, apoptosis. We applied this method to screen a wide range of fatty acids from mediumchain to very longchain 8 to 24 carbon atoms in human plasma samples. Although such interlipid species correlations have been conceptually implied, their complete characterization is currently lacking. A definitive lipidomics workflow for human plasma utilizing offline enrichment and class specific separation of phospholipids 4 using an automated liquid handler to process the plasma samples, as shown in figure 2, the welltowell reproducibility %cv improved compared to manually performing the extraction.
Human serum serum off the clot is derived from whole blood donations and then allowed to clot spontaneously prior to centrifugation. May 14, 20 lipidomic analysis was performed to explore differences in lipid profiles between plasma from lean and obese subjects, followed by in vitro methods to examine a role for the identified lipids in endothelial cell pathophysiology. Human plasma for fractionation adopted tby the 56 h meeting of the who expert committee on biological standardization, 2428 october 2005. It can offer simplicity, rapidity, robustness and high throughputness, without the need for further optimization in current sample. Mapping unsaturation in human plasma lipids by data. Apr 10, 2018 it is unknown if the plasma lipidome is a useful tool for improving our understanding of the acute respiratory distress syndrome ards.
Rpuplctofmse is now the lipidomics tool of choice and can provide the demanded specificity for detecting the great diversity of the lipidome. Aims we tested whether characteristic changes of the plasma lipidome in individuals with comparable total lipids level associate with future cardiovascular disease cvd outcome and whether 23 validated gene variants associated with coronary artery disease cad affect cvd associated lipid species. The effect of anticoagulants, temperature, and time on the human plasma metabolome and lipidome from healthy donors as determined by liquid chromatographymass spectrometry article pdf available. Genetic investigation of human plasma lipidome to get insights into.
1068 871 364 631 965 1010 1337 1036 282 570 942 1425 417 1072 296 738 862 514 1366 18 461 1528 561 262 401 382 850 1307 528 191 410 201 486 244 1458 1274 1374 1132 1216 798 136 638 453