Lipid Molecular Species Research Articles

Study of Total Lipidome of the Sinularia siaesensis Soft Coral

The rapid development of lipidomics of human and higher animals stimulated the study of the lipidome of certain groups of marine organisms. Soft corals are an integral part of the tropical and cold-water ecosystems of the World Ocean, but there is almost no data on the lipidome of these animals. The total lipidome of a tropical soft coral Sinularia siaesensis (Cnidaria: Anthozoa: Octocorallia: Alcionacea) containing intracellular symbiotic microalgae (zooxanthellae) was studied by gas and liquid chromatography-mass spectrometry. The structure and content of 144 molecular species of the main classes of acyl lipids of this alcyonaria were determined, including waxes, triglycerides (TG), monoalkyldiacylglycerides (MADAG), ethanolamine, choline, serine, and inositol glycerophospholipids (PE, PC, PS, and PI), ceramide aminoethylphosphonate (CAEP), sulfoquinovosyldiacylglyceride (SQDG), and mono- and digalactosyldiacylglycerides (MGDG and DGDG). The main components of S. siaesensis lipids were waxes 16:0/16:0, 16:0/18:0, and 18:0/16:0; TG 16:0/16:0/16:0 and 16:2/16:0/16:0; MADAG 18:0e/16:0/16:0, 16:0e/16:0/18:0, and 16:0e/16:0/16:0; and PS 18:0e/24:5, lyso-PC 18:0e, PE 18:1e/20:4, PC 18:0e/20:4, CAEP 18:2b/16:0, SQDG 14:0/16:0, and PI 18:0/24:5. The dominance of saturated waxes in reserve lipids is a species-specific feature of tropical alcyonarians. Waxes are synthesized in the host organism, and zooxanthellae can increase the proportion of saturated waxes by transferring saturated fatty acids (FA). The residues of polyunsaturated FA (PUFA) are found in the molecules of TG and MADAG, mainly in the sn-1 and sn-2 positions, respectively. Detection of MADAG with residues of marker FA of zooxanthellae (18:0e/18:3/16:0, 18:0e/18:4/16:0, and 16:0e/18:3/16:0) confirms the transfer of PUFA from the symbionts to the host. Tetracosapolyenoic FA, which is a chemotaxonomic markers of octocorals, are concentrated in molecular species of PS and PI. Most molecular species of PE, PC, and PS are in alkylacyl form, while for PI molecules, a diacyl form is characteristic. A significant proportion of MGDG, DGDG, and SQDG points to the importance of zooxanthellae in the formation of the lipid profile of symbiotic soft corals. Determination of the profile of lipid molecular species requires the development of a lipidomic approach in the study of biochemistry and ecology of corals and other cnidarians.

Plasma lipidomic analysis reveals strong similarities between lipid fingerprints in human, hamster and mouse compared to other animal species

Cardiovascular diseases are often associated with impaired lipid metabolism. Animal models are useful for deciphering the physiological mechanisms underlying these pathologies. However, lipid metabolism is contrasted between species limiting the transposition of findings from animals to human. Hence, we aimed to compare extended lipid profiles of several animal species to bring new insights in animal model selections. Human lipid phenotype was compared with those of 10 animal species. Standard plasma lipids and lipoprotein profiles were obtained by usual methods and lipidomic analysis was conducted by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). As anticipated, we found contrasted lipid profiles between species. Some of them exhibited similar plasma lipids to human (non-human primate, rat, hamster, pig), but only usual lipid profiles of pigs were superimposable with human. LC-HRMS analyses allowed the identification of 106 other molecular species of lipids, common to all samples and belonging to major lipid families. Multivariate analyses clearly showed that hamster and, in a lower extent mouse, exhibited close lipid fingerprints to that of human. Besides, several lipid candidates that were previously reported to study cardiovascular diseases ranged similarly in human and hamster. Hence, hamster appeared to be the best option to study physiological disturbances related to cardiovascular diseases.

Lipidomic signature of the green macroalgae Ulva rigida farmed in a sustainable integrated multi-trophic aquaculture

Ulva species, green macroalgae, are widely distributed across the globe, being one of the most heavily traded edible seaweeds. Nonetheless, although this genus has been largely used in scientific studies, its lipidome remains rather unexplored. The present study sheds light over the lipid profile of Ulva rigida produced in a land-based integrated multi-trophic aquaculture (IMTA) system using liquid chromatography coupled to high-resolution mass spectrometry for molecular lipid species identification. The lipidome of U. rigida revealed the presence of distinct beneficial n-3 fatty acids for human health, namely alpha-linoleic acid (ALA) and docosapentaenoic acid (DPA). A total of 87 molecular species of glycolipids, 58 molecular species of betaine lipids, and 57 molecular species of phospholipids were identified in the lipidome of U. rigida including some species bearing PUFA and with described bioactive properties. Overall, the present study contributes to the valorization and quality validation of sustainably farmed U. rigida.

Tracing of lipid markers of soft corals in a polar lipidome of the nudibranch mollusk Tritonia tetraquetra from the Sea of Okhotsk

To trace predator‒prey interactions in the marine environment, fatty acids (FAs) were widely applied as qualitative markers. Recently, two tetracosapolyenoic acids (TPA), which are specific markers of soft corals, have been found in the nudibranch mollusk Tritonia tetraquetra collected in the deep waters of the Sea of Okhotsk. This mollusk does not synthesize TPA but preys mostly on the soft coral Gersemia fruticosa. Both invertebrates are common species in Arctic and boreal regions and may be a simple model for the investigation of FA marker transfer from one trophic level to another. A lipidomic approach was applied to study the transfer of the FA markers in this predator–prey system. The structure and content of the molecular species of polar lipids (polar lipidome) of both animal species were analyzed by high-performance liquid chromatography with high-resolution tandem mass spectrometry. The distribution of several principal FA markers in lipid molecular species was determined. C20 monoenoic FAs of the coral were not integrated in the most of nudibranch lipids. Arachidonic and eicosapentaenoic acids mainly esterified ethanolamine and choline glycerophospholipids (PE and PC) in both invertebrates. In the coral polar lipidome, TPA concentrated in serine glycerophospholipids (PS). The nudibranch decomposed coral lipids and reallocated TPA to PS, PE, and PC. We suppose that this reallocation is responsible for the accumulation of TPA in the nudibranch. The nudibranch differed from the coral in biosynthetic relationships of phospholipid classes. The lipidomic approach explains the rearrangement of dietary FAs in the predator lipids. This rearrangement can be important for the trophic uptake and transfer of lipids in polar marine ecosystems.

Lipidomic profiling of extracellular vesicles derived from prostate and prostate cancer cell lines

BackgroundExtracellular vesicles (EVs) are produced and secreted from most cells of the body and can be recovered in biological fluids. Although there has been extensive characterisation of the protein and nucleic acid component of EVs, their lipidome has received little attention and may represent a unique and untapped source of biomarkers for prostate cancer diagnosis and prognosis.MethodsEVs were isolated from non-tumourigenic (RWPE1), tumourigenic (NB26) and metastatic (PC-3) prostate cell lines. Lipids were extracted and subsequently used for targeted lipidomics analysis for the quantitation of molecular lipid species.ResultsA total of 187 molecular lipid species were quantitatively identified in EV samples showing differential abundance between RWPE1, NB26 and PC-3 EV samples. Fatty acids, glycerolipids and prenol lipids were more highly abundant in EVs from non-tumourigenic cells, whereas sterol lipids, sphingolipids and glycerophospholipids were more highly abundant in EVs from tumourigenic or metastatic cells.ConclusionsThis study identified differences in the molecular lipid species of prostate cell-derived EVs, increasing our understanding of the changes that occur to the EV lipidome during prostate cancer progression. These differences highlight the importance of characterising the EV lipidome, which may lead to improved diagnostic and prognostic biomarkers for prostate cancer.

Plasma concentrations of molecular lipid species predict long-term clinical outcome in coronary artery disease patients

We investigated the associations of ten previously identified high risk molecular lipid species and three ceramide ratios with the occurrence of major adverse cardiac events (MACEs) during a median follow-up of 4.7 years in patients with coronary artery disease (CAD). Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris (SAP) or acute coronary syndrome (ACS). Blood was drawn prior to the index procedure and lipid species were determined. The primary endpoint was the occurrence of a MACE, comprising all-cause mortality, nonfatal ACS, or unplanned coronary revascularization. The secondary endpoint comprised all-cause mortality or nonfatal ACS. During a median follow-up of 4.7 [IQR: 4.2-5.6] years, 155 patients (27%) had MACEs. In multivariable analyses, Cer(d18:1/16:0) concentration was associated with MACEs {hazard ratio 2.32; 95% CI [1.09-4.96] per natural logarithm (ln) (pmol/ml) P = 0.030} after adjustment for cardiac risk factors, clinical presentation, statin use at baseline, and admission nonHDL cholesterol level. Furthermore, after multivariable adjustment, concentrations of Cer(d18:1/16:0), Cer(d18:1/20:0), Cer(d18:1/24:1), and their ratios to Cer(d18:1/24:0) were associated with the composite endpoint death or nonfatal ACS. The data together show the circulating ceramide lipids we investigated here are associated with adverse cardiac outcome during long-term follow-up independent of clinical risk factors.

Lipidomics Reveals a Tissue-Specific Fingerprint.

In biological systems lipids generate membranes and have a key role in cell signaling and energy storage. Therefore, there is a wide diversity of molecular lipid expressed at the compositional level in cell membranes and organelles, as well as in tissues, whose lipid distribution remains unclear. Here, we report a mass spectrometry study of lipid abundance across 7 rat tissues, detecting and quantifying 652 lipid molecular species from the glycerolipid, glycerophospholipid, fatty acyl, sphingolipid, sterol lipid and prenol lipid categories. Our results demonstrate that every tissue analyzed presents a specific lipid distribution and concentration. Thus, glycerophospholipids are the most abundant tissue lipid, they share a similar tissue distribution but differ in particular lipid species between tissues. Sphingolipids are more concentrated in the renal cortex and sterol lipids can be found mainly in both liver and kidney. Both types of white adipose tissue, visceral and subcutaneous, are rich in glycerolipids but differing the amount. Acylcarnitines are mainly in the skeletal muscle, gluteus and soleus, while heart presents higher levels of ubiquinone than other tissues. The present study demonstrates the existence of a rat tissue-specific fingerprint.

Lipidomics Reveals Changes in Metabolism, Indicative of Anesthetic-Induced Neurotoxicity in Developing Brains

Numerous studies have demonstrated that treatment with high dose anesthetics for a prolonged duration induces brain injury in infants. However, whether anesthetic treatment leading to neurotoxicity is associated with alterations in lipid metabolism and homeostasis is still unclear. This review first outlines the lipidomics tools for analysis of lipid molecular species that can inform alterations in lipid species after anesthetic exposure. Then the available data indicating anesthetics cause changes in lipid profiles in the brain and serum of infant monkeys in preclinical studies are summarized, and the potential mechanisms leading to the altered lipid metabolism and their association with anesthetic-induced brain injury are also discussed. Finally, whether lipid changes identified in serum of infant monkeys can serve as indicators for the early detection of anesthetic-induced brain injury is described. We believe extensive studies on alterations in lipids after exposure to anesthetics will allow us to better understand anesthetic-induced neurotoxicity, unravel its underlying biochemical mechanisms, and develop powerful biomarkers for early detection/monitoring of the toxicity.

Comprehensive high-resolution multiple-reaction monitoring mass spectrometry for targeted eicosanoid assays

Eicosanoids comprise a class of bioactive lipids derived from a unique group of essential fatty acids that mediate a variety of important physiological functions. Owing to the structural diversity of these lipids, their analysis in biological samples is often a major challenge. Advancements in mass spectrometric have been helpful for the characterization and quantification of these molecular lipid species in complex matrices. However, there are technical limitations to this approach, including low-abundant and/or poorly ionizable lipids. Using high-resolution multiple-reaction monitoring (MRMHR), we were able to develop a targeted bioanalytical method for eicosanoid quantification. For this, we optimized the LC-MS/MS conditions and evaluated several parameters, including linearity, limits of quantification, matrix effects and recovery yields. For validation purposes, we looked at the method’s precision and accuracy. A library of high-resolution fragmentation spectra for eicosanoids was developed. Our comprehensive dataset meets benchmark standards for targeted analysis, having been derived using best-practice workflows and rigorous quality assessments. As such, our method has applications for determining complex eicosanoid profiles in the biomedical field.

Biosíntesis de novo de glicerofosfolípidos y longevidad

BackgroundThe glycerophospholipids, synthesised from diacylglycerol (DAG), are one of the main lipid components of cell membranes. The lipid profile is an optimised feature associated with animal longevity. In this context, the hypothesis is presented that the DAG biosynthesis rate, and thus, the glycerophospholipids content, is related to animal longevity. Material and methodsA plasma lipidomic analysis was performed based on the mass spectrometry of 11 mammalian species with a maximum longevity ranging from 3.5 to 120 years. Lipid identification was based on exact mass, retention time, and isotopic distribution. ANOVA test was applied to differentiate the lipids between animal species. The relationship between these lipids and longevity was carried out with a Spearman correlation. Data was analysed using SPSS and MetaboAnalyst. ResultsAmong the 1,061 different lipid molecular species found between species, 47 were defined as DAG. Interestingly, 14 of them showed a negative correlation with mammalian maximum longevity. Multivariate statistics revealed that 14 DAGs were enough to define mammalian species and their maximum longevity. ConclusionsData suggest that long-lived mammalian species have a lower rate of glycerophospholipids synthesis through the de novo pathway, possibly associated with a lower rate of membrane lipid exchange, which in turn is related to lower energy expenditure.

Effects of aging on serum levels of lipid molecular species as determined by lipidomics analysis in Japanese men and women

BackgroundAging is known to be associated with increased risk of lipid disorders related to the development of type 2 diabetes. Recent evidence revealed that change of lipid molecule species in blood is associated with the risk of type 2 diabetes. However, changes in lipid molecular species induced by aging are still unknown.We assessed the effects of age on the serum levels of lipid molecular species as determined by lipidomics analysis.MethodsSerum samples were collected from ten elderly men (71.7 ± 0.5 years old) and women (70.2 ± 1.0 years old), ten young men (23.9 ± 0.4 years old), and women (23.9 ± 0.7 years old). Serum levels of lipid molecular species were determined by liquid chromatography mass spectrometry-based lipidomics analysis.ResultsOur mass spectrometry analysis revealed increases in the levels of multiple triacylglycerol molecular species in the serum of elderly men and women. Moreover, serum levels of total ester-linked phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were increased by aging. In contrast, serum levels of specific ether-linked PC and PE molecular species were lower in elderly individuals than in young individuals.ConclusionsOur finding indicates that specific lipid molecular species, such as ether- and ester- linked phospholipids, may be selectively altered by aging.

Abstract 395: Changes in the HDL Lipidome With Regular Exercise: a Pilot Study

Background: Over 200 individual molecular lipid species have been found to reside on high-density lipoproteins (HDL). The effects of exercise on the HDL lipidome profile is unknown. Methods: We examined changes in the HDL lipidome after regular exercise in 20 individuals who completed a 20-week endurance exercise program as part of the HERITAGE Family Study. The 20 subjects were selected based on discordance for exercise-induced increases in mean HDL particle (HDL-P) size (10 high-responders, 10 non-responders). The abundance of 184 known individual lipid species was quantified in baseline and post-training HDL plasma samples by UPLC-QTOF-MS. HDL was isolated through gel filtration chromatography. Results: Seven lipid species, particularly classes of triacylglycerols, cholesteryl esters, phosphatidylcholines, and sphingomyelins, showed nominal (p<0.05) increases in abundance with exercise training, with fold changes ranging from 1.13 to 1.65 ( Figure 1 ). Three lipids showed differential responses to exercise between high- and non-responders of HDL-P size, including one lipid and metabolite each that showed an overall effect of training ( Figure 1 ). For example, the abundance of sphingomyelin d39:2 decreased by an average of 23% in the high-responders of HDL size to exercise, whereas abundance increased by 71% in the non-responders (p=0.004 for difference between groups). None of the exercise-induced changes in lipid levels were statistically significant after accounting for multiple testing. Discussion: This pilot study showed limited evidence of systematic remodeling of the HDL lipidome in response to regular endurance exercise. Future studies are needed with larger sample sizes, diverse populations, and differing exercise protocols to further examine how the molecular composition of HDL particles changes in response to exercise and potentially contributes to its atheroprotective functions.

Serum lipidomic analysis for the discovery of biomarkers for major depressive disorder in drug-free patients

Lipidomic analysis can be used to efficiently identify hundreds of lipid molecular species in biological materials and has been recently established as an important tool for biomarker discovery in various neuropsychiatric disorders including major depressive disorder (MDD). In this study, quantitative targeted serum lipidomic profiling was performed on female subjects using liquid chromatography–mass spectrometry. Global lipid profiling of pooled serum samples from 10 patients currently with MDD (cMDD), 10 patients with remitted MDD (rMDD), and 10 healthy controls revealed 37 differentially regulated lipids (DRLs). DRLs were further verified using multiple-reaction monitoring (MRM) in each of the 25 samples from the three groups of independent cohorts. Using multivariate analysis and MRM data we identified serum biomarker panels of discriminatory lipids that differentiated between pairs of groups: lysophosphatidic acid (LPA)(16:1), triglycerides (TG)(44:0), and TG(54:8) distinguished cMDD from controls with 76% accuracy; lysophosphatidylcholines(16:1), TG(44:0), TG(46:0), and TG(50:1) distinguished between cMDD and rMDD at 65% accuracy; and LPA(16:1), TG(52:6), TG(54:8), and TG(58:10) distinguished between rMDD and controls with 60% accuracy. Our lipidomic analysis identified peripheral lipid signatures of MDD, which thereby provides providing important biomarker candidates for MDD.

Lipidomic insight into cardiovascular diseases

Cardiovascular disease is a primary cause of mortality worldwide. Therefore, it is of major interest to identify sensitive molecular markers that predict cardiovascular events and point to therapeutic strategies that will increase lifespans. Dysregulated lipid metabolism is recognized as an established risk factor in cardiovascular diseases. However, it is still largely unknown which specific lipid molecular species reflect cardiovascular risk. In addition, understanding the whole lipidome signature in vascular pathophysiology is challenging. Recent advancements of mass-spectrometry allow researchers to detect each individual lipid species from unbiased small samples. In this review, we update the current research on lipidomic approaches in cardiovascular diseases.

Defects in TM6SF2 Impairs Lipidation of Nascent VLDL and Leads to Accumulation of Liver Fat

Non‐alcoholic fatty liver disease (NAFLD) is a burgeoning health problem in Western countries. Population‐based surveys indicate that one out of every three adults in the United States has excess liver fat (hepatic steatosis), the first stage of fatty liver disease. Despite the clinical importance of NAFLD, major questions remain regarding its etiology. As a step towards elucidating the pathophysiology of this disorder, we screened individuals in a population‐based study, the Dallas Heart Study (DHS) for DNA sequence variations associated with increased liver fat content. This analysis revealed that a common variant (E167K) in transmembrane 6 superfamily 2 (TM6SF2), a gene of unknown function, was associated with increased hepatic triglyceride (TG) content, reduced plasma lipid levels, and increased levels of circulating liver enzymes. TM6SF2 is expressed at highest levels in the small intestine, liver and kidney. Immunolocalization and biochemical studies localized the protein to the ER and the Golgi. To determine why individuals with the risk variant develop hepatic steatosis, we developed mice expressing no TM6SF2 (Tm6sf2−/−, KO). The Tm6sf2−/− mice have elevated levels of neutral lipids, including TG and cholesteryl esters (CE) in the liver and elevated levels of liver enzymes in the circulation, consistent with liver inflammation. At steady state the Tm6sf2−/− mice have decreased plasma levels of cholesterol and very low density lipoprotein (VLDL)‐TG. Treatment with Triton WR1339 to inhibit peripheral lipases was associated with a non‐specific and dramatic reduction in all of the VLDL associated lipid molecular species, but not apolipoprotein (Apo)‐B100. In addition, it was found that de novo synthesis of radioactive and stable labeled lipids was marginally changed in the liver, but secretion of the newly synthesized labelled lipids was dramatically decreased in the Tm6sf2−/− mouse. As expected, given these observations, VLDL was reduced in size in the KO mice. Thus, TM6SF2 plays a key role in the expansion of the nascent particle, but not in the secretion of nascent VLDL, thereby causes steatosis.Support or Funding InformationFunding was provided by the NIH through research grants R01‐DK090066 and F32‐DK112529.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Endurance exercise training and high-fat diet differentially affect composition of diacylglycerol molecular species in rat skeletal muscle.

Insulin resistance of peripheral muscle is implicated in the etiology of metabolic syndrome in obesity. Although accumulation of glycerolipids, such as triacylglycerol and diacylglycerol (DAG), in muscle contributes to insulin resistance in obese individuals, endurance-trained athletes also have higher glycerolipid levels but normal insulin sensitivity. We hypothesized that the difference in insulin sensitivity of skeletal muscle between athletes and obese individuals stems from changes in fatty acid composition of accumulated lipids. Here, we evaluated the effects of intense endurance exercise and high-fat diet (HFD) on the accumulation and composition of lipid molecular species in rat skeletal muscle using a lipidomic approach. Sprague-Dawley female rats were randomly assigned to three groups and received either normal diet (ND) in sedentary conditions, ND plus endurance exercise training, or HFD in sedentary conditions. Rats were fed ND or HFD between 4 and 12 wk of age. Rats in the exercise group ran on a treadmill for 120 min/day, 5 days/wk, for 8 wk. Soleus muscle lipidomic profiles were obtained using liquid chromatography/tandem mass spectrometry. Total DAG levels, particularly those of palmitoleate-containing species, were increased in muscle by exercise training. However, whereas the total DAG level in the muscle was also increased by HFD, the levels of DAG molecular species containing palmitoleate were decreased by HFD. The concentration of phosphatidylethanolamine molecular species containing palmitoleate was increased by exercise but decreased by HFD. Our results indicate that although DAG accumulation was similar levels in trained and sedentary obese rats, specific changes in molecular species containing palmitoleate were opposite.

High-Resolution Lipidomics of the Early Life Stages of the Red Seaweed Porphyra dioica.

Porphyra dioica is a commercial seaweed consumed all over the world, mostly in the shape of nori sheets used for “sushi” preparation. It is a well-known part of the Asian diet with health benefits, which have been associated, among others, to the high levels of n-3 and n-6 fatty acids in this red alga. However, other highly valued lipids of Porphyra are polar lipids that remain largely undescribed and can have both nutritional value and bioactivity, thus could contribute to the valorization of this seaweed. In this context, the present work aims to identify the lipidome of two life cycle stages of the Atlantic species Porphyra dioica: the early life stage conchocelis produced in an indoor-nursery, and young blades produced outdoors using an integrated multitrophic aquaculture (IMTA) framework. Both the blades (gametophyte) and conchocelis (sporophyte) are commercialized in the food and cosmetics sectors. Liquid chromatography coupled to Q–Exactive high resolution-mass spectrometry (MS) platform was used to gain insight into the lipidome of these species. Our results allowed the identification of 110 and 100 lipid molecular species in the lipidome of the blade and conchocelis, respectively. These lipid molecular species were distributed as follows (blade/conchocelis): 14/15 glycolipids (GLs), 93/79 phospholipids (PLs), and 3/6 betaine lipids. Both life stages displayed a similar profile of GLs and comprised 20:4(n-6) and 20:5(n-3) fatty acids that contribute to n-3 and n-6 fatty acid pool recorded and rank among the molecular species with higher potential bioactivity. PLs’ profile was different between the two life stages surveyed, mainly due to the number and relative abundance of molecular species. This finding suggests that differences between both life stages were more likely related with shifts in the lipids of extraplastidial membranes rather than in plastidial membranes. PLs contained n-6 and n-3 precursors and in both life stages of Porphyra dioica the n-6/n-3 ratio recorded was less than 2, highlighting the potential benefits of using these life stages in human diet to prevent chronic diseases. Atherogenic and thrombogenic indexes of blades (0.85 and 0.49, respectively) and conchocelis (0.34 and 0.30, respectively) are much lower than those reported for other Rhodophyta, which highlights their potential application as food or as functional ingredients. Overall, MS-based platforms represent a powerful tool to characterize lipid metabolism and target lipids along different life stages of algal species displaying complex life cycles (such as Porphyra dioica), contributing to their biotechnological application.

Lipidomic Analysis: From Archaea to Mammals.

Lipids are among the most important organic compounds found in all living cells, from primitive archaebacteria to flowering plants or mammalian cells. They form part of cell walls and constitute cell storage material. Their biosynthesis and metabolism play key roles in faraway topics such as biofuel production (third-generation biofuels produced by microorganisms, e.g. algae) and human diseases such as adrenoleukodystrophy, Zellweger syndrome, or Refsum disease. Current lipidomic analysis requires fast and accurate processing of samples and especially their characterization. Because the number of possible lipids and, more specifically, molecular species of lipids is of the order of hundreds to thousands, it is necessary to process huge amounts of data in a short time. There are two basic approaches to lipidomic analysis: shotgun and liquid chromatography-mass spectometry. Both methods have their pros and cons. This review deals with lipidomics not according to the type of ionization or the lipid classes analyzed but according to the types of samples (organisms) under study. Thus, it is divided into lipidomic analysis of archaebacteria, bacteria, yeast, fungi, algae, plants, and animals.

Direct Infusion-Tandem Mass Spectrometry (DI-MS/MS) Analysis of Complex Lipids in Human Plasma and Serum Using the Lipidyzer™ Platform.

Lipids play a key role in the signaling pathways of cancer, cardiovascular, diabetic, and inflammatory diseases. A major challenge in the analysis of lipids is the many isobaric interferences present in highly complex samples that confound identification and accurate quantitation. After obtaining the total lipid extract from a sample, differential mobility separation has proven to be a powerful tool for gas-phase fractionation of lipid classes. When combined with mass spectrometry, this allows the unambiguous identification and thus quantification of lipid molecular species. These components, sample extraction, gas-phase separation, and mass spectrometry, form the basis of a novel integrated quantitative lipid analysis platform.

Quantitative structural multiclass lipidomics using differential mobility: electron impact excitation of ions from organics (EIEIO) mass spectrometry

We report a method for comprehensive structural characterization of lipids in animal tissues using a combination of differential ion mobility spectrometry (DMS) with electron-impact excitation of ions from organics (EIEIO) mass spectrometry. Singly charged lipid ions in protonated or sodiated forms were dissociated by an electron beam having a kinetic energy of 10 eV in a branched radio-frequency ion trap. We established a comprehensive set of diagnostics to characterize the structures of glycerophospholipids, sphingolipids, and acylglycerols, including glycosylated, plasmalogen, and ester forms. This EIEIO mass spectrometer was combined with DMS as a separation tool to analyze complex lipid extracts. Deuterated quantitative standards, which were added during extraction, allowed for the quantitative analysis of the lipid molecular species in various lipid classes. We applied this technique to the total lipids extracted from porcine brain, and we structurally characterized over 300 lipids (with the exception of cis/trans double-bond isomerism in the acyl chains). The structural dataset of the lipidomes, whose regioisomers were distinguished, exhibit a uniquely defined distribution of acyl chains within each lipid class; that is, sn-1 and sn-2 in the cases of glycerophospholipids or sn-2 and (sn-1, sn-3) in the cases of triacylglycerols.