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An over-active renin-angiotensin system (RAS) is characterized by elevated angiotensin II (Ang II). While Ang II can promote metabolic and mitochondrial dysfunction in tissues, little is known about its role in the gastrointestinal system (GI). Here, we treated rat primary colonic epithelial cells with Ang II (1–5000 nM) to better define their role in the GI. We hypothesized that Ang II would negatively affect mitochondrial bioenergetics as these organelles express Ang II receptors. Ang II increased cellular ATP production but reduced the mitochondrial membrane potential (MMP) of colonocytes. However, cells maintained mitochondrial oxidative phosphorylation and glycolysis with treatment, reflecting metabolic compensation with impaired MMP. To determine whether lipid dysregulation was evident, untargeted lipidomics were conducted. A total of 1949 lipids were detected in colonocytes spanning 55 distinct (sub)classes. Ang II (1 nM) altered the abundance of some sphingosines [So(d16:1)], ceramides [Cer-AP(t18:0/24:0)], and phosphatidylcholines [OxPC(16:0_20:5(2O)], while 100 nM Ang II altered some triglycerides and phosphatidylserines [PS(19:0_22:1). Ang II did not alter the relative expression of several enzymes in lipid metabolism; however, the expression of pyruvate dehydrogenase kinase 2 (PDK2) was increased, and PDK2 can be protective against dyslipidemia. This study is the first to investigate the role of Ang II in colonic epithelial cell metabolism. [ABSTRACT FROM AUTHOR]

The skin surface is an important sample source that the metabolomics community has only just begun to explore. Alterations in sebum, the lipid-rich mixture coating the skin surface, correlate with age, sex, ethnicity, diet, exercise, and disease state, making the skin surface an ideal sample source for future noninvasive biomarker exploration, disease diagnosis, and forensic investigation. The potential of sebum sampling has been realized primarily via electrospray ionization mass spectrometry (ESI-MS), an ideal approach to assess the skin surface lipidome. However, a better understanding of sebum collection and subsequent ESI-MS analysis is required before skin surface sampling can be implemented in routine analyses. Challenges include ambiguity in definitive lipid identification, inherent biological variability in sebum production, and methodological, technical variability in analyses. To overcome these obstacles, avoid common pitfalls, and achieve reproducible, robust outcomes, every portion of the workflow—from sample collection to data analysis—should be carefully considered with the specific application in mind. This review details current practices in sebum sampling, sample preparation, ESI-MS data acquisition, and data analysis, and it provides important considerations in acquiring meaningful lipidomic datasets from the skin surface. Forensic researchers investigating sebum as a means for suspect elimination in lieu of adequate fingerprint ridge detail or database matches, as well as clinical researchers interested in noninvasive biomarker exploration, disease diagnosis, and treatment monitoring, can use this review as a guide for developing methods of best-practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Horses often suffer from two common respiratory diseases: mild–moderate equine asthma and severe equine asthma. Symptoms of these conditions include coughing, nasal discharge, reduced performance (especially in physically demanding activities), and difficulties breathing. These symptoms mainly result from inflammation deep within the lungs, the severity of which veterinarians and researchers struggle to accurately assess. Even the best method available, obtaining a sample of bronchoalveolar lavage fluid, has limitations. Lipidomics, a relatively unexplored field in veterinary medicine, represents an intriguing avenue for exploration. Lipidomics focuses on studying cellular mechanisms and interactions, which are crucial in inflammation. Researchers aim to uncover fresh insights into equine lower airway diseases using lipidomics, potentially leading to improved treatments. This review article aims to compile the latest knowledge in this area. Mild–moderate and severe equine asthma (MEA and SEA) are prevalent inflammatory airway conditions affecting horses of numerous breeds and disciplines. Despite extensive research, detailed disease pathophysiology and the differences between MEA and SEA are still not completely understood. Bronchoalveolar lavage fluid cytology, broadly used in clinical practice and in equine asthma research, has limited means to represent the inflammatory status in the lower airways. Lipidomics is a field of science that can be utilized in investigating cellular mechanisms and cell-to-cell interactions. Studies in lipidomics have a broad variety of foci, of which fatty acid and lipid mediator profile analyses and global lipidomics have been implemented in veterinary medicine. As many crucial proinflammatory and proresolving mediators are lipids, lipidomic studies offer an interesting yet largely unexplored means to investigate inflammatory reactions in equine airways. The aim of this review article is to collect and summarize the findings of recent lipidomic studies on equine airway inflammation. [ABSTRACT FROM AUTHOR]

The interest in lipid composition profiling is significantly increasing as research reveals the immense importance of lipids in medicine, plant science, food and agriculture. However, lipidomic analysis requires high-end specialty equipment. We used two-dimensional thin-layer chromatography (2D-TLC) as a readily available, low-cost tool for basic lipidomic profiling of lipid classes in algal samples in the models Chlamydomonas reinhardtii, Auxenochlorella protothecoides, and Euglena gracilis, validating lipid class identification using an LC-MS/MS analysis. Algal lipid extracts were separated on a 2D-TLC plate, and TLC analysis was followed by scraping individual TLC spots off the plate, and a subsequent liquid chromatography separation and tandem mass spectrometry (LC-MS/MS) analysis. For comparison, crude lipid extracts were also injected directly to the LC-MS/MS system. Lipid class annotation was achieved by a combination of accurate mass, retention time information, neutral loss and fragment ion analysis by MS2Analyzer, and by matching spectra to LipidBlast MS/MS library. Overall, we were able to identify 15 lipid classes, and to adequately profile the lipid classes in all three organisms. This TLC method is thus suggested as an accessible tool for lipid class profiling of algal, plant, and food lipids, alike, when a rapid and simple analysis is required, e.g., for screening purposes. [ABSTRACT FROM AUTHOR]

For either healthy or diseased organisms, lipids are key components for cellular membranes; they play important roles in numerous cellular processes including cell growth, proliferation, differentiation, energy storage and signaling. Exercise and disease development are examples of cellular environment alterations which produce changes in these networks. There are indications that alterations in lipid metabolism contribute to the development and progression of a variety of cancers. Measuring such alterations and understanding the pathways involved is critical to fully understand cellular metabolism. The demands for this information have led to the emergence of lipidomics, which enables the large-scale study of lipids using mass spectrometry (MS) techniques. Mass spectrometry has been widely used in lipidomics and allows us to analyze detailed lipid profiles of cancers. In this article, we discuss emerging strategies for lipidomics by mass spectrometry; targeted, as opposed to global, lipid analysis provides an exciting new alternative method. Additionally, we provide an introduction to lipidomics, lipid categories and their major biological functions, along with lipidomics studies by mass spectrometry in cancer samples. Further, we summarize the importance of lipid metabolism in oncology and tumor microenvironment, some of the challenges for lipodomics, and the potential for targeted approaches for screening pharmaceutical candidates to improve the therapeutic efficacy of treatment in cancer patients. [ABSTRACT FROM AUTHOR]

Alzheimer disease (AD) is a heterogeneous and complex disease in which different pathophysiological mechanisms are involved. This heterogenicity can be reflected in different atrophy patterns or clinical manifestations. Regarding biochemical pathways involved in early AD, lipid metabolism plays an important role; therefore, lipid levels have been evaluated as potential AD diagnosis biomarkers, and their levels could be related to different AD clinical manifestations. Therefore, the aim of this work is to study AD lipid profiles from early AD patients and evaluate their clinical significance. For this purpose, untargeted plasma lipidomic analysis was carried out in early AD patients (n = 31) diagnosed with cerebrospinal fluid (CSF) biomarkers. Cluster analysis was carried out to define early AD subgroups according to the lipid levels. Then, the clinical significance of each lipid profile subgroup was studied, analyzing differences for other variables (cognitive status, CSF biomarkers, medication, comorbidities, age, and gender). The cluster analysis revealed two different groups of AD patients. Cluster 1 showed higher levels of plasma lipids and better cognitive status than Cluster 2. However, no differences were found for the other variables (age, gender, medication, comorbidities, cholesterol, and triglycerides levels) between both groups. Plasma lipid levels could differentiate two early AD subgroups, which showed different cognitive statuses. However, further research with a large cohort and longitudinal study evaluating the clinical evolution of these patients is required. In general, it would involve a relevant advance in the knowledge of AD pathological mechanisms, potential treatments, and precision medicine. [ABSTRACT FROM AUTHOR]

Detailed investigation of the lipidome remodeling upon normal weight conditions, obesity, or weight loss, as well as the influence of physical activity, can help to understand the mechanisms underlying dyslipidemia in metabolic conditions correlated to the emergence and progression of non-alcoholic fatty liver disease (NAFLD). C57BL/6 male mice were fed a normal diet (ND) or a high-fat diet (HFD) for 20 weeks. Subgroups within the high-fat diet (HFD) group underwent different interventions: some engaged in exercise (HFDex), others were subjected to weight loss (WL) by changing from the HFD to ND, and some underwent a combination of weight loss and exercise (WLex) during the final 8 weeks of the 20-week feeding period. To support our understanding, not only tissue-specific lipid remodeling mechanisms but also the cross-talk between different tissues and their impact on the systemic regulation of lipid metabolism are essential. Exercise and weight loss-induced specific adaptations in the liver and visceral adipose tissue lipidomes of mice were explored by the UPLC–TOF–MS/MS untargeted lipidomics methodology. Lipidomic signatures of ND and HFD-fed mice undergoing weight loss were compared with animals with and without physical exercise. Several lipid classes were identified as contributing factors in the discrimination of the groups by multivariate analysis models, such as glycerolipids, glycerophospholipids, sphingolipids, and fatty acids, with respect to liver samples, whereas triglycerides were the only lipid class identified in visceral adipose tissue. Lipids found to be dysregulated in HFD animals are related to well-established pathways involved in the biosynthesis of PC, PE, and TG metabolism. These show a reversing trend back to basic levels of ND when animals change to a normal diet after 12 weeks, whereas the impact of exercise, though in some cases it slightly enhances the reversing trend, is not clear. [ABSTRACT FROM AUTHOR]

In this work, Microwave-Assisted Extraction (MAE) was proposed as an alternative and environmentally friendly technique in lipidomics to study the lipid fingerprint of soft cheeses, such as mozzarella. For method development, a first step concerning an evaluation of extraction solvents was carried out via testing three different mixtures, including methanol/ethyl acetate, isopropanol/ethyl acetate, and ethanol/ethyl acetate, at a 1:2 v/v ratio. The latter was chosen as a solvent mixture for subsequent method optimization. MAE conditions, in terms of solvent volume, time, and temperature, were explored to define their effects on extraction capability through a full factorial experimental design. The best compromise to extract more lipids at the same time was obtained with 24 mL g−1 for solvent-to-solid ratio, 65 °C for temperature, and 18 min for time. Lipid analyses were conducted by UHPLC-Q-Orbitrap-MS associated with multivariate statistics. The developed lipidomic workflow allowed for the extraction of over 400 lipids grouped into 18 different subclasses. The results confirmed that MAE is a suitable technique for lipid extraction in the omics approach with high efficiency, even using low-cost and less toxic solvents. Moreover, a comprehensive structure characterization of extracted lipids, in terms of fatty acid composition and regiochemistry, was carried out. [ABSTRACT FROM AUTHOR]

The severity of COVID-19 is linked to an imbalanced immune response. The dysregulated metabolism of small molecules and bioactive lipids has also been associated with disease severity. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyze over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). This is the third publication in a series, and it reports the results of comprehensive lipidome profiling using targeted LC-MS/MS. We identified 1076 lipid features across 25 subclasses, including glycerophospholipids, sterols, glycerolipids, and sphingolipids, among which 531 lipid features were dramatically changed in the plasma of intensive care unit (ICU) patients compared to patients in the ward. Patients in the ICU showed 1.3–57-fold increases in ceramides, (lyso-)glycerophospholipids, diglycerides, triglycerides, and plasmagen phosphoethanolamines, and 1.3–2-fold lower levels of a cyclic lysophosphatidic acid, sphingosine-1-phosphates, sphingomyelins, arachidonic acid-containing phospholipids, lactosylceramide, and cholesterol esters compared to patients in the ward. Specifically, phosphatidylinositols (PIs) showed strong fatty acid saturation-dependent behavior, with saturated fatty acid (SFA)- and monosaturated fatty acid (MUFA)-derived PI decreasing and polystaturated (PUFA)-derived PI increasing. We also found ~4000 significant Spearman correlations between lipids and multiple clinical markers of immune response with |R| ≥ 0.35 and FDR corrected Q < 0.05. Except for lysophosphatidic acid, lysophospholipids were positively associated with the CD4 fraction of T cells, and the cytokines IL-8 and IL-18. In contrast, sphingosine-1-phosphates were negatively correlated with innate immune markers such as CRP and IL-6. Further indications of metabolic changes in moderate COVID-19 disease were demonstrated in recovering ward patients compared to those at the start of hospitalization, where 99 lipid species were altered (6 increased by 30–62%; 93 decreased by 1.3–2.8-fold). Overall, these findings support and expand on early reports that dysregulated lipid metabolism is involved in COVID-19. [ABSTRACT FROM AUTHOR]

Ectopic fat accumulation in non-adipose tissues is closely related to diabetes-related myocardial dysfunction. Nevertheless, the complete picture of the lipid metabolites involved in the metabolic-related myocardial alterations is not fully characterized. The aim of this study was to characterize the specific lipid profile in hearts in an animal model of obesity/insulin resistance induced by a high-fat diet (HFD). The cardiac lipidome profiles were assessed via liquid chromatography–mass spectrometry (LC–MS)/MS-MS and laser desorption/ionization–mass spectrometry (LDI–MS) tissue imaging in hearts from C57BL/6J mice fed with an HFD or standard-diet (STD) for 12 weeks. Targeted lipidome analysis identified a total of 63 lipids (i.e., 48 triacylglycerols (TG), 5 diacylglycerols (DG), 1 sphingomyelin (SM), 3 phosphatidylcholines (PC), 1 DihydroPC, and 5 carnitines) modified in hearts from HFD-fed mice compared to animals fed with STD. Whereas most of the TG were up-regulated in hearts from animals fed with an HFD, most of the carnitines were down-regulated, thereby suggesting a reduction in the mitochondrial β-oxidation. Roughly 30% of the identified metabolites were oxidated, pointing to an increase in lipid peroxidation. Cardiac lipidome was associated with a specific biochemical profile and a specific liver TG pattern. Overall, our study reveals a specific cardiac lipid fingerprint associated with metabolic alterations induced by HFD. [ABSTRACT FROM AUTHOR]

The presence of per- and polyfluoroalkyl substances (PFASs) in aquatic environments is often persistent and widespread. Understanding the potential adverse effects from this group of chemicals on aquatic communities allows for better hazard characterization. This study examines impacts on zebrafish (Danio rerio) embryo physiology, behavior, and lipid levels from exposure to perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and heptadecafluorooctanesulfonic acid (PFOS). Embryos were exposed to lethal and sublethal levels of each chemical and monitored for alterations in physiological malformations, mortality, lipid levels, and behavior (only PFOA and PFHxS). The predicted 50% lethal concentrations for 120 hpf embryos were 528.6 ppm PFOA, 14.28 ppm PFHxS, and 2.14 ppm PFOS. Spine curvature and the inability of the 120 hpf embryos to maintain a dorsal-up orientation was significantly increased at 10.2 ppm PFHxS and 1.9 ppm PFOS exposure. All measured 120 hpf embryo behaviors were significantly altered starting at the lowest levels tested, 188 ppm PFOA and 6.4 ppm PFHxS. Lipid levels decreased at the highest PFAS levels tested (375 PFOA ppm, 14.4 PFHxS ppm, 2.42 ppm PFOS). In general, the PFAS chemicals, at the levels examined in this study, increased morphological deformities, embryo activity, and startle response time, as well as decreased lipid levels in 120 hpf zebrafish embryos. [ABSTRACT FROM AUTHOR]

Urinary tract cancers, including those of the bladder, the kidneys, and the prostate, represent over 12% of all cancers, with significant global incidence and mortality rates. The continuous challenge that these cancers present necessitates the development of innovative diagnostic and prognostic methods, such as identifying specific biomarkers indicative of cancer. Biomarkers, which can be genes, proteins, metabolites, or lipids, are vital for various clinical purposes including early detection and prognosis. Mass spectrometry (MS), particularly soft ionization techniques such as electrospray ionization (ESI) and laser desorption/ionization (LDI), has emerged as a key tool in metabolic profiling for biomarker discovery, due to its high resolution, sensitivity, and ability to analyze complex biological samples. Among the LDI techniques, matrix-assisted laser desorption/ionization (MALDI) and surface-assisted laser desorption/ionization (SALDI) should be mentioned. While MALDI methodology, which uses organic compounds as matrices, is effective for larger molecules, SALDI, based on the various types of nanoparticles and nanostructures, is preferred for smaller metabolites and lipids due to its reduced spectral interference. This study highlights the application of LDI techniques, along with mass spectrometry imaging (MSI), in identifying potential metabolic and lipid biomarkers for urological cancers, focusing on the most common bladder, kidney, and prostate cancers. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a global public health issue characterized by excess weight, abdominal obesity, dyslipidemia, hyperglycemia, and a progressive increase in insulin resistance. Human population studies of T2D development and its effects on systemic metabolism are confounded by many factors that cannot be controlled, complicating the interpretation of results and the identification of early biomarkers. Aged, sedentary, and overweight/obese non-human primates (NHPs) are one of the best animal models to mimic spontaneous T2D development in humans. We sought to identify and distinguish a set of plasma and/or fecal metabolite biomarkers, that have earlier disease onset predictability, and that could be evaluated for their predictability in subsequent T2D studies in human cohorts. In this study, a single plasma and fecal sample was collected from each animal in a colony of 57 healthy and dysmetabolic NHPs and analyzed for metabolomics and lipidomics. The samples were comprehensively analyzed using untargeted and targeted LC/MS/MS. The changes in each animal's disease phenotype were monitored using IVGTT, HbA1c, and other clinical metrics, and correlated with their metabolic profile. The plasma and fecal lipids, as well as bile acid profiles, from Healthy, Dysmetabolic (Dys), and Diabetic (Dia) animals were compared. Following univariate and multivariate analyses, including adjustments for weight, age, and sex, several plasma lipid species were identified to be significantly different between these animal groups. Medium and long-chain plasma phosphatidylcholines (PCs) ranked highest at distinguishing Healthy from Dys animals, whereas plasma triglycerides (TG) primarily distinguished Dia from Dys animals. Random Forest (RF) analysis of fecal bile acids showed a reduction in the secondary bile acid glycoconjugate, GCDCA, in diseased animals (AUC 0.76[0.64, 0.89]). Moreover, metagenomics results revealed several bacterial species, belonging to the genera Roseburia, Ruminococcus, Clostridium, and Streptococcus, to be both significantly enriched in non-healthy animals and associated with secondary bile acid levels. In summary, our results highlight the detection of several elevated circulating plasma PCs and microbial species associated with fecal secondary bile acids in NHP dysmetabolic states. The lipids and metabolites we have identified may help researchers to differentiate individual NHPs more precisely between dysmetabolic and overtly diabetic states. This could help assign animals to study groups that are more likely to respond to potential therapies where a difference in efficacy might be anticipated between early vs. advanced disease. [ABSTRACT FROM AUTHOR]

The effect of nitrogen-modified atmosphere storage (NS) on peanut lipid oxidation was investigated in this paper. Non-targeted lipidomics was employed to detect the lipid metabolites in peanuts with the aim of exploring the mechanism of lipid oxidation in peanuts under different storage conditions. The results showed that compared with conventional storage (CS), NS significantly (p < 0.05) delayed the increase in acid value, carbonyl value, and 2-thiobarbituric acid value and the decrease in vitamin E content. However, the storage time has a much greater effect on lipid oxidation than the oxygen level in the storage environment. Lipidomics analysis revealed that there were significant differences in metabolite changes between CS and NS. NS reduced the decline of most glycerophospholipids by regulating lipid metabolism in peanuts. NS maintained higher levels of Diacylglycerol (DAG), sulfoquinovosyl diacylglycerol (SQDG), lysophophatidylcholine (LPC), lysophosphatidylethanolamine (LPE) and phosphatidylinositol (PI) compared to CS. This work provided a basis for the application of NS technology to peanut storage. [ABSTRACT FROM AUTHOR]

Blood serves as the primary global biological matrix for health surveillance, disease diagnosis, and response to drug treatment, holding significant promise for personalized medicine. The diverse array of lipids and metabolites in the blood provides a snapshot of both physiological and pathological processes, with many routinely monitored during conventional wellness checks. The conventional method involves intravenous blood collection, extracting a few milliliters via venipuncture, a technique limited to clinical settings due to its dependence on trained personnel. Microsampling methods have evolved to be less invasive (collecting ≤150 µL of capillary blood), user-friendly (enabling self-collection), and suitable for remote collection in longitudinal studies. Dried blood spot (DBS), a pioneering microsampling technique, dominates clinical and research domains. Recent advancements in device technology address critical limitations of classical DBS, specifically variations in hematocrit and volume. This review presents a comprehensive overview of state-of-the-art microsampling devices, emphasizing their applications and potential for monitoring metabolites and lipids in blood. The scope extends to diverse areas, encompassing population studies, nutritional investigations, drug discovery, sports medicine, and multi-omics research. [ABSTRACT FROM AUTHOR]

Targeting bioactive compounds to prevent lipid droplet accumulation in the liver, we explored an antioxidative extract from vanilla bean (Vainilla planifolia) after chemo-selective derivatization through heating and acid modification. The chemical analysis of vanilla bean extract through chemoselective derivatization resulted in the identification of sixteen compounds (34–50) using LC-MS/MS analysis. A β-carboline alkaloid with a piperidine C-ring and a vanillin moiety at C-1 (34) was identified by molecular networking and diagnostic fragmentation filtering approaches. β-carboline alkaloid 34 exhibited significant inhibitory activity of lipid droplet accumulation (LDAI) in oleic acid-loaded hepatocellular carcinoma HepG2 cells. The LDAI activity was associated with both activation of lipolysis and suppression of lipogenesis in the cells. The study indicates that crude plant extracts, following chemoselective derivatization, may contain bioactive compounds that could be beneficial in preventing hepatosteatosis and could serve as a source of lead compounds for drug development. This approach may be useful to investigate other mixtures of natural products and food resources. [ABSTRACT FROM AUTHOR]

The primary prevention, early detection, and treatment of cardiovascular disease (CVD) have been long-standing scientific research goals worldwide. In the past decades, traditional blood lipid profiles have been routinely used in clinical practice to estimate the risk of CVDs such as atherosclerotic cardiovascular disease (ASCVD) and as treatment targets for the primary prevention of adverse cardiac events. These blood lipid panel tests often fail to fully predict all CVD risks and thus need to be improved. A comprehensive analysis of molecular species of lipids and metabolites (defined as lipidomics and metabolomics, respectively) can provide molecular insights into the pathophysiology of the disease and could serve as diagnostic and prognostic indicators of disease. Mass spectrometry (MS) and nuclear magnetic resonance (NMR)-based lipidomics and metabolomics analysis have been increasingly used to study the metabolic changes that occur during CVD pathogenesis. In this review, we provide an overview of various MS-based platforms and approaches that are commonly used in lipidomics and metabolomics workflows. This review summarizes the lipids and metabolites in human plasma/serum that have recently (from 2018 to December 2022) been identified as promising CVD biomarkers. In addition, this review describes the potential pathophysiological mechanisms associated with candidate CVD biomarkers. Future studies focused on these potential biomarkers and pathways will provide mechanistic clues of CVD pathogenesis and thus help with the risk assessment, diagnosis, and treatment of CVD. [ABSTRACT FROM AUTHOR]

Lysosomes are degradative organelles that facilitate the removal and recycling of potentially cytotoxic materials and mediate a variety of other cellular processes, such as nutrient sensing, intracellular signaling, and lipid metabolism. Due to these central roles, lysosome dysfunction can lead to deleterious outcomes, including the accumulation of cytotoxic material, inflammation, and cell death. We previously reported that cationic amphiphilic drugs, such as imipramine, alter pH and lipid metabolism within macrophage lysosomes. Therefore, the ability for imipramine to induce changes to the lipid content of isolated macrophage lysosomes was investigated, focusing on sphingomyelin, cholesterol, and glycerophospholipid metabolism as these lipid classes have important roles in inflammation and disease. The lysosomes were isolated from control and imipramine-treated macrophages using density gradient ultracentrifugation, and mass spectrometry was used to measure the changes in their lipid composition. An unsupervised hierarchical cluster analysis revealed a clear differentiation between the imipramine-treated and control lysosomes. There was a significant overall increase in the abundance of specific lipids mostly composed of cholesterol esters, sphingomyelins, and phosphatidylcholines, while lysophosphatidylcholines and ceramides were overall decreased. These results support the conclusion that imipramine's ability to change the lysosomal pH inhibits multiple pH-sensitive enzymes in macrophage lysosomes. [ABSTRACT FROM AUTHOR]

Microalgae are recognized as a relevant source of bioactive compounds. Among these bioactive products, lipids, mainly glycolipids, have been shown to present immunomodulatory properties with the potential to mitigate chronic inflammation. This study aimed to evaluate the anti-inflammatory effect of polar lipids isolated from Nannochloropsis oceanica and Chlorococcum amblystomatis. Three fractions enriched in (1) digalactosyldiacylglycerol (DGDG) and sulfoquinovosyldiacylglycerol (SQDG), (2) monogalactosyldiacylglycerol (MGDG), and (3) diacylglyceryl-trimethylhomoserine (DGTS) and phospholipids (PL) were obtained from the total lipid extracts (TE) of N. oceanica and C. amblystomatis, and their anti-inflammatory effect was assessed by analyzing their capacity to counteract nitric oxide (NO) production and transcription of pro-inflammatory genes Nos2, Ptgs2, Tnfa, and Il1b in lipopolysaccharide (LPS)-activated macrophages. For both microalgae, TE and Fractions 1 and 3 strongly inhibited NO production, although to different extents. A strong reduction in the LPS-induced transcription of Nos2, Ptgs2, Tnfa, and Il1b was observed for N. oceanica and C. amblystomatis lipids. The most active fractions were the DGTS-and-PL-enriched fraction from N. oceanica and the DGDG-and-SQDG-enriched fraction from C. amblystomatis. Our results reveal that microalgae lipids have strong anti-inflammatory capacity and may be explored as functional ingredients or nutraceuticals, offering a natural solution to tackle chronic inflammation-associated diseases. [ABSTRACT FROM AUTHOR]

Honeybee drone larvae are male bees that develop from unfertilized eggs and play a role in colony reproduction. The nutritional value of honeybee drone larvae is due to their high protein, lipid, and other nutrient contents, making them a profitable food source for humans in some cultures. Drone larvae lipids (DLLs) contribute to drone development; however, few studies have explored their substantial compositions and bioactive functions. In this study, we carried out DLL lipidomics analysis using UPLC-Q-Exactive-Orbitrap–MS prior to in vitro anti-inflammatory activity analysis. The results highlighted the importance of the extraction temperature on the DLL composition. A total of 21 lipids were found in the DLL extract, mostly categorized into five groups: nine phospholipids, three sphingolipids, two neutral lipids, one plant glycoglycerolipid, four lipid acyl, and others. Drying extraction at −20 °C produced more sphingolipids, phospholipids, and unsaturated fatty acids. Of 37 fatty acids, 18 were displayed at −20 °C degrees, as shown by GC–MS quantitative analysis. Myristic (246.99 ± 13.19 μg/g), palmitic (1707.87 ± 60.53 μg/g), stearic (852.32 ± 24.17 μg/g), and oleic (2463.03 ± 149.61 μg/g) acids were the predominant fatty acids. Furthermore, we examined the significant in vitro anti-inflammatory effects of DLL (−20 °C) using lipopolysaccharide (LPS)-challenged RAW264.7 cells. Nitric oxide (NO) and reactive oxygen (ROS) production and mRNA expression of IL-6, IL-10, COX-2, and iNOS were significantly decreased, demonstrating the anti-inflammatory function of DLL. Overall, this study provided insight into the lipid composition of DLL, revealed the influence of temperature, and explored the functionality of DLL (−20 °C), allowing for further application of DLLs as functional foods. [ABSTRACT FROM AUTHOR]

Patients with subarachnoid hemorrhage (SAH) may develop posthemorrhagic hydrocephalus (PHH), which is treated with surgical cerebrospinal fluid (CSF) diversion. This diversion is associated with risk of infection and shunt failure. Biomarkers for PHH etiology, CSF dynamics disturbances, and potentially subsequent shunt dependency are therefore in demand. With the recent demonstration of lipid-mediated CSF hypersecretion contributing to PHH, exploration of the CSF lipid signature in relation to brain pathology is of interest. Despite being a relatively new addition to the omic's landscape, lipidomics are increasingly recognized as a tool for biomarker identification, as they provide a comprehensive overview of lipid profiles in biological systems. We here employ an untargeted mass spectroscopy-based platform and reveal the complete lipid profile of cisternal CSF from healthy control subjects and demonstrate its bimodal fluctuation with age. Various classes of lipids, in addition to select individual lipids, were elevated in the ventricular CSF obtained from patients with SAH during placement of an external ventricular drain. The lipidomic signature of the CSF in the patients with SAH suggests dysregulation of the lipids in the CSF in this patient group. Our data thereby reveal possible biomarkers present in a brain pathology with a hemorrhagic event, some of which could be potential future biomarkers for hypersecretion contributing to ventriculomegaly and thus pharmacological targets for pathologies involving disturbed CSF dynamics. [ABSTRACT FROM AUTHOR]

Lipidomics refers to the full characterization of lipids present within a cell, tissue, organism, or biological system. One of the bottlenecks affecting reliable lipidomic analysis is the extraction of lipids from biological samples. An ideal extraction method should have a maximum lipid recovery and the ability to extract a broad range of lipid classes with acceptable reproducibility. The most common lipid extraction relies on either protein precipitation (monophasic methods) or liquid–liquid partitioning (bi- or triphasic methods). In this study, three monophasic extraction systems, isopropanol (IPA), MeOH/MTBE/CHCl3 (MMC), and EtOAc/EtOH (EE), alongside three biphasic extraction methods, Folch, butanol/MeOH/heptane/EtOAc (BUME), and MeOH/MTBE (MTBE), were evaluated for their performance in characterization of the mouse lipidome of six different tissue types, including pancreas, spleen, liver, brain, small intestine, and plasma. Sixteen lipid classes were investigated in this study using reversed-phase liquid chromatography/mass spectrometry. Results showed that all extraction methods had comparable recoveries for all tested lipid classes except lysophosphatidylcholines, lysophosphatidylethanolamines, acyl carnitines, sphingomyelines, and sphingosines. The recoveries of these classes were significantly lower with the MTBE method, which could be compensated by the addition of stable isotope-labeled internal standards prior to lipid extraction. Moreover, IPA and EE methods showed poor reproducibility in extracting lipids from most tested tissues. In general, Folch is the optimum method in terms of efficacy and reproducibility for extracting mouse pancreas, spleen, brain, and plasma. However, MMC and BUME methods are more favored when extracting mouse liver or intestine. [ABSTRACT FROM AUTHOR]

The relationship between the type and intensities of lipids of blood and pancreas and the pathological changes in the pancreas during severe acute pancreatitis (SAP) remains unclear. In our study, we employed a rat model of SAP induced through intraperitoneal ornithine injections. We collected serum and pancreas samples at various time points (0–144 h) for histopathological and biochemical assessments, followed by lipidomic analyses using LC-MS/MS or in situ mass spectrometry imaging (MSI) To discern changes over time or at specific points, we employed time-course and univariate analyses for lipid screening, respectively. Our findings indicated that the peak inflammation in the Orn-SAP model occurred within the 24–30 h timeframe, with evident necrosis emerging from 24 h onwards, followed by regeneration starting at 48 h. Time-course analysis revealed an overall decrease in glycerophospholipids (PEs, PCs, LPEs, LPCs), while CEs exhibited an increase within the pancreas. Univariate analysis unveiled a significant reduction in serum TAGs containing 46–51 carbon atoms at 24 h, and CERs in the pancreas significantly increased at 30 h, compared with 0 h. Moreover, a substantial rise in TAGs containing 56–58 carbon atoms was observed at 144 h, both in serum and pancreas. MSI demonstrated the CERs containing saturated mono-acyl chains of 16 and 18 carbon atoms influenced pancreatic regeneration. Tracing the origin of FFAs hydrolyzed from pancreatic glycerophospholipids and serum TAGs during the early stages of inflammation, as well as FFAs utilized for CEs and CERs synthesis during the repair phase, may yield valuable strategies for diagnosing and managing SAP. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a highly prevalent neurodegenerative movement disorder with an unclear etiology and a lack of definite diagnostic tests and effective treatments. About 95% of PD cases are idiopathic, in which none of the well-known genes underlying familial parkinsonism are mutated. We used untargeted liquid chromatography–mass spectrometry (LC-MS/MS) to profile the serum lipidome of 50 patients with different stages of idiopathic PD (early, mid, or advanced) and 45 age-matched controls. When comparing the PD patients to the control subjects, 169 lipids were significantly altered in both a univariate analysis and a multivariate partial least-squares discriminant analysis (PLS-DA). Compared to the controls, the patients with PD had higher levels of unsaturated triacylglycerides (e.g., TG O-56:9 and TG 52:3), saturated lysophosphatidylcholines (LPC 17:0, 16:0, and 15:0), and hydroxyeicosatetraenoic acid (12-HETE), while lower levels of phosphatidylserines (e.g., PS 40:4 and PS 16:0_22:4), sphingomyelins (SM 42:1), and ceramides (e.g., Cer 40:0 and 42:0) were found between the PD patients and the controls. A panel of 10 significantly altered lipids (PS 40:0, Cer 40:0, Cer 42:0, LPC 17:0, LPC 15:0, PC 37:7, PE O-40:8, PC O-42:4, FA 23:0, and SM 42:1) resulted in a strong receiver operating characteristic curve with an AUC = 0.974. This panel may, therefore, be useful for diagnosing PD. In addition, lipid panels may prove useful for distinguishing among the progression stages of PD. Using one-way ANOVA, 155 lipid species were significantly altered among the PD stages. Parkinson's disease progressed from the early to advanced stages with decreasing levels of PC 31:1, PC 38:4, and LPE 22:5. Conversely, LPC-O 20:0, PC O-42:3, FA 19:0, and FA 22:2 showed an increase in their levels with disease progression. Overall, this study shows an intriguing number of robust changes in specific serum lipids that may become useful for diagnosing PD and its progression, once panels have been validated in larger clinical trials and prospective studies. [ABSTRACT FROM AUTHOR]

Liquid chromatography–mass spectrometry (LC-MS) is the key technique for analyzing complex lipids in biological samples. Various LC-MS modes are used for lipid separation, including different stationary phases, mobile-phase solvents, and modifiers. Quality control in lipidomics analysis is crucial to ensuring the generated data's reliability, reproducibility, and accuracy. While several quality control measures are commonly discussed, the impact of organic solvent quality during LC-MS analysis is often overlooked. Additionally, the annotation of complex lipids remains prone to biases, leading to potential misidentifications and incomplete characterization of lipid species. In this study, we investigate how LC-MS-grade isopropanol from different vendors may influence the quality of the mobile phase used in LC-MS-based untargeted lipidomic profiling of biological samples. Furthermore, we report the occurrence of an unusual, yet highly abundant, ethylamine adduct [M+46.0651]+ that may form for specific lipid subclasses during LC-MS analysis in positive electrospray ionization mode when acetonitrile is part of the mobile phase, potentially leading to lipid misidentification. These findings emphasize the importance of considering solvent quality in LC-MS analysis and highlight challenges in lipid annotation. [ABSTRACT FROM AUTHOR]

The lipid profile is affected following menstrual cessation (MC). We aimed to evaluate the effects of goserelin-induced MC and subsequent menstrual restoration (MR) on lipid metabolism. Premenopausal women with histologically verified endometriosis (n = 15) received goserelin monthly for 6 months (6mο), resulting in MC, and were followed-up for another 6 months after MR (12mο). Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a ([Lp(a)] and lipidomics were measured at baseline, 6mo and 12mo. Shotgun quantitative deep lipidomics were determined at the level of lipid class category, subclass, species, and fatty acyl chain lengths and degree of saturation. TC (p = 0.006), LDL-C (p = 0.028), HDL-C (p = 0.002), and apoA1 (p = 0.013) increased during goserelin-induced MC and remained practically unchanged during MR. TG, apoB, and Lp(a) did not change. From the deep lipidomics analysis, multivariate statistical analysis demonstrated profound alterations in lipid species with MC, whereas no statistically valid models could be fitted for the restoration period. In conclusion, GnRH-analog-induced MC alters lipid profiles at various levels, from standard blood lipid and lipoprotein profiles to several lipid species as detected by lipidomics analysis. Changes largely persist for at least 6 m after MR. [ABSTRACT FROM AUTHOR]

Different mutations in the SERPINA1 gene result in alpha-1 antitrypsin (AAT) deficiency and in an increased risk for the development of liver diseases. More than 90% of severe deficiency patients are homozygous for Z (Glu342Lys) mutation. This mutation causes Z-AAT polymerization and intrahepatic accumulation which can result in hepatic alterations leading to steatosis, fibrosis, cirrhosis, and/or hepatocarcinoma. We aimed to investigate lipid status in hepatocytes carrying Z and normal M alleles of the SERPINA1 gene. Hepatic organoids were developed to investigate lipid alterations. Lipid accumulation in HepG2 cells overexpressing Z-AAT, as well as in patient-derived hepatic organoids from Pi*MZ and Pi*ZZ individuals, was evaluated by Oil-Red staining in comparison to HepG2 cells expressing M-AAT and liver organoids from Pi*MM controls. Furthermore, mass spectrometry-based lipidomics analysis and transcriptomic profiling were assessed in Pi*MZ and Pi*ZZ organoids. HepG2 cells expressing Z-AAT and liver organoids from Pi*MZ and Pi*ZZ patients showed intracellular accumulation of AAT and high numbers of lipid droplets. These latter paralleled with augmented intrahepatic lipids, and in particular altered proportion of triglycerides, cholesterol esters, and cardiolipins. According to transcriptomic analysis, Pi*ZZ organoids possess many alterations in genes and cellular processes of lipid metabolism with a specific impact on the endoplasmic reticulum, mitochondria, and peroxisome dysfunction. Our data reveal a relationship between intrahepatic accumulation of Z-AAT and alterations in lipid homeostasis, which implies that liver organoids provide an excellent model to study liver diseases related to the mutation of the SERPINA1 gene. [ABSTRACT FROM AUTHOR]

The administration of low doses of D2O to living organisms was used for decades for the investigation of metabolic pathways and for the measurement of the turnover rate for specific compounds. Usually, the investigation of the deuterium uptake in lipids is performed by measuring the deuteration level of the palmitic acid residue using GC-MS instruments, and to our knowledge, the application of the modern untargeted LC-MS/MS lipidomics approaches was only reported a few times. Here, we investigated the deuterium uptake for >500 lipids for 13 organs and body liquids of mice (brain, lung, heart, liver, kidney, spleen, plasma, urine, etc.) after 4 days of 100% D2O administration. The maximum deuteration level was observed in the liver, plasma, and lung, while in the brain and heart, the deuteration level was lower. Using MS/MS, we demonstrated the incorporation of deuterium in palmitic and stearic fragments in lipids (PC, PE, TAG, PG, etc.) but not in the corresponding free forms. Our results were analyzed based on the metabolic pathways of lipids. [ABSTRACT FROM AUTHOR]

An integrative multi-modal metabolic phenotyping model was developed to assess the systemic plasma sequelae of SARS-CoV-2 (rRT-PCR positive) induced COVID-19 disease in patients with different respiratory severity levels. Plasma samples from 306 unvaccinated COVID-19 patients were collected in 2020 and classified into four levels of severity ranging from mild symptoms to severe ventilated cases. These samples were investigated using a combination of quantitative Nuclear Magnetic Resonance (NMR) spectroscopy and Mass Spectrometry (MS) platforms to give broad lipoprotein, lipidomic and amino acid, tryptophan-kynurenine pathway, and biogenic amine pathway coverage. All platforms revealed highly significant differences in metabolite patterns between patients and controls (n = 89) that had been collected prior to the COVID-19 pandemic. The total number of significant metabolites increased with severity with 344 out of the 1034 quantitative variables being common to all severity classes. Metabolic signatures showed a continuum of changes across the respiratory severity levels with the most significant and extensive changes being in the most severely affected patients. Even mildly affected respiratory patients showed multiple highly significant abnormal biochemical signatures reflecting serious metabolic deficiencies of the type observed in Post-acute COVID-19 syndrome patients. The most severe respiratory patients had a high mortality (56.1%) and we found that we could predict mortality in this patient sub-group with high accuracy in some cases up to 61 days prior to death, based on a separate metabolic model, which highlighted a different set of metabolites to those defining the basic disease. Specifically, hexosylceramides (HCER 16:0, HCER 20:0, HCER 24:1, HCER 26:0, HCER 26:1) were markedly elevated in the non-surviving patient group (Cliff's delta 0.91–0.95) and two phosphoethanolamines (PE.O 18:0/18:1, Cliff's delta = −0.98 and PE.P 16:0/18:1, Cliff's delta = −0.93) were markedly lower in the non-survivors. These results indicate that patient morbidity to mortality trajectories is determined relatively soon after infection, opening the opportunity to select more intensive therapeutic interventions to these "high risk" patients in the early disease stages. [ABSTRACT FROM AUTHOR]

Spectrophotometric- and liquid chromatography/mass spectrometry (LC/MS)-based lipidomics analyses were performed to explore the changes of lipid profiles in pike eel (Muraenesox cinereus) under stable chlorine dioxides (ClO2) and vacuum-packed treatment during chilled storage. The peroxide value (PV) and malondialdehyde (MDA) content in ClO2 treated and vacuum-packaged (VP) samples were significantly reduced compared to simple-packaged (SP) samples during whole chilled storage. The LC/MS-based lipidomics analyses identified 2182 lipid species in the pike eel muscle classified into 39 subclasses, including 712 triglycerides (TGs), 310 phosphatidylcholines (PCs), 153 phosphatidylethanolamines (PEs), and 147 diglycerides (DGs), among others. Further, in comparison with fresh pike eel (FE) muscle, 354 and 164 higher and 420 and 193 lower abundant levels of differentially abundant lipids (DALs) were identified in SP samples and VP samples, respectively. Compared with the VP batch, 396 higher and 404 lower abundant levels of DALs were identified in the SP batch. Among these, PCs, PEs, TGs, and DGs were more easily oxidized/hydrolyzed, which could be used as biomarkers to distinguish FE, SP, and VP samples. This research provides a reference for controlling lipid oxidation in fatty fish. [ABSTRACT FROM AUTHOR]

Synovial fluid (SF) from human knee joints with osteoarthritis (OA) has elevated levels of lysophosphatidylcholine (LPC) species, but their functional role is not well understood. This in vitro study was designed to test the hypothesis that various LPCs found elevated in OA SF and their metabolites, lysophosphatidic acids (LPAs), modulate the abundance of proteins and phospholipids (PLs) in human fibroblast-like synoviocytes (FLSs), with even minute chemical variations in lysophospholipids determining the extent of regulation. Cultured FLSs (n = 5–7) were treated with one of the LPC species, LPA species, IL-1β, or a vehicle. Tandem mass tag peptide labeling coupled with LC-MS/MS/MS was performed to quantify proteins. The expression of mRNA from regulated proteins was analyzed using RT-PCR. PL synthesis was determined via ESI-MS/MS, and the release of radiolabeled PLs was determined by means of liquid scintillation counting. In total, 3960 proteins were quantified using multiplexed MS, of which 119, 8, and 3 were significantly and reproducibly regulated by IL-1β, LPC 16:0, and LPC 18:0, respectively. LPC 16:0 significantly inhibited the release of PLs and the synthesis of phosphatidylcholine, LPC, and sphingomyelin. Neither LPC metabolite—LPA 16:0 nor LPA 18:0—had any reproducible effect on the levels of each protein. In conclusion, small chemical variations in LPC species can result in the significantly altered expression and secretion of proteins and PLs from FLSs. IL-1β influenced all proteins that were reproducibly regulated by LPC 16:0. LPC species are likely to modulate FLS protein expression only in more advanced OA stages with low IL-1β levels. None of the eight proteins being significantly regulated by LPC 16:0 have been previously reported in OA. However, our in vitro findings show that the CD81 antigen, calumenin, and B4E2C1 are promising candidates for further study, focusing in particular on their potential ability to modulate inflammatory and catabolic mechanisms. [ABSTRACT FROM AUTHOR]

Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed the lipidome, metabolome and immune cell recruitment in livers in both diseases. Mice harboring ASH or NASH had comparable disease severities regarding mortality rate, neurological behavior, expression of fibrosis marker and albumin levels. Lipid droplet size was higher in NASH than ASH and qualitative differences in the lipidome were mainly based on incorporation of diet-specific fatty acids into triglycerides, phosphatidylcholines and lysophosphatidylcholines. Metabolomic analysis showed downregulated nucleoside levels in both models. Here, the corresponding uremic metabolites were only upregulated in NASH suggesting stronger cellular senescence, which was supported by lower antioxidant levels in NASH as compared to ASH. While altered urea cycle metabolites suggest increased nitric oxide synthesis in both models, in ASH, this depended on increased L-homoarginine levels indicating a cardiovascular response mechanism. Interestingly, only in NASH were the levels of tryptophan and its anti-inflammatory metabolite kynurenine upregulated. Fittingly, high-content immunohistochemistry showed a decreased macrophage recruitment and an increased polarization towards M2-like macrophages in NASH. In conclusion, with comparable disease severity in both models, higher lipid storage, oxidative stress and tryptophan/kynurenine levels were seen in NASH, leading to distinct immune responses. [ABSTRACT FROM AUTHOR]

Lipids play important biological roles, such as providing essential fatty acids and signaling. The wide variety and structural diversity of lipids, and the limited technical means to study them, have seriously hampered the resolution of the mechanisms of action of lipids. With advances in mass spectrometry (MS) and bioinformatic technologies, large amounts of lipids have been detected and analyzed quickly using MS-based lipidomic techniques. Milk lipids, as complex structural metabolites, play a crucial role in human health. In this review, the lipidomic techniques and their applications to dairy products, including compositional analysis, quality identification, authenticity identification, and origin identification, are discussed, with the aim of providing technical support for the development of dairy products. [ABSTRACT FROM AUTHOR]

The fruit of the oil palm (Elaeis guineensis Jacq.) has fleshy mesocarpic tissue rich in lipids. This edible vegetable oil is economically and nutritionally significant across the world. The core concepts of oil biosynthesis in oil palms remain to be researched as the knowledge of oil biosynthesis in plants improves. In this study, we utilized a metabolite approach and mass spectral analysis to characterize metabolite changes and identify the sequences of protein accumulation during the physiological processes that regulate oil synthesis during oil palm fruit ripening. Here, we performed a comprehensive lipidomic data analysis in order to understand the role of lipid metabolism in oil biosynthesis mechanisms. The experimental materials were collected from the mesocarp of oil palm (Tenera) at 95 days (early accumulation of fatty acid, first stage), 125 days (rapid growth of fatty acid accumulation, second stage), and 185 days (stable period of fatty acid accumulation, third stage) after pollination. To gain a clear understanding of the lipid changes that occurred during the growth of the oil palm, the metabolome data were found using principal component analysis (PCA). Furthermore, the accumulations of diacylglycerols, ceramides, phosphatidylethanolamine, and phosphatidic acid varied between the developmental stages. Differentially expressed lipids were successfully identified and functionally classified using KEGG analysis. Proteins related to the metabolic pathway, glycerolipid metabolism, and glycerphospholipid metabolism were the most significantly changed proteins during fruit development. In this study, LC-MS analysis and evaluation of the lipid profile in different stages of oil palm were performed to gain insight into the regulatory mechanisms that enhance fruit quality and govern differences in lipid composition and biosynthesis. [ABSTRACT FROM AUTHOR]

Levels of high-density lipoprotein cholesterol (HDL-C) are inversely associated with the incidence of coronary artery disease (CAD). However, the underlying mechanism of CAD in the context of elevated HDL-C levels is unclear. Our study aimed to explore the lipid signatures in patients with CAD and elevated HDL-C levels and to identify potential diagnostic biomarkers for these conditions. We measured the plasma lipidomes of forty participants with elevated HDL-C levels (men with >50 mg/dL and women with >60 mg/dL), with or without CAD, using liquid chromatography–tandem mass spectrometry. We analyzed four hundred fifty-eight lipid species and identified an altered lipidomic profile in subjects with CAD and high HDL-C levels. In addition, we identified eighteen distinct lipid species, including eight sphingolipids and ten glycerophospholipids; all of these, except sphingosine-1-phosphate (d20:1), were higher in the CAD group. Pathways for sphingolipid and glycerophospholipid metabolism were the most significantly altered. Moreover, our data led to a diagnostic model with an area under the curve of 0.935, in which monosialo-dihexosyl ganglioside (GM3) (d18:1/22:0), GM3 (d18:0/22:0), and phosphatidylserine (38:4) were combined. We found that a characteristic lipidome signature is associated with CAD in individuals with elevated HDL-C levels. Additionally, the disorders of sphingolipid as well as glycerophospholipid metabolism may underlie CAD. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) relies on cellular lipid pathways for virus replication and also induces liver steatosis, but the mechanisms involved are not clear. We performed a quantitative lipidomics analysis of virus-infected cells by combining high-performance thin-layer chromatography (HPTLC) and mass spectrometry, using an established HCV cell culture model and subcellular fractionation. Neutral lipid and phospholipids were increased in the HCV-infected cells; in the endoplasmic reticulum there was an ~four-fold increase in free cholesterol and an ~three-fold increase in phosphatidyl choline (p < 0.05). The increase in phosphatidyl choline was due to the induction of a non-canonical synthesis pathway involving phosphatidyl ethanolamine transferase (PEMT). An HCV infection induced expression of PEMT while knocking down PEMT with siRNA inhibited virus replication. As well as supporting virus replication, PEMT mediates steatosis. Consistently, HCV induced the expression of the pro-lipogenic genes SREBP 1c and DGAT1 while inhibiting the expression of MTP, promoting lipid accumulation. Knocking down PEMT reversed these changes and reduced the lipid content in virus-infected cells. Interestingly, PEMT expression was over 50% higher in liver biopsies from people infected with the HCV genotype 3 than 1, and three times higher than in people with chronic hepatitis B, suggesting that this may account for genotype-dependent differences in the prevalence of hepatic steatosis. PEMT is a key enzyme for promoting the accumulation of lipids in HCV-infected cells and supports virus replication. The induction of PEMT may account for virus genotype specific differences in hepatic steatosis. [ABSTRACT FROM AUTHOR]

The unambiguous identification of lipids is a critical component of lipidomics studies and greatly impacts the interpretation and significance of analyses as well as the ultimate biological understandings derived from measurements. The level of structural detail that is available for lipid identifications is largely determined by the analytical platform being used. Mass spectrometry (MS) coupled with liquid chromatography (LC) is the predominant combination of analytical techniques used for lipidomics studies, and these methods can provide fairly detailed lipid identification. More recently, ion mobility spectrometry (IMS) has begun to see greater adoption in lipidomics studies thanks to the additional dimension of separation that it provides and the added structural information that can support lipid identification. At present, relatively few software tools are available for IMS-MS lipidomics data analysis, which reflects the still limited adoption of IMS as well as the limited software support. This fact is even more pronounced for isomer identifications, such as the determination of double bond positions or integration with MS-based imaging. In this review, we survey the landscape of software tools that are available for the analysis of IMS-MS-based lipidomics data and we evaluate lipid identifications produced by these tools using open-access data sourced from the peer-reviewed lipidomics literature. [ABSTRACT FROM AUTHOR]

Objective: Preeclampsia (PE) is a prevalent pregnancy disorder worldwide with limited preventative treatments available. Obesity triples the risk for PE, yet only 10% of women with obesity develop PE. The factors that distinguish PE from uncomplicated pregnancies in the context of obesity have not been fully established. Methods: We studied a cohort of women with obesity throughout pregnancy to identify lipid mediators and/or biomarkers of PE. Blood samples were collected at each trimester and analyzed by both targeted lipidomics and standard lipid panels. Individual lipid species were compared by PE status at each trimester, as well as by self-identified race (Black vs. White) and fetal sex. Results: Standard lipid panels and clinical measurements revealed few differences between PE and uncomplicated pregnancies. Targeted lipidomics, however, identified plasmalogen, phosphatidylethanolamine, and free fatty acid species that were elevated in the third trimester of women with PE. Furthermore, race and trimester of pregnancy were considerable sources of plasma lipidomic variation in women with obesity. Conclusions: First and second trimester individual plasma lipid species do not predict the development of PE in obese women. In the third trimester, PE patients have elevated levels of plasmalogens—a class of lipoprotein-associated phospholipids that have been implicated in the response to oxidative stress. [ABSTRACT FROM AUTHOR]

Lipidomics is a term used to define the field that analyzes the structure, functions, and interactions of lipids. Inflammatory dermatoses and lipid disturbances are interrelated, especially due to chronic inflammatory conditions. This review discusses lipidomics in selected inflammatory skin diseases: psoriasis, lichen planus, and atopic dermatitis, as well as the less commonly mentioned hidradenitis suppurativa, rosacea, and acne vulgaris. Lipid homeostasis disorders are common; they are especially well-documented in psoriasis, lichen planus, and atopic dermatitis. Future studies are required for better insight into this issue, particularly on the skin lipidome. Understanding lipidomics, in particular skin diseases, increases our knowledge about their pathogenesis, and may become useful in adjusting tailored management for each patient as well establishing prognosis. Noteworthily, it seems advisable to alert doctors to the need to analyze lipid parameters and the complications of abnormal lipid metabolism in dermatological patients, which could decrease their comorbidities and improve the life quality and health condition of dermatological patients. [ABSTRACT FROM AUTHOR]

The microalga Chlorella vulgaris is a popular food ingredient widely used in the industry, with an increasing market size and value. Currently, several edible strains of C. vulgaris with different organoleptic characteristics are commercialized to meet consumer needs. This study aimed to compare the fatty acid (FA) and lipid profile of four commercialized strains of C. vulgaris (C-Auto, C-Hetero, C-Honey, and C-White) using gas- and liquid-chromatography coupled to mass-spectrometry approaches, and to evaluate their antioxidant and anti-inflammatory properties. Results showed that C-Auto had a higher lipid content compared to the other strains and higher levels of omega-3 polyunsaturated FAs (PUFAs). However, the C-Hetero, C-Honey, and C-White strains had higher levels of omega-6 PUFAs. The lipidome signature was also different between strains, as C-Auto had a higher content of polar lipids esterified to omega-3 PUFAs, while C-White had a higher content of phospholipids with omega-6 PUFAs. C-Hetero and C-Honey showed a higher content of triacylglycerols. All extracts showed antioxidant and anti-inflammatory activity, highlighting C-Auto with greater potential. Overall, the four strains of C. vulgaris can be selectively chosen as a source of added-value lipids to be used as ingredients in food and nutraceutical applications for different market needs and nutritional requirements. [ABSTRACT FROM AUTHOR]

Lipids are biomolecules involved in numerous (patho-)physiological processes and their elucidation in tissue samples is of particular interest. However, tissue analysis goes hand in hand with many challenges and the influence of pre-analytical factors can intensively change lipid concentrations ex vivo, compromising the results of the whole research project. Here, we study the influence of pre-analytical factors on lipid profiles during the processing of homogenized tissues. Homogenates from four different mice tissues (liver, kidney, heart, spleen) were stored at room temperature as well as in ice water for up to 120 min and analyzed via ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). Lipid class ratios were calculated since their suitability as indicators for sample stability has been previously illustrated. Only approx. 40% of lipid class ratios were unchanged after 35 min, which was further reduced to 25% after 120 min during storage at room temperature. In contrast, lipids in tissue homogenates were generally stable when samples were kept in ice water, as more than 90% of investigated lipid class ratios remained unchanged after 35 min. Ultimately, swift processing of tissue homogenates under cooled conditions represents a viable option for lipid analysis and pre-analytical factors require more attention to achieve reliable results. [ABSTRACT FROM AUTHOR]

Although there has been limited application in the field to date, human milk omics research continues to gain traction. Human milk lipidomics and metabolomics research is particularly important, given the significance of milk lipids and metabolites for infant health. For researchers conducting compositional milk analyses, it is important to consider the origins of these compounds. The current review aims to provide a summary of the existing evidence on the sources of human milk lipids and small metabolites. Here, we describe five major sources of milk lipids and metabolites: de novo synthesis from mammary cells, production by the milk microbiota, dietary consumption, release from non-mammary tissue, and production by the gut microbiota. We synthesize the literature to provide evidence and understanding of these pathways in the context of mammary gland biology. We recommend future research focus areas to elucidate milk lipid and small metabolite synthesis and transport pathways. Better understanding of the origins of human milk lipids and metabolites is important to improve translation of milk omics research, particularly regarding the modulation of these important milk components to improve infant health outcomes. [ABSTRACT FROM AUTHOR]

We conducted a lipidomic analysis of the whole body of female Aedes aegypti mosquitoes at different time points over the course of feeding and reproduction. There were temporal biphasic increases of more than 80% of lipids identified at the time of feeding and from 16 h to 30 h post blood meal (PBM). During these two increases, the abundance of many lipids dropped while body weight remained stable, probably reflecting blood lipid digestion and the synthesis of vitellogenin in this period. A concerted temporal pattern was particularly strong at the second peak for membrane and signalling lipids such as phosphatidylethanolamine (PE), phosphatidylinositol (PI), cardiolipin (CL), hexosylceramide (HexCer) and lyso-phosphatidic acid (LPA). Lyso-glycerophospholipids showed three distinct change patterns that are functionally related: Lyso-PE and Lyso-phosphatidylcholine (LPC), which are membrane lipids, showed little change; LPA, a signalling lipid, showed a significant increase from 16 to 30 h PBM; Lyso-PI, a bioactive lipid, and both lyso-phosphatidylglycerol (LPG) and lyso-phosphatidylserine (LPS), which are bacterial membrane lipids, showed one significant increase from the time of feeding to 16 h post blood meal. The result of our study on the anautogenous insect Ae. aegypti point to specific lipids likely to be important in the reproductive process with a role in the formation and growth of ovarian follicles. [ABSTRACT FROM AUTHOR]

In the United States, besides the US territory Puerto Rico, Hawai'i is the only state that grows commercial coffee. In Hawai'i, coffee is the second most valuable agricultural commodity. Health benefits associated with moderate coffee consumption, including its antioxidant capacity, have been correlated to its bioactive components. Post-harvest techniques, coffee variety, degree of roasting, and brewing methods significantly impact the metabolites, lipids, minerals, and/or antioxidant capacity of brewed coffees. The goal of our study was to understand the impact of roasting and brewing methods on metabolites, lipids, biogenic amines, minerals, and antioxidant capacity of two Hawai'i-grown coffee (Coffea arabica) varieties, "Kona Typica" and "Yellow Catuai". Our results indicated that both roasting and coffee variety significantly modulated several metabolites, lipids, and biogenic amines of the coffee brews. Furthermore, regardless of coffee variety, the antioxidant capacity of roasted coffee brews was higher in cold brews. Similarly, total minerals were higher in "Kona Typica" cold brews followed by "Yellow Catuai" cold brews. Hawai'i-grown coffees are considered "specialty coffees" since they are grown in unique volcanic soils and tropical microclimates with unique flavors. Our studies indicate that both Hawai'i-grown coffees contain several health-promoting components. However, future studies are warranted to compare Hawai'i-grown coffees with other popular brand coffees and their health benefits in vivo. [ABSTRACT FROM AUTHOR]

Lipids, especially lysophosphatidylcholine LPC16:0, have been shown to be involved in chronic joint pain through the activation of acid-sensing ion channels (ASIC3). The aim of the present study was to investigate the lipid contents of the synovial fluids from controls and patients suffering from chronic joint pain in order to identify characteristic lipid signatures associated with specific joint diseases. For this purpose, lipids were extracted from the synovial fluids and analyzed by mass spectrometry. Lipidomic analyses identified certain choline-containing lipid classes and molecular species as biomarkers of chronic joint pain, regardless of the pathology, with significantly higher levels detected in the patient samples. Moreover, correlations were observed between certain lipid levels and the type of joint pathologies. Interestingly, LPC16:0 levels appeared to correlate with the metabolic status of patients while other choline-containing lipids were more specifically associated with the inflammatory state. Overall, these data point at selective lipid species in synovial fluid as being strong predictors of specific joint pathologies which could help in the selection of the most adapted treatment. [ABSTRACT FROM AUTHOR]

Altered cellular metabolism is a well-established hallmark of cancer. Although most studies have focused on the metabolism of glucose and glutamine, the upregulation of lipid metabolism is also frequent in cells undergoing oncogenic transformation. In fact, cancer cells need to meet the enhanced demand of plasma membrane synthesis and energy production to support their proliferation. Moreover, lipids are precursors of signaling molecules, termed lipid mediators, which play a role in shaping the tumor microenvironment. Recent methodological advances in lipid analysis have prompted studies aimed at investigating the whole lipid content of a sample (lipidome) to unravel the complexity of lipid changes in cancer patient biofluids. This review focuses on the application of mass spectrometry-based lipidomics for the discovery of cancer biomarkers. Here, we have summarized the main lipid alteration in cancer patients' biofluids and uncovered their potential use for the early detection of the disease and treatment selection. We also discuss the advantages of using biofluid-derived extracellular vesicles as a platform for lipid biomarker discovery. These vesicles have a molecular signature that is a fingerprint of their originating cells. Hence, the analysis of their molecular cargo has emerged as a promising strategy for the identification of sensitive and specific biomarkers compared to the analysis of the unprocessed biofluid. [ABSTRACT FROM AUTHOR]

Royal jelly is a specific product secreted by honeybees, and has been sought after to maintain health because of its valuable bioactive substances, e.g., lipids and vitamins. The lipids in royal jelly come from the bee pollen consumed by honeybees, and different plant source of bee pollen affects the lipid composition of royal jelly. However, the effect of bee pollen consumption on the lipid composition of royal jelly remains unclear. Herein, we examined the influence of two factors on the lipid composition of royal jelly: first, two plant sources of bee pollen, i.e., Acer mono Maxim. (BP-Am) and Phellodendron amurense Rupr. (BP-Pa); secondly, different feeding times. Lipidomic analyses were conducted on the royal jelly produced by honeybees fed BP-Am or BP-Pa using ultra-high performance liquid chromatography (UPLC)-Q-Exactive Orbitrap mass spectrometry. The results showed that the phospholipid and fatty acid contents differed in royal jelly produced by honeybees fed BP-Am compared to those fed BP-Pa. There were also differences between timepoints, with many lipid compounds decreasing in abundance soon after single-pollen feeding began, slowly increasing over time, then decreasing again after 30 days of single-pollen feeding. The single bee pollen diet destroyed the nutritional balance of bee colonies and affected the development of hypopharyngeal and maxillary glands, resulting in differences in royal jelly quality. This study provides guidance for optimal selection of honeybee feed for the production of high-quality royal jelly. [ABSTRACT FROM AUTHOR]

Triacylglycerols (TAGs) and cholesterol lipoprotein levels are widely used to predict cardiovascular risk and metabolic disorders. The aim of this study is to determine how the comprehensive lipidome (individual molecular lipid species) determined by mass spectrometry is correlated to the serum whole-lipidic profile of adults with different lipidemic conditions. The study included samples from 128 adults of both sexes, and they were separated into four groups according to their lipid profile: Group I—normolipidemic (TAG < 150 mg/dL, LDL-C < 160 mg/dL and HDL-c > 40 mg/dL); Group II—isolated hypertriglyceridemia (TAG ≥ 150 mg/dL); Group III—isolated hypercholesterolemia (LDL-C ≥ 160 mg/dL) and Group IV—mixed dyslipidemia. An untargeted mass spectrometry (MS)-based approach was applied to determine the lipidomic signature of 32 healthy and 96 dyslipidemic adults. Limma linear regression was used to predict the correlation of serum TAGs and cholesterol lipoprotein levels with the abundance of the identified MS-annotated lipids found in the subgroups of subjects. Serum TAG levels of dyslipidemic adults have a positive correlation with some of the MS-annotated specific TAGs and ceramides (Cer) and a negative correlation with sphingomyelins (SMs). High-density lipoprotein-cholesterol (HDL-C) levels are positively correlated with some groups of glycerophosphocholine, while low-density lipoprotein-cholesterol (LDL-C) has a positive correlation with SMs. [ABSTRACT FROM AUTHOR]

Studies have indicated that increasing plasma bilirubin levels might be useful for preventing and treating hepatic lipid accumulation that occurs with metabolic diseases such as obesity and diabetes. We have previously demonstrated that mice with hyperbilirubinemia had significantly less lipid accumulation in a diet-induced non-alcoholic fatty liver disease (NAFLD) model. However, bilirubin's effects on individual lipid species are currently unknown. Therefore, we used liquid chromatography-mass spectroscopy (LC-MS) to determine the hepatic lipid composition of obese mice with NAFLD treated with bilirubin nanoparticles or vehicle control. We placed the mice on a high-fat diet (HFD) for 24 weeks and then treated them with bilirubin nanoparticles or vehicle control for 4 weeks while maintaining the HFD. Bilirubin nanoparticles suppressed hepatic fat content overall. After analyzing the lipidomics data, we determined that bilirubin inhibited the accumulation of ceramides in the liver. The bilirubin nanoparticles significantly lowered the hepatic expression of two essential enzymes that regulate ceramide production, Sgpl1 and Degs1. Our results demonstrate that the bilirubin nanoparticles improve hepatic fat content by reducing ceramide production, remodeling the liver fat content, and improving overall metabolic health. [ABSTRACT FROM AUTHOR]

Sample preparation is usually a complex and time-consuming procedure, which can directly affect the quality of the analysis. Recent efforts have been made to establish analytical methods involving minimal sample preparation, automatized and performed online with the analytical techniques. Online Extraction coupled with Liquid Chromatography–Mass Spectrometry (OLE–LC–MS) allows a fully connected extraction, separation, and analysis system. In this work, the lecithin profile was investigated in commercial sunflower, almonds, peanuts, and pistachio seeds to demonstrate that the concept of extraction, followed by the online analysis of the extract, could be applied to analyze this class of analytes in such complex solid matrices without a prior off-line solvent extraction step. The extraction phase gradient method was optimized. Two different analytical columns were explored, one being a conventional C18 (50 × 2.1 mm, 1.7 µm SPP) and the other a novel self-packed SIGO-C18ec (100 × 0.5, 5 µm FPP), which resulted in better separation. The analysis repeatability was investigated, and suggestions to improve it were pointed out. A characteristic ion with a m/z of 184, related to lysophosphatidylcholine structure, was used to identify the lecithin compounds. The temperature effect on the chromatograms was also explored. In short, it was found that the OLE–LC–MS approach is suitable for the analysis of lecithin compounds in seeds, being a promising alternative for lipidomics approaches in the near future. [ABSTRACT FROM AUTHOR]