Journal articles on the topic 'Lipidome profile'
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1
Koh, Jung Hee, Sang Jun Yoon, Mina Kim, Seonghun Cho, Johan Lim, Youngjae Park, Hyun-Sook Kim, Sung Won Kwon, and Wan-Uk Kim. "Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis." Experimental & Molecular Medicine 54, no. 2 (February 2022): 143–55. http://dx.doi.org/10.1038/s12276-022-00725-z.
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AbstractLipid mediators are crucial for the pathogenesis of rheumatoid arthritis (RA); however, global analyses have not been undertaken to systematically define the lipidome underlying the dynamics of disease evolution, activation, and resolution. Here, we performed untargeted lipidomics analysis of synovial fluid and serum from RA patients at different disease activities and clinical phases (preclinical phase to active phase to sustained remission). We found that the lipidome profile in RA joint fluid was severely perturbed and that this correlated with the extent of inflammation and severity of synovitis on ultrasonography. The serum lipidome profile of active RA, albeit less prominent than the synovial lipidome, was also distinguishable from that of RA in the sustained remission phase and from that of noninflammatory osteoarthritis. Of note, the serum lipidome profile at the preclinical phase of RA closely mimicked that of active RA. Specifically, alterations in a set of lysophosphatidylcholine, phosphatidylcholine, ether-linked phosphatidylethanolamine, and sphingomyelin subclasses correlated with RA activity, reflecting treatment responses to anti-rheumatic drugs when monitored serially. Collectively, these results suggest that analysis of lipidome profiles is useful for identifying biomarker candidates that predict the evolution of preclinical to definitive RA and could facilitate the assessment of disease activity and treatment outcomes.
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Wallace, Martina, Ciara Morris, Colm M. O'Grada, Miriam Ryan, Eugene T. Dillon, Eilish Coleman, Eileen R. Gibney, Michael J. Gibney, Helen M. Roche, and Lorraine Brennan. "Relationship between the lipidome, inflammatory markers and insulin resistance." Mol. BioSyst. 10, no. 6 (2014): 1586–95. http://dx.doi.org/10.1039/c3mb70529c.
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The objectives of the present study were to (1) examine the effects of the phenotypic factors age, gender and BMI on the lipidomic profile and (2) investigate the relationship between the lipidome, inflammatory markers and insulin resistance.
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Dahdah, Norma, Alba Gonzalez-Franquesa, Sara Samino, Pau Gama-Perez, Laura Herrero, José Carlos Perales, Oscar Yanes, Maria Del Mar Malagón, and Pablo Miguel Garcia-Roves. "Effects of Lifestyle Intervention in Tissue-Specific Lipidomic Profile of Formerly Obese Mice." International Journal of Molecular Sciences 22, no. 7 (April 1, 2021): 3694. http://dx.doi.org/10.3390/ijms22073694.
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Lipids are highly diverse in their composition, properties and distribution in different biological entities. We aim to establish the lipidomes of several insulin-sensitive tissues and to test their plasticity when divergent feeding regimens and lifestyles are imposed. Here, we report a proton nuclear magnetic resonance (1H-NMR) study of lipid abundance across 4 tissues of C57Bl6J male mice that includes the changes in the lipid profile after every lifestyle intervention. Every tissue analysed presented a specific lipid profile irrespective of interventions. Glycerolipids and fatty acids were most abundant in epididymal white adipose tissue (eWAT) followed by liver, whereas sterol lipids and phosphoglycerolipids were highly enriched in hypothalamus, and gastrocnemius had the lowest content in all lipid species compared to the other tissues. Both when subjected to a high-fat diet (HFD) and after a subsequent lifestyle intervention (INT), the lipidome of hypothalamus showed no changes. Gastrocnemius and liver revealed a pattern of increase in content in many lipid species after HFD followed by a regression to basal levels after INT, while eWAT lipidome was affected mainly by the fat composition of the administered diets and not their caloric density. Thus, the present study demonstrates a unique lipidome for each tissue modulated by caloric intake and dietary composition.
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Sikorskaya, Tatyana V., Ekaterina V. Ermolenko, Kseniya V. Efimova, and Ly T. P. Dang. "Coral Holobionts Possess Distinct Lipid Profiles That May Be Shaped by Symbiodiniaceae Taxonomy." Marine Drugs 20, no. 8 (July 28, 2022): 485. http://dx.doi.org/10.3390/md20080485.
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Symbiotic relationships are very important for corals. Abiotic stressors cause the acclimatization of cell membranes in symbionts, which possess different membrane acclimatization strategies. Membrane stability is determined by a unique lipid composition and, thus, the profile of thylakoid lipids can depend on coral symbiont species. We have analyzed and compared thylakoid lipidomes (mono- and digalactosyldiacylglycerols (MGDG and DGDG), sulfoquinovosyldiacylglycerols (SQDG), and phosphatidylglycerols (PG)) of crude extracts from symbiotic reef-building coral Acropora sp., the hydrocoral Millepora platyphylla, and the octocoral Sinularia flexibilis. S. flexibilis crude extracts were characterized by a very high SQDG/PG ratio, a DGDG/MGDG ratio < 1, a lower degree of galactolipid unsaturation, a higher content of SQDG with polyunsaturated fatty acids, and a thinner thylakoid membrane which may be explained by the presence of thermosensitive dinoflagellates Cladocopium C3. In contrast, crude extracts of M. platyphylla and Acropora sp. exhibited the lipidome features of thermotolerant Symbiodiniaceae. M. platyphylla and Acropora sp. colonies contained Cladocopium C3u and Cladocopium C71/C71a symbionts, respectively, and their lipidome profiles showed features that indicate thermotolerance. We suggest that an association with symbionts that exhibit the thermotolerant thylakoid lipidome features, combined with a high Symbiodiniaceae diversity, may facilitate further acclimatization/adaptation of M. platyphylla and Acropora sp. holobionts in the South China Sea.
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Guerra, Inês M. S., Helena B. Ferreira, Tânia Melo, Hugo Rocha, Sónia Moreira, Luísa Diogo, Maria Rosário Domingues, and Ana S. P. Moreira. "Mitochondrial Fatty Acid β-Oxidation Disorders: From Disease to Lipidomic Studies—A Critical Review." International Journal of Molecular Sciences 23, no. 22 (November 11, 2022): 13933. http://dx.doi.org/10.3390/ijms232213933.
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Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial β-oxidation. The most common FAODs are characterized by the accumulation of medium-chain FAs and long-chain (3-hydroxy) FAs (and their carnitine derivatives), respectively. These deregulations are associated with lipotoxicity which affects several organs and potentially leads to life-threatening complications and comorbidities. Changes in the lipidome have been associated with several diseases, including some IEMs. In FAODs, the alteration of acylcarnitines (CARs) and FA profiles have been reported in patients and animal models, but changes in polar and neutral lipid profile are still scarcely studied. In this review, we present the main findings on FA and CAR profile changes associated with FAOD pathogenesis, their correlation with oxidative damage, and the consequent disturbance of mitochondrial homeostasis. Moreover, alterations in polar and neutral lipid classes and lipid species identified so far and their possible role in FAODs are discussed. We highlight the need of mass-spectrometry-based lipidomic studies to understand (epi)lipidome remodelling in FAODs, thus allowing to elucidate the pathophysiology and the identification of possible biomarkers for disease prognosis and an evaluation of therapeutic efficacy.
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Lamichhane, Santosh, Linda Ahonen, Thomas Sparholt Dyrlund, Alex M. Dickens, Heli Siljander, Heikki Hyöty, Jorma Ilonen, et al. "Cord-Blood Lipidome in Progression to Islet Autoimmunity and Type 1 Diabetes." Biomolecules 9, no. 1 (January 21, 2019): 33. http://dx.doi.org/10.3390/biom9010033.
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Previous studies suggest that children who progress to type 1 diabetes (T1D) later in life already have an altered serum lipid molecular profile at birth. Here, we compared cord blood lipidome across the three study groups: children who progressed to T1D (PT1D; n = 30), children who developed at least one islet autoantibody but did not progress to T1D during the follow-up (P1Ab; n = 33), and their age-matched controls (CTR; n = 38). We found that phospholipids, specifically sphingomyelins, were lower in T1D progressors when compared to P1Ab and the CTR. Cholesterol esters remained higher in PT1D when compared to other groups. A signature comprising five lipids was predictive of the risk of progression to T1D, with an area under the receiver operating characteristic curve (AUROC) of 0.83. Our findings provide further evidence that the lipidomic profiles of newborn infants who progress to T1D later in life are different from lipidomic profiles in P1Ab and CTR.
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Heintz, Melissa M., Ramiya Kumar, Kristal M. Maner-Smith, Eric A. Ortlund, and William S. Baldwin. "Age- and Diet-Dependent Changes in Hepatic Lipidomic Profiles of Phospholipids in Male Mice: Age Acceleration in Cyp2b-Null Mice." Journal of Lipids 2022 (March 29, 2022): 1–17. http://dx.doi.org/10.1155/2022/7122738.
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Increases in traditional serum lipid profiles are associated with obesity, cancer, and cardiovascular disease. Recent lipidomic analysis has indicated changes in serum lipidome profiles, especially in regard to specific phosphatidylcholines, associated with obesity. However, little work has evaluated murine hepatic liver lipidomic profiles nor compared these profiles across age, high-fat diet, or specific genotypes, in this case the lack of hepatic Cyp2b enzymes. In this study, the effects of age (9 months old), high-fat diet (4.5 months old), and the loss of three primarily hepatic xeno- and endobiotic metabolizing cytochrome P450 (Cyp) enzymes, Cyp2b9, Cyp2b10, and Cyp2b13 (Cyp2b-null mice), on the male murine hepatic lipidome were compared. Hierarchical clustering and principal component analysis show that age perturbs hepatic phospholipid profiles and serum lipid markers the most compared to young mice, followed by a high-fat diet and then loss of Cyp2b. Several lipid biomarkers such as PC/PE ratios, PE 38 : 6, and LPC concentrations indicate greater potential for NAFLD and hypertension with mixed effects in Cyp2b-null mice(less NAFLD and greater hypertension-associated markers). Lipid profiles from older mice contain greater total and n-6 fatty acids than normal diet (ND)-fed young mice; however, surprisingly, young Cyp2b-null mice contain high n-6 : n-3 ratios. Overall, the lack of Cyp2b typically enhanced adverse physiological parameters observed in the older (9 mo) mice with increased weight gain combined with a deteriorating cholesterol profile, but not necessarily all phospholipid profiles were adversely perturbed.
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Jové, Mariona, Natàlia Mota-Martorell, Irene Pradas, José Daniel Galo-Licona, Meritxell Martín-Gari, Èlia Obis, Joaquim Sol, and Reinald Pamplona. "The Lipidome Fingerprint of Longevity." Molecules 25, no. 18 (September 22, 2020): 4343. http://dx.doi.org/10.3390/molecules25184343.
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Lipids were determinants in the appearance and evolution of life. Recent studies disclose the existence of a link between lipids and animal longevity. Findings from both comparative studies and genetics and nutritional interventions in invertebrates, vertebrates, and exceptionally long-lived animal species—humans included—demonstrate that both the cell membrane fatty acid profile and lipidome are a species-specific optimized evolutionary adaptation and traits associated with longevity. All these emerging observations point to lipids as a key target to study the molecular mechanisms underlying differences in longevity and suggest the existence of a lipidome profile of long life.
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da Costa, Elisabete, Fernando Ricardo, Tânia Melo, Renato Mamede, Maria H. Abreu, Pedro Domingues, M. Rosário Domingues, and Ricardo Calado. "Site-Specific Lipidomic Signatures of Sea Lettuce (Ulva spp., Chlorophyta) Hold the Potential to Trace Their Geographic Origin." Biomolecules 10, no. 3 (March 23, 2020): 489. http://dx.doi.org/10.3390/biom10030489.
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The wild harvest and aquaculture of Ulva spp. has deserved growing attention in Europe. However, the impact of geographical origin on the biochemical composition of different species and/or strains is yet to be described in detail. Hence, the present study aimed to detect the variability of the lipidome of different species and/or strains of Ulva originating from different geographic locations. We hypothesized that lipidomic signatures can be used to trace the geographic origin post-harvesting of these valuable green seaweeds. Ulva spp. was sampled from eight distinct ecosystems along the Atlantic Iberian coast and Ulva rigida was sourced from an aquaculture farm operating a land-based integrated production site. Results showed significant differences in the lipidomic profile displayed by Ulva spp. originating from different locations, namely, due to different levels of polyunsaturated betaine lipids and galactolipids; saturated betaine lipids and sulfolipids; and some phospholipid species. Overall, a set of 25 site-specific molecular lipid species provide a unique lipidomic signature for authentication and geographic origin certification of Ulva species. Present findings highlight the potential of lipidome plasticity as a proxy to fight fraudulent practices, but also to ensure quality control and prospect biomass for target bioactive compounds.
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Horvath, Lisa, Hui-Ming Lin, Kate Lynette Mahon, Jacquelyn Weir, Piyushkumar Mundra, Calan Spielman, Karen P. Briscoe, et al. "The plasma lipidome in castration-resistant prostate cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 5055. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.5055.
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5055 Background: Biomarker studies of metastatic castration-resistant prostate cancer (CRPC) have mainly focused on changes in the cancer, however, the host environment and its interactions with cancer is increasingly important, especially given the increasing association of PC outcomes and obesity. We sought associations between the plasma lipidome and clinical outcome in CRPC. Methods: Plasma samples were obtained from a Phase 1 discovery cohort of 96 CRPC patients before and after the first cycle of docetaxel chemotherapy. Lipidomic profiling of the plasma samples was performed by liquid chromatography and electrospray ionisation-tandem mass spectrometry. Results were subsequently assessed in a Phase 2 validation cohort of 63 CRPC patients. Results: Lipidomic profiling detected 323 lipid species in plasma samples from the Phase 1 cohort. Patients could be classified into two subgroups with significant survival differences according to their baseline lipidomic profiles (median overall survival 13.7 vs 21.7 months; HR 2.31, 95% CI 1.44-3.68, p = 0.0005). The baseline levels of 46 lipids were individually prognostic (p < 0.01) and predominantly sphingolipids. A prognostic three-lipid signature was derived (ceramide (d18:1/24:1), sphingomyelin (d18:2/16:0), phosphatidylcholine (16:0/16:0)) (11.7 versus 21.7 months, p = 0.00001; HR 2.94, 95% CI 1.80-4.81, p = 0.00002). The signature was associated with shorter overall survival in the Phase 2 cohort (HR 4.78, 95% CI 2.06-11.1, p = 0.0003), and was an independent prognostic factor when modeled with clinicopathological factors and metabolic characteristics (BMI, cholesterol and triacylglycerol). The AUC of ROC analysis of 12 month survival for a clinicopathological model (AUC 0.70, 95% CI 0.54-0.87, p = 0.03) was enhanced by the addition of the 3-lipid signature (AUC 0.73, 95% CI 0.57-0.89, p = 0.01). Conclusions: Our study is the first to comprehensively profile the plasma lipidome of men with CRPC using cutting-edge lipidomic profiling technology, to identify a plasma lipid signature that can reproducibly predict outcome in CRPC and can improve on clinicopathological models. Therapeutic modulation of the levels of these lipids by targeting their metabolic pathways may improve patient outcome.
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Wan, Qin-Li, Zhong-Lin Yang, Xiao-Gang Zhou, Ai-Jun Ding, Yuan-Zhu Pu, Huai-Rong Luo, and Gui-Sheng Wu. "The Effects of Age and Reproduction on the Lipidome of Caenorhabditis elegans." Oxidative Medicine and Cellular Longevity 2019 (May 9, 2019): 1–14. http://dx.doi.org/10.1155/2019/5768953.
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Aging is a complex life process, and a unified view is that metabolism plays key roles in all biological processes. Here, we determined the lipidomic profile of Caenorhabditis elegans (C. elegans) using ultraperformance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Using a nontargeted approach, we detected approximately 3000 species. Analysis of the lipid metabolic profiles at young adult and ten-day-old ages among wild-type N2, glp-1 defective mutant, and double mutant daf-16;glp-1 uncovered significant age-related differences in the total amount of phosphatidylcholines (PC), sphingomyelins (SM), ceramides (Cer), diglycerides (DG), and triglycerides (TG). In addition, the age-associated lipid profiles were characterized by ratio of polyunsaturated (PUFA) over monounsaturated (MUFA) lipid species. Lipid metabolism modulation plays an important role in reproduction-regulated aging; to identify the variations of lipid metabolites during germ line loss-induced longevity, we investigated the lipidomic profiles of long-lived glp-1/notch receptor mutants, which have reproductive deficiency when grown at nonpermissive temperature. The results showed that there was some age-related lipid variation, including TG 40:2, TG 40:1, and TG 41:1, which contributed to the long-life phenotype. The longevity of glp-1 mutant was daf-16-dependent; the lipidome analysis of daf-16;glp-1 double mutant revealed that the changes of some metabolites in the glp-1 mutant were daf-16-dependent, while other metabolites displayed more complex epistatic patterns. We first conducted a comprehensive lipidome analysis to provide novel insights into the relationships between longevity and lipid metabolism regulated by germ line signals in C. elegans.
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Pradas, Irene, Mariona Jové, Kevin Huynh, Marta Ingles, Consuelo Borras, Natalia Mota-Martorell, Jose Daniel Galo-Licona, et al. "Long-lived Humans Have a Unique Plasma Sphingolipidome." Journals of Gerontology: Series A 77, no. 4 (December 5, 2021): 728–35. http://dx.doi.org/10.1093/gerona/glab360.
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Abstract A species-specific lipidome profile is an inherent feature linked to longevity in the animal kingdom. However, there is a lack of lipidomic studies on human longevity. Here, we use mass spectrometry-based lipidomics to detect and quantify 151 sphingolipid molecular species and use these to define a phenotype of healthy humans with exceptional life span. Our results demonstrate that this profile specifically comprises a higher content of complex glycosphingolipids (hexosylceramides and gangliosides), and lower levels of ceramide species from the de novo pathway, sphingomyelin and sulfatide; while for ceramide-derived signaling compounds, their content remains unchanged. Our findings suggest that structural glycosphingolipids may be more relevant to achieve the centenarian condition than signaling sphingolipids.
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Lindqvist, Helen M., Linnea Bärebring, Inger Gjertsson, Antti Jylhä, Reijo Laaksonen, Anna Winkvist, and Mika Hilvo. "A Randomized Controlled Dietary Intervention Improved the Serum Lipid Signature towards a Less Atherogenic Profile in Patients with Rheumatoid Arthritis." Metabolites 11, no. 9 (September 17, 2021): 632. http://dx.doi.org/10.3390/metabo11090632.
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Diet is a major modifiable risk factor for cardiovascular disease (CVD). One explanation for this is its effect on specific lipids. However, knowledge on how the lipidome is affected is limited. We aimed to investigate if diet can change the new ceramide- and phospholipid-based CVD risk score CERT2 and the serum lipidome towards a more favorable CVD signature. In a crossover trial (ADIRA), 50 patients with rheumatoid arthritis (RA) had 10 weeks of a Mediterranean-style diet intervention or a Western-style control diet and then switched diets after a 4-month wash-out-period. Five hundred and thirty-eight individual lipids were measured in serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Lipid risk scores were analyzed by Wilcoxon signed-rank test or mixed model and lipidomic data with multivariate statistical methods. In the main analysis, including the 46 participants completing ≥1 diet period, there was no significant difference in CERT2 after the intervention compared with the control, although several CERT2 components were changed within periods. In addition, triacylglycerols, cholesteryl esters, phosphatidylcholines, alkylphosphatidylcholines and alkenylphosphatidylcholines had a healthier composition after the intervention compared to after the control diet. This trial indicates that certain dietary changes can improve the serum lipid signature towards a less atherogenic profile in patients with RA.
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Monteiro, João P., Felisa Rey, Tânia Melo, Ana S. P. Moreira, Jean-François Arbona, Jorunn Skjermo, Silje Forbord, et al. "The Unique Lipidomic Signatures of Saccharina latissima Can Be Used to Pinpoint Their Geographic Origin." Biomolecules 10, no. 1 (January 8, 2020): 107. http://dx.doi.org/10.3390/biom10010107.
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The aquaculture of macroalgae for human consumption and other high-end applications is experiencing unprecedented development in European countries, with the brown algae Saccharina latissima being the flag species. However, environmental conditions in open sea culture sites are often unique, which may impact the biochemical composition of cultured macroalgae. The present study compared the elemental compositions (CHNS), fatty acid profiles, and lipidomes of S. latissima originating from three distinct locations (France, Norway, and the United Kingdom). Significant differences were found in the elemental composition, with Norwegian samples displaying twice the lipid content of the others, and significantly less protein (2.6%, while French and UK samples contained 6.3% and 9.1%, respectively). The fatty acid profiles also differed considerably, with UK samples displaying a lower content of n-3 fatty acids (21.6%), resulting in a higher n-6/n-3 ratio. Regarding the lipidomic profile, samples from France were enriched in lyso lipids, while those from Norway displayed a particular signature of phosphatidylglycerol, phosphatidylinositol, and phosphatidylcholine. Samples from the UK featured higher levels of phosphatidylethanolamine and, in general, a lower content of galactolipids. These differences highlight the influence of site-specific environmental conditions in the shaping of macroalgae biochemical phenotypes and nutritional value. It is also important to highlight that differences recorded in the lipidome of S. latissima make it possible to pinpoint specific lipid species that are likely to represent origin biomarkers. This finding is relevant for future applications in the field of geographic origin traceability and food control.
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Jové, Mariona, Rosanna Cabré, Natàlia Mota-Martorell, Meritxell Martin-Garí, Èlia Obis, Paula Ramos, Iván Canales, et al. "Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age." International Journal of Molecular Sciences 22, no. 22 (November 20, 2021): 12517. http://dx.doi.org/10.3390/ijms222212517.
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Lipids are closely associated with brain structure and function. However, the potential changes in the lipidome induced by aging remain to be elucidated. In this study, we used chromatographic techniques and a mass spectrometry-based approach to evaluate age-associated changes in the lipidome of the frontal cortex and cerebellum obtained from adult male Wistar rats (8 months), aged male Wistar rats (26 months), and aged male Wistar rats submitted to a methionine restriction diet (MetR)—as an anti-aging intervention—for 8 weeks. The outcomes revealed that only small changes (about 10%) were observed in the lipidome profile in the cerebellum and frontal cortex during aging, and these changes differed, in some cases, between regions. Furthermore, a MetR diet partially reversed the effects of the aging process. Remarkably, the most affected lipid classes were ether-triacylglycerols, diacylglycerols, phosphatidylethanolamine N-methylated, plasmalogens, ceramides, and cholesterol esters. When the fatty acid profile was analyzed, we observed that the frontal cortex is highly preserved during aging and maintained under MetR, whereas in the cerebellum minor changes (increased monounsaturated and decreased polyunsaturated contents) were observed and not reversed by MetR. We conclude that the rat cerebellum and frontal cortex have efficient mechanisms to preserve the lipid profile of their cell membranes throughout their adult lifespan in order to maintain brain structure and function. A part of the small changes that take place during aging can be reversed with a MetR diet applied in old age.
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Jonas, Wenke, Kristin Schwerbel, Lisa Zellner, Markus Jähnert, Pascal Gottmann, and Annette Schürmann. "Alterations of Lipid Profile in Livers with Impaired Lipophagy." International Journal of Molecular Sciences 23, no. 19 (October 6, 2022): 11863. http://dx.doi.org/10.3390/ijms231911863.
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Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Various mechanisms such as an increased uptake in fatty acids or de novo synthesis contribute to the development of steatosis and progression to more severe stages. Furthermore, it has been shown that impaired lipophagy, the degradation of lipids by autophagic processes, contributes to NAFLD. Through an unbiased lipidome analysis of mouse livers in a genetic model of impaired lipophagy, we aimed to determine the resulting alterations in the lipidome. Observed changes overlap with those of the human disease. Overall, the entire lipid content and in particular the triacylglycerol concentration increased under conditions of impaired lipophagy. In addition, we detected a reduction in long-chain polyunsaturated fatty acids (PUFAs) and an increased ratio of n-6 PUFAs to n-3 PUFAs, which was due to the depletion of n-3 PUFAs. Although the abundance of major phospholipid classes was reduced, the ratio of phosphatidylcholines to phosphatidylethanolamines was not affected. In conclusion, this study demonstrates that impaired lipophagy contributes to the pathology of NAFLD and is associated with an altered lipid profile. However, the lipid pattern does not appear to be specific for lipophagic alterations, as it resembles mainly that described in relation to fatty liver disease.
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Lin, Hui-Ming, Nicole Yeung, Jordan F. Hastings, David R. Croucher, Kevin Huynh, Thomas G. Meikle, Natalie A. Mellett, et al. "Relationship between Circulating Lipids and Cytokines in Metastatic Castration-Resistant Prostate Cancer." Cancers 13, no. 19 (October 1, 2021): 4964. http://dx.doi.org/10.3390/cancers13194964.
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Circulating lipids or cytokines are associated with prognosis in metastatic castration-resistant prostate cancer (mCRPC). This study aimed to understand the interactions between lipid metabolism and immune response in mCRPC by investigating the relationship between the plasma lipidome and cytokines. Plasma samples from two independent cohorts of men with mCRPC (n = 146, 139) having life-prolonging treatments were subjected to lipidomic and cytokine profiling (290, 763 lipids; 40 cytokines). Higher baseline levels of sphingolipids, including ceramides, were consistently associated with shorter overall survival in both cohorts, whereas the associations of cytokines with overall survival were inconsistent. Increasing levels of IL6, IL8, CXCL16, MPIF1, and YKL40 correlated with increasing levels of ceramide in both cohorts. Men with a poor prognostic 3-lipid signature at baseline had a shorter time to radiographic progression (poorer treatment response) if their lipid profile at progression was similar to that at baseline, or their cytokine profile at progression differed to that at baseline. In conclusion, baseline levels of circulating lipids were more consistent as prognostic biomarkers than cytokines. The correlation between circulating ceramides and cytokines suggests the regulation of immune responses by ceramides. The association of treatment response with the change in lipid profiles warrants further research into metabolic interventions.
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Morrow, Danielle, Jenna Minami, Nicholas Bayley, Kevin Williams, Robert Prins, Linda Liau, Timothy Cloughesy, Steven Bensinger, and David Nathanson. "CBIO-03. A COMPREHENSIVE CHARACTERIZATION OF THE GBM LIPIDOME REVEALS A MOLECULARLY-DEFINED SUB-GROUP WITH HEIGHTENED SENSITIVITY TO FERROPTOSIS." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi27. http://dx.doi.org/10.1093/neuonc/noab196.104.
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Abstract Cancers, including the universally lethal glioblastoma (GBM), have reprogrammed lipid metabolism to fuel tumor growth. However, the molecular alterations responsible for aberrant lipid metabolism, and the potential for identifying new therapeutic opportunities are not fully understood. To systematically investigate the GBM lipidome, we performed integrated transcriptomic, genomic and shotgun lipidomic analysis of an extensive library of molecularly diverse patient-derived GBM tumors and model systems. Using this comprehensive approach, we discovered two GBM sub-groups defined by their combined molecular and lipidomic profile. Among the most significant differences between the two groups were lipid length and desaturation. As a consequence of this signature, a subset was more sensitive to lipid peroxidation and ferroptosis. Our findings suggest a novel association between specific molecular signatures of GBM, lipid metabolism and lipid peroxidation-induced cell death. This relationship may present a new therapeutic opportunity to target reprogrammed lipid metabolism in a molecularly-defined subset of GBMs.
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Morrow, Danielle, Nicholas Bayley, Kevin Williams, Hayato Muranaka, Robert Prins, Linda Liau, Timothy Cloughesy, Steven Bensinger, and David Nathanson. "CBMT-43. INTEGRATED LIPIDOMIC AND MOLECULAR ANALYSIS REVEALS A SUBSET OF GLIOBLASTOMA VULNERABLE TO FERROPTOSIS." Neuro-Oncology 21, Supplement_6 (November 2019): vi42. http://dx.doi.org/10.1093/neuonc/noz175.165.
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Abstract Cancers, including the universally lethal glioblastoma (GBM), have reprogrammed lipid metabolism to fuel tumor growth. However, the molecular alterations responsible for aberrant lipid metabolism, and the potential for identifying new therapeutic opportunities are not fully understood. To systematically investigate the GBM lipidome, we performed integrated transcriptomic, genomic and shotgun lipidomic analysis of a library of molecularly diverse patient-derived GBM cells (n=30). Using this comprehensive approach, we discovered two GBM sub-groups defined by their combined molecular and lipidomic profile. Polyunsaturated fatty acids (PUFAs) were among the most significant lipids that distinguished these two groups of GBM tumors. Intriguingly, this lipid metabolic phenotype was associated with heightened sensitivity to ferroptosis – a newly discovered form of regulated cell death. As PUFA oxidation is a critical feature of ferroptosis, our findings suggest a novel association between specific molecular signatures of GBM, lipid metabolism and ferroptosis. This relationship may present a new therapeutic opportunity to target ferroptosis in a molecularly-defined subset of GBMs.
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Sudano, M. J., T. D. S. Rascado, A. Tata, K. R. A. Belaz, V. G. Santos, R. S. Valente, F. S. Mesquita, et al. "160 LIPIDOME SIGNATURES IN EARLY BOVINE EMBRYO DEVELOPMENT." Reproduction, Fertility and Development 28, no. 2 (2016): 210. http://dx.doi.org/10.1071/rdv28n2ab160.
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Mammalian pre-implantation embryonic development is a complex, conserved, and well-orchestrated process involving dynamic molecular and structural changes. Understanding the membrane lipid profile fluctuation during this crucial period is fundamental to address cellular and molecular mechanisms governing embryogenesis. A full understanding of stage-specific lipid signatures in early bovine embryo development is, however, still lacking. The aim of the present work was to characterise stage-specific changes in lipid profiles during early bovine embryonic development. Immature oocytes were recovered from slaughterhouse-derived bovine ovaries and assigned among 5 in vitro developmental stages for lipid characterisation: immature oocytes, 2-cell embryos (32–40 h post-insemination), 8 to 16-cell embryos (72 h post-insemination), morulas (120 h post-insemination), and blastocysts (168 h post-insemination). Two different culture media were used for in vitro embryo production, SOFaaci medium supplemented with 2.5% of serum and serum-free SOF-BE1 medium. Cytoplasmic lipid droplets content and membrane phospholipids profiles for each development stage were assessed by lipid staining (Nile red; n = 5–9) and matrix-assisted laser desorption ionization as a mass spectrometry imaging (MALDI-MS; n = 5–9), respectively. For statistical analysis, univariate and multivariate models were used to compare lipid droplets content and membrane phospholipids profiles. Cytoplasmic lipid droplets content increased from minimum in the immature oocyte stage to maximum at the morula stage, followed by a sharp drop at the blastocyst stage (58.4 ± 10.5ac, 62.5 ± 9.4ac, 85.9 ± 8.2a, 148.3 ± 7.4b, 37.4 ± 9.9c of fluorescence intensity per embryo area, respectively, for immature oocyte, 2-cells, 8 to 16-cells, morulas, and blastocysts; abcP < 0.05). More cytoplasmic lipid droplets were detected in morulas and blastocyts cultured in SOFaaci than in SOF-BE1 (morulas, 162.6 ± 11.3 v. 137.1 ± 9.2 of fluorescence intensity per embryo area, respectively, P < 0.05; blastocysts, 49.9 ± 9.9 v. 20.7 ± 9.9 of fluorescence intensity per embryo area, respectively, P < 0.05). Characteristic dynamic changes of unsaturation level, acyl chain length and class composition (phosphatidylcholines, sphingomyelins, and phosphatidylethanolamines) of phospholipid profiles were observed during early embryo development. This study provides a comprehensive analysis, involving lipid staining and mass spectrometry evaluation, of stage-specific lipid signatures during bovine in vitro embryo development. These results may be useful for assessing the role of specific lipid species during important events of embryogenesis. Research was supported by CNPq, FAPESP, and FAPERGS.
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Gerspach, C., S. Imhasly, M. Gubler, H. Naegeli, M. Ruetten, and E. Laczko. "Altered plasma lipidome profile of dairy cows with fatty liver disease." Research in Veterinary Science 110 (February 2017): 47–59. http://dx.doi.org/10.1016/j.rvsc.2016.10.001.
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Sah, Samyukta, Xin Ma, Andro Botros, David Gaul, Sylvia Yun, Eun Young Park, Olga Kim, Samuel Moore, Jaeyeon Kim, and Facundo M. Fernández. "Space- and Time-Resolved Metabolomics of a High-Grade Serous Ovarian Cancer Mouse Model." Cancers 14, no. 9 (April 30, 2022): 2262. http://dx.doi.org/10.3390/cancers14092262.
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The dismally low survival rate of ovarian cancer patients diagnosed with high-grade serous carcinoma (HGSC) emphasizes the lack of effective screening strategies. One major obstacle is the limited knowledge of the underlying mechanisms of HGSC pathogenesis at very early stages. Here, we present the first 10-month time-resolved serum metabolic profile of a triple mutant (TKO) HGSC mouse model, along with the spatial lipidome profile of its entire reproductive system. A high-coverage liquid chromatography mass spectrometry-based metabolomics approach was applied to longitudinally collected serum samples from both TKO (n = 15) and TKO control mice (n = 15), tracking metabolome and lipidome changes from premalignant stages to tumor initiation, early stages, and advanced stages until mouse death. Time-resolved analysis showed specific temporal trends for 17 lipid classes, amino acids, and TCA cycle metabolites, associated with HGSC progression. Spatial lipid distributions within the reproductive system were also mapped via ultrahigh-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry and compared with serum lipid profiles for various lipid classes. Altogether, our results show that the remodeling of lipid and fatty acid metabolism, amino acid biosynthesis, TCA cycle and ovarian steroidogenesis are critical components of HGSC onset and development. These metabolic alterations are accompanied by changes in energy metabolism, mitochondrial and peroxisomal function, redox homeostasis, and inflammatory response, collectively supporting tumorigenesis.
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Wang, Yang, Chang-Tao Jiang, Jie-Yun Song, Qi-Ying Song, Jun Ma, and Hai-Jun Wang. "Lipidomic Profile Revealed the Association of Plasma Lysophosphatidylcholines with Adolescent Obesity." BioMed Research International 2019 (December 13, 2019): 1–9. http://dx.doi.org/10.1155/2019/1382418.
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Objective. The human lipidomic profile reflects lipid metabolism, including the early phase of pathophysiological changes associated with diseases. An investigation of the association between the plasma lipidomic profile and adolescent obesity might provide new insights into the biological mechanisms of obesity. Therefore, we aimed to investigate the association of the plasma lipidome with obesity in Chinese adolescents using lipidomics. Methods. Using a combination of liquid chromatography and electrospray ionization tandem mass spectrometry, we quantified 328 lipid species from 24 lipid classes and subclasses in 100 male adolescents aged 14–16 years who were categorized into four groups: (1) normal weight with traditional normal clinical plasma lipid levels (NN); (2) normal weight with traditional abnormal clinical plasma lipid levels (NA); (3) obese with traditional normal clinical plasma lipid levels (ON); and (4) obese with traditional abnormal clinical plasma lipid levels (OA). The concentrations of all the lipid species were compared between obese and normal-weight adolescents at different traditional clinical plasma lipid levels using the Kruskal–Wallis test followed by the Mann–Whitney U test. A partial least squares discriminant analysis (PLS-DA) was applied to select lipids with a significant ability to discriminate adolescent obesity. Results. The lipidomic profile distinguished obese adolescents from normal-weight subjects. Regardless of whether traditional clinical plasma lipid levels were normal or abnormal, we observed a significant reduction in the levels of five lysophosphatidylcholines (LPC) species (LPC18:2, LPC18:1, LPC20:2, LPC20:1, and LPC20:0) in the obese group compared with the normal-weight group (difference = −31.29% to −13.19%; P=9.91×10−5 to 2.28×10−2). The ability of these five LPC species to discriminate adolescent obesity was confirmed in the PLS-DA model. Conclusions. The findings provided evidence for the association of some LPC species with adolescent obesity. The discriminatory effects of five LPC species were identified between normal-weight and obese adolescents, independent of traditional clinical plasma lipid levels. These results will provide a basis for validation in subsequent studies.
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Chmiel, Elżbieta, Christina E. Galuska, Piotr Koper, Bożena Kowalczyk, Teresa Urbanik-Sypniewska, Marta Palusińska-Szysz, and Beate Fuchs. "Unusual Lipid Components of Legionella gormanii Membranes." Metabolites 12, no. 5 (May 6, 2022): 418. http://dx.doi.org/10.3390/metabo12050418.
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Legionella spp. cause Legionnaires’ disease with pneumonia as the predominant clinical symptom. L. gormanii is the second most prevalent causative agent of community-acquired pneumonia after L. pneumophila. The study aimed to characterize the lipidome of L. gormanii membranes and the importance of these analyses in bacterial chemotaxonomy. Lipidomic analyses based on ultra-high performance liquid chromatography-mass spectrometry allowed the detection of individual molecular species of a wide range of L. gormanii membrane lipids contained in the outer (OM) and inner membranes (IM). The lipid profile comprised glycerolipids (triglycerides, diglycerides), phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, cardiolipin), and sphingolipids (ceramides, hexosylceramides). The most abundant lipid fraction in the IM and OM were phospholipids. The lipidomic analysis showed that two independent phosphatidylcholine (PC) synthesis pathways operating in L. gormanii: the PE-methylation (PmtA) pathway and the PC synthase (Pcs) pathway. Comparison of the molecular profile of PC species contained in the lipids of L. gormanii membranes cultured on the medium, with and without exogenous choline, showed quantitative differences in the PC pool. An unusual feature of the L. gormanii lipids was the presence of ceramides and hexosylceramides, which are typical components of eukaryotic cells and a very small group of bacteria. To the best of our knowledge, this is the first report of the occurrence of ceramides in Legionella bacteria.
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Bianchi, Flavia, Urban Spitaler, Peter Robatscher, Rudi F. Vogel, Silvia Schmidt, and Daniela Eisenstecken. "Comparative Lipidomics of Different Yeast Species Associated to Drosophila suzukii." Metabolites 10, no. 9 (August 28, 2020): 352. http://dx.doi.org/10.3390/metabo10090352.
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Yeasts constitute a dietary source for the spotted wing drosophila (SWD) and produce compounds that attract these flies. The study of the chemical composition of the yeast communities associated with SWD should therefore help to understand the relationship between the biology of the insect and the yeast’s metabolism. In the present study, the lipidome of five yeast species isolated from grapes infested by SWD (three Hanseniaspora uvarum strains, Candida sp., Issatchenkia terricola, Metschnikowia pulcherrima and Saccharomycopsis vini) and a laboratory strain of Saccharomyces cerevisiae was explored using an untargeted approach. Additionally, the lipid profile of two species, S. cerevisiae and H. uvarum, which were reported to elicit different responses on SWD flies based on feeding and behavioral trials, was compared with a chemical enrichment approach. Overall, 171 lipids were annotated. The yeast species could be distinguished from each other based on their lipid profile, except for the three strains of H. uvarum, which were very similar to each other. The chemical enrichment analysis emphasized diversities between S. cerevisiae and H. uvarum, that could not be detected based on their global lipid profile. The information concerning differences between species in their lipidome may be of interest to future entomological studies concerning the yeast-insect interaction and could help to explain the responses of SWD to diverse yeast species.
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da Costa Faria, Nieli Rodrigues, Adriano Britto Chaves-Filho, Luiz Carlos Junior Alcantara, Isadora Cristina de Siqueira, Juan Ignacio Calcagno, Sayuri Miyamoto, Ana Maria Bispo de Filippis, and Marcos Yukio Yoshinaga. "Plasma lipidome profiling of newborns with antenatal exposure to Zika virus." PLOS Neglected Tropical Diseases 15, no. 4 (April 30, 2021): e0009388. http://dx.doi.org/10.1371/journal.pntd.0009388.
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The 2015–2016 Zika virus (ZIKV) outbreak in Brazil was remarkably linked to the incidence of microcephaly and other deleterious clinical manifestations, including eye abnormalities, in newborns. It is known that ZIKV targets the placenta, triggering an inflammatory profile that may cause placental insufficiency. Transplacental lipid transport is delicately regulated during pregnancy and deficiency on the delivery of lipids such as arachidonic and docosahexaenoic acids may lead to deficits in both brain and retina during fetal development. Here, plasma lipidome profiles of ZIKV exposed microcephalic and normocephalic newborns were compared to non-infected controls. Our results reveal major alterations in circulating lipids from both ZIKV exposed newborns with and without microcephaly relative to controls. In newborns with microcephaly, the plasma concentrations of hydroxyoctadecadienoic acid (HODE), primarily as 13-HODE isomer, derived from linoleic acid were higher as compared to normocephalic ZIKV exposed newborns and controls. Total HODE concentrations were also positively associated with levels of other oxidized lipids and several circulating free fatty acids in newborns, indicating a possible plasma lipidome signature of microcephaly. Moreover, higher concentrations of lysophosphatidylcholine in ZIKV exposed normocephalic newborns relative to controls suggest a potential disruption of polyunsaturated fatty acids transport across the blood-brain barrier of fetuses. The latter data is particularly important given the neurocognitive and neurodevelopmental abnormalities observed in follow-up studies involving children with antenatal ZIKV exposure, but normocephalic at birth. Taken together, our data reveal that plasma lipidome alterations associated with antenatal exposure to ZIKV could contribute to identification and monitoring of the wide spectrum of clinical phenotypes at birth and further, during childhood.
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Sieber-Ruckstuhl, Nadja S., Wai Kin Tham, Franziska Baumgartner, Jeremy John Selva, Markus R. Wenk, Bo Burla, and Felicitas S. Boretti. "Serum Lipidome Signatures of Dogs with Different Endocrinopathies Associated with Hyperlipidemia." Metabolites 12, no. 4 (March 30, 2022): 306. http://dx.doi.org/10.3390/metabo12040306.
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Hyperlipidemia (hypertriglyceridemia, hypercholesterolemia) is a common finding in human and veterinary patients with endocrinopathies (e.g., hypothyroidism and hypercortisolism (Cushing’s syndrome; CS)). Despite emerging use of lipidomics technology in medicine, the lipid profiles of these endocrinopathies have not been evaluated and characterized in dogs. The aim of this study was to compare the serum lipidomes of dogs with naturally occurring CS or hypothyroidism with those of healthy dogs. Serum samples from 39 dogs with CS, 45 dogs with hypothyroidism, and 10 healthy beagle dogs were analyzed using a targeted lipidomics approach with liquid chromatography-mass spectrometry. There were significant differences between the lipidomes of dogs with CS, hypothyroidism, and the healthy dogs. The most significant changes were found in the lysophosphatidylcholines, lysophosphatidylethanolamines, lysophosphatidylinositols, phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, ceramides, and sphingosine 1-phosphates. Lipid alterations were especially pronounced in dogs with hypothyroidism. Several changes suggested a more atherogenic lipid profile in dogs with HT than in dogs with CS. In this study, we found so far unknown effects of naturally occurring hypothyroidism and CS on lipid metabolism in dogs. Our findings provide starting points to further examine differences in occurrence of atherosclerotic lesion formation between the two diseases.
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Beyene, Habtamu B., Gavriel Olshansky, Corey Giles, Kevin Huynh, Michelle Cinel, Natalie A. Mellett, Adam Alexander T. Smith, Jonathan E. Shaw, Dianna J. Magliano, and Peter J. Meikle. "Lipidomic Signatures of Changes in Adiposity: A Large Prospective Study of 5849 Adults from the Australian Diabetes, Obesity and Lifestyle Study." Metabolites 11, no. 9 (September 21, 2021): 646. http://dx.doi.org/10.3390/metabo11090646.
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Lipid metabolism is tightly linked to adiposity. Comprehensive lipidomic profiling offers new insights into the dysregulation of lipid metabolism in relation to weight gain. Here, we investigated the relationship of the human plasma lipidome and changes in waist circumference (WC) and body mass index (BMI). Adults (2653 men and 3196 women), 25–95 years old who attended the baseline survey of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) and the 5-year follow-up were enrolled. A targeted lipidomic approach was used to quantify 706 distinct molecular lipid species in the plasma samples. Multiple linear regression models were used to examine the relationship between the baseline lipidomic profile and changes in WC and BMI. Metabolic scores for change in WC were generated using a ridge regression model. Alkyl-diacylglycerol such as TG(O-50:2) [NL-18:1] displayed the strongest association with change in WC (β-coefficient = 0.125 cm increment per SD increment in baseline lipid level, p = 2.78 × 10−11. Many lipid species containing linoleate (18:2) fatty acids were negatively associated with both WC and BMI gain. Compared to traditional models, multivariate models containing lipid species identify individuals at a greater risk of gaining WC: top quintile relative to bottom quintile (odds ratio, 95% CI = 5.4, 3.8–6.6 for women and 2.3, 1.7–3.0 for men). Our findings define metabolic profiles that characterize individuals at risk of weight gain or WC increase and provide important insight into the biological role of lipids in obesity.
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Morrow, Danielle, David Nathanson, Timothy Cloughesy, Robert Prins, Nicholas Bayley, Linda Liau, Steven Bensinger, and Kevin Williams. "CBIO-05. LIPID METABOLIC REPROGRAMMING SENSITIZES A MOLECULARLY-DEFINED SUBSET OF GLIOBLASTOMAS TO FERROPTOSIS." Neuro-Oncology 22, Supplement_2 (November 2020): ii16. http://dx.doi.org/10.1093/neuonc/noaa215.065.
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Abstract Cancers, including the universally lethal glioblastoma (GBM), have reprogrammed lipid metabolism to fuel tumor growth. However, the molecular alterations responsible for aberrant lipid metabolism, and the potential for identifying new therapeutic opportunities are not fully understood. To systematically investigate the GBM lipidome, we performed integrated transcriptomic, genomic and shotgun lipidomic analysis of an extensive library of molecularly diverse patient-derived GBM samples. Using this comprehensive approach, we discovered two GBM sub-groups defined by their combined molecular and lipidomic profile. Triacylglycerides (TAGs) enriched in polyunsaturated fatty acids (PUFAs) were among the most significantly altered lipids between the two groups of GBM tumors. TAGs are the main components of lipid droplets, which sequester PUFA-TAGs away from membrane phospholipids where their peroxidation can lead to ferroptosis – a regulated from of PUFA-peroxidation dependent cell death. Accordingly, the GBM subgroup with a depletion of PUFA TAGs showed heightened sensitivity to ferroptosis. Our findings suggest a novel association between specific molecular signatures of GBM, lipid metabolism and ferroptosis. This relationship may present a new therapeutic opportunity to target reprogrammed lipid metabolism in a molecularly-defined subset of GBMs.
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Schultz, Daniel, Karen Methling, Michael Rothe, and Michael Lalk. "Eicosanoid Profile of Influenza A Virus Infected Pigs." Metabolites 9, no. 7 (July 3, 2019): 130. http://dx.doi.org/10.3390/metabo9070130.
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Respiratory tract infections caused by the Influenza A virus (IAV) are a worldwide problem for human and animal health. Within this study, we analyzed the impact of IAV infection on the immune-related lipidome (eicosanoids) of the pig as new infection model. For this purpose, we performed HPLC-MS/MS using dynamic multiple reaction monitoring and analyzed lung, spleen, blood plasma and bronchoalveolar lavages. IAV infection leads to collective changes in the levels of the analyzed hydroxyeicosatrienoic acids (HETEs), hydroxydocosahexaenoic acids (HDHAs) and epoxyeicosatrienoic acids (EETs), and moreover, unique eicosanoid changes in several sample types, even under mild infection conditions. In accordance with different mouse infection studies, we observed infection-related patterns for 12-HETE, 15-HETE and 17-HDHA, which seem to be common for IAV infection. Using a long-term approach of 21 days we established an experimental setup that can be used also for bacterial-viral coinfection experiments.
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Yan, Bingpeng, Zijiao Zou, Hin Chu, Gabriella Chan, Jessica Oi-Ling Tsang, Pok-Man Lai, Shuofeng Yuan, et al. "Lipidomic Profiling Reveals Significant Perturbations of Intracellular Lipid Homeostasis in Enterovirus-Infected Cells." International Journal of Molecular Sciences 20, no. 23 (November 26, 2019): 5952. http://dx.doi.org/10.3390/ijms20235952.
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Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are the most common causes of hand, foot, and mouth disease. Severe EV-A71 and CV-A16 infections may be associated with life-threatening complications. However, the pathogenic mechanisms underlying these severe clinical and pathological features remain incompletely understood. Lipids are known to play critical roles in multiple stages of the virus replication cycle. The specific lipid profile induced upon virus infection is required for optimal virus replication. The perturbations in the host cell lipidomic profiles upon enterovirus infection have not been fully characterized. To this end, we performed ultra-high performance liquid chromatography–electrospray ionization–quadrupole–time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MS)-based lipidomics to characterize the change in host lipidome upon EV-A71 and CV-A16 infections. Our results revealed that 47 lipids within 11 lipid classes were significantly perturbed after EV-A71 and CV-A16 infection. Four polyunsaturated fatty acids (PUFAs), namely, arachidonic acid (AA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA), were consistently upregulated upon EV-A71 and CV-A16 infection. Importantly, exogenously supplying three of these four PUFAs, including AA, DHA, and EPA, in cell cultures significantly reduced EV-A71 and CV-A16 replication. Taken together, our results suggested that enteroviruses might specifically modulate the host lipid pathways for optimal virus replication. Excessive exogenous addition of lipids that disrupted this delicate homeostatic state could prevent efficient viral replication. Precise manipulation of the host lipid profile might be a potential host-targeting antiviral strategy for enterovirus infection.
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Chicanne, Gaëtan, Maria N. Barrachina, Anaelle Durbec, Justine Bertrand-Michel, Sara Troitiño, Lidia Hermida-Nogueira, Aurelio M. Sueiro, María Pardo, Bernard Payrastre, and Ángel García. "Platelet Lipidome Fingerprint: New Assistance to Characterize Platelet Dysfunction in Obesity." International Journal of Molecular Sciences 23, no. 15 (July 28, 2022): 8326. http://dx.doi.org/10.3390/ijms23158326.
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Obesity is associated with a pro-inflammatory and pro-thrombotic state that supports atherosclerosis progression and platelet hyper-reactivity. During the last decade, the platelet lipidome has been considered a treasure trove, as it is a source of biomarkers for preventing and treating different pathologies. The goal of the present study was to determine the lipid profile of platelets from non-diabetic, severely obese patients compared with their age- and sex-matched lean controls. Lipids from washed platelets were isolated and major phospholipids, sphingolipids and neutral lipids were analyzed either by gas chromatography or by liquid chromatography coupled to mass spectrometry. Despite a significant increase in obese patient’s plasma triglycerides, there were no significant differences in the levels of triglycerides in platelets among the two groups. In contrast, total platelet cholesterol was significantly decreased in the obese group. The profiling of phospholipids showed that phosphatidylcholine and phosphatidylethanolamine contents were significantly reduced in platelets from obese patients. On the other hand, no significant differences were found in the sphingomyelin and ceramide levels, although there was also a tendency for reduced levels in the obese group. The outline of the glycerophospholipid and sphingolipid molecular species (fatty-acyl profiles) was similar in the two groups. In summary, these lipidomics data indicate that platelets from obese patients have a unique lipid fingerprint that may guide further studies and provide mechanistic-driven perspectives related to the hyperactivate state of platelets in obesity.
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Crisi, Paolo Emidio, Alessia Luciani, Morena Di Tommaso, Paraskevi Prasinou, Francesca De Santis, Chryssostomos Chatgilialoglu, Marco Pietra, et al. "The Fatty Acid-Based Erythrocyte Membrane Lipidome in Dogs with Chronic Enteropathy." Animals 11, no. 9 (September 5, 2021): 2604. http://dx.doi.org/10.3390/ani11092604.
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Canine chronic enteropathies (CEs) are inflammatory processes resulting from complex interplay between the mucosal immune system, intestinal microbiome, and dietary components in susceptible dogs. Fatty acids (FAs) play important roles in the regulation of physiologic and metabolic pathways and their role in inflammation seems to be dual, as they exhibit pro–inflammatory and anti–inflammatory functions. Analysis of red blood cell (RBC) membrane fatty acid profile represents a tool for assessing the quantity and quality of structural and functional molecular components. This study was aimed at comparing the FA membrane profile, determined by Gas Chromatography and relevant lipid parameter of 48 CE dogs compared with 68 healthy dogs. In CE patients, the levels of stearic (p < 0.0001), dihomo–gamma–linolenic, eicosapentaenoic (p = 0.02), and docosahexaenoic (p = 0.02) acids were significantly higher, and those of palmitic (p < 0.0001) and linoleic (p = 0.0006) acids were significantly lower. Non-responder dogs presented higher percentages of vaccenic acid (p = 0.007), compared to those of dogs that responded to diagnostic trials. These results suggest that lipidomic status may reflect the “gut health”, and the non–invasive analysis of RBC membrane might have the potential to become a candidate biomarker in the evaluation of dogs affected by CE.
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Li, Mengying, Mohammad Rahman, Yiqing Song, Wei Perng, Ellen Francis, Michael Tsai, and Cuilin Zhang. "Lipidomic Profile in Pregnancy and Neonatal Size: A Prospective and Longitudinal Study." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 1026. http://dx.doi.org/10.1093/cdn/nzaa054_098.
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Abstract Objectives The roles of maternal lipidomic profile in fetal growth are rarely studied. This study aims to examine the association of lipidomic profiles over pregnancy with birth weight (BW), neonatal sum of skinfolds (SS) and length, and risks of large- and small-for-gestational-age (LGA, SGA). Methods Lipidome analyses were performed among 321 pregnant women from the NICHD Fetal Growth Study-Singletons in the plasma collected at gestational weeks 10–14, 15–26 (fasting), 23–31 and 33–39, using untargeted liquid chromatography-mass spectrometry (LC-MS). The associations of neonatal outcomes with 328 annotated lipid metabolites and 6–9 lipid networks constructed using weighted correlation network analysis were assessed using linear mixed-effects models adjusting for age, race, pre-pregnancy BMI, gestational age of blood collection, and infant sex. False discovery rate (FDR) <0.05 was considered significant. Results Both individual metabolites and networks were significantly related to neonatal outcomes. The relations varied by lipid molecular structure and timing in gestation. At weeks 10–14, two networks of medium-chain triglycerides (TG) were positively related to BW, neonatal SS and length. For instance, the beta for TG (50:5) abundance related to SS (1 mm) was 0.21 (FDR = 2.72E-11). In contrast, a network of lysophosphatidylcholines (LPC) and a network mainly of phospholipids (PC) and cholesteryl esters (CE) were inversely related to BW, whereas the network of LPC and a network of longer-chain TGs were inversely related to SS. For instance, the beta for LPC (18:3) abundance related to SS (1 mm) was −0.11 (FDR = 0.004). At weeks 15–26, a network mainly of medium-chain higher-saturation TGs was positively, whereas a network mainly of sphingomyelins (SM) and PCs was inversely related to BW, SS and length. Further, the network of LPC at weeks 15–26 was inversely related to LGA risk; the relative risk for each standard deviation of the eigenvalue was 0.52 (95% confidence interval: 0.34, 0.81, FDR = 0.02). Conclusions Generally, lipid networks of medium-chain TGs in the 1st and 2nd trimesters were positively whereas a network mainly of SMs and PCs in the 2nd trimester was inversely related to BW, SS, and length. Funding Sources National Institutes of Health.
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Sánchez-Vinces, Salvador, Pedro Henrique Dias Garcia, Alex Ap Rosini Silva, Anna Maria Alves de Piloto Fernandes, Joyce Aparecida Barreto, Gustavo Henrique Bueno Duarte, Marcia Aparecida Antonio, Alexander Birbrair, Andreia M. Porcari, and Patricia de Oliveira Carvalho. "Mass-Spectrometry-Based Lipidomics Discriminates Specific Changes in Lipid Classes in Healthy and Dyslipidemic Adults." Metabolites 13, no. 2 (February 3, 2023): 222. http://dx.doi.org/10.3390/metabo13020222.
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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.
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Zandl-Lang, Martina, Thomas Züllig, Martin Trötzmüller, Yvonne Naegelin, Lucia Abela, Bernd Wilken, Sabine Scholl-Buergi, et al. "Changes in the Cerebrospinal Fluid and Plasma Lipidome in Patients with Rett Syndrome." Metabolites 12, no. 4 (March 25, 2022): 291. http://dx.doi.org/10.3390/metabo12040291.
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Rett syndrome (RTT) is defined as a rare disease caused by mutations of the methyl-CpG binding protein 2 (MECP2). It is one of the most common causes of genetic mental retardation in girls, characterized by normal early psychomotor development, followed by severe neurologic regression. Hitherto, RTT lacks a specific biomarker, but altered lipid homeostasis has been found in RTT model mice as well as in RTT patients. We performed LC-MS/MS lipidomics analysis to investigate the cerebrospinal fluid (CSF) and plasma composition of patients with RTT for biochemical variations compared to healthy controls. In all seven RTT patients, we found decreased CSF cholesterol levels compared to age-matched controls (n = 13), whereas plasma cholesterol levels were within the normal range in all 13 RTT patients compared to 18 controls. Levels of phospholipid (PL) and sphingomyelin (SM) species were decreased in CSF of RTT patients, whereas the lipidomics profile of plasma samples was unaltered in RTT patients compared to healthy controls. This study shows that the CSF lipidomics profile is altered in RTT, which is the basis for future (functional) studies to validate selected lipid species as CSF biomarkers for RTT.
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Pikó, Péter, László Pál, Sándor Szűcs, Zsigmond Kósa, János Sándor, and Róza Ádány. "Obesity-Related Changes in Human Plasma Lipidome Determined by the Lipidyzer Platform." Biomolecules 11, no. 2 (February 21, 2021): 326. http://dx.doi.org/10.3390/biom11020326.
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Obesity is an increasing public health concern both in the developed and developing countries. Previous studies have demonstrated that considerable alterations in lipid metabolism and consequently marked changes in lipid profile are associated with the onset and progression of obesity-related complications. To characterize the full spectrum of obesity-induced changes in lipid metabolism, direct infusion tandem mass spectrometry analysis is the most promising approach. To better understand which of the many lipid species are the most strongly associated with obesity, the aim of our work was to measure and profile plasma lipids in normal (n = 57), overweight (n = 31), and obese (n = 48) individuals randomly selected from samples of Hungarian general and Roma populations by using the targeted quantitative lipidomics platform, the Lipidyzer. Principal component and stepwise regression analyses were used to identify the most significant clusters and species of lipids by increasing body mass index (BMI). From the 18 clusters identified four key lipid species (PE P-16:0/20:3, TG 20:4_33:1, TG 22:6_36:4, TG 18:3_33:0) showed a strong significant positive and three others (Hex-Cer 18:1;O2/22:0, LPC 18:2, PC 18:1_18:1) significant negative association with BMI. Compared to individual lipid species alone, the lipid species ratio (LSR) we introduced showed an extremely strong, at least 9 orders of magnitude stronger, association with BMI. The LSR can be used as a sensitive and predictive indicator to monitor obesity-related alterations in human plasma and control the effectiveness of treatment of obesity associated non-communicable diseases.
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Del Duca, Elisabetta, Anna Sansone, Mayla Sgrulletti, Federica Di Nolfo, Loredana Chini, Carla Ferreri, and Viviana Moschese. "Fatty-Acid-Based Membrane Lipidome Profile of Peanut Allergy Patients: An Exploratory Study of a Lifelong Health Condition." International Journal of Molecular Sciences 24, no. 1 (December 21, 2022): 120. http://dx.doi.org/10.3390/ijms24010120.
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Peanut allergy is a lifelong, increasingly prevalent, and potentially life-threatening disease burdening families and communities. Dietary, particularly polyunsaturated fatty acids (PUFAs), intakes can exert positive effects on immune and inflammatory responses, and the red blood cell (RBC) membrane lipidome contains stabilized metabolic and nutritional information connected with such responses. The fatty-acid-based membrane lipidome profile has been exploratorily evaluated in a small cohort of patients (eight males and one female, age range 4.1–21.7 years old, body mass index BMI < 25) with angioedema and/or anaphylaxis after peanut ingestion. This analysis was performed according to an ISO 17025 certified robotic protocol, isolating mature RBCs, extracting membrane lipids, and transforming them to fatty acid methyl esters for gas chromatography recognition and quantification. Comparison with a group of age- and BMI-matched healthy individuals and with benchmark interval values of a healthy population evidenced significant differences, such as higher levels of ω-6 (arachidonic acid), lower values of ω-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), together with an increased ω-6/ω-3 ratio in allergic patients. A significant inverse correlation was also found between specific immunoglobulin E (IgE) levels and ω-6 di-homo-gamma-linolenic acid (DGLA) and total PUFAs. Results of this preliminary study encourage screenings in larger cohorts, also in view of precision nutrition and nutraceuticals strategies, and stimulate interest to expand basic and applied research for unveiling molecular mechanisms that are still missing and individuating treatments in chronic allergic disorders.
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Berdún, Rebeca, Mariona Jové, Joaquim Sol, Weijing Cai, John C. He, Reyna Rodriguez‐Mortera, Meritxell Martin‐Garí, Reinald Pamplona, Jaime Uribarri, and Manuel Portero‐Otin. "Restriction of Dietary Advanced Glycation End Products Induces a Differential Plasma Metabolome and Lipidome Profile." Molecular Nutrition & Food Research 65, no. 23 (October 20, 2021): 2000499. http://dx.doi.org/10.1002/mnfr.202000499.
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Marchand, Jérémy, Yann Guitton, Estelle Martineau, Anne-Lise Royer, David Balgoma, Bruno Le Bizec, Patrick Giraudeau, and Gaud Dervilly. "Extending the Lipidome Coverage by Combining Different Mass Spectrometric Platforms: An Innovative Strategy to Answer Chemical Food Safety Issues." Foods 10, no. 6 (May 28, 2021): 1218. http://dx.doi.org/10.3390/foods10061218.
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From a general public health perspective, a strategy combining non-targeted and targeted lipidomics MS-based approaches is proposed to identify disrupted patterns in serum lipidome upon growth promoter treatment in pigs. Evaluating the relative contributions of the platforms involved, the study aims at investigating the potential of innovative analytical approaches to highlight potential chemical food safety threats. Serum samples collected during an animal experiment involving control and treated pigs, whose food had been supplemented with ractopamine, were extracted and characterised using three MS strategies: Non-targeted RP LC-HRMS; the targeted Lipidyzer™ platform (differential ion mobility associated with shotgun lipidomics) and a homemade LC-HRMS triglyceride platform. The strategy enabled highlighting specific lipid profile patterns involving various lipid classes, mainly in relation to cholesterol esters, sphingomyelins, lactosylceramide, phosphatidylcholines and triglycerides. Thanks to the combination of non-targeted and targeted MS approaches, various compartments of the pig serum lipidome could be explored, including commonly characterised lipids (Lipidyzer™), triglyceride isomers (Triglyceride platform) and unique lipid features (non-targeted LC-HRMS). Thanks to their respective characteristics, the complementarity of the three tools could be demonstrated for public health purposes, with enhanced coverage, level of characterization and applicability.
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Morrow, Danielle, Jenna Minami, Nicholas Bayley, Kevin Williams, Steven Bensinger, Robert Prins, Linda Liau, Timothy Cloughesy, and David Nathanson. "DDRE-23. A COMPREHENSIVE CHARACTERIZATION OF THE GBM LIPIDOME REVEALS A MOLECULARLY-DEFINED SUB-GROUP WITH HEIGHTENED SENSITIVITY TO LIPID PEROXIDATION INDUCED CELL DEATH." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i11. http://dx.doi.org/10.1093/noajnl/vdab024.045.
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Abstract Cancers, including the universally lethal glioblastoma (GBM), have reprogrammed lipid metabolism to fuel tumor growth and promote survival. However, the full extent to which lipid content is altered across molecularly heterogeneous patient tumors has yet to be fully elucidated. Additionally, the molecular alterations responsible for aberrant lipid metabolism, and the potential for identifying new therapeutic opportunities are not fully understood. To systematically investigate the GBM lipidome, we performed integrated transcriptomic, genomic and shotgun lipidomic analysis of an extensive library of molecularly diverse patient-derived GBM tumors across tumor microenvironments both in vivo (n=23) and in vitro (n=30). Using this comprehensive approach, we discovered two GBM sub-groups defined by their combined molecular and lipidomic profile. Triacylglycerides (TAGs) enriched in polyunsaturated fatty acids (PUFAs) were among the most significantly altered lipids between the two groups of GBM tumors. TAGs are the main components of lipid droplets, which have been shown to sequester PUFAs away from membrane phospholipids where their sensitivity to peroxidation leads to cell death. The GBM subgroup with a depletion of PUFA TAGs showed heightened sensitivity to lipid peroxidation both under basal conditions and in response to pro-oxidant compounds in vitro. Our findings suggest a novel association between specific molecular signatures of GBM, lipid metabolism and lipid peroxidation-induced cell death. This relationship may present a new therapeutic opportunity to target reprogrammed lipid metabolism in a molecularly-defined subset of GBMs.
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Fraser, Karl, Hanna Lagstrom, Shikha Pundir, David Cameron-Smith, and Nicole Roy. "Infant Feeding Frequency Impacts Human Milk Composition: A Metabolomic Analysis." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 986. http://dx.doi.org/10.1093/cdn/nzaa054_058.
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Abstract Objectives The nutritional composition of human milk is affected by many factors, including stage of lactation and time of day. Metabolomic profiling of milk provides a biochemical fingerprint of hundreds of metabolites being consumed by the infant, which may help to understand potential factors affecting infant health, growth and nutritional status. We hypothesized that frequency of daily lactations would alter the profile of metabolites and lipids in the milk. Methods Human milk samples from 630 individuals [378 mothers exclusively breast feeding and 252 mothers partially breast feeding (i.e., infant supplemented with formula feeding)] from a single sample (infant aged 3 months) were subjected to biphasic extraction and metabolite profiling performed using two separate untargeted liquid chromatography high resolution mass spectrometry analysis methods (polar metabolites and the lipidome). Results Univariate statistical analysis of the lipidome data matrix revealed considerable differences in lipid concentrations between partial or exclusive feeding. Of the 241 lipids measured in the non-polar extracts, 203 were significantly different between the two groups after multiple testing correction (FDR corrected p-value <0.05). These included 96 triglycerides, 78 phospholipids, 27 sphingomyelins and 2 ceramides, all significantly elevated with exclusive feeding. Of the 320 metabolite features measured in the polar extracts, 69 were significantly different between the two groups, including carnitine and metabolites from the lysine degradation pathway, all reduced with exclusive feeding. Random forest analysis highlighted that overall profiles in both polar metabolite and lipid extracts were more consistent across the exclusive feeding group. Conclusions This study provides insight into effects of feeding frequency on metabolite/lipid profiles, showing impact of possible altered milk synthesis and storage on relative abundances of discrete polar metabolites, with a broad impact on many lipid species. Funding Sources Funded by AgResearch Strategic Science Investment Fund via the New Zealand Ministry of Business, Innovation and Employment.
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Ruan, Jing, Bing Han, Zhao Wang, Chen Yang, Yali Du, and Miao Chen. "Plasma Lipidome Acts As Diagnostic Marker and Predictor for Cyclosporin Response in Patients with Aplastic Anemia." Blood 138, Supplement 1 (November 5, 2021): 2199. http://dx.doi.org/10.1182/blood-2021-145843.
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Abstract Background：The lipid metabolomic profile has been well defined in the pathogenesis and differential diagnosis in patients with different myeloid diseases. However, the role of plasma lipidome was rarely explored, especially in aplastic anemia (AA), a disease which has close connection with lipid metabolism. Methods: Peripheral fasting serum levels of patients newly diagnosed with AA from March 2019 to December 2019 were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the serum lipid profiles. Meanwhile, the lipidomes for patients with hypocellular myelodysplastic syndrome (h-MDS) and age and sex matched healthy volunteers were taken as controls. The lipid profiles were tested again 6 months after standard cyclosporin A（CsA）treatment in patients with AA. For all the patients, those with a history of hyperlipidemia, diabetes, obesity (body mass index > 28 kg/m 2) or complications with other malignant diseases at diagnosis were excluded. Results: The study enrolled 15 patients with AA, 11 patients with h-MDS and 20 healthy controls. All the enrolled AA patients were non-severe and transfusion dependent, and were treated with CsA 3-5mg/kg/d for at least 6 months. For h-MDS patients, five were MDS with single lineage dysplasia, three were MDS with multilineage dysplasia, and three were MDS-Excess Blasts 1 (MDS-RAEB1). Metabolites in arachidonic acid pathway and retinol metabolism were significantly decreased in the AA patients compared with the healthy controls (P<0.05). AA patients had decreased arachidonic acid pathway metabolites and retinol metabolism-related metabolites as compared with h-MDS（P<0.05), whereas h-MDS patients had increased metabolism of proline and threonine and abnormal sphingolipid metabolism compared with AA patients and the normal controls. After 6-month of CsA treatment, leukotriene B4, 15(S)-HETE, all-trans-retinal and protectin D1 decreased significantly. Patients who had response to CsA had higher levels of baseline protectin D1 (p=0.011), leukotriene B4 (p=0.011), 15(S)-HETE (p=0.004) and all-trans-retinal (p=0.000) than those who had no response. Conclusion: The lipid profiles showed significant difference not only between patients with AA and healthy controls, but also between AA and h-MDS. Meanwhile, some of baseline value and the change in lipid molecules may predict the CsA response at 6 months. Disclosures No relevant conflicts of interest to declare.
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Bogusiewicz, J., P. Z. Goryńska, K. Jaroch, K. Goryński, D. Paczkowski, J. Furtak, M. Harat, and B. Bojko. "P13.05 Chemical Biopsy as an Alternative Sampling Method in Neurooncology." Neuro-Oncology 21, Supplement_3 (August 2019): iii63. http://dx.doi.org/10.1093/neuonc/noz126.226.
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Abstract BACKGROUND Histopathology is a gold standard for diagnostics of brain tumors but it is time consuming, demands removal of the part of the tissue what makes it highly invasive. That is why it seems to be relevant to develop new diagnostic methods addressing the abovementioned drawbacks. Ideal tool should be easy to use, as low invasive as possible and of high clinical value. The aim of the study was to assess the usefulness of chemical biopsy based on solid phase microextraction as a sampling method for lipidomic analysis of brain tumors. MATERIAL AND METHODS The experiment was carried out on 38 brain tumors. Sampling was performed ex vivo, directly after removal of brain tumors. SPME fibers (coated with biocompatible extraction phase, length and diameter of the coating 7mm and 200um, respectively) were inserted into the sample without prior preparation of the tissue. Desorption of lipids was performed in isopropanol-methanol mixture. Analysis of extracts was carried out using liquid chromatography coupled to high resolution mass spectrometry. RESULTS Wide range of tentative lipid species was obtained in the studies. Two histologically different types of brain tumors: gliomas and meningiomas were subjected to the chemical biopsy. The results showed very good separation between the tumor types in unsupervised chemometric tests. The lipid species responsible for this separation were previously reported in the literature as cancer biomarkers. With regards to malignancy grading of gliomas the separation was notable but not as clear as between the tumor types, what is probably related to high heterogeneity of this cancerous tissue and subjectivity of histopathological analysis which were a referring point in methods comparison. Very good agreement was noted for changes in lipidome obtained by chemical biopsy and histological subtypes of gliomas. However, the most promising results showed impact of IDH1 R132H mutation on lipidome of gliomas. CONCLUSION Chemical biopsy seems to be useful method in lipidomics studies and for differentiation of brain tumors according their histological origin and malignancy. It also enables to find a relation between IDH1 mutation and lipidomic profile. ACKNOWLEDGMENTS The work was supported by the grant 2015/18/M/ST4/00059 funded by National Science Centre, Poland. The authors want to acknowledge Supelco/MilliporeSigma for the SPME probes, Thermo Fisher Scientific for the access to Q-Exactive Focus mass spectrometer, Anchem for the technical support and Shim-Pol for the access to LCMS-8060 mass spectrometer and technical support.
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Kostara, Christina E., Kiriaki S. Karakitsou, Matilda Florentin, Eleni T. Bairaktari, and Vasilis Tsimihodimos. "Progressive, Qualitative, and Quantitative Alterations in HDL Lipidome from Healthy Subjects to Patients with Prediabetes and Type 2 Diabetes." Metabolites 12, no. 8 (July 25, 2022): 683. http://dx.doi.org/10.3390/metabo12080683.
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Prediabetes is a clinically silent, insulin-resistant state with increased risk for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD). Since glucose homeostasis and lipid metabolism are highly intersected and interrelated, an in-depth characterization of qualitative and quantitative abnormalities in lipoproteins could unravel the metabolic pathways underlying the progression of prediabetes to T2D and also the proneness of these patients to developing premature atherosclerosis. We investigated the HDL lipidome in 40 patients with prediabetes and compared it to that of 40 normoglycemic individuals and 40 patients with established T2D using Nuclear Magnetic Resonance (NMR) spectroscopy. Patients with prediabetes presented significant qualitative and quantitative alterations, potentially atherogenic, in HDL lipidome compared to normoglycemic characterized by higher percentages of free cholesterol and triglycerides, whereas phospholipids were lower. Glycerophospholipids and ether glycerolipids were significantly lower in prediabetic compared to normoglycemic individuals, whereas sphingolipids were significantly higher. In prediabetes, lipids were esterified with saturated rather than unsaturated fatty acids. These changes are qualitatively similar, but quantitatively milder, than those found in patients with T2D. We conclude that the detailed characterization of the HDL lipid profile bears a potential to identify patients with subtle (but still proatherogenic) abnormalities who are at high risk for development of T2D and CVD.
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Aveiro, Susana S., Tânia Melo, Ana Figueiredo, Pedro Domingues, Hugo Pereira, Inês B. Maia, Joana Silva, M. Rosário Domingues, Cláudia Nunes, and Ana S. P. Moreira. "The Polar Lipidome of Cultured Emiliania huxleyi: A Source of Bioactive Lipids with Relevance for Biotechnological Applications." Biomolecules 10, no. 10 (October 12, 2020): 1434. http://dx.doi.org/10.3390/biom10101434.
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Polar lipids from microalgae have aroused greater interest as a natural source of omega-3 (n-3) polyunsaturated fatty acids (PUFA), an alternative to fish, but also as bioactive compounds with multiple applications. The present study aims to characterize the polar lipid profile of cultured microalga Emiliania huxleyi using hydrophilic interaction liquid chromatography coupled with high-resolution mass spectrometry (HILIC–MS) and fatty acids (FA) analysis by gas chromatography (GC–MS). The lipidome of E. huxleyi revealed the presence of distinct n-3 PUFA (40% of total FA), namely docosahexaenoic acid (22:6n-3) and stearidonic acid (18:4n-3), which give this microalga an increased commercial value as a source of n-3 PUFA present in the form of polar lipids. A total of 134 species of polar lipids were identified and some of these species, particularly glycolipids, have already been reported for their bioactive properties. Among betaine lipids, the diacylglyceryl carboxyhydroxymethylcholine (DGCC) class is the least reported in microalgae. For the first time, monomethylphosphatidylethanolamine (MMPE) has been found in the lipidome of E. huxleyi. Overall, this study highlights the potential of E. huxleyi as a sustainable source of high-value polar lipids that can be exploited for different applications, namely human and animal nutrition, cosmetics, and pharmaceuticals.
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Lastovetsky, Olga A., Maria L. Gaspar, Stephen J. Mondo, Kurt M. LaButti, Laura Sandor, Igor V. Grigoriev, Susan A. Henry, and Teresa E. Pawlowska. "Lipid metabolic changes in an early divergent fungus govern the establishment of a mutualistic symbiosis with endobacteria." Proceedings of the National Academy of Sciences 113, no. 52 (December 12, 2016): 15102–7. http://dx.doi.org/10.1073/pnas.1615148113.
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The recent accumulation of newly discovered fungal–bacterial mutualisms challenges the paradigm that fungi and bacteria are natural antagonists. To understand the mechanisms that govern the establishment and maintenance over evolutionary time of mutualisms between fungi and bacteria, we studied a symbiosis of the fungus Rhizopus microsporus (Mucoromycotina) and its Burkholderia endobacteria. We found that nonhost R. microsporus, as well as other mucoralean fungi, interact antagonistically with endobacteria derived from the host and are not invaded by them. Comparison of gene expression profiles of host and nonhost fungi during interaction with endobacteria revealed dramatic changes in expression of lipid metabolic genes in the host. Analysis of the host lipidome confirmed that symbiosis establishment was accompanied by specific changes in the fungal lipid profile. Diacylglycerol kinase (DGK) activity was important for these lipid metabolic changes, as its inhibition altered the fungal lipid profile and caused a shift in the host–bacterial interaction into an antagonism. We conclude that adjustments in host lipid metabolism during symbiosis establishment, mediated by DGKs, are required for the mutualistic outcome of the Rhizopus–Burkholderia symbiosis. In addition, the neutral and phospholipid profiles of R. microsporus provide important insights into lipid metabolism in an understudied group of oleaginous Mucoromycotina. Lastly, our study revealed that the DGKs involved in the symbiosis form a previously uncharacterized clade of DGK domain proteins.
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Höfner, Lisa, Anne-Marie Luther, Alessandra Palladini, Thomas Fröhlich, and Dagmar Waberski. "Tolerance of Stored Boar Spermatozoa to Autologous Seminal Plasma: A Proteomic and Lipidomic Approach." International Journal of Molecular Sciences 21, no. 18 (September 4, 2020): 6474. http://dx.doi.org/10.3390/ijms21186474.
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Long-term exposure of liquid preserved boar spermatozoa to seminal plasma (SP) can cause dramatic sperm injury. This study examined whether boar specificity exists in the sensitivity of spermatozoa to SP and whether correspondent biomarkers can be identified. Consecutive ejaculates (n = 4–5) collected from 19 boars were centrifuged, diluted with a pH-stablising extender with 10% (v/v) autologous SP and evaluated by computer-assisted semen analysis and flow cytometry. Up until 144 h storage, four boars showed consistently high sperm motility, viability and mitochondria activity, and one boar showed consistently low values. Intra-boar variability was high in the other boars. Screening of SP (n = 12 samples) for protein markers using mass spectrometry identified three protein candidates of which the granulin precursor, legumain and AWN were 0.5 to 0.9 log2-fold less abundant (p < 0.05) in SP-resistant compared to SP-sensitive samples. Lipidome analysis by mass spectrometry revealed 568 lipids showing no difference between the SP-groups. The most abundant lipids were cholesterol (42,442 pmol), followed by phosphatidylserine (20,956 pmol) and ether-linked phosphatidylethanolamine (13,039 pmol). In conclusion, three candidate proteins were identified which might be indicative of SP-tolerance of sperm during long-term storage. Noteworthy, a first lipidomic profile of boar SP is presented.
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Natera, Siria H. A., Camilla B. Hill, Thusitha W. T. Rupasinghe, and Ute Roessner. "Salt-stress induced alterations in the root lipidome of two barley genotypes with contrasting responses to salinity." Functional Plant Biology 43, no. 2 (2016): 207. http://dx.doi.org/10.1071/fp15253.
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Changes in lipid metabolism and composition as well as in distinct lipid species have been linked with altered plant growth, development and responses to environmental stresses including salinity. However, there is little information available in the literature focusing on lipids in roots under soil-related stresses such as salinity. Barley (Hordeum vulgare L.) is a major cereal grain and, as a glycophyte, suffers substantial yield loss when grown under saline conditions. Relatively little is understood of adaptation and tolerance mechanisms involving lipids and lipid metabolism in barley roots during development and under exposure to salinity stress. In this study we investigated the lipid composition of barley roots of Clipper and Sahara – two genotypes with contrasting responses to salinity – before and after salinity stress using a combination of three lipidomics techniques: Fatty acid compositional analysis, untargeted lipid profiling, and targeted analysis to profile quantitatively the individual molecular species of key plant lipid classes. Our results provide new insight into the effect of salinity on fatty acid profiles and key lipid classes within barley roots of two different genotypes, which is discussed in the context of current knowledge of the root metabolic responses of cereal crops to salinity stress.
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Simintiras, Constantine A., José M. Sánchez, Michael McDonald, and Pat Lonergan. "Progesterone alters the bovine uterine fluid lipidome during the period of elongation." Reproduction 157, no. 4 (April 2019): 399–411. http://dx.doi.org/10.1530/rep-18-0615.
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Successful bovine pregnancy establishment hinges on conceptus elongation, a key reproductive phenomenon coinciding with the period during which most pregnancies fail. Elongation is yet to be recapitulated in vitro, whereas in vivo it is directly driven by uterine secretions and indirectly influenced by prior circulating progesterone levels. To better understand the microenvironment evolved to facilitate this fundamental developmental event, uterine fluid was recovered on Days 12–14 of the oestrous cycle – the window of conceptus elongation initiation – from cycling heifers supplemented, or not, with progesterone. Subsequent lipidomic profiling of uterine luminal fluid by advanced high-throughput metabolomics revealed the consistent presence of 75 metabolites, of which 47% were intricately linked to membrane biogenesis, and with seven displaying a day by progesterone interaction (P ≤ 0.05). Four metabolic pathways were correspondingly enriched according to day and P4 – i.e. comprised metabolites whose concentrations differed between groups (normal vs high P4) at different times (Days 12 vs 13 vs 14). These were inositol, phospholipid, glycerolipid and primary bile acid metabolism. Moreover, P4 elevated total uterine luminal fluid lipid content on Day 14 (P < 0.0001) relative to all other comparisons. The data combined suggest that maternal lipid supply during the elongation-initiation window is primarily geared towards conceptus membrane biogenesis. In summary, progesterone supplementation alters the lipidomic profile of bovine uterine fluid during the period of conceptus elongation initiation.