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BACKGROUND: Soybean is one of the most cultivated crops globally and a staple food for much of the world's population. The annual global crop losses due to infection by Phytophthora sojae is currently estimated at $20B USD, yet we have limited understanding of the role of lipid mediators in the adaptative strategies used by the host plant to limit infection. Since root is the initial site of this infection, we examined the infection process in soybean root infected with Phytophthora sojae using scanning electron microscopy to observe the changes in root morphology and a multi-modal lipidomics approach to investigate how soybean cultivars remodel their lipid mediators to successfully limit infection by Phytophthora sojae. RESULTS: The results reveal the presence of elevated biogenic crystals and more severe damaged cells in the root morphology of the infected susceptible cultivar compared to the infected tolerant cultivars. Furthermore, induced accumulation of stigmasterol was observed in the susceptible cultivar whereas, induced accumulation of phospholipids and glycerolipids occurred in tolerant cultivar. CONCLUSION: The altered lipidome reported in this study suggest diacylglycerol and phosphatidic acid mediated lipid signalling impacting phytosterol anabolism appears to be a strategy used by tolerant soybean cultivars to successfully limit infection and colonization by Phytophthora sojae.
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Glycine max , Phytophthora , Phytophthora/fisiologia , Resistência à Doença , Imunidade Vegetal , Fosfolipídeos , Doenças das PlantasRESUMO
Lysophosphatidic acid acyltransferase1 (LPAT1) catalyzes the second step of de novo glycerolipid biosynthesis in chloroplasts. However, the embryonic-lethal phenotype of the knockout mutant suggested an unknown role for LPAT1 in non-photosynthetic reproductive organs. Reciprocal genetic crossing of the lpat1-1 heterozygous line suggested a female gametophytic defect of the lpat1-1 knockout mutant. By suppressing LPAT1 specifically during seed development, we showed that LPAT1 suppression affected silique growth and seed production. Glycerolipid analysis of the LPAT1 knockdown lines revealed a pronounced decrease of phosphatidylcholine (PC) content in mature siliques along with an altered polyunsaturation level of the polar glycerolipids. In seeds, the acyl composition of triacylglycerol (TAG) was altered albeit not the content. These results indicate that plastidic LPAT1 plays an important role in reproductive growth and extraplastidic glycerolipid metabolism involving PC and TAG.
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The conditionally essential very-long-chain polyunsaturated fatty acids (VLC-PUFAs), such as eicosapentaenoic acid (EPA, C20:5 n-3), play a vital role in human nutrition. Their biological activity is thereby greatly influenced by the distinct glycerolipid molecule that they are esterified to. Here, microalgae differ from the conventional source, fish oil, both in quantity and distribution of VLC-PUFAs among the glycerolipidome. Therefore, the aim of this study was to develop a fast and reliable one-dimensional high-performance thin-layer chromatography (HPTLC)-based method that allows the separation and quantification of the main microalgal glycerolipid classes (e.g., monogalactosyldiacylglycerol (MGDG), sulfoquinovosyl diacylglycerol (SQDG), phosphatidylglycerol (PG)), as well as the subsequent analysis of their respective fatty acid distribution via gas chromatography (GC) coupled to mass spectrometry (MS). Following optimization, method validation was carried out for 13 different lipid classes, based on the International Conference on Harmonization (ICH) guidelines. In HPTLC, linearity was effective between 100 and 2100 ng, with a limit of quantification between 62.99 and 90.09 ng depending on the glycerolipid class, with strong correlation coefficients (R2 > 0.995). The recovery varied between 93.17 and 108.12%, while the inter-day precision measurements showed coefficients of variation of less than 8.85%, close to the limit of detection. Applying this method to crude lipid extracts of four EPA producing microalgae of commercial interest, the content of different glycerolipid classes was assessed together with the respective FA distribution subsequent to band elution. The results showed that the described precise and accurate HPTLC method offers the possibility to be used routinely to follow variations in the glycerolipid class levels throughout strain screening, cultivation, or bioprocessing. Thus, additional quantitative analytical information on the complex lipidome of microalgae can be obtained, especially for n-3 and n-6 enriched lipid fractions.
Assuntos
Microalgas , Humanos , Cromatografia em Camada Fina/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Ácidos Graxos/análise , Espectrometria de MassasRESUMO
Lipids are a diverse group of compounds that play several important roles in insect physiology. Among biological lipids, the fundamental category comprises fatty acyl structures, with significant members being fatty acids (FAs). They play several crucial functions in insect physiology; they are used as the source of energy for flight and play key roles in the insect immune system. The FAs present in the insect cuticle are known to demonstrate antibacterial and antifungal activity and are considered as potential insecticides. The most abundant family of lipids are the glycerolipids, with numerous cellular functions including storage of energy, structural compartmentation of cells and organelles, and important signaling activities required for regulation of physiological processes (i.e., growth, development, reproduction, diapause, and overwintering). The phospholipids are also highly diversified key components of all cell membranes; they can modify cellular components in response to rapid cold-hardening (RCH), enhancing membrane fluidity and improving survival at low temperatures. The sphingolipids are important structural and signaling bioactive compounds, mostly detected in membranes.Insects are sterol-auxotrophs: they do not have genes, which code enzymes converting farnesyl pyrophosphate to squalene. Similarly, to mammals, the production of steroids in insects is regulated by cytochrome P450 enzymes that convert sterols (mostly cholesterol) to hormonally active steroids. The major molting hormone in insects is 20-hydroxyecdysone, and cholesterol is the required precursor; however, several exemptions from this rule have been noted. This manuscript also reviews the roles of prenol lipids, isoprenoids, lipid vitamins, polyketides, and waxes in the vital processes of insects.
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Due to the high prevalence and clinical relevance, scorpionism is a critical public health issue in several Brazilian regions. Tityus serrulatus, commonly known as the Brazilian yellow scorpion, is the most venomous genus found in Brazilian fauna and associated with severe clinical manifestations such as localized pain, hypertension, sweating, tachycardia and complex hyperinflammatory responses. In general, T. serrulatus venom contains a complex mixture of active compounds, including proteins, peptides, and amino acids. Although knowledge of the protein fractions of scorpion venom is available, venom lipid components are not yet comprehensively known. The aim of the present study was to determine and characterize the lipid constituents/profile of the T. serratus venom utilizing liquid chromatography coupled with high-resolution mass spectrometry. Lipid species (164 in total) belonging to 3 different lipid categories, glycerophospholipids, sphingolipids, and glycerolipids, were identified. A further search on MetaCore/MetaDrug platform, which is based upon a manually curated database of molecular interactions, molecular pathways, gene-disease associations, chemical metabolism, and toxicity information, exhibited several metabolic pathways for 24 of previously identified lipid species, including activation of nuclear factor kappa B and oxidative stress pathways. Further several bioactive compounds, such as plasmalogens, lyso-platelet-activating factors, and sphingomyelins, associated with systemic responses triggered by T. serrulatus envenomation were detected. Finally, lipidomic data presented provide advanced and valuable information to better comprehend the mechanisms underlying the complex pathophysiology induced by T. serrulatus envenomation.
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Venenos de Escorpião , Animais , Venenos de Escorpião/toxicidade , Venenos de Escorpião/química , Escorpiões , Brasil , Lipidômica , LipídeosRESUMO
Two new glycerolipids, syngaculipids A and B (1 and 2), one first naturally occurring metabolite (8), together with five known compounds (3-7) were isolated from the AcOEt fraction of Syngnathus acus L. (Hai-Long). Their structures were elucidated by comprehensive spectral analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. All the isolated compounds were evaluated for their cytotoxicity against A549 and HCT-116â cell lines. Compound 8 exhibited moderate cytotoxicity with IC50 values of 34.5 and 38.9â µM on the A549 and HCT-116â cell lines, respectively.
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Medicina Tradicional Chinesa , Humanos , Estrutura Molecular , Células HCT116RESUMO
Glycerol-3-phosphate acyltransferase GPAT9 catalyzes the first acylation of glycerol-3-phosphate (G3P), a committed step of glycerolipid synthesis in Arabidopsis. The role of GPAT9 in Brassica napus remains to be elucidated. Here, we identified four orthologs of GPAT9 and found that BnaGPAT9 encoded by BnaC01T0014600WE is a predominant isoform and promotes seed oil accumulation and eukaryotic galactolipid synthesis in Brassica napus. BnaGPAT9 is highly expressed in developing seeds and is localized in the endoplasmic reticulum (ER). Ectopic expression of BnaGPAT9 in E. coli and siliques of Brassica napus enhanced phosphatidic acid (PA) production. Overexpression of BnaGPAT9 enhanced seed oil accumulation resulting from increased 18:2-fatty acid. Lipid profiling in developing seeds showed that overexpression of BnaGPAT9 led to decreased phosphatidylcholine (PC) and a corresponding increase in phosphatidylethanolamine (PE), implying that BnaGPAT9 promotes PC flux to storage triacylglycerol (TAG). Furthermore, overexpression of BnaGPAT9 also enhanced eukaryotic galactolipids including monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), with increased 36:6-MGDG and 36:6-DGDG, and decreased 34:6-MGDG in developing seeds. Collectively, these results suggest that ER-localized BnaGPAT9 promotes PA production, thereby enhancing seed oil accumulation and eukaryotic galactolipid biosynthesis in Brassica napus.
Assuntos
Arabidopsis , Brassica napus , Brassica napus/genética , Brassica napus/metabolismo , Galactolipídeos/metabolismo , Glicerol/metabolismo , Escherichia coli/metabolismo , Glicerol-3-Fosfato O-Aciltransferase/genética , Glicerol-3-Fosfato O-Aciltransferase/metabolismo , Sementes/genética , Sementes/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Ácidos Fosfatídicos/metabolismo , Óleos de Plantas/metabolismo , Fosfatos/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Glycerol is a symmetrical, small biomolecule with high flexibility in molecular conformations. Using a 1H-NMR spectroscopic Karplus analysis in our way, we analyzed a rotational isomerism in the glycero backbone which generates three kinds of staggered conformers, namely gt (gauche-trans), gg (gauche-gauche), and tg (trans-gauche), at each of sn-1,2 and sn-2,3 positions. The Karplus analysis has disclosed that the three rotamers are consistently equilibrated in water keeping the relation of 'gt:gg:tg = 50:30:20 (%)' at a wide range of concentrations (5 mM~540 mM). The observed relation means that glycerol in water favors those symmetric conformers placing 1,2,3-triol groups in a gauche/gauche geometry. We have found also that the rotational isomerism is remarkably changed when the solvent is replaced with DMSO-d6 or dimethylformamide (DMF-d7). In these solvents, glycerol gives a relation of 'gt:gg:tg = 40:30:30 (%)', which means that a remarkable shift occurs in the equilibrium between gt and tg conformers. By this shift, glycerol turns to also take non-symmetric conformers orienting one of the two vicinal diols in an antiperiplanar geometry.
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Glicerol , Água , Solventes/química , Glicerol/química , Isomerismo , Espectroscopia de Prótons por Ressonância Magnética , Conformação MolecularRESUMO
In-depth structural characterization of lipids is an essential component of lipidomics. There has been a rapid expansion of mass spectrometry methods that are capable of resolving lipid isomers at various structural levels over the past decade. These developments finally make deep-lipidotyping possible, which provides new means to study lipid metabolism and discover new lipid biomarkers. In this review, we discuss recent advancements in tandem mass spectrometry (MS/MS) methods for identification of complex lipids beyond the species (known headgroup information) and molecular species (known chain composition) levels. These include identification at the levels of carbon-carbon double bond (C=C) location and sn-position, as well as characterization of acyl chain modifications. We also discuss the integration of isomer-resolving MS/MS methods with different lipid analysis workflows and their applications in lipidomics. The results showcase the distinct capabilities of deep-lipidotyping in untangling the metabolism of individual isomers and sensitive phenotyping by using relative fractional quantitation of the isomers.
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Lipidômica , Espectrometria de Massas em Tandem , Carbono , Isomerismo , Lipídeos/química , Espectrometria de Massas em Tandem/métodosRESUMO
Unsymmetric lipophilic polyamine derivatives are considered as potential antitumor agents. Here, a series of novel symmetric lipophilic polyamines (LPAs) based on norspermine and triethylenetetramine (TETA) backbones bearing alkyl substituents with different lengths (from decyl to octadecyl) at C(1) atom of glycerol were synthesized. Performed screening of the cytotoxicity of novel compounds on the panel of tumor cell lines (MCF-7, KB-3-1, B16) and non-malignant fibroblasts hFF3 in vitro revealed a correlation between the length of the aliphatic moieties in LPAs and their toxic effects - LPAs with the shortest decyl substituent were found to exhibit the highest cytotoxicity. Furthermore, norspermine-based LPAs displayed somewhat more pronounced cytotoxicity compared with their TETA-based counterparts. Further mechanistic studies demonstrated that hit LPAs containing the norspermine backbone and tetradecyl or decyl substituents efficiently induced apoptosis in KB-3-1 cells. Moreover, decyl-bearing LPA inhibited motility and enhanced adhesiveness of murine B16 melanoma cells in vitro, showing promising antimetastatic potential. Thus, developed novel symmetric norspermine-based LPAs can be considered as promising anticancer chemotherapeutic candidates.
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Poliaminas , Animais , Camundongos , Poliaminas/farmacologiaRESUMO
Fatty acid-derived volatile organic compounds (FA-VOCs) make significant contributions to tomato (Solanum lycopersicum) fruit flavor and human preferences. Short-chain FA-VOCs (C5 and C6) are among the most abundant and important volatile compounds in tomato fruits. The precursors of these volatiles, linoleic acid (18:2) and linolenic acid (18:3), are derived from cleavage of glycerolipids. However, the initial step in synthesis of these FA-VOCs has not been established. A metabolite-based genome-wide association study combined with genetic mapping and functional analysis identified a gene encoding a novel class III lipase family member, Sl-LIP8, that is associated with accumulation of short-chain FA-VOCs in tomato fruit. In vitro assays indicated that Sl-LIP8 can cleave 18:2 and 18:3 acyl groups from glycerolipids. A CRISPR/Cas9 gene edited Sl-LIP8 mutant had much lower content of multiple fruit short-chain FA-VOCs, validating an important role for this enzyme in the pathway. Sl-LIP8 RNA abundance was correlated with FA-VOC content, consistent with transcriptional regulation of the first step in the pathway. Taken together, our work indicates that glycerolipid turnover by Sl-LIP8 is an important early step in the synthesis of multiple short-chain FA-VOCs.
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Frutas/metabolismo , Lipase/metabolismo , Solanum lycopersicum/metabolismo , Ácidos Graxos/metabolismo , Frutas/genética , Estudo de Associação Genômica Ampla , Hexanóis/metabolismo , Lipase/genética , Solanum lycopersicum/genéticaRESUMO
Arctic warming associated with global climate change poses a significant threat to populations of wildlife in the Arctic. Since lipids play a vital role in adaptation of organisms to variations in temperature, high-resolution mass-spectrometry-based lipidomics can provide insights into adaptive responses of organisms to a warmer environment in the Arctic and help to illustrate potential novel roles of lipids in the process of thermal adaption. In this study, we studied an ecologically and economically important species-Arctic char (Salvelinus alpinus)-with a detailed multi-tissue analysis of the lipidome in response to chronic shifts in temperature using a validated lipidomics workflow. In addition, dynamic alterations in the hepatic lipidome during the time course of shifts in temperature were also characterized. Our results showed that early life stages of Arctic char were more susceptible to variations in temperature. One-year-old Arctic char responded to chronic increases in temperature with coordinated regulation of lipids, including headgroup-specific remodeling of acyl chains in glycerophospholipids (GP) and extensive alterations in composition of lipids in membranes, such as less lyso-GPs, and more ether-GPs and sphingomyelin. Glycerolipids (e.g., triacylglycerol, TG) also participated in adaptive responses of the lipidome of Arctic char. Eight-week-old Arctic char exhibited rapid adaptive alterations of the hepatic lipidome to stepwise decreases in temperature while showing blunted responses to gradual increases in temperature, implying an inability to adapt rapidly to warmer environments. Three common phosphatidylethanolamines (PEs) (PE 36:6|PE 16:1_20:5, PE 38:7|PE 16:1_22:6, and PE 40:7|PE 18:1_22:6) were finally identified as candidate lipid biomarkers for temperature shifts via machine learning approach. Overall, this work provides additional information to a better understanding of underlying regulatory mechanisms of the lipidome of Arctic organisms in the face of near-future warming.
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Lipidômica , Truta , Animais , Regiões Árticas , Mudança Climática , TemperaturaRESUMO
BACKGROUND: Developing an understanding of the biochemistry of aging in both sexes is critical for managing disease throughout the lifespan. Lipidomic associations with age and sex have been reported, but prior studies are limited by measurements in serum rather than plasma or by participants taking lipid-lowering medications. METHODS: Our study included lipidomic data from 980 participants aged 18-87 years old from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN). Participants were off lipid-lowering medications for at least 4 weeks, and signal intensities of 413 known lipid species were measured in plasma. We examined linear age and sex associations with signal intensity of (a) 413 lipid species; (b) 6 lipid classes (glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, fatty acids, and acylcarnitines); and (c) 15 lipid subclasses; as well as with the particle sizes of three lipoproteins. RESULTS: Significant age associations were identified in 4 classes, 11 subclasses, 147 species, and particle size of one lipoprotein while significant sex differences were identified in 5 classes, 12 subclasses, 248 species, and particle sizes of two lipoproteins. For many lipid species (n = 97), age-related associations were significantly different between males and females. Age*sex interaction effects were most prevalent among phosphatidylcholines, sphingomyelins, and triglycerides. CONCLUSION: We identified several lipid species, subclasses, and classes that differ by age and sex; these lipid phenotypes may serve as useful biomarkers for lipid changes and associated cardiovascular risk with aging in the future. Future studies of age-related changes throughout the adult lifespan of both sexes are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00083369 ; May 21, 2004.
Assuntos
Lipidômica , Lipídeos/sangue , Caracteres Sexuais , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Lipídeos/classificação , Lipoproteínas/química , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Adulto JovemRESUMO
Algae have evolved several mechanisms to adjust to changing environmental conditions. To separate from their surroundings, algal cell membranes form a hydrophobic barrier that is critical for life. Thus, it is important to maintain or adjust the physical and biochemical properties of cell membranes which are exposed to environmental factors. Especially glycerolipids of thylakoid membranes, the site of photosynthesis and photoprotection within chloroplasts, are affected by different light conditions. Since little is known about membrane lipid remodeling upon different light treatments, we examined light induced alterations in the glycerolipid composition of the two Chlorella species, C. vulgaris and C. sorokiniana, which differ strongly in their ability to cope with different light intensities. Lipidomic analysis and isotopic labeling experiments revealed differences in the composition of their galactolipid species, although both species likely utilize galactolipid precursors originated from the endoplasmic reticulum. However, in silico research of de novo sequenced genomes and ortholog mapping of proteins putatively involved in lipid metabolism showed largely conserved lipid biosynthesis pathways suggesting species specific lipid remodeling mechanisms, which possibly have an impact on the response to different light conditions.
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Luz , Lipídeos de Membrana/metabolismo , Chlorella/efeitos da radiação , Metabolismo dos Lipídeos/efeitos da radiação , Oxigênio/metabolismo , Filogenia , RNA Ribossômico 18S/genéticaRESUMO
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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Envelhecimento/genética , Lobo Frontal/metabolismo , Lipídeos/genética , Metionina/metabolismo , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Cerebelo/metabolismo , Cerebelo/patologia , Cromatografia , Lobo Frontal/patologia , Humanos , Lipidômica/normas , Espectrometria de Massas , Estresse Oxidativo/genética , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.
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Lipídeos/química , Espectrometria de Massas , Terminologia como AssuntoRESUMO
The prevalence of food allergy is raising in industrialized countries, but the mechanisms behind this increased incidence are not fully understood. Environmental factors are believed to play a role in allergic diseases, including lifestyle influences, such as diet. There is a close relationship between allergens and lipids, with many allergenic proteins having the ability to bind lipids. Dietary lipids exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to cells of the adaptive immunity. In addition to modifying the immunostimulating properties of proteins, lipids also alter their digestibility and intestinal absorption, changing allergen bioavailability. This study provides an overview of the role of dietary lipids in food allergy, taking into account epidemiological information, as well as results of mechanistic investigations using in vivo, ex vivo and in vitro models. The emerging link among high-fat diets, obesity, and allergy is also discussed.
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Gorduras na Dieta , Hipersensibilidade Alimentar , Alérgenos/química , Humanos , Lipídeos/química , ObesidadeRESUMO
Considering the emergence of multidrug resistance (MDR) in prevalent human pathogen, Mycobacterium tuberculosis (MTB), there is parallel spurt in development of novel strategies aimed to disrupt MDR. The cell envelope of MTB comprises a wealth of lipid moieties contributing towards long-term survival of pathogen that could be exploited as efficient antitubercular target owing to advancements made in mass spectrometry-based lipidomics technology. This study aimed to utilize the lipidomics approach to unveil several lipid associated changes in response to natural antimycobacterial compound vanillin (Van) in Mycobacterium smegmatis, a surrogate for MTB. Lipidomic analyses revealed that that Van alters the composition of fatty acid (FA), glycerolipid (GL), glycerophospholipid (GP), and saccharolipids (SL). Furthermore, Van leads to potentiation of ampicillin and displayed additive effect. The differential expressions of various lipid biosynthetic pathway genes by RT-PCR corroborated with the lipidomics data. Lastly, we demonstrated enhanced survival of Mycobacterium-infected Caenorhabditis elegans model in presence of Van. Thus, lipidomics approach provided detailed insight into mechanisms of membrane disruption by Van in Mycobacterium smegmatis. Our work offers the basis of further understanding the regulation of lipid homeostasis in MTB so that better therapeutic targets could be identified to combat MDR.
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Benzaldeídos/farmacologia , Membrana Celular/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Mycobacterium smegmatis/efeitos dos fármacos , Antituberculosos/farmacologia , Proteínas de Bactérias/efeitos dos fármacos , Parede Celular/química , Parede Celular/efeitos dos fármacos , Ácidos Graxos/metabolismo , Glicerofosfolipídeos/metabolismo , Glicolipídeos/metabolismo , Humanos , Lipidômica/métodos , Mycobacterium tuberculosis/efeitos dos fármacosRESUMO
Most phospholipids constituting biological membranes are chiral molecules with a hydrophilic head group and hydrophobic alkyl chains, rendering biphasic property characteristic of membrane lipids. Some lipids assemble into small domains via chirality-dependent homophilic and heterophilic interactions, the latter of which sometimes include cholesterol to form lipid rafts and other microdomains. On the other hand, lipid mediators and hormones derived from chiral lipids are recognized by specific membrane or nuclear receptors to induce downstream signaling. It is crucial to clarify the physicochemical properties of the lipid self-assembly for the study of the functions and behavior of biological membranes, which often become elusive due to effects of membrane proteins and other biological events. Three major lipids with different skeletal structures were discussed: sphingolipids including ceramides, phosphoglycerolipids, and cholesterol. The physicochemical properties of membranes and physiological functions of lipid enantiomers and diastereomers were described in comparison to natural lipids. When each enantiomer formed a self-assembly or interacted with achiral lipids, both lipid enantiomers exhibited identical membrane physicochemical properties, while when the enantiomer interacted with chiral lipids or with the opposite enantiomer, mixed membranes exhibited different properties. For example, racemic membranes comprising native sphingomyelin and its antipode exhibited phase segregation due to their strong homophilic interactions. Therefore, lipid enantiomers and diastereomers can be good probes to investigate stereospecific lipid-lipid and lipid-protein interactions occurring in biological membranes.
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Colesterol/química , Lipídeos de Membrana/química , Fosfolipídeos/química , Ceramidas/química , Glicerofosfolipídeos/química , Microdomínios da Membrana , Esfingomielinas/química , Esfingosina/química , Estereoisomerismo , Esteróis/químicaRESUMO
Plastid-localized glycerol-3-phosphate acyltransferase (ATS1) catalyzes the first-step reaction in glycerolipid assembly through transferring an acyl moiety to glycerol-3-phosphate (G3P) to generate lysophosphatidic acid (LPA), an intermediate in lipid metabolism. The effect of ATS1 overexpression on glycerolipid metabolism and growth remained to be elucidated in plants, particularly oil crop plants. Here, we found that overexpression of BnATS1 from Brassica napus enhanced plant growth and prokaryotic glycerolipid biosynthesis. BnATS1 is localized in chloroplasts and an in vitro assay showed that BnATS1 had acylation activity toward glycerol 3-phosphate to produce LPA. Lipid profiling showed that overexpression of BnATS1 led to increases in multiple glycerolipids including phosphatidylglycerol (PG), monogalactosyldiacylglycerol (MGDG), phosphatidylcholine (PC), and phosphatidylinositol (PI), with increased polyunsaturated fatty acids. Moreover, increased MGDG was attributed to the elevation of 34:6- and 34:5-MGDG, which were derived from the prokaryotic pathway. These results suggest that BnATS1 promotes accumulation of polyunsaturated fatty acids in cellular membranes, thus enhances plant growth under low-temperature conditions in Brassica napus.