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1.
EMBO J ; 42(6): e112202, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36795015

RESUMO

Lipids play a major role in inflammatory diseases by altering inflammatory cell functions, either through their function as energy substrates or as lipid mediators such as oxylipins. Autophagy, a lysosomal degradation pathway that limits inflammation, is known to impact on lipid availability, however, whether this controls inflammation remains unexplored. We found that upon intestinal inflammation visceral adipocytes upregulate autophagy and that adipocyte-specific loss of the autophagy gene Atg7 exacerbates inflammation. While autophagy decreased lipolytic release of free fatty acids, loss of the major lipolytic enzyme Pnpla2/Atgl in adipocytes did not alter intestinal inflammation, ruling out free fatty acids as anti-inflammatory energy substrates. Instead, Atg7-deficient adipose tissues exhibited an oxylipin imbalance, driven through an NRF2-mediated upregulation of Ephx1. This shift reduced secretion of IL-10 from adipose tissues, which was dependent on the cytochrome P450-EPHX pathway, and lowered circulating levels of IL-10 to exacerbate intestinal inflammation. These results suggest an underappreciated fat-gut crosstalk through an autophagy-dependent regulation of anti-inflammatory oxylipins via the cytochrome P450-EPHX pathway, indicating a protective effect of adipose tissues for distant inflammation.


Assuntos
Ácidos Graxos não Esterificados , Oxilipinas , Humanos , Adipócitos/metabolismo , Autofagia/fisiologia , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/farmacologia , Ácidos Graxos não Esterificados/metabolismo , Ácidos Graxos não Esterificados/farmacologia , Inflamação/genética , Inflamação/metabolismo , Interleucina-10/genética , Oxilipinas/metabolismo
2.
Molecules ; 26(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064018

RESUMO

Recent studies have implicated synucleins in several reactions during the biosynthesis of lipids and fatty acids in addition to their recognised role in membrane lipid binding and synaptic functions. These are among aspects of decreased synuclein functions that are still poorly acknowledged especially in regard to pathogenesis in Parkinson's disease. Here, we aimed to add to existing knowledge of synuclein deficiency (i.e., the lack of all three family members), with respect to changes in fatty acids and lipids in plasma, liver, and two brain regions in triple synuclein-knockout (TKO) mice. We describe changes of long-chain polyunsaturated fatty acids (LCPUFA) and palmitic acid in liver and plasma, reduced triacylglycerol (TAG) accumulation in liver and non-esterified fatty acids in plasma of synuclein free mice. In midbrain, we observed counterbalanced changes in the relative concentrations of phosphatidylcholine (PC) and cerebrosides (CER). We also recorded a notable reduction in ethanolamine plasmalogens in the midbrain of synuclein free mice, which is an important finding since the abnormal ether lipid metabolism usually associated with neurological disorders. In summary, our data demonstrates that synuclein deficiency results in alterations of the PUFA synthesis, storage lipid accumulation in the liver, and the reduction of plasmalogens and CER, those polar lipids which are principal compounds of lipid rafts in many tissues. An ablation of all three synuclein family members causes more profound changes in lipid metabolism than changes previously shown to be associated with γ-synuclein deficiency alone. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed.


Assuntos
Metabolismo dos Lipídeos , Sinucleínas/genética , Animais , Encéfalo/metabolismo , Ácidos Graxos/metabolismo , Lipídeos/sangue , Fígado/metabolismo , Camundongos , Camundongos Knockout
3.
New Phytol ; 224(2): 700-711, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400160

RESUMO

Lysophosphatidate acyltransferase (LPAAT) catalyses the second step of the Kennedy pathway for triacylglycerol (TAG) synthesis. In this study we expressed Trapaeolum majus LPAAT in Brassica napus (B. napus) cv 12075 to evaluate the effects on lipid synthesis and estimate the flux control coefficient for LPAAT. We estimated the flux control coefficient of LPAAT in a whole plant context by deriving a relationship between it and overall lipid accumulation, given that this process is a exponential. Increasing LPAAT activity resulted in greater TAG accumulation in seeds of between 25% and 29%; altered fatty acid distributions in seed lipids (particularly those of the Kennedy pathway); and a redistribution of label from 14 C-glycerol between phosphoglycerides. Greater LPAAT activity in seeds led to an increase in TAG content despite its low intrinsic flux control coefficient on account of the exponential nature of lipid accumulation that amplifies the effect of the small flux increment achieved by increasing its activity. We have also developed a novel application of metabolic control analysis likely to have broad application as it determines the in planta flux control that a single component has upon accumulation of storage products.


Assuntos
Aciltransferases/metabolismo , Brassica napus/enzimologia , Sementes/química , Triglicerídeos/metabolismo , Aciltransferases/genética , Brassica napus/metabolismo , DNA de Plantas , Regulação Enzimológica da Expressão Gênica/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Plantas Geneticamente Modificadas , Triglicerídeos/química , Tropaeolum/enzimologia , Tropaeolum/genética
4.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1863(3): 339-348, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29275220

RESUMO

With dwindling available agricultural land, concurrent with increased demand for oil, there is much current interest in raising oil crop productivity. We have been addressing this issue by studying the regulation of oil accumulation in oilseed rape (Brassica napus L). As part of this research we have carried out a detailed lipidomic analysis of developing seeds. The molecular species distribution in individual lipid classes revealed quite distinct patterns and showed where metabolic connections were important. As the seeds developed, the molecular species distributions changed, especially in the period of early (20days after flowering, DAF) to mid phase (27DAF) of oil accumulation. The patterns of molecular species of diacylglycerol, phosphatidylcholine and acyl-CoAs were used to predict the possible relative contributions of diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase to triacylglycerol production. Our calculations suggest that DGAT may hold a more important role in influencing the molecular composition of TAG. Enzyme selectivity had an important influence on the final molecular species patterns. Our data contribute significantly to our understanding of lipid accumulation in the world's third most important oil crop.


Assuntos
Brassica napus/metabolismo , Metabolismo dos Lipídeos/fisiologia , Sementes/crescimento & desenvolvimento , Brassica napus/genética , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Sementes/genética
5.
Plant Physiol ; 173(4): 1998-2009, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28188274

RESUMO

The regulation of lipid synthesis in oil seeds is still not fully understood. Oilseed rape (Brassica napus) is the third most productive vegetable oil crop on the global market; therefore, increasing our understanding of lipid accumulation in oilseed rape seeds is of great economic, as well as intellectual, importance. Matrix-assisted laser/desorption ionization-mass spectrometry imaging (MALDI-MSI) is a technique that allows the mapping of metabolites directly onto intact biological tissues, giving a spatial context to metabolism. We have used MALDI-MSI to study the spatial distribution of two major lipid species, triacylglycerols and phosphatidylcholines. A dramatic, heterogenous landscape of molecular species was revealed, demonstrating significantly different lipid compositions between the various tissue types within the seed. The embryonic axis was found to be particularly enriched in palmitic acid, while the seed coat/aleurone layer accumulated vaccenic, linoleic, and α-linoleic acids. Furthermore, the lipid composition of the inner and outer cotyledons differed from each other, a remarkable discovery given the supposed identical functionality of these two tissues. Triacylglycerol and phosphatidylcholine molecular species distribution was analyzed through a developmental time series covering early seed lipid accumulation to seed maturity. The spatial patterning of lipid molecular species did not vary significantly during seed development. Data gathered using MALDI-MSI was verified through gas chromatography analysis of dissected seeds. The distinct lipid distribution profiles observed imply differential regulation of lipid metabolism between the different tissue types of the seed. Further understanding of this differential regulation will enhance efforts to improve oilseed rape productivity and quality.


Assuntos
Brassica napus/metabolismo , Lipídeos/biossíntese , Óleos de Plantas/metabolismo , Sementes/metabolismo , Análise Espaço-Temporal , Cromatografia Gasosa , Cotilédone/metabolismo , Ácido Linoleico/análise , Lipídeos/química , Espectroscopia de Ressonância Magnética , Ácidos Oleicos/análise , Ácido Palmítico/análise , Fosfatidilcolinas/biossíntese , Fosfatidilcolinas/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fatores de Tempo , Triglicerídeos/biossíntese , Triglicerídeos/química
6.
Biochim Biophys Acta ; 1861(6): 524-37, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26968097

RESUMO

Alzheimer's disease (AD) is of major concern in ageing populations and we have used the Tg2576 mouse model to understand connections between brain lipids and amyloid pathology. Because dietary docosahexaenoic acid (DHA) has been identified as beneficial, we compared mice fed with a DHA-supplemented diet to those on a nutritionally-sufficient diet. Major phospholipids from cortex, hippocampus and cerebellum were separated and analysed. Each phosphoglyceride had a characteristic fatty acid composition which was similar in cortex and hippocampus but different in the cerebellum. The biggest changes on DHA-supplementation were within ethanolamine phospholipids which, together with phosphatidylserine, had the highest proportions of DHA. Reciprocal alterations in DHA and arachidonate were found. The main diet-induced alterations were found in ethanolamine phospholipids, (and included their ether derivatives), as were the changes observed due to genotype. Tg mice appeared more sensitive to diet with generally lower DHA percentages when on the standard diet and higher relative proportions of DHA when the diet was supplemented. All four major phosphoglycerides analysed showed age-dependent decreases in polyunsaturated fatty acid contents. These data provide, for the first time, a detailed evaluation of phospholipids in different brain areas previously shown to be relevant to behaviour in the Tg2576 mouse model for AD. The lipid changes observed with genotype are consistent with the subtle alterations found in AD patients, especially for the ethanolamine phospholipid molecular species. They also emphasise the contrasting changes in fatty acid content induced by DHA supplementation within individual phospholipid classes.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Fosfolipídeos/metabolismo , Doença de Alzheimer/genética , Animais , Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos/metabolismo , Glicerofosfolipídeos/metabolismo , Hipocampo/metabolismo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos Transgênicos , Fosfatidiletanolaminas/metabolismo , Fosfatidilserinas/metabolismo , Espectrometria de Massas em Tandem/métodos
7.
Biochim Biophys Acta ; 1838(6): 1488-500, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24565795

RESUMO

Although there is much knowledge of the enzymology (and genes coding the proteins) of lipid biosynthesis in higher plants, relatively little attention has been paid to regulation. We have demonstrated the important role for cholinephosphate cytidylyltransferase in the biosynthesis of the major extra-plastidic membrane lipid, phosphatidylcholine. We followed this work by applying control analysis to light-induced fatty acid synthesis. This was the first such application to lipid synthesis in any organism. The data showed that acetyl-CoA carboxylase was very important, exerting about half of the total control. We then applied metabolic control analysis to lipid accumulation in important oil crops - oilpalm, olive, and rapeseed. Recent data with soybean show that the block of fatty acid biosynthesis reactions exerts somewhat more control (63%) than lipid assembly although both are clearly very important. These results suggest that gene stacks, targeting both parts of the overall lipid synthesis pathway will be needed to increase significantly oil yields in soybean. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.


Assuntos
Regulação da Expressão Gênica de Plantas , Glycine max/metabolismo , Metabolismo dos Lipídeos , Lipídeos/biossíntese
8.
Proc Natl Acad Sci U S A ; 109(51): 20943-8, 2012 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-23213245

RESUMO

Synucleins are a family of homologous proteins principally known for their involvement in neurodegeneration. γ-Synuclein is highly expressed in human white adipose tissue and increased in obesity. Here we show that γ-synuclein is nutritionally regulated in white adipose tissue whereas its loss partially protects mice from high-fat diet (HFD)-induced obesity and ameliorates some of the associated metabolic complications. Compared with HFD-fed WT mice, HFD-fed γ-synuclein-null mutant mice display increased lipolysis, lipid oxidation, and energy expenditure, and reduced adipocyte hypertrophy. Knockdown of γ-synuclein in adipocytes causes redistribution of the key lipolytic enzyme ATGL to lipid droplets and increases lipolysis. γ-Synuclein-deficient adipocytes also contain fewer SNARE complexes of a type involved in lipid droplet fusion. We hypothesize that γ-synuclein may deliver SNAP-23 to the SNARE complexes under lipogenic conditions. Via these independent but complementary roles, γ-synuclein may coordinately modulate lipid storage by influencing lipolysis and lipid droplet formation. Our data reveal γ-synuclein as a regulator of lipid handling in adipocytes, the function of which is particularly important in conditions of nutrient excess.


Assuntos
Tecido Adiposo/metabolismo , Lipólise , Obesidade/metabolismo , Células 3T3 , Adipócitos/citologia , Animais , Dieta , Genótipo , Lipídeos/química , Lipogênese , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Biológicos , gama-Sinucleína
9.
J Lipid Res ; 55(10): 2064-72, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25121984

RESUMO

Lipoprotein-apheresis (apheresis) removes LDL-cholesterol in patients with severe dyslipidemia. However, reduction is transient, indicating that the long-term cardiovascular benefits of apheresis may not solely be due to LDL removal. Microparticles (MPs) are submicron vesicles released from the plasma membrane of cells. MPs, particularly platelet-derived MPs, are increasingly being linked to the pathogenesis of many diseases. We aimed to characterize the effect of apheresis on MP size, concentration, cellular origin, and fatty acid concentration in individuals with familial hypercholesterolemia (FH). Plasma and MP samples were collected from 12 individuals with FH undergoing routine apheresis. Tunable resistive pulse sensing (np200) and nanoparticle tracking analysis measured a fall in MP concentration (33 and 15%, respectively; P < 0.05) pre- to post-apheresis. Flow cytometry showed MPs were predominantly annexin V positive and of platelet (CD41) origin both pre- (88.9%) and post-apheresis (88.4%). Fatty acid composition of MPs differed from that of plasma, though apheresis affected a similar profile of fatty acids in both compartments, as measured by GC-flame ionization detection. MP concentration was also shown to positively correlate with thrombin generation potential. In conclusion, we show apheresis nonselectively removes annexin V-positive platelet-derived MPs in individuals with FH. These MPs are potent inducers of coagulation and are elevated in CVD; this reduction in pathological MPs could relate to the long-term benefits of apheresis.


Assuntos
Remoção de Componentes Sanguíneos , Micropartículas Derivadas de Células/metabolismo , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/terapia , Idoso , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade
10.
Hum Mol Genet ; 21(22): 4836-44, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22869679

RESUMO

The interrelationship between brown adipose tissue (BAT) and white adipose tissue (WAT) is emerging as an important factor in obesity, but the effect of impairing non-shivering thermogenesis in BAT on lipid storage in WAT remains unclear. To address this, we have characterized the metabolic phenotype of a mouse model for Costeff syndrome, in which a point mutation in the mitochondrial membrane protein Opa3 impairs mitochondrial activity. Opa3(L122P) mice displayed an 80% reduction in insulin-like growth factor 1, postnatal growth retardation and hepatic steatosis. A 90% reduction in uncoupling protein 1 (UCP1) expression in interscapular BAT was accompanied by a marked reduction in surface body temperature, with a 2.5-fold elevation in interscapular BAT mass and lipid storage. The sequestration of circulating lipid into BAT resulted in profound reductions in epididymal and retroperitoneal WAT mass, without affecting subcutaneous WAT. The histological appearance and intense mitochondrial staining in intra-abdominal WAT suggest significant 'browning', but with UCP1 expression in WAT of Opa3(L122P) mice only 62% of that in wild-type littermates, any precursor differentiation does not appear to result in thermogenically active beige adipocytes. Thus, we have identified Opa3 as a novel regulator of lipid metabolism, coupling lipid uptake with lipid processing in liver and with thermogenesis in BAT. These findings indicate that skeletal and metabolic impairment in Costeff syndrome may be more significant than previously thought and that uncoupling lipid uptake from lipid metabolism in BAT may represent a novel approach to controlling WAT mass in obesity.


Assuntos
Gordura Abdominal/metabolismo , Adiposidade/genética , Síndrome de Costello/genética , Síndrome de Costello/metabolismo , Mitocôndrias/metabolismo , Proteínas/genética , Termogênese/genética , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Animais , Síndrome de Costello/sangue , Modelos Animais de Doenças , Feminino , Genótipo , Metabolismo dos Lipídeos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Knockout , Fenótipo , Proteínas/metabolismo
11.
Am J Pathol ; 179(4): 1601-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21816131

RESUMO

Atherosclerosis, the leading cause of death in the Western world, is driven by chronic inflammation within the artery wall. Elements of the complement cascade are implicated in the pathogenesis, because complement proteins and their activation products are found in the atherosclerotic plaque. We examined the role of CD55, a membrane inhibitor of the complement component 3 (C3) convertase, which converts C3 into C3a and C3b, in atherosclerosis. CD55-deficient (CD55(-/-)) mice were crossed onto the atherosclerosis-prone apolipoprotein E (apoE)-deficient (apoE(-/-)) background. High fat-fed male apoE(-/-)/CD55(-/-) mice were strongly protected from developing atherosclerosis compared with apoE(-/-) controls. Lipid profiling showed significantly lower levels of triglycerides, nonesterified fatty acids, and cholesterol in apoE(-/-)/CD55(-/-) mice than that in controls after high-fat feeding, whereas body fat in apoE(-/-)/CD55(-/-) mice content was increased. Plasma levels of C3 fell, whereas concentrations of C3adesArg (alias acylation stimulating protein; ASP), produced by serum carboxypeptidase N-mediated desargination of C3a, increased in nonfasted high fat-fed apoE(-/-)/CD55(-/-) mice, indicating complement activation. Thus, complement dysregulation in the absence of CD55 provoked increased C3adesArg production that, in turn, caused altered lipid handling, resulting in atheroprotection and increased adiposity. Interventions that target complement activation in adipose tissue should be explored as lipid-decreasing strategies.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Antígenos CD55/metabolismo , Complemento C3a/metabolismo , Metabolismo dos Lipídeos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adiposidade , Animais , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Aterosclerose/patologia , Colesterol/sangue , Camundongos , Triglicerídeos/sangue
12.
New Phytol ; 196(2): 414-426, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22901003

RESUMO

Metabolic control analysis allows the study of metabolic regulation. We applied both single- and double-manipulation top-down control analysis to examine the control of lipid accumulation in developing oilseed rape (Brassica napus) embryos. The biosynthetic pathway was conceptually divided into two blocks of reactions (fatty acid biosynthesis (Block A), lipid assembly (Block B)) connected by a single system intermediate, the acyl-coenzyme A (acyl-CoA) pool. Single manipulation used exogenous oleate. Triclosan was used to inhibit specifically Block A, whereas diazepam selectively manipulated flux through Block B. Exogenous oleate inhibited the radiolabelling of fatty acids from [1-(14)C]acetate, but stimulated that from [U-14C]glycerol into acyl lipids. The calculation of group flux control coefficients showed that c. 70% of the metabolic control was in the lipid assembly block of reactions. Monte Carlo simulations gave an estimation of the error of the resulting group flux control coefficients as 0.27±0.06 for Block A and 0.73±0.06 for Block B. The two methods of control analysis gave very similar results and showed that Block B reactions were more important under our conditions. This contrasts notably with data from oil palm or olive fruit cultures and is important for efforts to increase oilseed rape lipid yields.


Assuntos
Brassica napus/embriologia , Brassica napus/metabolismo , Lipídeos/biossíntese , Metabolômica/métodos , Óleos de Plantas/metabolismo , Sementes/metabolismo , Acil Coenzima A/metabolismo , Brassica napus/efeitos dos fármacos , Radioisótopos de Carbono , Diazepam/farmacologia , Ácidos Graxos Monoinsaturados , Lipídeos/classificação , Ácido Oleico/farmacologia , Óleo de Brassica napus , Sementes/efeitos dos fármacos , Fatores de Tempo , Triclosan/farmacologia
13.
J Chromatogr A ; 1676: 463267, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35767906

RESUMO

Phosphatidylglycerol (1,2-diacyl-sn-glycero-3-phospho-glycerol) (PG) is one of the most abundant lipids in bacteria. However, the chirality of the carbon atom on glycerol phosphate is different between the three kingdoms, Archaea, Bacteria, and Eukarya. Archaea membranes consist of phospholipids with glycerol-1-phosphate (G1P) in the S configuration, whereas phospholipids of the other two kingdoms contain glycerol-3-phosphate (G3P) having R stereochemistry. In the present study, GC/MS and LC/MS methods sensitively detected G3P and G1P from four bacterial strains (Bacillus amyloliquefaciens, B. subtilis, Clavibacter michiganensis, and Geobacillus stearothermophilus). Strain selection was carried out based on a GenBank search that revealed bacterial sequences associated with both enzymes involved in glycerol-phosphate synthesis, i.e., glycerol-3-phosphate dehydrogenase and glycerol-1-phosphate dehydrogenase. The detection of G1P and G3P was made by comparing the retention times of synthetic standards with those of analyzed samples. The structures of both glycerol phosphates were confirmed by selected ion monitoring (SIM) at m/z 171.006. The total concentration of G3P and G1P was around 30 µM, with a ratio of G3P to G1P of 4:1. We showed that PG was the most abundant phospholipid in all four bacteria by using the following analytical techniques and chromatographic modes: hydrophilic interaction liquid chromatography (HILIC), reversed-phase high-performance liquid chromatography high-resolution electrospray ionization tandem mass spectrometry (RP-HPLC/HR-ESI tandem MS) in negative and positive ionization modes, and an enzymatic cleavage by phospholipase C. By using chiral chromatography, the presence of both enantiomers in the glycerol backbone of some molecular species of PG was revealed. These results allow us to conclude that the bacteria examined here produce both enantiomer glycerol phosphates.


Assuntos
Glicerol , Fosfolipídeos , Bactérias , Cromatografia Líquida , Fosfatos , Fosfatidilgliceróis , Fosfolipídeos/química
14.
Environ Pollut ; 263(Pt B): 114425, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32229374

RESUMO

Despite growing concern about the occurrence of microplastics in aquatic ecosystems there is only rudimentary understanding of the pathways through which any adverse effects might occur. Here, we assess the effects of polystyrene microplastics (PS-MPs; <70 µm) on a common and widespread algal species, Chlorella sorokiniana. We used laboratory exposure to test the hypothesis that the lipids and fatty acids (FAs) are important molecules in the response reactions of algae to this pollutant. Cultivation with PS-MPs systematically reduced the concentration of essential linoleic acid (ALA, C18:3n-3) in C. sorokiniana, concomitantly increasing oleic acid (C18:1n-9). Among the storage triacylglycerols, palmitoleic and oleic acids increased at the expenses of two essential fatty acids, linoleic (LIN, C18:2n-6) and ALA, while PS-MPs had even more pronounced effects on the fatty acid and hydrocarbon composition of waxes and steryl esters. The FA composition of two major chloroplast galactolipids, monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), were affected implying changes in the conformational structure of photosynthetic complexes in ways that can impair the photosynthesis. These data reveal how exposure to polystyrene microplastics can modify the concentrations of lipid molecules that are important intrinsically in cell membranes, and hence the lipid bilayers that could form an important barrier between algal cellular compartments and plastics in the aquatic environment. Changes in lipid synthesis and fatty acid composition in algae could also have repercussions for food quality, growth and stressor resistance in primary consumers. We advocate further studies of microplastics effects on the lipid composition of primary producers, and of their potential propagation through aquatic food webs.


Assuntos
Chlorella , Poliestirenos , Ecossistema , Ácidos Graxos , Ácidos Graxos Essenciais , Água Doce , Microplásticos , Plásticos
15.
J Eukaryot Microbiol ; 56(1): 52-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19335774

RESUMO

Previous lipid analysis of trichomonads has led to controversy as to whether these hydrogenosome-containing organisms contain cardiolipin (CL), which is a characteristic component of mitochondria. Here we report a careful lipid analysis of the sexually transmitted protist Trichomonas vaginalis. Major lipids were phosphatidylethanolamine (42%) and phosphatidylcholine (20%) with lesser amounts of phosphatidylglycerol (PG) (12%) and non-polar components. Two unusual lipids, acyl-PG (8%) and ceramide phosphorylethanolamine (2%), were also significant components. The structures of these lipids were confirmed by tandem mass spectrometry following reverse-phase high-performance liquid chromatography. This is the first time ceramide phosphorylethanolamine has been reported in a trichomonad. In contrast, CL (diphosphatidylglycerol) could not be detected either by two-dimensional thin-layer chromatography or by mass spectrometry. These data are discussed in relation to the organism's phylogenetic origin as a parasite showing secondary adaptation to microaerobic conditions.


Assuntos
Cardiolipinas/análise , Lipídeos/análise , Trichomonas vaginalis/química , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Espectrometria de Massas em Tandem
16.
Biochim Biophys Acta Mol Basis Dis ; 1865(9): 2538-2550, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31202985

RESUMO

Atherosclerosis and its complications are responsible for one in three global deaths. Nutraceuticals show promise in the prevention and treatment of atherosclerosis but require an indepth understanding of the mechanisms underlying their actions. A previous study showed that the omega-6 fatty acid, dihomo-γ-linolenic acid (DGLA), attenuated atherosclerosis in the apolipoprotein E deficient mouse model system. However, the mechanisms underlying such protective effects of DGLA are poorly understood and were therefore investigated. We show that DGLA attenuates chemokine-driven monocytic migration together with foam cell formation and the expression of key pro-atherogenic genes induced by three pro-inflammatory cytokines in human macrophages. The effect of DGLA on interferon-γ signaling was mediated via inhibition of signal transducer and activator of transcription-1 phosphorylation on serine 727. In relation to anti-foam cell action, DGLA inhibits modified LDL uptake by both macropinocytosis and receptor-mediated endocytosis, the latter by reduction in expression of two key scavenger receptors (SR-A and CD36), and stimulates cholesterol efflux from foam cells. DGLA also improves macrophage mitochondrial bioenergetic profile by decreasing proton leak. Gamma-linolenic acid and prostaglandin E1, upstream precursor and key metabolite respectively of DGLA, also acted in an anti-atherogenic manner. The actions of DGLA extended to other key atherosclerosis-associated cell types with attenuation of endothelial cell proliferation and migration of smooth muscle cells in response to platelet-derived growth factor. This study provides novel insights into the molecular mechanisms underlying the anti-atherogenic actions of DGLA and supports further assessments on its protective effects on plaque regression in vivo and in human trials.


Assuntos
Ácido 8,11,14-Eicosatrienoico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Citocinas/metabolismo , Células Espumosas/citologia , Células Espumosas/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Monócitos/citologia
17.
J Exp Bot ; 59(9): 2425-35, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18515829

RESUMO

Callus cultures from olive (Olea europaea L.) were used to study characteristics of desaturation in this oil-rich tissue. The incorporation of [1-(14)C]oleate and [1-(14)C]linoleate into complex lipids and their further desaturation was followed in incubations of up to 48 h. Both radiolabelled fatty acids were rapidly incorporated into lipids, especially phosphatidylcholine and triacylglycerol. Radiolabelling of these two lipids peaked after 1-4 h, after which it fell. In contrast, other phosphoglycerides and the galactosylglycerides were labelled in a more sustained manner. [1-(14)C]Linoleate was almost exclusively found in the galactolipids. With [1-(14)C]linoleate as a precursor, the only significant desaturation to linolenate was in the galactolipids. Monogalactosyldiacylglycerol was the first lipid in which [1-(14)C]linoleate and [1-(14)C]linolenate appeared after incubation of the calli with [1-(14)C]oleate and [1-(14)C]linoleate, respectively. The presence of radioactivity in the plastidial lipids shows that both [1-(14)C]oleate and [1-(14)C]linoleate can freely enter the chloroplast. Two important environmental effects were also examined. Raised incubation temperatures (30-35 degrees C) reduced oleate desaturation and this was also reflected in the endogenous fatty acid composition. Low light also caused less oleate desaturation. The data indicate that lysophosphatidylcholine acyltransferase is important for the entry of oleate and linoleate into olive callus lipid metabolism and phospholipid:diacylglycerol acyltransferase may be involved in triacylglycerol biosynthesis. In addition, it is shown that plastid desaturases are mainly responsible for the production of polyunsaturated fatty acids. Individual fatty acid desaturases were differently susceptible to environmental stresses with FAD2 being reduced by both high temperature and low light, whereas FAD7 was only affected by high temperature.


Assuntos
Frutas/metabolismo , Ácido Linoleico/metabolismo , Lipídeos/biossíntese , Olea/metabolismo , Ácidos Oleicos/metabolismo , Radioisótopos de Carbono/metabolismo , Células Cultivadas , Ácidos Graxos Dessaturases/metabolismo , Frutas/química , Luz , Ácido Linoleico/química , Olea/química , Ácidos Oleicos/química , Proteínas de Plantas/metabolismo , Temperatura
18.
Prog Lipid Res ; 45(2): 160-86, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16492482

RESUMO

Eukaryotic algae are a very diverse group of organisms which inhabit a huge range of ecosystems from the Antarctic to deserts. They account for over half the primary productivity at the base of the food chain. In recent years studies on the lipid biochemistry of algae has shifted from experiments with a few model organisms to encompass a much larger number of, often unusual, algae. This has led to the discovery of new compounds, including major membrane components, as well as the elucidation of lipid signalling pathways. A major drive in recent research have been attempts to discover genes that code for expression of the various proteins involved in the production of very long-chain polyunsaturated fatty acids such as arachidonic, eicosapentaenoic and docosahexaenoic acids. Such work is described here together with information about how environmental factors, such as light, temperature or minerals, can change algal lipid metabolism and how adaptation may take place.


Assuntos
Eucariotos/metabolismo , Metabolismo dos Lipídeos/fisiologia , Adaptação Fisiológica , Animais , Chlamydomonas reinhardtii/metabolismo , Meio Ambiente , Células Eucarióticas/metabolismo , Ácidos Graxos Insaturados/biossíntese , Regulação da Expressão Gênica , Transdução de Sinais/fisiologia
19.
Nutr J ; 6: 4, 2007 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-17254329

RESUMO

BACKGROUND: The health benefits of increased intakes of omega-3 fatty acids are well established but palatability often presents a problem. The process of emulsification is used in the food industry to provide a wider spectrum of use, often with the result of increased consumption. Moreover, as emulsification is an important step in the digestion and absorption of fats, the pre-emulsification process may enhance digestion and absorption. In this study the levels of plasma fatty acid and triacylglycerol (TAG) following the ingestion of either an oil mixture or an emulsified oil mixture have been compared. METHODS: In this randomised cross-over study, 13 volunteers received the oil mixture and 11 received the oil emulsion as part of an otherwise fat free meal. Blood samples were collected at 0, 1.5, 3, 4.5, 6, 7.5 and 9 hours after ingestion of oil, separated and stored at -20 degrees C. Plasma triacylglycerols were assessed spectrophotometrically and fatty acids were determined by gas chromatography. Following a washout period of twenty days the procedure was repeated with the assignments reversed. RESULTS: The postprandial plasma TAG and the C18:3 (n-6), C18:3(n-3), C20:5(n-3) and C22:6 (n-3) polyunsaturated fatty acid (PUFA) levels for the emulsified oil group were increased significantly (P = 0.0182; P = 0.0493; P = 0.0137; P < 0.0001; P = 0.0355 respectively) compared with the non-emulsified oil group. The C16:0 and C18:0 saturated fatty acids, the C18:1 (n-9) monounsaturated fatty acid and the C18:2 PUFA were not significantly different for the oil and emulsified oil groups. CONCLUSION: Pre-emulsification of an oil mixture prior to ingestion increases the absorption of longer chain more highly unsaturated fatty acids (especially eicosapentaenoic acid and docosahexaenoic acid) but does not affect absorption of shorter chain less saturated fatty acids, suggesting that pre-emulsification of fish oils may be a useful means of boosting absorption of these beneficial fatty acids.


Assuntos
Ácidos Graxos Ômega-3/farmacocinética , Adulto , Estudos Cross-Over , Dieta , Emulsões/farmacocinética , Jejum , Ácidos Graxos/sangue , Ácidos Graxos Insaturados/sangue , Feminino , Óleos de Peixe/farmacocinética , Alimentos , Humanos , Óleo de Semente do Linho/farmacocinética , Masculino , Pessoa de Meia-Idade , Óleos de Plantas/farmacocinética , Triglicerídeos/sangue , Ácido gama-Linolênico/farmacocinética
20.
Chemosphere ; 70(1): 119-25, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17675209

RESUMO

Endocrine disrupting chemicals (EDCs) can alter endocrine function in exposed animals. Such critical effects, combined with the ubiquity of EDCs in sewage effluent and potentially in tapwater, have led to concerns that they could be major physiological disruptors for wildlife and more controversially for humans. Although sewage effluent is known to be a rich source of EDCs, there is as yet no evidence for EDC uptake by invertebrates that live within the sewage treatment system. Here, we describe the use of an extraction method and GC-MS for the first time to determine levels of EDCs (e.g., dibutylphthalate, dioctylphthalate, bisphenol-A and 17beta-estradiol) in tissue samples from earthworms (Eisenia fetida) living in sewage percolating filter beds and garden soil. To the best of our knowledge, this is the first such use of these techniques to determine EDCs in tissue samples in any organism. We found significantly higher concentrations of these chemicals in the animals from sewage percolating filter beds. Our data suggest that earthworms can be used as bioindicators for EDCs in these substrates and that the animals accumulate these compounds to levels well above those reported for waste water. The potential transfer into the terrestrial food chain and effects on wildlife are discussed.


Assuntos
Disruptores Endócrinos/metabolismo , Oligoquetos/metabolismo , Esgotos/análise , Poluentes Químicos da Água/metabolismo , Animais , Biofilmes , Cromatografia em Gel , Estrogênios não Esteroides/análise , Estrogênios não Esteroides/isolamento & purificação , Hormônios/análise , Padrões de Referência , Solo/análise
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