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1.
BMJ ; 366: l4009, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266749

RESUMO

OBJECTIVE: To assess the association of dietary fatty acids with cardiovascular disease mortality and total mortality among patients with type 2 diabetes. DESIGN: Prospective, longitudinal cohort study. SETTING: Health professionals in the United States. PARTICIPANTS: 11 264 participants with type 2 diabetes in the Nurses' Health Study (1980-2014) and Health Professionals Follow-Up Study (1986-2014). EXPOSURES: Dietary fat intake assessed using validated food frequency questionnaires and updated every two to four years. MAIN OUTCOME MEASURE: Total and cardiovascular disease mortality during follow-up. RESULTS: During follow-up, 2502 deaths including 646 deaths due to cardiovascular disease were documented. After multivariate adjustment, intake of polyunsaturated fatty acids (PUFAs) was associated with a lower cardiovascular disease mortality, compared with total carbohydrates: hazard ratios comparing the highest with the lowest quarter were 0.76 (95% confidence interval 0.58 to 0.99; P for trend=0.03) for total PUFAs, 0.69 (0.52 to 0.90; P=0.007) for marine n-3 PUFAs, 1.13 (0.85 to 1.51) for α-linolenic acid, and 0.75 (0.56 to 1.01) for linoleic acid. Inverse associations with total mortality were also observed for intakes of total PUFAs, n-3 PUFAs, and linoleic acid, whereas monounsaturated fatty acids of animal, but not plant, origin were associated with a higher total mortality. In models that examined the theoretical effects of substituting PUFAs for other fats, isocalorically replacing 2% of energy from saturated fatty acids with total PUFAs or linoleic acid was associated with 13% (hazard ratio 0.87, 0.77 to 0.99) or 15% (0.85, 0.73 to 0.99) lower cardiovascular disease mortality, respectively. A 2% replacement of energy from saturated fatty acids with total PUFAs was associated with 12% (hazard ratio 0.88, 0.83 to 0.94) lower total mortality. CONCLUSIONS: In patients with type 2 diabetes, higher intake of PUFAs, in comparison with carbohydrates or saturated fatty acids, is associated with lower total mortality and cardiovascular disease mortality. These findings highlight the important role of quality of dietary fat in the prevention of cardiovascular disease and total mortality among adults with type 2 diabetes.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Carboidratos da Dieta/metabolismo , Ácidos Graxos Insaturados/metabolismo , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Correlação de Dados , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
2.
Food Chem ; 295: 26-35, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31174758

RESUMO

Bell peppers are susceptible to chilling injury (CI). To uncover the metabolism of membrane lipid fatty acids (FAs) accompanying CI, a gas chromatography-mass spectrometry (GC-MS)-based approach was used to quantitatively profile major membrane lipid FAs in bell peppers. RT-qPCR was performed to investigate the expression of the key genes that regulate the synthesis of unsaturated FAs. Additionally, we used microstructural, organoleptic, and physicochemical investigations to monitor the primary physiological metabolism of bell peppers. The study revealed that CI symptoms mostly resulted from the destabilization of the cytomembrane, which was induced by decreasing FA desaturation. Moreover, three times lower level of the double bond index in chilled fruits, than the control, further proved that membrane FA unsaturation can be considered a key factor during CI. In conclusion, this study revealed that the metabolism of membrane lipid FAs is involved in responses to CI.


Assuntos
Capsicum/metabolismo , Ácidos Graxos/metabolismo , Conservação de Alimentos/métodos , Lipídeos de Membrana/metabolismo , Capsicum/química , Capsicum/genética , Ácidos Graxos/análise , Ácidos Graxos Insaturados/genética , Ácidos Graxos Insaturados/metabolismo , Frutas/química , Frutas/genética , Frutas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Regulação da Expressão Gênica de Plantas , Lipoxigenase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Temperatura Ambiente
3.
Lett Appl Microbiol ; 69(2): 121-127, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148180

RESUMO

In this study, a total of 172 putative omega-3 producers were isolated from 28 sediment samples from the Arabian Gulf employing a selective isolation procedure using marine agar containing 0·1% triphenyl tetrazolium chloride (TTC). Out of these 172 isolates, 19 isolates produced eicosapentaenoic acid (EPA) as confirmed by Gas Chromatography-Mass Spectrometry (GC-MS). The EPA content of the isolated bacterial strain varied from 1·76 to 6·52% of total fatty acids. Among the 19 isolates of EPA producers, while 17 isolates harboured both pfaA gene and Δ6 desaturase gene, only five isolates harboured Δ5 desaturase gene. Two of the EPA positive strains harbour none of the three genes tested. The 16s RNA identification of these isolates revealed that except one, all the EPA producers were Gram-positive marine bacteria belonging to the phylum Firmicutes, family Bacillacea, genera Bacillus and Oceanobacillus. Halomonas pacifica was the only Gram-negative Gamma-Proteobacteria detected to produce EPA from this region. SIGNIFICANCE AND IMPACT OF THE STUDY: Recently, marine bacteria are considered as a promising source of polyunsaturated fatty acid (PUFA) over marine fishes and microalgae. PUFA producers reported from polar and deep-sea sources were restricted to five well-known marine genera under two distinct domains of bacteria such as proteobacteria (Shewanella, Colwellia, and Moritella) and cytophaga group (Flexibacter, Psychroflexus). This study revealed that subtropical marine environment could also be the source of PUFA producing bacteria, and they predominantly belonged to the class of Firmibacteria. This finding opens up new avenue for research to study the inherent mechanism and physiology of such organisms from this unique environment.


Assuntos
Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos/metabolismo , Firmicutes/metabolismo , Bactérias Gram-Positivas/metabolismo , Halomonas/metabolismo , Animais , Ácidos Graxos/análise , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/análise , Ácidos Graxos Insaturados/metabolismo , Firmicutes/química , Firmicutes/genética , Sedimentos Geológicos/microbiologia , Bactérias Gram-Positivas/química , Bactérias Gram-Positivas/genética , Bactérias Gram-Positivas/isolamento & purificação , Halomonas/química , Halomonas/genética , Halomonas/isolamento & purificação
4.
J Sci Food Agric ; 99(13): 6066-6075, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228262

RESUMO

BACKGROUND: Isochrysis sp. is a marine microalga, rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The potential use of its biomass as an alternative source of polyunsaturated fatty acids (PUFAs) has not been studied in animal models. Male albino Wistar rats were divided into three groups and treated for 28 days. The rats were fed with (1) standard chow (control group), (2) microalgal biomass rich in EPA and DHA along with standard chow (microalga group), and (3) fish oil that contains equivalent amounts of EPA and DHA along with standard chow (fish oil group). After intervention, biochemical indices, histopathological indices, relative mRNA expression of PUFA genes, antioxidant genes, inflammatory markers, and the fatty acid profile of major tissues were studied. RESULTS: Animals treated with microalgal biomass showed significantly increased serum HDL levels (P < 0.05) and reduced oxidative stress markers with a concomitant decrease in urea and creatinine levels. Oral supplementation of microalgal biomass did not show any toxicity or damage in any major organs. The mRNA expression of PUFA genes was significantly downregulated (P < 0.05) and antioxidant genes were upregulated. Furthermore, the mRNA expression of pro-inflammatory markers was significantly downregulated (P < 0.05) and anti-inflammatory markers were upregulated. Oral supplementation of microalgal biomass improved DHA status in brain and liver. CONCLUSION: The present study demonstrated that Isochrysis sp. can be used as a safe, alternative food supplement for ω-3 fatty acids. © 2019 Society of Chemical Industry.


Assuntos
Antioxidantes/metabolismo , Suplementos Nutricionais/análise , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Haptófitas/química , Lipídeos/sangue , Microalgas/química , Animais , Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Insaturados/metabolismo , Expressão Gênica , Haptófitas/crescimento & desenvolvimento , Haptófitas/metabolismo , Fígado/metabolismo , Masculino , Microalgas/crescimento & desenvolvimento , Microalgas/metabolismo , Ratos , Ratos Wistar
5.
Food Chem Toxicol ; 131: 110558, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31175915

RESUMO

Effects of Spirulina platensis 55% ethanol extract (SPL55) on lipid metabolism in high-fat diet-induced hyperlipidaemic rats were investigated. Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry indicated that SPL55 was enriched with polyunsaturated fatty acids. Meanwhile, serum and liver lipid levels, including total triglyceride, total cholesterol, and low-density-lipoprotein cholesterol, were significantly decreased in hyperlipidaemic rats of SPL55. Analysis of tissue sections showed that SPL55 treatment could markedly inhibit hepatic lipid accumulation and steatosis. Moreover, SPL55 regulated the mRNA and protein expression levels of SREBP-1c, HMG-CoA, PEPCK, ACC, and AMPK genes involved in lipid metabolism. Furthermore, SPL55 led to decrease the abundances of Turicibacter, Clostridium_XlVa, and Romboutsia, which were positive correlation with lipid metabolism indicators, and has also enriched Alloprevotella, Prevotella, Porphyromonadaceae, and Barnesiella. These results provided evidence that SPL55 might be developed as a functional food to ameliorate lipid metabolic disorders and hyperlipidaemia.


Assuntos
Ácidos Graxos Insaturados/farmacologia , Fígado Gorduroso/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Spirulina/química , Animais , Peso Corporal/efeitos dos fármacos , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Dieta Hiperlipídica , Ácidos Graxos Insaturados/metabolismo , Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/patologia , Microalgas/química , Ratos , Ratos Wistar , Triglicerídeos/sangue , Triglicerídeos/metabolismo
6.
Food Chem ; 296: 63-68, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31202307

RESUMO

A Chinese-style sausage was processed using pork as the raw material. During the whole process, 13-hydroxyoctadecadienoic acid (13-HODE), 9-hydroxyoctadecadienoic acid (9-HODE), 9,10-dihydroxyoctadecenoic acid (9,10-DHODE) and 9,10,13-trihydroxyoctadecenoic acid (9,10,13-THODE) kept increasing. All of them were found to be correlated negatively and significantly with lipoxygenases (LOX) activity, and positively and significantly with peroxide value (POV) and thiobarbituric acid reactive substances (TBARS). The ratio of 13-HODE to 9-HODE decreased slowly during drying stage and stayed higher than 2 during the whole process, and it was found to be positively and significantly with LOX activity. The ratio of variation of 13-HODE to variation of 9-HODE in every sampling period (the ratio of Δ13-HODE to Δ9-HODE) decreased sharply from 2.75 in the stage of curing for 12 h to 1.37 in the stage drying from 24 d to 30 d. The changes of ratio of 13HODE to 9-HODE and ratio of Δ13-HODE to Δ9-HODE indicated LOX-catalyzed oxidation predominated in curing and early drying stages, and such predominance was taken over by non-enzymatic oxidation during late drying stage; LOX-catalyzed oxidation was the major contributor to lipids oxidation during the whole process of the Chinese-style sausage preparing.


Assuntos
Manipulação de Alimentos/métodos , Ácidos Linoleicos/metabolismo , Peroxidação de Lipídeos , Produtos da Carne/análise , China , Ácidos Graxos Insaturados/metabolismo , Ácidos Linoleicos/química , Ácidos Linoleicos Conjugados/química , Ácidos Linoleicos Conjugados/metabolismo , Lipoxigenases/metabolismo
7.
Anim Sci J ; 90(8): 999-1007, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148331

RESUMO

Bovine mastitis is one of the most prevalent and costly diseases in the dairy industry. Lipid mediators are signaling molecules which coordinately and intricately modulate inflammation. They are produced from polyunsaturated fatty acids (PUFAs) in the cellular membrane via several enzymes including cyclooxygenase (COX) and lipoxygenase (LOX). In the present study, we performed comprehensive analysis of lipid production in milk obtained from clinical or subclinical mastitic cows using liquid chromatography/mass spectrometry. We detected 26, 24, and 40 kinds of lipid constantly in healthy, subclinical, and clinical mastitic milk, respectively. In clinical mastitic milk, the amount of a major n-6 PUFA, arachidonic acid (AA), tended to increase, whereas amounts of major n-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid, tended to decrease. The amounts of several AA-derived lipids including COX-catalyzed prostaglandin (PG) D2 and PGE2 , and LOX-catalyzed leukotriene (LT) B4 were increased in clinical mastitic milk. Although subclinical mastitic milk represented similar trend of lipid production to healthy milk, amounts of several lipids such as LTD4 , 14,15-dihydroxyeicosatrienoic acid, and 14-epoxyeicosatrienoic acid changed. These findings would be helpful for better understanding of mastitis pathology and give us some insights to develop a new diagnostic and therapeutic strategy.


Assuntos
Mastite Bovina/metabolismo , Leite/metabolismo , Animais , Ácido Araquidônico/metabolismo , Biomarcadores/metabolismo , Bovinos , Dinoprostona/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Leucotrieno B4/metabolismo , Lipoxigenase/metabolismo , Mastite Bovina/diagnóstico , Mastite Bovina/etiologia , Prostaglandina D2/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo
8.
Ecotoxicol Environ Saf ; 181: 146-154, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31177079

RESUMO

The impact of lead (Pb) on Spirodela polyrhiza was studied to determine the subcellular distribution, chemical forms, and resulting morphophysiological modifications after treatments with 20 or 80 µM Pb(NO3)2 for 10 days. At the subcellular level, the Pb uptake by S. polyrhiza was mainly compartmentalized in the cell walls (70%), and the majority of Pb (approximately 70%) was extracted using 1 M NaCl and 2% acetic acid (HAc). Visual symptoms of phytotoxcity, surface roughness and closure of stomata, were observed in Pb-treated fronds. Electron-dense precipitates were present in cell walls, and changes to the ultrastructure were most noticeably exhibited in organelle shape, internal organization, and size of the plastoglobules of chloroplasts. Toxic concentrations of Pb induced oxidative stress in fronds, characterized by an accumulation of malondialdehyde (MDA) and decreased chlorophyll and unsaturated fatty acid contents. Pb exposure increased ABS/RC, TRo/RC, DIo/RC, Vj, and φDo (Fv/Fm), indicating that reaction centers were transformed to dissipation sinks, leading to a decrease in the efficiency of photosystem II, which was evident from the decreased values of Fv/Fo, Fv/Fm, ψEo, φEo, RC/ABS, and PIabs. These results indicated that decreased photosynthesis in Pb-treated fronds was partially ascribed to the lower pigment content, inhibition of electron transport, inactivation of the reaction centers, damage to the chloroplast ultrastructure, and stomatal closure. The physiological implications of subcellular distribution and chemical forms are discussed in relation to Pb accumulation and detoxification. However, Pb accumulation significantly impaired photosynthesis and membrane integrity in the fronds of S. polyrhiza.


Assuntos
Araceae/efeitos dos fármacos , Chumbo/toxicidade , Araceae/anatomia & histologia , Araceae/metabolismo , Araceae/ultraestrutura , Clorofila/metabolismo , Cloroplastos/efeitos dos fármacos , Cloroplastos/ultraestrutura , Transporte de Elétrons/efeitos dos fármacos , Ácidos Graxos Insaturados/metabolismo , Chumbo/farmacocinética , Malondialdeído/metabolismo , Fotossíntese/efeitos dos fármacos , Complexo de Proteína do Fotossistema II/metabolismo
9.
Biol Pharm Bull ; 42(5): 850-855, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061331

RESUMO

Acyl-CoA synthetase long-chain family members (ACSLs) are a family of enzymes that convert long-chain free fatty acids into their acyl-CoAs. ACSL4 is an ACSL isozyme with a strong preference for arachidonic acid (AA) and has been hypothesized to modulate the metabolic fates of AA. There are two ACSL4 splice variants: ACSL4V1, which is the more abundant transcript, and ACSL4V2, which is believed to be restricted to the brain. In the present study, we expressed recombinant human ACSL4V1 and V2 in Spodoptera frugiperda 9 (Sf9) cells using the baculovirus expression system and then partially purified both variants by cobalt affinity column chromatography. We then established a novel ACSL assay system with LC-MS/MS, which is highly sensitive and applicable to various kinds of fatty acids, and used it to investigate the substrate specificity of recombinant human ACSL4V1 and V2. The results showed that both ACSL4 variants preferred various kinds of highly unsaturated fatty acids (HUFAs), including docosahexaenoic acid (DHA), adrenic acid (docosatetraenoic acid) and eicosapentaenoic acid (EPA), as well as AA as a substrate. Moreover, our kinetic studies revealed that the two variants had similar relative affinities for AA, EPA and DHA but different reaction rates for each HUFA. These results confirmed the importance of both of ACSL4 variants in the maintenance of membrane phospholipids bearing HUFAs. Structural analysis of these variants might reveal the molecular mechanism by which they maintain membrane phospholipids bearing HUFAs.


Assuntos
Coenzima A Ligases/metabolismo , Ácidos Graxos Insaturados/metabolismo , Animais , Baculoviridae/genética , Linhagem Celular , Cromatografia Líquida , Coenzima A Ligases/genética , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Proteínas Recombinantes/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Spodoptera , Especificidade por Substrato , Espectrometria de Massas em Tandem
10.
Adv Exp Med Biol ; 1127: 97-115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31140174

RESUMO

Modern society has changed its diet composition, transitioning to a higher intake of saturated fat with a 50% increase of cardiovascular risk (CVD). Within the context of increased CVD, there is an induction of a prothrombotic phenotype mainly due to increased platelet reactivity as well as decreased platelet response to inhibitors. Platelets maintain haemostasis through both blood components and endothelial cells that secrete inhibitory or stimulatory molecules to regulate thrombus formation. There exist a correlation between platelets' polyunsaturated fatty acid (PUFA) and the increase in platelet reactivity. The aim of this chapter is to review the metabolism of the main PUFAs involved in platelet function associated with the role that their enzyme-derived oxidized metabolites exert in platelet function and fate. Finally, how lipid metabolism in the organism affect platelet aggregation and activation and the pharmacological modulation of these processes will also be discussed.


Assuntos
Plaquetas/citologia , Ácidos Graxos Insaturados/metabolismo , Metabolismo dos Lipídeos , Agregação Plaquetária , Transdução de Sinais , Humanos
11.
PLoS Comput Biol ; 15(5): e1007033, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31107861

RESUMO

G protein-coupled receptors (GPCRs) control cellular signaling and responses. Many of these GPCRs are modulated by cholesterol and polyunsaturated fatty acids (PUFAs) which have been shown to co-exist with saturated lipids in ordered membrane domains. However, the lipid compositions of such domains extracted from the brain cortex tissue of individuals suffering from GPCR-associated neurological disorders show drastically lowered levels of PUFAs. Here, using free energy techniques and multiscale simulations of numerous membrane proteins, we show that the presence of the PUFA DHA helps helical multi-pass proteins such as GPCRs partition into ordered membrane domains. The mechanism is based on hybrid lipids, whose PUFA chains coat the rough protein surface, while the saturated chains face the raft environment, thus minimizing perturbations therein. Our findings suggest that the reduction of GPCR partitioning to their native ordered environments due to PUFA depletion might affect the function of these receptors in numerous neurodegenerative diseases, where the membrane PUFA levels in the brain are decreased. We hope that this work inspires experimental studies on the connection between membrane PUFA levels and GPCR signaling.


Assuntos
Ácidos Docosa-Hexaenoicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Células Receptoras Sensoriais/metabolismo , Encéfalo/metabolismo , Colesterol/metabolismo , Biologia Computacional , Simulação por Computador , Ácidos Docosa-Hexaenoicos/química , Ácidos Graxos Insaturados/metabolismo , Humanos , Microdomínios da Membrana/química , Microdomínios da Membrana/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Modelos Moleculares , Modelos Neurológicos , Conformação Proteica , Receptor A2A de Adenosina/química , Receptor A2A de Adenosina/metabolismo , Receptores Acoplados a Proteínas-G/química , Células Receptoras Sensoriais/química , Transdução de Sinais , Termodinâmica
12.
Nat Commun ; 10(1): 2334, 2019 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133642

RESUMO

Pseudomonas aeruginosa, a significant opportunistic pathogen, can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals leads to altered biofilm formation and increased tolerance to various antibiotics, and requires the histidine kinase PA1396. Here, we show that the membrane-associated sensory input domain of PA1396 has five transmembrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds to develop novel adjuvants improving the efficacy of existing antibiotics.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Ácidos Graxos Insaturados/metabolismo , Histidina Quinase/metabolismo , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/fisiologia , Animais , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Modelos Animais de Doenças , Farmacorresistência Bacteriana , Feminino , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/imunologia , Histidina Quinase/genética , Humanos , Lipossomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Mutagênese , Fosforilação , Polimixinas/farmacologia , Polimixinas/uso terapêutico , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
13.
Gene ; 706: 106-114, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31039437

RESUMO

Biological significance of 18-carbon polyunsaturated fatty acids, γ-linolenic acid (GLA; C18:3 n-6) and dihomo-γ-linolenic acid (DGLA; C20:3 n-6) has gained much attention in the systematic development of optimized strains for industrial applications. In this work, a n-6 PUFAs-producing strain of Aspergillus oryzae was generated by manipulating metabolic reactions in fatty acid modification and triacylglycerol biosynthesis. The codon-optimized genes coding for Δ6-desaturase and Δ6-elongase of Pythium sp., and diacylglycerol acyltransferase 2 (mMaDGAT2) of Mortierella alpina were co-transformed in a single vector into A. oryzae BCC14614, yielding strain TD6E6-DGAT2. Comparative phenotypic analysis showed that a 70% increase of lipid titer was found in the engineered strain, which was a result of a significant increase in triacylglycerol (TAG) content (52.0 ±â€¯1.8% of total lipids), and corresponded to the increased size of lipid particles observed in the fungal cells. Interestingly, the proportions of GLA and DGLA in neutral lipids of the engineered strain were similar, with the highest titers obtained in the high C:N culture (29:0; 6% glucose) during the lipid-accumulating stage of growth. Time-course expression analysis of the engineered strain revealed transcriptional control of TAG biosynthesis through a co-operation between the native DGAT2 of A. oryzae and the transformed mMaDGAT2.


Assuntos
Aspergillus oryzae/metabolismo , Lipídeos/biossíntese , Engenharia Metabólica/métodos , Ácido 8,11,14-Eicosatrienoico/metabolismo , Ácido Araquidônico/biossíntese , Aspergillus oryzae/genética , Aspergillus oryzae/fisiologia , Vias Biossintéticas , Ácidos Graxos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Proteínas Fúngicas/genética , Mortierella/genética , Triglicerídeos/biossíntese , Ácido gama-Linolênico/biossíntese
14.
Int J Mol Sci ; 20(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30979019

RESUMO

Osteoclasts are the sole bone resorbing cell in the body and their over activity is key in the development of osteoporosis. Osteoclastogenesis is mediated by receptor activator of nuclear factor κB ligand (RANKL) signalling pathways. Unsaturated fatty acids (UFA) are known to inhibit osteoclastogenesis by targeting RANKL signalling. However, the mechanisms of action remain unclear. Peroxisome proliferator activated receptors (PPARs) are a family of nuclear receptors, with three known isoforms (PPAR-α, PPAR-ß/δ and PPAR-γ), that are known to bind UFAs and are expressed in osteoclasts. In this study, we aimed to determine how different families of UFAs activate PPARs and how PPAR activation influences osteoclast signalling. Human CD14+ monocytes were seeded into cluster plates with RANKL and macrophage colony stimulating factor (M-CSF) in the presence of PPAR agonists or different types of UFAs. All the PPAR agonists were shown to upregulate the activity of their respective receptors. Polyunsaturated fatty acids increased PPAR-α to a greater extent than monounsaturated fatty acids (MUFAs), which favoured PPAR-ß/δ activation. All PPAR agonists inhibited osteoclastogenesis. The activation of RANKL signalling pathways and expression of key osteoclast genes were downregulated by PPAR agonists. This study reveals that PPAR activation can inhibit osteoclastogenesis through modulation of RANKL signalling.


Assuntos
Ácidos Graxos Insaturados/metabolismo , Receptores de Lipopolissacarídeos/análise , Monócitos/citologia , Osteoclastos/citologia , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais , Adolescente , Adulto , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Masculino , Monócitos/metabolismo , Osteoclastos/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Ligante RANK/metabolismo , Adulto Jovem
15.
Lipids ; 54(4): 221-230, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31025717

RESUMO

The long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in health, but previous National Health and Nutrition Examination Survey (NHANES) analyses have shown that EPA and DHA intake in the United States is far below recommendations (~250-500 mg/day EPA + DHA). Less is known about docosapentaenoic acid (DPA), the metabolic intermediate of EPA and DHA; however, evidence suggests DPA may be an important contributor to long-chain n-3 fatty acid intake and impart unique benefits. We used NHANES 2003-2014 data (n = 45,347) to assess DPA intake and plasma concentrations, as well as the relationship between intake and plasma concentrations of EPA, DPA, and DHA. Mean DPA intake was 22.3 ± 0.8 mg/day from 2013 to 2014, and increased significantly over time (p < 0.001), with the lowest values from 2003 to 2004 (16.2 ± 1.2 mg/day). DPA intake was higher in adults (20-55 years) and seniors (55+ years) compared to younger individuals. In regression analyses, DPA intake was a significant predictor of plasma EPA (ß = 138.5; p < 0.001) and DHA (ß = 318.9; p < 0.001). Plasma DPA was predicted by EPA and DHA intake (ß = 13.15; p = 0.001 and ß = 7.4; p = 0.002), but not dietary DPA (p = 0.3). This indicates that DPA intake is not a good marker of plasma DPA status (or vice versa), and further research is needed to understand the factors that affect the interconversion of EPA and DPA. These findings have implications for future long-chain n-3 fatty acids dietary recommendations.


Assuntos
Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/administração & dosagem , Adolescente , Adulto , Criança , Estudos Transversais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Insaturados/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos/fisiologia , Masculino , Estados Unidos , Adulto Jovem
16.
Genome Biol Evol ; 11(5): 1417-1430, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30942856

RESUMO

The metabolic conversion of dietary omega-3 and omega-6 18 carbon (18C) to long chain (>20 carbon) polyunsaturated fatty acids (LC-PUFAs) is vital for human life. The rate-limiting steps of this process are catalyzed by fatty acid desaturase (FADS) 1 and 2. Therefore, understanding the evolutionary history of the FADS genes is essential to our understanding of hominin evolution. The FADS genes have two haplogroups, ancestral and derived, with the derived haplogroup being associated with more efficient LC-PUFA biosynthesis than the ancestral haplogroup. In addition, there is a complex global distribution of these haplogroups that is suggestive of Neanderthal introgression. We confirm that Native American ancestry is nearly fixed for the ancestral haplogroup, and replicate a positive selection signal in Native Americans. This positive selection potentially continued after the founding of the Americas, although simulations suggest that the timing is dependent on the allele frequency of the ancestral Beringian population. We also find that the Neanderthal FADS haplotype is more closely related to the derived haplogroup and the Denisovan clusters closer to the ancestral haplogroup. Furthermore, the derived haplogroup has a time to the most recent common ancestor of 688,474 years before present. These results support an ancient polymorphism, as opposed to Neanderthal introgression, forming in the FADS region during the Pleistocene with possibly differential selection pressures on both haplogroups. The near fixation of the ancestral haplogroup in Native American ancestry calls for future studies to explore the potential health risk of associated low LC-PUFA levels in these populations.


Assuntos
Evolução Molecular , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Insaturados/metabolismo , Hominidae/genética , Animais , Ácidos Graxos Dessaturases/metabolismo , Hominidae/metabolismo , Humanos , Índios Norte-Americanos/genética , Seleção Genética , Sibéria
17.
Gene ; 702: 75-82, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30928362

RESUMO

Coconut (Cocos nucifera L.) is one of the most characteristic plants of tropical areas. Coconut oil and its derivatives have been widely used in various industries. In this paper, a type 2 diacylglycerol acyltransferase (DGAT2), which is one of the key enzymes involved in triacylglycerol (TAG) biosynthesis, was first characterized in coconut pulp (endosperm). The results indicated that CoDGAT2 was highly expressed in coconut pulp approximately 7 months after pollination. The heterologous expression of CoDGAT2 in the mutant yeast H1246 restored TAG biosynthesis in the yeast, which exhibited substrate preference for two unsaturated fatty acids (UFAs), palmitoleic acid (C16:1) and oleic acid (C18:1). Moreover, the seed-specific overexpression of CoDGAT2 in Arabidopsis thaliana led to a significant increase in the linoleic acid (C18:2) content (approximately 6%) compared with that in the wild type. In contrast, the proportions of eicosadienoic acid (C20:1) and arachidic acid (C20:0) were decreased. These results offer new insights on the function of CoDGAT2 in coconut and provide a novel molecular target for lipid genetic modification to change the fatty acid (FA) composition of oils.


Assuntos
Cocos/enzimologia , Diacilglicerol O-Aciltransferase/metabolismo , Endosperma/enzimologia , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Cocos/genética , Diacilglicerol O-Aciltransferase/genética , Endosperma/genética , Ácidos Graxos Insaturados/metabolismo , Genes de Plantas , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/metabolismo , RNA Mensageiro/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Sementes/metabolismo
18.
Lipids ; 54(4): 211-219, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30883776

RESUMO

Population-based data suggest that individuals who consume large dietary amounts of n-3 polyunsaturated fatty acids (PUFA) have lower odds of peripheral artery disease (PAD); however, clinical studies examining n-3 PUFA levels in patients with PAD are sparse. The objective of this study is to compare erythrocyte membrane fatty acid (FA) content between patients with PAD and controls. We conducted a cross-sectional study of 179 vascular surgery outpatients (controls, 34; PAD, 145). A blood sample was drawn and the erythrocyte FA content was assayed using capillary gas chromatography. We calculated the ratio of the n-3 PUFA eicosapentaenoic acid (EPA) to the n-6 PUFA arachidonic acid (ARA) as well as the omega-3 index (O3I), a measure of erythrocyte content of the n-3 PUFA, EPA, and docosahexaenoic acid (DHA), expressed as a percentage of total erythrocyte FA. Compared with controls, patients with PAD smoked more and were more likely to have hypertension and hyperlipidemia (p < 0.05). Patients with PAD had a lower mean O3I (5.0 ± 1.7% vs 6.0 ± 1.6%, p < 0.001) and EPA:ARA ratio (0.04 ± 0.02 vs 0.05 ± 0.05, p < 0.001), but greater mean total saturated fats (39.5 ± 2.5% vs 38.5 ± 2.6%, p = 0.01). After adjusting for several patient characteristics, comorbidities, and medications, an absolute decrease of 1% in the O3I was associated with 39% greater odds of PAD (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.03-1.86, and p = 0.03). PAD was associated with a deficiency of erythrocyte n-3 PUFA, a lower EPA:ARA ratio, and greater mean total saturated fats. These alterations in FA content may be involved in the pathogenesis or development of poor outcomes in PAD.


Assuntos
Membrana Eritrocítica/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/metabolismo , Doença Arterial Periférica/metabolismo , Doença Arterial Periférica/patologia , Idoso , Ácido Araquidônico/metabolismo , Cromatografia Gasosa , Estudos Transversais , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Biotechnol Lett ; 41(4-5): 575-582, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30825045

RESUMO

OBJECTIVE: To quantitatively hydroxylate 8S- and 10S-positions on polyunsaturated fatty acids by recombinant Escherichia coli cells expressing mouse arachidonate 8S-lipoxygenase (8S-LOX). RESULTS: Hydroxylated products gained from the conversion of arachidonic acid (20:4Δ5Z,8Z,11Z,14Z, AA), eicosapentanoic acid (20:5Δ5Z,8Z,11Z,14Z,17Z, EPA), and (22:6Δ4Z,7Z,10Z,13Z,16Z,19Z, DHA) by recombinant E. coli cells containing 8S-LOX from mouse were identified as 8S-hydroxy-5,9,11,14(Z,E,Z,Z)-eicosatetranoic acid (8S-HETE), 8S-hydroxy-5,9,11,14,17(Z,E,Z,Z,Z)-eicosapentanoic acid (8S-HEPE), and 10S-hydroxy-4,8,12,14,16,19(Z,E,Z,Z,Z,Z)-docosahexaenoic acid (10S-HDoHE), respectively. Under the optimal hydroxylation conditions of pH 7.5, 30 °C, 5% (v/v) ethanol, 15 g cells l-1, and 5 mM substrate, AA, EPA, and DHA were hydroxylated into 4.37 mM 8S-HETE, 3.77 mM 8S-HEPE, and 3.13 mM 10S-HDoHE for 60, 90, and 60 min, with 87, 75, and 63% molar conversions, respectively. CONCLUSION: To the best of our knowledge, this is the first quantitatively biotechnological production of 8S-HETE, 8S-HEPE, and 10S-HDoHE.


Assuntos
Araquidonato Lipoxigenases/metabolismo , Escherichia coli/metabolismo , Ácidos Graxos Insaturados/metabolismo , Proteínas Recombinantes/metabolismo , Animais , Araquidonato Lipoxigenases/genética , Escherichia coli/genética , Concentração de Íons de Hidrogênio , Camundongos , Proteínas Recombinantes/genética , Temperatura Ambiente
20.
Proc Natl Acad Sci U S A ; 116(13): 6292-6297, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30862734

RESUMO

Inflammation in the tumor microenvironment is a strong promoter of tumor growth. Substantial epidemiologic evidence suggests that aspirin, which suppresses inflammation, reduces the risk of cancer. The mechanism by which aspirin inhibits cancer has remained unclear, and toxicity has limited its clinical use. Aspirin not only blocks the biosynthesis of prostaglandins, but also stimulates the endogenous production of anti-inflammatory and proresolving mediators termed aspirin-triggered specialized proresolving mediators (AT-SPMs), such as aspirin-triggered resolvins (AT-RvDs) and lipoxins (AT-LXs). Using genetic and pharmacologic manipulation of a proresolving receptor, we demonstrate that AT-RvDs mediate the antitumor activity of aspirin. Moreover, treatment of mice with AT-RvDs (e.g., AT-RvD1 and AT-RvD3) or AT-LXA4 inhibited primary tumor growth by enhancing macrophage phagocytosis of tumor cell debris and counter-regulating macrophage-secreted proinflammatory cytokines, including migration inhibitory factor, plasminogen activator inhibitor-1, and C-C motif chemokine ligand 2/monocyte chemoattractant protein 1. Thus, the pro-resolution activity of AT-resolvins and AT-lipoxins may explain some of aspirin's broad anticancer activity. These AT-SPMs are active at considerably lower concentrations than aspirin, and thus may provide a nontoxic approach to harnessing aspirin's anticancer activity.


Assuntos
Antineoplásicos/farmacologia , Aspirina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Animais , Aspirina/administração & dosagem , Quimiocina CCL2/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/metabolismo , Eicosanoides/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Inflamação/tratamento farmacológico , Lipoxinas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metabolômica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/prevenção & controle , Proteínas do Tecido Nervoso/metabolismo , Fagocitose/efeitos dos fármacos , Inativadores de Plasminogênio/metabolismo , Prostaglandinas/metabolismo
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