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1.
Biosci Biotechnol Biochem ; 84(3): 633-639, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31710276

RESUMO

To evaluate the suitability of the new nutritional composition of renewed commercial Formula A (protein reduced to 2.2 g/100 kcal, arachidonic acid increased to 13.2 mg/100 kcal, and docosahexaenoic acid maintained at 20 mg/100 kcal), we examined whether the growth of Formula A-fed infants was equivalent to that of breastfed infants. In this observational study, 1,053 infants were followed-up to 12 months. Growth, stool consistency, and the health condition of 99 infants fed with Formula A and 295 breastfed infants were compared. Body weight, body mass index, and head circumference of Formula A-fed infants were similar to those of breastfed infants. Additionally, there were no differences in the stool consistency and the health condition (infection and allergy prevalence) between the two groups. Formula A-fed infants grew as well as breastfed infants, suggesting the appropriate nutritional composition of Formula A. The findings may contribute to further improvements in infant formulas.


Assuntos
Desenvolvimento Infantil , Proteínas na Dieta/administração & dosagem , Ingestão de Energia , Fórmulas Infantis/química , Ácido Araquidônico/metabolismo , Peso Corporal , Aleitamento Materno , Ácidos Docosa-Hexaenoicos/metabolismo , Seguimentos , Nível de Saúde , Humanos , Lactente , Recém-Nascido
2.
Appl Biochem Biotechnol ; 190(1): 218-231, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332676

RESUMO

Yeast surface display has emerged as a viable approach for self-immobilization enzyme as whole-cell catalysts. Herein, we displayed Candida rugosa lipase 1 (CRL LIP1) on the cell wall of Pichia pastoris for docosahexaenoic acid (DHA) enrichment in algae oil. After a 96-h culture, the displayed CRL LIP1 achieved the highest activity (380 ± 2.8 U/g) for hydrolyzing olive oil under optimal pH (7.5) and temperature (45 °C) conditions. Additionally, we improved the thermal stability of displayed LIP1, enabling retention of 50% of its initial bioactivity following 6 h of incubation at 45 °C. Furthermore, the content of DHA enhanced from 40.61% in original algae oil to 50.44% in glyceride, resulting in a 1.24-fold increase in yield. The displayed CRL LIP1 exhibited an improved thermal stability and a high degree of bioactivity toward its native macromolecule substrates algae oil and olive oil, thereby expanding its potential for industrial applications in fields of food and pharmaceutical. These results suggested that surface display provides an effective strategy for simultaneous convenient expression and target protein immobilization.


Assuntos
Proteínas de Bactérias/metabolismo , Candida/enzimologia , Ácidos Docosa-Hexaenoicos/metabolismo , Temperatura Alta , Lipase/metabolismo , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo
3.
Adv Exp Med Biol ; 1161: 13-25, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562618

RESUMO

The present review focuses on the role of one of the D-series resolvins (Rv) RvD1 in the regulation of conjunctival goblet cell secretion and its role in ocular surface health. RvD1 is the most thoroughly studied of the specialized proresolution mediators in the goblet cells. The anterior surface of the eye consists of the cornea (the transparent central area) and the conjunctiva (opaque tissue that surrounds the cornea and lines the eyelids). The secretory mucin MUC5AC produced by the conjunctival goblet cells is protective of the ocular surface and especially helps to maintain clear vision through the cornea. In health, a complex neural reflex stimulates goblet cell secretion to maintain an optimum amount of mucin in the tear film. The specialized pro-resolution mediator, D-series resolvin (RvD1) is present in human tears and induces goblet cell mucin secretion. RvD1 interacts with its receptors ALX/FPR2 and GPR32, activates phospholipases C, D, and A2, as well as the EGFR. This stimulation increases the intracellular [Ca2+] and activates extracellular regulated kinase (ERK) 1/2 to cause mucin secretion into the tear film. This mucin secretion protects the ocular surface from the challenges in the external milieu thus maintaining a healthy interface between the eye and the environment. RvD1 forms a second important mechanism along with activation of a neural reflex pathway to regulate goblet cell mucin secretion and protect the ocular surface in health.


Assuntos
Túnica Conjuntiva , Córnea , Ácidos Docosa-Hexaenoicos , Fenômenos Fisiológicos Oculares , Túnica Conjuntiva/citologia , Túnica Conjuntiva/fisiologia , Córnea/fisiologia , Ácidos Docosa-Hexaenoicos/metabolismo , Células Caliciformes/metabolismo , Humanos
4.
Nat Commun ; 10(1): 3945, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477726

RESUMO

Neuroinflammation is one of the hallmarks of Parkinson's disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, the effects of stimulating the resolution of inflammation in PD - to modulate disease progression - still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA neuron properties, reduced striatal DA outflow and motor deficits prior to nigral degeneration. These early alterations are coupled with microglia activation and perturbations of inflammatory and pro-resolving mediators, namely IFN-γ and resolvin D1 (RvD1). Chronic and early RvD1 administration in Syn rats prevents central and peripheral inflammation, as well as neuronal dysfunction and motor deficits. We also show that endogenous RvD1 is decreased in human patients with early-PD. Our results suggest there is an imbalance between neuroinflammatory and pro-resolving processes in PD.


Assuntos
Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/administração & dosagem , Inflamação/prevenção & controle , Degeneração Neural/prevenção & controle , Doença de Parkinson/prevenção & controle , Animais , Ácidos Docosa-Hexaenoicos/genética , Ácidos Docosa-Hexaenoicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Humanos , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
5.
Nat Commun ; 10(1): 4055, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492836

RESUMO

Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly the omega-3 LC-PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), have been associated with beneficial health effects. Consequently, sustainable sources have to be developed to meet the increasing demand for these PUFAs. Here, we demonstrate the design and construction of artificial PUFA biosynthetic gene clusters (BGCs) encoding polyketide synthase-like PUFA synthases from myxobacteria adapted for the oleaginous yeast Yarrowia lipolytica. Genomic integration and heterologous expression of unmodified or hybrid PUFA BGCs yielded different yeast strains with specific LC-PUFA production profiles at promising yield and thus valuable for the biotechnological production of distinct PUFAs. Nutrient screening revealed a strong enhancement of PUFA production, when cells were phosphate limited. This represents, to the best of our knowledge, highest concentration of DHA (16.8 %) in total fatty acids among all published PUFA-producing Y. lipolytica strains.


Assuntos
Proteínas de Bactérias/metabolismo , Ácido Graxo Sintases/metabolismo , Ácidos Graxos Insaturados/biossíntese , Myxococcales/enzimologia , Yarrowia/metabolismo , Proteínas de Bactérias/genética , Biotecnologia/métodos , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Graxo Sintases/genética , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/metabolismo , Engenharia Metabólica/métodos , Myxococcales/genética , Reprodutibilidade dos Testes
6.
J Agric Food Chem ; 67(34): 9683-9693, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31379160

RESUMO

Schizochytrium sp. A-2 is a heterotrophic marine fungus used for the commercial production of docosahexaenoic acid (DHA). However, the pattern of the distribution of DHA and how DHA is channeled into phospholipid (PL) and triacylglycerol (TAG) are unknown. In this study, we systematically analyzed the distribution of DHA in TAG and PL during the growth of the cell. The migration of DHA from PL to TAG was presumed during the fermentation cycle. DHA and docosapentaenoic acid were accumulated in both TAG and phosphatidylcholine (PC), whereas eicosapentaenoic acid was mainly deposited in PC. RNA seq revealed that malic enzyme may provide lipogenic NADPH. In addition, long-chain acyl-CoA synthase and acyl-CoA:lysophosphatidylcholine acyltransferase may participate in the accumulation of DHA in PL. No phosphatidylcholine:diacylglycerol cholinephosphotransferase was identified from the genome sequence. In contrast, phospholipid:diacylglycerol acyltransferase-mediated acyl-CoA-independent TAG synthesis pathway and phospholipase C may contribute to the channeling of DHA from PC to TAG.


Assuntos
Ácidos Docosa-Hexaenoicos/metabolismo , Estramenópilas/genética , Estramenópilas/metabolismo , Transcriptoma , 1-Acilglicerofosfocolina O-Aciltransferase/genética , 1-Acilglicerofosfocolina O-Aciltransferase/metabolismo , Acil Coenzima A/genética , Acil Coenzima A/metabolismo , Transporte Biológico , Fosfolipídeos/metabolismo , Estramenópilas/química , Triglicerídeos/metabolismo , Fosfolipases Tipo C/genética , Fosfolipases Tipo C/metabolismo
7.
PLoS One ; 14(7): e0219465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291354

RESUMO

Accumulation of amyloid ß (Aß) peptides, the major component of amyloid fibrils in senile plaques, is one of the main causes of Alzheimer's disease. Docosahexaenoic acid (DHA) is a fatty acid abundant in the brain, and is reported to have protective effects against Alzheimer's disease, although the mechanistic effects of DHA against Alzheimer's pathophysiology remain unclear. Because dietary supplementation of DHA in Aß precursor protein transgenic mice ameliorates Aß pathology and behavioral deficits, we hypothesize that DHA may affect the fibrillization and deposition of Aß. Here we studied the effect of different types of fatty acids on Aß fibril formation by in vitro Aß fibrillization assay. Formation of amyloid fibrils consists of two steps, i.e., the initial nucleation phase and the following elongation phase. We found that unsaturated fatty acids, especially DHA, accelerated the formation of Aß fibrils with a unique short and curved morphology in its nucleation phase, which did not elongate further into the long and straight, mature Aß fibrils. Addition of DHA afterwards did not modify the morphology of the mature Aß(1-40) fibrils. The short and curved Aß fibrils formed in the presence of DHA did not facilitate the elongation phase of Aß fibril formation, suggesting that DHA promotes the formation of "off-pathway" conformers of Aß. Our study unravels a possible mechanism of how DHA acts protectively against the pathophysiology of Alzheimer's disease.


Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Ácidos Graxos Insaturados/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Amiloide/genética , Amiloide/metabolismo , Peptídeos beta-Amiloides/química , Precursor de Proteína beta-Amiloide/metabolismo , Amiloidose/genética , Amiloidose/metabolismo , Amiloidose/patologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos Insaturados/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo
8.
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
9.
Methods Mol Biol ; 1995: 229-248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31148133

RESUMO

Microbes can produce not only commodity fatty acids, such as palmitic acid (16:0) and stearic acid (18:0), but also high-value fatty acids (essential fatty acids). Most high value fatty acids belong to long chain polyunsaturated fatty acids (PUFA), such as omega-3 fatty acids (e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and omega-6 fatty acids (e.g., arachidonic acid (ARA) and γ-linolenic acid (GLA)). EPA (20:5n-3) is a 20-carbon fatty acid with five double bonds, and the first double bond is in the n-3 position. DHA (22:6n-3) is a 22-carbon fatty acid with 6 double bonds and the first double bond is also in the n-3 position. Both EPA and DHA play an essential role in cardiovascular health including prevention of atherosclerotic disease development (Zehr and Walker, Prostaglandins Other Lipid Mediat 134:131-140, 2018). ARA (20:4n-6) is a 20-carbon fatty acid with four double bonds, and the first double bond is in the n-6 position. GLA (18:3n-6) is an 18-carbon fatty acid with three double bonds, and the first double bond is in the n-6 position. ARA and GLA have multiple biological effects, such as lowering blood cholesterol, and lowering cardiovascular mortality (Poli and Visioli, Eur J Lipid Sci Technol 117(11):1847-1852, 2015). This chapter provides details on microbial production of EAP, DHA, ARA, and GLA.


Assuntos
Bactérias/metabolismo , Ácidos Graxos Insaturados/metabolismo , Fungos/metabolismo , Microbiologia Industrial/métodos , Ácido Araquidônico/metabolismo , Técnicas de Cultura de Células/métodos , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Fermentação , Microalgas/metabolismo , Ácido gama-Linolênico/metabolismo
10.
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
11.
Science ; 364(6443): 886-889, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31147520

RESUMO

Colonization of new ecological niches has triggered large adaptive radiations. Although some lineages have made use of such opportunities, not all do so. The factors causing this variation among lineages are largely unknown. Here, we show that deficiency in docosahexaenoic acid (DHA), an essential ω-3 fatty acid, can constrain freshwater colonization by marine fishes. Our genomic analyses revealed multiple independent duplications of the fatty acid desaturase gene Fads2 in stickleback lineages that subsequently colonized and radiated in freshwater habitats, but not in close relatives that failed to colonize. Transgenic manipulation of Fads2 in marine stickleback increased their ability to synthesize DHA and survive on DHA-deficient diets. Multiple freshwater ray-finned fishes also show a convergent increase in Fads2 copies, indicating its key role in freshwater colonization.


Assuntos
Adaptação Biológica/genética , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Dessaturases/genética , Água Doce , Duplicação Gênica , Smegmamorpha/fisiologia , Animais , Dosagem de Genes , Água do Mar , Smegmamorpha/genética , Smegmamorpha/metabolismo
12.
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
13.
Nutrients ; 11(5)2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31035600

RESUMO

Although the correlation between polyunsaturated fatty acids (PUFA) and the production of pro- and anti-inflammatory metabolites is well documented, little is known about the simultaneous effect of different PUFA on the production of cyclooxygenase and lipoxygenase metabolites. The present research examines the association between different omega-3 (ω-3) and omega-6 (ω-6) PUFA and the release of four cyclooxygenase and six lipoxygenase metabolites in cell medium by human umbilical vein endothelial cells (HUVEC). The different combinations of ω-3 and ω-6 PUFA were prepared according to a full 24 factorial design that enables studying not only the main effects but also the different interactions between fatty acids. In addition, interactions diagrams and principal component analysis were useful tools for interpreting higher order interactions. To the best of our knowledge, this is the first report addressing the combined effect of ω-3 and ω-6 PUFA on the signaling of prostaglandins, prostacyclins, leukotrienes and resolvins by HUVEC.


Assuntos
Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Lipoxigenases/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Células Cultivadas , Ácidos Docosa-Hexaenoicos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Prostaglandinas/genética , Prostaglandinas/metabolismo
14.
J Agric Food Chem ; 67(23): 6497-6507, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31083936

RESUMO

This experiment was to enrich docosahexaenoic acid (DHA) in broiler tissues through feeding a DHA-rich microalgal biomass and to explore the underlying metabolic and molecular mechanisms. Hatchling Cornish male broilers (total = 192) were fed a corn-soybean meal basal diet containing a full-fatted microalgae ( Aurantiochytrium) at 0%, 1%, 2%, and 4% for 6 weeks ( n = 6 cages/treatment, 8 birds/cage). The inclusion of microalgae led to dose-dependent ( P < 0.01) enrichments of DHA and decreases ( P < 0.01) of n-6/n-3 fatty acids (FAs) in plasma, liver, muscle, and adipose tissue. The microalgae supplementation also lowered ( P < 0.05-0.1) nonesterified FAs concentrations in the plasma, liver and adipose tissue. The mRNA abundances of most assayed genes involved in lipid metabolism were decreased ( P < 0.05) in the liver but elevated ( P < 0.05) in the adipose in response to the biomass supplementation. In conclusion, the biomass-resultant DHA enrichments in the broiler tissues were associated with a distinctive difference in the expression of lipid metabolism-controlling genes between the liver and adipose tissue.


Assuntos
Ração Animal/análise , Galinhas/metabolismo , Suplementos Nutricionais/análise , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos/metabolismo , Microalgas/metabolismo , Estramenópilas/metabolismo , Tecido Adiposo/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas/genética , Ácidos Graxos/química , Feminino , Fígado/metabolismo , Masculino , Microalgas/química , Músculos/metabolismo , Estramenópilas/química
15.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(8): 1134-1144, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31048041

RESUMO

The interest in understanding the capacity of aquatic invertebrates to biosynthesise omega-3 (ω3) long-chain (≥C20) polyunsaturated fatty acids (LC-PUFA) has increased in recent years. Using the common octopus Octopus vulgaris as a model species, we previously characterised a ∆5 desaturase and two elongases (i.e. Elovl2/5 and Elovl4) involved in the biosynthesis of LC-PUFA in molluscs. The aim of this study was to characterise both molecularly and functionally, two methyl-end (or ωx) desaturases that have been long regarded to be absent in most animals. O. vulgaris possess two ωx desaturase genes encoding enzymes with ∆12 and ω3 regioselectivities enabling the de novo biosynthesis of the C18 PUFA 18:2ω6 (LA, linoleic acid) and 18:3ω3 (ALA, α-linolenic acid), generally regarded as dietary essential for animals. The O. vulgaris ∆12 desaturase ("ωx2") mediates the conversion of 18:1ω9 (oleic acid) into LA, and subsequently, the ω3 desaturase ("ωx1") catalyses the ∆15 desaturation from LA to ALA. Additionally, the O. vulgaris ω3 desaturase has ∆17 capacity towards a variety of C20 ω6 PUFA that are converted to their ω3 PUFA products. Particularly relevant was the affinity of the ω3 desaturase towards 20:4ω6 (ARA, arachidonic acid) to produce 20:5ω3 (EPA, eicosapentaenoic acid), as supported by yeast heterologous expression, and enzymatic activity exhibited in vivo when paralarvae were incubated in the presence of [1-14C]20:4ω6. These results confirmed that several routes enabling EPA biosynthesis are operative in O. vulgaris whereas ARA and docosahexaenoic acid (DHA, 22:6ω3) should be considered essential fatty acids since endogenous production appears to be limited.


Assuntos
Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos Insaturados/biossíntese , Octopodiformes/metabolismo , Animais , Ácido Araquidônico/biossíntese , Ácido Araquidônico/metabolismo , Ácidos Docosa-Hexaenoicos/biossíntese , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/biossíntese , Ácidos Graxos Dessaturases/genética , Ácido Linoleico/biossíntese , Octopodiformes/enzimologia , Ácido alfa-Linoleico/biossíntese
16.
J Oleo Sci ; 68(6): 503-510, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31092799

RESUMO

Assessing dietary intake is critical for understanding the relationship between diet and health. Fatty acid blood biomarkers have been particularly useful in determining dietary intakes and assessing the risk of chronic disease. However, fatty acid analysis involves the removal of fatty acids from their complex lipid structures resulting in a loss of potentially useful biological information. "Lipidomics" involves the use of mass spectrometry to identify lipids in their native form. Lipidomic approaches present challenges as an alternative to fatty acid analysis. This includes different types of lipidomic approaches and a lack of consensus on the lipids reported in different studies. Distinguishing between macrolipidomic approaches to characterize highly abundant lipids and microlipidomic approaches examining low abundant bioactive lipids and the use of brutto, medio, genio, and infinio to describe the level of information of lipidomic data can provide clarity to the field. Using lipidomic measurements for understanding docosahexaenoic acid metabolism during pregnancy will also be examined.


Assuntos
Doença Crônica , Dieta , Ácidos Graxos/sangue , Saúde , Lipídeos/química , Metabolômica/métodos , Biomarcadores/sangue , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Ômega-3/sangue , Feminino , Humanos , Espectrometria de Massas , Gravidez , Risco
17.
Med Sci Monit ; 25: 3069-3076, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31023998

RESUMO

BACKGROUND Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Mesenchymal stem cells (MSCs) treatment has been proved to be effective in DN models by protecting renal function and preventing fibrosis. However, the underlying mechanism is unclear. Previous research indicated diabetes and associated complications may be attributed to failed resolution of inflammation, which is deliberately regulated by pro-resolving lipids, including lipoxins (LXs), resolvins (Rv) D and E series, protectins, and maresins. In this study, we monitored pro-resolving mediators in a DN model to explore the mechanism of MSCs treatment. MATERIAL AND METHODS The DN model was induced by STZ injection in SD rats. UPLC-MS/MS was performed to determine pro-resolving lipids in kidney tissue and serum of DN model before and after MSCs treatment, as well as in supernatants of HBZY-1-MSCs co-culture. RESULTS LXA4 was highly accumulated in renal tissue of DN rats with MSCs treatment; ex vivo, LXA4 was significantly increased in the supernatants of HBZY-1 cells co-cultured with MSCs in a high-glucose (HG) medium. Western blot analysis indicated that ALX/FPR2, the receptor of LXA4, was markedly expressed in renal tissue of the DN-MSC group and HBZY-1 after incubating with MSCs in HG. Intraperitoneal injection of LXA4 inhibited renal fibrosis by targeting TGF-ß/Smad signaling and downregulated serum TNF-alpha, IL-6, IL-8, and IFN-γ in DN rats. Notably, all the protective effects induced by MSCs or LXA4 were abolished by ALX/FRP2 blocking. CONCLUSIONS Our results demonstrate that MSCs intervention prevented DN procession via the LXA4-ALX/FPR2 axis, which inhibited glomerulosclerosis and pro-inflammatory cytokines, eventually contributing to kidney homeostasis.


Assuntos
Citocinas/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/terapia , Lipoxinas/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/patologia , Ácidos Docosa-Hexaenoicos/metabolismo , Fibrose/metabolismo , Fibrose/patologia , Mediadores da Inflamação/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
18.
Int J Mol Sci ; 20(7)2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30959940

RESUMO

Fatty acid (FA) profiles in the plasma of patients with metabolic syndrome and chronic kidney disease (CKD) seem to be identical despite their different etiology (dietary mistakes vs. cachexia). The aim of this study was to compare both profiles and to highlight the differences that could influence the improvement of the treatment of patients in both groups. The study involved 73 women, including 24 patients with chronic kidney disease treated with haemodialysis, 19 patients with metabolic syndrome (MetS), and 30 healthy women in the control group. A total of 35 fatty acids and derivatives were identified and quantified by gas chromatography. Intensified elongation processes from acid C10:0 to C16:0 were noted in both groups (more intense in MetS), as well as an increased synthesis of arachidonic acid (C20:4n6), which was more intense in CKD. Significant correlations of oleic acid (C18:1n9), gamma linoleic acid (C18:3n6), and docosatetraenoate acid (C22:4n6) with parameters of CKD patients were observed. In the MetS group, auxiliary metabolic pathways of oleic acid were activated, which simultaneously inhibited the synthesis of eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) from alpha lipoic acid (ALA). On the other hand, in the group of female patients with CKD, the synthesis of EPA and DHA was intensified. Activation of the synthesis of oleic acid (C18: 1n9 ct) and trans-vaccinic acid (C18:1) is a protective mechanism in kidney diseases and especially in MetS due to the increased concentration of saturated fatty acid (SFA) in plasma. The cause of the increased amount of all FAs in plasma in the CKD group, especially in the case of palmitic (C16:0) and derivatives stearic (C18:0) acids, may be the decomposition of adipose tissue and the progressing devastation of the organism, whereas, in the MetS group, dietary intake seems to be the main reason for the increase in SFA. Moreover, in MetS, auxiliary metabolic pathways are activated for oleic acid, which cause the simultaneous inhibition of EPA and DHA synthesis from ALA, whereas, in the CKD group, we observe an increased synthesis of EPA and DHA. The higher increase of nervonic acid (C24:1) in CKD suggests a higher degree of demyelination and loss of axons.


Assuntos
Ácidos Graxos/metabolismo , Síndrome Metabólica/metabolismo , Insuficiência Renal Crônica/metabolismo , Ácido Araquidônico/metabolismo , Cromatografia Gasosa , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Feminino , Humanos , Ácido Oleico/metabolismo
19.
Br Poult Sci ; 60(4): 414-422, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30955350

RESUMO

1. The consumption of sufficient quantities of long chain omega-3 fatty acids (n-3 LCPUFA) from meat and other animal products can lead to a variety of health benefits in humans. The fatty acid content of poultry meat can be increased by feeding birds ingredients that are rich in n-3 LCFUFA 2. The effect of feeding a docosahexaenoic acid (DHA) rich Aurantiochytrium limacinum biomass (AURA) on the fatty acid content of breast and thigh tissues was investigated in a feeding trial with 2880 male Ross 308 broilers. The broiler diets were supplemented with either 0, 0.25, 0.5 or 1% AURA from day 21 to 42 of age. 3. Supplementation significantly increased the DHA content of both breast and thigh meat at an inclusion rate of 1% in the diet, leading to a total of 42 and 46 mg DHA/100 g of fresh breast or thigh tissue respectively. Significant increases in the tissue eicosapentaenoic acid (EPA) concentration were seen alongside a reduced omega-6/omega-3 ratio, improving the nutritional value of the meat for consumers and identifying supplementation of broiler diets with A. limacinum as an effective and sustainable method to increase n-3 LCPUFA consumption in the human population.


Assuntos
Galinhas/fisiologia , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Estramenópilas/química , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Ácidos Docosa-Hexaenoicos/administração & dosagem , Relação Dose-Resposta a Droga , Ácidos Graxos Ômega-3/metabolismo , Masculino , Distribuição Aleatória
20.
Int J Mol Med ; 43(6): 2523-2531, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31017264

RESUMO

Docosahexaenoic acid (DHA) is an omega­3 polyunsaturated fatty acid, derived mainly from fish oil. It is well known that DHA is present in high concentrations in nervous tissue and plays an important role in brain development and neuroprotection. However, the molecular mechanisms underlying its role remain to be fully elucidated. In this study, to enhance our understanding of the pathophysiological role of DHA, we investigated the possible neuroprotective mechanisms of action of DHA against hydrogen peroxide (H2O2)­induced oxidative damage in a rat pheochromocytoma cell line (PC12). Specifically, we evaluated the viability, oxidation potential, and the expression and production of antioxidant/cytoprotective enzymes, and eventual apoptosis. We found that pre­treatment with DHA (24 h) protected the cells from H2O2­induced oxidative damage. In particular, pre­treatment with DHA: i) Antagonized the consistent decrease in viability observed following exposure to H2O2 for 24 h; ii) reduced the high levels of intracellular reactive oxygen species (ROS) associated with H2O2­induced oxidative stress; iii) increased the intracellular levels of enzymatic antioxidants [superoxide dismutase (SOD) and glutathione peroxidase (GSH­Px)] both under basal conditions and following H2O2 exposure; iv) augmented the intracellular levels of reduced glutathione (GSH) and ascorbic acid, while it reduced the malondialdehyde (MDA) levels under conditions of oxidative stress; v) upregulated the expression of nuclear factor (erythroid­derived 2)­like 2 (NFE2L2) and its downstream target protein, heme­oxygenase­1 (HO­1); and vi) induced an anti­apoptotic effect by decreasing Bax and increasing Bcl2 expression. These findings provide evidence suggesting that DHA is able to prevent H2O2­induced oxidative damage to PC12 cells, which is attributed to its antioxidant and anti­apoptotic effects via the regulation NFE2L2/HO­1 signaling. Therefore, DHA may play protective role in neurodegenerative diseases associated with oxidative stress.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/metabolismo , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/metabolismo , Fármacos Neuroprotetores/metabolismo , Células PC12 , Ratos , Superóxido Dismutase/metabolismo
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