RESUMO
Massive changes have occurred in our diet. A growing consumption of vegetal oils rich in omega-6 (ω-6) and a depletion of omega-3 (ω-3) fatty acids (FAs) in our food has led to an imbalance between ω-3 and ω-6. In particular, eicosapentaenoic (EPA)/arachidonic acid (AA) ratio seems to be an indicator of this derangement, whose reduction is associated to the development of metabolic diseases, such as diabetes mellitus. Our aim was therefore to investigate the literature on the effects of ω-3 and ω-6 FAs on glucose metabolism. We discussed emerging evidence from pre-clinical studies and from clinical trials. Notably, conflicting results emerged. Source of ω-3, sample size, ethnicity, study duration and food cooking method may be responsible for the lack of univocal results. High EPA/AA ratio seems to be a promising indicator of better glycemic control and reduced inflammation. On the other hand, linoleic acid (LA) appears to be also associated to a minor incidence of type 2 diabetes mellitus, although it is still not clear if the outcome is related to a reduced production of AA or to its intrinsic effect. More data derived from multicenter, prospective randomized clinical trials are needed.
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Diabetes Mellitus Tipo 2 , Ácidos Graxos Ômega-3 , Humanos , Estudos Prospectivos , Ácidos Graxos Ômega-6 , Ácido Araquidônico/metabolismo , Glucose , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos , Estudos Multicêntricos como AssuntoRESUMO
Sickle cell disease (SCD) induces red blood cell sickling, which causes debilitating symptoms including vaso-occlusion and inflammation. We investigated a food enriched with omega-3 fatty acids to determine its effect on certain factors: blood cell membrane fatty acid composition (including anti-inflammatory elements-docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-and the pro-inflammatory, arachidonic acid (AA)); the inflammation biomarker, C-reactive protein (CRP); and vaso-occlusive crisis (VOC) pain. Ten adults with SCD ingested the food, daily, for 28 days. Evaluated measures included blood cell membrane fatty acid ratios (AA vs omega-3 (DHA+EPA)), CRP (mg/L) levels, and Visual Analogue Scale (VAS) scores (a VOC assessment). The food was well tolerated and led to a statistically significant CRP reduction (39%). However, changes in omega-3 fatty acid ratios and VAS scores were not significant. Overall, while the omega-3-enriched food reduced inflammation, larger, blinded studies are needed to assess its effectiveness on other measures.
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Anemia Falciforme , Ácidos Graxos Ômega-3 , Compostos Orgânicos Voláteis , Adulto , Humanos , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Proteína C-Reativa/metabolismo , Inflamação , Ácidos Graxos , Ácido AraquidônicoRESUMO
Marine heterotrophic dinoflagellate Crypthecodinium cohnii is an aerobic oleaginous microorganism that accumulates intracellular lipid with high content of 4,7,10,13,16,19-docosahexaenoic acid (DHA), a polyunsaturated ω-3 (22:6) fatty acid with multiple health benefits. C. cohnii can grow on glucose and ethanol, but not on sucrose or fructose. For conversion of sucrose-containing renewables to C. cohnii DHA, we investigated a syntrophic process, involving immobilized cells of ethanologenic bacterium Zymomonas mobilis for fermenting sucrose to ethanol. The non-respiring, NADH dehydrogenase-deficient Z. mobilis strain Zm6-ndh, with high ethanol yield both under anaerobic and aerobic conditions, was taken as the genetic background for inactivation of levansucrase (sacB). SacB mutation eliminated the levan-forming activity on sucrose. The double mutant Zm6-ndh-sacB cells were immobilized in Ca alginate, and applied for syntrophic conversion of sucrose to DHA of C. cohnii, either taking the ethanol-containing fermentation medium from the immobilized Z. mobilis for feeding to the C. cohnii fed-batch culture, or directly coculturing the immobilized Zm6-ndh-sacB with C. cohnii on sucrose. Both modes of cultivation produced C. cohnii CCMP 316 biomass with DHA content around 2-3 % of cell dry weight, corresponding to previously reported results for this strain on glucose.
Assuntos
Dinoflagellida , Zymomonas , Ácidos Docosa-Hexaenoicos , Fermentação , Sacarose , Zymomonas/genéticaRESUMO
Paediatric ependymomas are aggressive, treatment-resistant tumours with a tendency towards relapse, consistent with a sub-population of therapy-resistant cancer stem cells. These cells are believed to derive from brain lipid binding protein (BLBP)-expressing radial glia, hence we proposed that BLBP may be a marker for ependymoma therapy resistance. BLBP protein expression correlated with reduced overall survival (OS) in patients from two trials (CNS9204, a chemotherapy-led infant trial-5 y OS 45% vs. 80%, p = 0.011-and CNS9904, a radiotherapy-led trial-OS 38% vs. 85%, p = 0.002). All ependymoma cell lines examined by qRT-PCR expressed BLBP, with expression elevated in stem cell-enriched neurospheres. Modulation of BLBP function in 2D and 3D assays, using either peroxisome proliferator activated receptor (PPAR) antagonists or BLBP's fatty acid substrate docosahexaneoic acid (DHA), potentiated chemotherapy response and reduced cell migration and invasion in ependymoma cell lines. BLBP is therefore an independent predictor of poor survival in paediatric ependymoma, and treatment with PPAR antagonists or DHA may represent effective novel therapies, preventing chemotherapy resistance and invasion in paediatric ependymoma patients.
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This study investigated dietary supplementation as a prophylactic for neuroinflammation following traumatic brain injury (TBI) in a preclinical model. Adult male Sprague-Dawley rats received 30 days of supplementation with either water or two dietary supplements. The first consisted of high-dose omega-3 fatty acid (O3FA) (supplement A) along with vitamin D3 and vitamin E. The second had the same ingredients at different doses with an addition of cannabidiol (supplement B). Rats were subjected to an impact TBI and then euthanized 7 days post-injury and neuroinflammation quantified by histological detection of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and CD68, a marker of microglial activity. There was a trend toward increased GFAP staining in injured, unsupplemented animals as compared to sham, unsupplemented animals, consistent with increased activation of astrocytes in response to trauma which was reversed by supplement A but not by supplement B. The pattern of CD68 staining across groups was similar to that of GFAP staining. There was a trend toward an increase in the injured unsupplemented group, relative to sham which was reversed by supplement A but not by supplement B. CD68 staining in injured animals was concentrated in the perivascular domain. The consistency between trends across different measures of neuroinflammation showing benefits of high-dose O3FA supplementation following TBI suggests that the observed effects are real. These findings are preliminary, but they justify further study to determine the functional benefits associated with improvements in histological outcomes and understand associated dose-response curves.
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Neurocognitive impairment (NCI) and gut microbiota dysbiosis are prevalent in patients with HIV infection. Docosahexanoic acid (DHA) supplementation may alleviate multiple neurocognitive diseases symptoms and plays important role in regulating gut microbiota. However, it is not known whether DHA algae oil supplements can alleviate neurocognitive impairment (NCI) and regulate gut microbiota and fecal metabolites. A randomized, double-blind, placebo-controlled trial was performed on 68 HIV-infected patients with NCI. Participants were randomized to receive a 3.15 g daily DHA algae oil supplement or placebo for 6 months. We collected blood and fecal samples from these patients before and after the trial. Mini mental state examination (MMSE) and neuropsychological tests (NP tests) were administered to assess the cognitive status of participants. The influence of DHA algae oil on the gut microbiota, fecal metabolomics, plasma proinflammatory, and oxidative stress factors was also investigated. There were no significant changes in NCI according to global diagnosis score (GDS) and MMSE score within the two groups, while patients receiving DHA had improvement in several blood lipids, pro-inflammatory and oxidative stress factors. The DHA supplement increased α-diversity indexes, increased abundances of Blautia, Bifidobacterium, Dorea, Lactobacillus, Faecalibacterium, Fusobacterium, and Agathobacter, and decreased abundances of Bacteroides and Prevotella_9. Furthermore, DHA supplement was correlated with improved fecal lipid metabolites as indicated by ceramides, bile acids, glycerophospholipids. In addition, the DHA supplement was associated with altered cholesterol metabolism and purine metabolism pathways. A daily supplement of DHA algae oil for 6 months has been shown to promote favorable transformations in gut microbiota, profiles of fecal metabolomic, and factors responsible for proinflammatory and oxidative stress, which might be beneficial for the prognosis of HIV-infected patients with NCI in the long-term. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04242004, identifier: NCT04242004.
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Docosahexaenoic acid (DHA) is an essential ω-3 long-chain polyunsaturated fatty acid (LCPUFA) and represents the dominant structural fatty acid in the retina and in the brain's gray matter. Due to its active participation in the development of the nervous system, DHA is one of the most studied LCPUFA and is currently considered a critical nutrient during pregnancy and breastfeeding. Increasing evidence in literature suggests that an adequate concentration of DHA is required from the fetal stage through to early life to ensure optimal neurological development. Likewise, many studies in literature demonstrated that an adequate supply of DHA during pregnancy and lactation is essential to promote proper brain development in utero and in early life. Daily supplementation of DHA in newborns has potentially stronger effects compared to maternal supplementation during pregnancy. Supplementation initiated in the second year of life in children born preterm did not result in global cognitive development improvements. Preliminary findings arising from metabolomics has reported that mother's milk and infant formula supplementation of Vitamin D associated with DHA results in a higher antioxidant and protective action, with a possible positive influence on renal function and body fat on preterm infants compared to those receiving only vitamin D. Recent applications of metabolomic studies on newborns may lead to a better understanding of the metabolic process linked to early nutrition and, subsequently, to the development of targeted and personalized nutritional strategies.
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A subset of individuals with major depressive disorder (MDD) elects treatment with complementary and alternative medicines (CAMs), including the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Previous studies in rodents suggest that DHA modulates neurodevelopmental processes, including adult neurogenesis and neuroplasticity, but the molecular and cellular mechanisms of DHA's potential therapeutic effect in the context of human neurobiology have not been well established. Here we sought to address this knowledge gap by investigating the effects of DHA using human iPSC-derived neural progenitor cells (NPCs) and post-mitotic neurons using pathway-selective reporter genes, multiplexed mRNA expression profiling, and a panel of metabolism-based viability assays. Finally, real-time, live-cell imaging was employed to monitor neurite outgrowth upon DHA treatment. Overall, these studies showed that DHA treatment (0-50⯵M) significantly upregulated both WNT and CREB signaling pathways in human neuronal cells in a dose-dependent manner with 2- to 3-fold increases in pathway activation. Additionally, we observed that DHA treatment enhanced survival of iPSC-derived NPCs and differentiation of post-mitotic neurons with live-cell imaging, revealing increased neurite outgrowth with DHA treatment within 24â¯h. Taken together, this study provides evidence that DHA treatment activates critical pathways regulating neuroplasticity, which may contribute to enhanced neuronal cell viability and neuronal connectivity. The extent to which these pathways represent molecular mechanisms underlying the potential beneficial effects of omega-3 fatty acids in MDD and other brain disorders merits further investigation.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Células-Tronco Neurais/metabolismo , Via de Sinalização Wnt , Linhagem Celular , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Crescimento NeuronalRESUMO
BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of neuroinflammatory disorders associated with autoimmune antibodies against aquaporin-4 (AQP4). Accumulating evidence suggests that inflammation is involved in NMOSD pathogenesis. Resolution of inflammation, which is a highly regulated process mediated by specialized pro-resolving lipid mediators (SPMs) is important to prevent over-responsive inflammation. Deficiency in resolution of inflammation may lead to or accelerates inflammatory diseases. However, whether resolution of inflammation is impaired in NMOSD is not known. The objective of this study was to analyze the levels of SPMs in the serum and cerebrospinal fluid (CSF) of NMOSD patients, and to explore the roles of SPMs in clinical features of NMOSD. METHODS: Thirty-five patients with NMOSD, 34 patients with multiple sclerosis, and 36 patients with non-inflammatory neurological diseases were enrolled in this study. Pro-resolving mediators including Annexin A1 (ANXA1) and resolvin D1 (RvD1), as well as pro-inflammatory lipid mediator leukotriene B4 (LTB4) levels were analyzed by enzyme-linked immunosorbent assay. Pro- and anti-inflammatory cytokines as well as chemokine levels were analyzed using cytometric beads array (CBA). RESULTS: Our results showed RvD1 levels were significantly decreased, whereas LTB4 levels were significantly increased in the CSF of NMOSD patients. AQP4-IgG titer was negatively correlated with RvD1 levels in the CSF of NMOSD patients. CONCLUSIONS: Decreased RvD1 levels indicate impaired resolution of inflammation in NMOSD patients. AQP4-IgG may contribute to increased inflammation and lead to unresolved inflammation in NMOSD.
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Inflamação/complicações , Neuromielite Óptica/complicações , Adulto , Anexina A1/sangue , Anexina A1/líquido cefalorraquidiano , Aquaporina 4/sangue , Barreira Hematoencefálica/metabolismo , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/líquido cefalorraquidiano , Feminino , Humanos , Inflamação/sangue , Inflamação/líquido cefalorraquidiano , Mediadores da Inflamação/sangue , Mediadores da Inflamação/líquido cefalorraquidiano , Leucotrieno B4/sangue , Leucotrieno B4/líquido cefalorraquidiano , Masculino , Neuromielite Óptica/sangue , Neuromielite Óptica/líquido cefalorraquidiano , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
The major facilitator superfamily domain-containing protein 2A (MFSD2A) is a constituent of the blood-brain barrier and functions to transport lysophosphatidylcholines (LPCs) into the central nervous system. LPCs such as that derived from docosahexanoic acid (DHA) are indispensable to neurogenesis and maintenance of neurons, yet cannot be synthesized within the brain and are dependent on MFSD2A for brain uptake. Recent studies have implicated MFSD2A mutations in lethal and non-lethal microcephaly syndromes, with the severity correlating to the residual activity of the transporter. We describe two siblings with shared parental ancestry, in whom we identified a homozygous missense mutation (c.1205C > A; p.Pro402His) in MFSD2A. Both affected individuals had microcephaly, hypotonia, appendicular spasticity, dystonia, strabismus, and global developmental delay. Neuroimaging revealed paucity of white matter with enlarged lateral ventricles. Plasma lysophosphatidylcholine (LPC) levels were elevated, reflecting reduced brain transport. Cell-based studies of the p.Pro402His mutant protein indicated complete loss of activity of the transporter despite the non-lethal, attenuated phenotype. The aggregate data of MFSD2A-associated genotypes and phenotypes suggest that additional factors, such as nutritional supplementation or modifying genetic factors, may modulate the severity of disease and call for consideration of treatment options for affected individuals.
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Doenças Desmielinizantes/genética , Ácidos Docosa-Hexaenoicos/metabolismo , Microcefalia/genética , Mutação de Sentido Incorreto , Proteínas Supressoras de Tumor/genética , Substituição de Aminoácidos , Animais , Transporte Biológico/genética , Barreira Hematoencefálica/metabolismo , Criança , Pré-Escolar , Doenças Desmielinizantes/metabolismo , Deficiências do Desenvolvimento/genética , Feminino , Células HEK293 , Homozigoto , Humanos , Metabolismo dos Lipídeos/genética , Lisofosfatidilcolinas/metabolismo , Masculino , Camundongos , Camundongos Knockout , Microcefalia/metabolismo , Modelos Moleculares , Bainha de Mielina/metabolismo , Linhagem , Irmãos , Simportadores , Proteínas Supressoras de Tumor/química , Proteínas Supressoras de Tumor/metabolismoRESUMO
The amount, composition, and sources of nutrition support provided to preterm infants is critical for normal growth and development, and particularly for structural and functional neurodevelopment. Although omega-3 long chain polyunsaturated fatty acids (LC-PUFA), and particularly docosahexanoic acid (DHA), are considered of particular importance, results from clinical trials with preterm infants have been inconclusive because of ethical limitations and confounding variables. A translational large animal model is needed to understand the structural and functional responses to DHA. Neurodevelopment of preterm pigs was evaluated in response to feeding formulas to term-equivalent age supplemented with DHA attached to phosphatidylserine (PS-DHA) or sunflower oil as the placebo. Newborn term pigs were used as a control for normal in utero neurodevelopment. Supplementing formula with PS-DHA increased weight of the brain, and particularly the cerebellum, at term-equivalent age compared with placebo preterm pigs (P's < 0.10 and 0.05 respectively), with a higher degree of myelination in all regions of the brain examined (all p < 0.06). Brains of pigs provided PS-DHA were similar in weight to newborn term pigs. Event-related brain potentials and performance in a novel object recognition test indicated the PS-DHA supplement accelerated development of sensory pathways and recognition memory compared with placebo preterm pigs. The PS-DHA did not increase weight gain, but was associated with higher survival. The benefits of PS-DHA include improving neurodevelopment and possibly improvement of survival, and justify further studies to define dose-response relations, compare benefits associated with other sources of DHA, and understand the mechanisms underlying the benefits and influences on the development of other tissues and organ systems.
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Encéfalo/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Neurogênese/efeitos dos fármacos , Fosfatidilserinas/administração & dosagem , Nascimento Prematuro , Fatores Etários , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Ácidos Docosa-Hexaenoicos/metabolismo , Potenciais Evocados/efeitos dos fármacos , Idade Gestacional , Imageamento por Ressonância Magnética , Fosfatidilserinas/metabolismo , Reconhecimento Psicológico/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Sus scrofa , Aumento de PesoRESUMO
For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism. Since the pathogenesis of non alcoholic fatty liver disease (NAFLD) begins with the accumulation of liver lipid and progresses with inflammation and then several years later with development of fibrosis; it has been thought in patients with NAFLD omega-3 fatty acid treatment would be beneficial in treating liver lipid and possibly also in ameliorating inflammation. Meta-analyses (of predominantly dietary studies and small trials) have tended to support the assertion that omega-3 fatty acids are beneficial in decreasing liver lipid, but recent randomised controlled trials have produced conflicting data. These trials have suggested that omega-3 fatty acid might be beneficial in decreasing liver triglyceride (docosahexanoic acid also possibly being more effective than eicosapentanoic acid) but not in decreasing other features of steatohepatitis (or liver fibrosis). The purpose of this review is to discuss recent evidence regarding biological mechanisms by which long chain omega-3 fatty acids might act to ameliorate liver disease in NAFLD; to consider the recent evidence from randomised trials in both adults and children with NAFLD; and finally to discuss key 'known unknowns' that need to be considered, before planning future studies that are focussed on testing the effects of omega-3 fatty acid treatment in patients with NAFLD.
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Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Inflamação/dietoterapia , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Hipertrigliceridemia/dietoterapia , Inflamação/metabolismo , Inflamação/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/dietoterapia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Omega-3 fatty acids have the potential to decrease inflammation and modify gene transcription. Whether docosahexanoic acid (DHA) supplementation can modify systemic inflammatory and subcutaneous adipose tissue (SAT) gene expression in HIV-infected patients is unknown. METHODS: A randomized, double-blind, placebo-controlled trial that enrolled 84 antiretroviral-treated patients who had fasting TG levels from 2.26 to 5.65â¯mmol/l and received DHA or placebo for 48â¯weeks was performed (ClinicalTrials.gov, NCT02005900). Systemic inflammatory and SAT gene expression was assessed at baseline and at week 48 in 39 patients. RESULTS: Patients receiving DHA had a 43.9% median decline in fasting TG levels at week 4 (IQR: -31% to -56%), compared with -2.9% (-18.6% to 16.5%) in the placebo group (Pâ¯<â¯0.0001). High sensitivity C reactive protein (hsCRP) and arachidonic acid levels significantly decreased in the DHA group. Adipogenesis-related and mitochondrial-related gene expression did not experience significant changes. Mitochondrial DNA (mtDNA) significantly decreased in the placebo group. SAT inflammation-related gene expression (Tumor necrosis factor alpha [TNF-α], and monocyte chemoattractant protein-1 [MCP-1]) significantly decreased in the DHA group. CONCLUSIONS: DHA supplementation down-regulated inflammatory gene expression in SAT. DHA impact on markers of systemic inflammation was restricted to hsCRP and arachidonic acid.
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Terapia Antirretroviral de Alta Atividade , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Regulação da Expressão Gênica , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Inflamação/genética , Gordura Subcutânea/metabolismo , Adipócitos/metabolismo , Adulto , Ácido Araquidônico/metabolismo , Biomarcadores/metabolismo , Glicemia/metabolismo , Diferenciação Celular/genética , DNA Mitocondrial/genética , Ácidos Docosa-Hexaenoicos/farmacologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/sangue , Homeostase , Humanos , Inflamação/sangue , Mediadores da Inflamação/metabolismo , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placebos , Gordura Subcutânea/efeitos dos fármacosRESUMO
PROPOSE: In this study, we evaluated the effects of different concentrations of docosahexanoic acid (DHA) supplement on preterm Sprague-Dawley rat pups, and in parallel, measured the phosphorylation activity of the mTOR pathway in the hippocampal CA1 area. METHODS: Preterm Sprague-Dawley rat pups were randomly assigned to experimental groups which included; a sufficient DHA group (100â¯mg/kg/day); an enriched DHA group (300â¯mg/kg/day); an excess DHA group (800â¯mg/kg/day); and a deficient DHA group (normal saline gavage 0.1â¯ml/10â¯g). Body weight (g) was measured at days 1/7/14/21/28/42, respectively. Spatial learning and memory were also tested using the Morris water maze at week 6 (day 42). Finally, activation of the mTOR signaling pathway in hippocampal CA1 area were evaluated by western blotting. RESULTS: Postnatal sufficient/enriched docosahexanoic acid supplement ameliorated body weight restriction, spatial learning and memory restriction, and decreased phosphorylation of AKT, mTOR, P70S6K1, and 4EBP1 in hippocampal CA1 area. Furthermore, excess docosahexanoic acid supplement impeded weight gain and spatial learning and memory, perturbed serum unsaturated fatty acid, and downregulated phosphorylation of AKT, mTOR, P70S6K1, and 4EBP1 in hippocampal CA1 area. CONCLUSION: Postnatal sufficient/enriched DHA supplement ameliorated growth and spatial learning and memory impairment and upregulated the mTOR pathway in preterm pups, although excessive DHA supplement did not have any beneficial effects.
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Deficiências do Desenvolvimento/dietoterapia , Ácidos Docosa-Hexaenoicos/farmacologia , Lactação/efeitos dos fármacos , Nascimento Prematuro/dietoterapia , Fatores Etários , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ácidos Graxos Insaturados/sangue , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Deficiências da Aprendizagem/dietoterapia , Deficiências da Aprendizagem/etiologia , Masculino , Transtornos da Memória/dietoterapia , Transtornos da Memória/etiologia , Gravidez , Nascimento Prematuro/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Hypertriglyceridemia is common in HIV-infected patients. Polyunsaturated fatty acids reduce fasting serum triglyceride (TG) levels in HIV-infected patients. It is not known whether docosahexanoic acid (DHA) supplementation can reduce hypertriglyceridemia and modify fat distribution in HIV-infected patients. METHODS: We conducted a randomized, double-blind, placebo-controlled trial with 84 antiretroviral-treated patients who had fasting TG levels from 2.26 to 5.65 mmol/l and were randomized to receive DHA or placebo for 48 weeks. TG levels were assessed at baseline, week 4 and every 12 weeks. Body composition was assessed at baseline and at week 48. Registered under ClinicalTrials.gov Identifier no. NCT02005900. RESULTS: Patients receiving DHA had a 43.9% median decline in fasting TG levels at week 4 (IQR: -31% to -56%), compared with -2.9% (-18.6% to 16.5%) in the placebo group (P < 0.0001). DHA levels and decrease in TG at week 4 in the DHA arm correlated significantly (r = 0.7110, P < 0.0001). The median reduction in TG levels in the DHA arm was -43.7% (-32.4% to -57.5%), and in the placebo arm +2.9% (-21.3% to +30.1%) at week 12. The difference remained statistically significant at week 48 (P = 0.0253). LDL cholesterol levels significantly increased at week 4 by 7.1% (IQR: -4.8% to +35.3%) in the DHA arm but not in the placebo group. No significant changes were observed in HDL cholesterol, insulin, and HOMA-IR during the study. Limb fat significantly increased in both arms, without statistically significant differences between groups (P = 0.3889). DHA was well tolerated; only 3 patients experienced treatment-limiting toxicity. CONCLUSIONS: Supplementation with DHA reduced fasting TG levels in antiretroviral-treated HIV-infected patients with mild hypertriglyceridemia. DHA was well tolerated with minor GI symptoms. Peripheral fat significantly increased in the DHA group but did not increase significantly compared with placebo.
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Tecido Adiposo/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Antirretrovirais/uso terapêutico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacologia , Tamanho Corporal/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/efeitos adversos , Ácidos Docosa-Hexaenoicos/farmacologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Infecções por HIV/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
Omega-3 polyunsaturated fatty acids have emerged as possible protective factors associated with a decreased risk for myocardial infarction in populations with a high marine food intake, which may relate to effects on lipid metabolism, thrombosis and inflammation. Omega-3 fatty acids decrease triglyceride levels and also compete as substrates for enzymes involved in the biosynthesis of lipid mediators. The balance between omega-3-derived specialized proresolving mediators and pro-inflammatory lipid mediators from arachidonic acid metabolism can be measured as the resolvin-to-leukotriene ratio, which has been shown to predict subclinical atherosclerosis. The results of experimental, observational and randomized studies of omega-3 fatty acids are somewhat variable and should be interpreted in view of the models used and the populations studied.
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Hematopoietic stem cells play the vital role of maintaining appropriate levels of cells in blood. Therefore, regulation of their fate is essential for their effective therapeutic use. Here we report the role of polyunsaturated fatty acids (PUFAs) in regulating hematopoiesis which has not been explored well so far. Mice were fed daily for 10 days with n-6/n-3 PUFAs, viz. linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid and docosahexanoic acid (DHA) in four separate test groups with phosphate-buffered saline fed mice as control set. The bone marrow cells of PUFA-fed mice showed a significantly higher hematopoiesis as assessed using side population, Lin-Sca-1+ckit+, colony-forming unit (CFU), long-term culture, CFU-spleen assay and engraftment potential as compared to the control set. Thrombopoiesis was also stimulated in PUFA-fed mice. A combination of DHA and AA was found to be more effective than when either was fed individually. Higher incorporation of PUFAs as well as products of their metabolism was observed in the bone marrow cells of PUFA-fed mice. A stimulation of the Wnt, CXCR4 and Notch1 pathways was observed in PUFA-fed mice. The clinical relevance of this study was evident when bone marrow-transplanted recipient mice, which were fed with PUFAs, showed higher engraftment of donor cells, suggesting that the bone marrow microenvironment may also be stimulated by feeding with PUFAs. These data indicate that oral administration of PUFAs in mice stimulates hematopoiesis and thrombopoiesis and could serve as a valuable supplemental therapy in situations of hematopoietic failure.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-6/uso terapêutico , Hematopoese , Trombopoese , Regulação para Cima , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Células Cultivadas , Suplementos Nutricionais/efeitos adversos , Ácidos Graxos Ômega-3/efeitos adversos , Ácidos Graxos Ômega-6/efeitos adversos , Feminino , Regulação da Expressão Gênica , Sobrevivência de Enxerto , Hematínicos/uso terapêutico , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Receptor Notch1/agonistas , Receptor Notch1/genética , Receptor Notch1/metabolismo , Receptores CXCR4/agonistas , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Condicionamento Pré-Transplante/efeitos adversos , Proteínas Wnt/agonistas , Proteínas Wnt/genética , Proteínas Wnt/metabolismoRESUMO
Young rabbits, the dams of which came from a full diallel cross among four maternal lines (A, V, H and LP) and the sires from a single paternal line (R), that produce sixteen genetic groups, was carried out to evaluate the genetic groups and to estimate the crossbreeding genetic parameters of meat quality. The meat quality traits were recorded by NIRS from a sample of 285 longissimus lumborum muscles. Crossbreeding parameters were estimated according to Dickerson model. No differences in protein were found. The line A had significant differences with V line for intramuscular fat, and fatty acids groups. Significant differences for these traits appeared between the crossbred AH and VV (in favor of AH). As conclusion, the significant contrasts between genetic types for chemical composition of the meat are mainly consequence of direct-maternal genetic effects, having grandmaternal and maternal heterosis effects a less relevant role.
Assuntos
Carne/análise , Coelhos/genética , Tecido Adiposo/metabolismo , Animais , Cruzamentos Genéticos , Proteínas Alimentares/análise , Ácidos Graxos/análise , Feminino , Vigor Híbrido , Hibridização Genética , Masculino , Músculo Esquelético/metabolismoRESUMO
BACKGROUND: Perinatal hypoxic-ischemic brain damage is a major cause of acute mortality and chronic neurological morbidity in infants and children. Oxidative stress due to free radical formation and the initiation of abnormal oxidative reactions appears to play a key role. Docosahexanoic acid (DHA), a main component of brain membrane phospholipids, may act as a neuroprotectant after hypoxia-ischemia by regulating multiple molecular pathways and gene expression. OBJECTIVES: The aims of this study were to test the hypothesis that DHA provides significant protection against lipoperoxidation damage in the cerebral cortex and hippocampus in a neonatal piglet model of severe hypoxia-reoxygenation. METHODS: Newborn piglets, Noroc (LYLD), were subjected to severe global hypoxia. One group was resuscitated with ambient air (21% group, n = 11) and another also received 5 mg/kg of DHA 4 h after the end of hypoxia (21% DHA group, n = 10). After 9.5 h, tissues from the prefrontal cortex and hippocampus were sampled and the levels of isoprostanes, neuroprostanes, neurofurans, and F2-dihomo-isoprostanes were determined by the liquid chromatography triple quadrupole mass spectrometry technique. RESULTS: Lipid peroxidation biomarkers were significantly lower in both the cortex and hippocampus in the DHA-treated group compared with the untreated group. CONCLUSIONS: The present study demonstrates that DHA administration after severe hypoxia in newborn piglets has an antioxidative effect in the brain, suggesting a protective potential of DHA if given after injuries to the brain.
Assuntos
Antioxidantes/farmacologia , Asfixia Neonatal/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/farmacologia , Hipocampo/efeitos dos fármacos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Asfixia Neonatal/metabolismo , Asfixia Neonatal/patologia , Biomarcadores/metabolismo , Modelos Animais de Doenças , Furanos/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Isoprostanos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Neuroprostanos/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Sus scrofaRESUMO
INTRODUCTION: Attention Deficit Hyperactivity Disorder (ADHD) is a common disorder of childhood. Studies have indicated nutritional deficiencies, particularly Poly Unsaturated Fatty Acids (PUFA) deficiency in these children and have suggested supplementation with PUFA for clinical improvement. AIM: The present study aimed at evaluating the effect of PUFA administration in Indian children with ADHD. SETTINGS AND DESIGN: The study was conducted in the paediatrics and psychiatry departments of a tertiary care hospital. We conducted a prospective double blind randomized control trial on children aged 4-11 years, diagnosed with ADHD according to DSM-IV TR criterias and Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and lifetime version. MATERIALS AND METHODS: The study subjects were randomized into study and control groups. The control group was administered Atomoxetine, while the study group received Atomoxetine along with Eicosapentanoic acid (EPA) and Docosahexanoic acid (DHA). Both groups were followed up every 2 weeks over the next 4 months using Conner's Parent Rating Scale - Revised (CPRS-R). STATISTICAL ANALYSIS: The data was carefully analysed by SPSS (17th version) software with the help of a statistician. Confidence interval of 95% was used. The complete data was analysed using appropriate parametric and non parametric tests. Correlation was done between various socio-demographic and illness related parameters. For all analyses, probability of 5% or less was assumed to represent statistical significance. RESULTS: Fifty children diagnosed with ADHD were randomized to study group (n=25) and control group (n=25). The study group had greater reduction in ADHD scores as compared to the control group, although not statistically significant (p = 0.08). Improvement was more significant in male study subjects with combined type of ADHD. CONCLUSION: It may be concluded that PUFA supplementation improves the symptoms of ADHD. However, the effect is not clinically significant if supplementation is not given for prolonged duration and in adequate doses.