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Background: Human milk contains both arachidonic acid (ARA) and docosahexaenoic acid (DHA). Supplementation of infant formula with ARA and DHA results in fatty acid (FA) profiles, neurodevelopmental outcomes, and immune responses in formula-fed infants that are more like those observed in breastfed infants. Consequently, ARA and DHA have been historically added together to infant formula. This study investigated the impact of ARA or DHA supplementation alone or in combination on tissue FA incorporation, immune responses, and neurodevelopment in the young pig. Methods: Male pigs (N = 48 total) received one of four dietary treatments from postnatal day (PND) 2-30. Treatments targeted the following ARA/DHA levels (% of total FA): CON (0.00/0.00), ARA (0.80/0.00), DHA (0.00/0.80), and ARA+DHA (0.80/0.80). Plasma, red blood cells (RBC), and prefrontal cortex (PFC) were collected for FA analysis. Blood was collected for T cell immunophenotyping and to quantify a panel of immune outcomes. Myelin thickness in the corpus callosum was measured by transmission electron microscopy and pig movement was measured by actigraphy. Results: There were no differences in formula intake or growth between dietary groups. DHA supplementation increased brain DHA, but decreased ARA, compared with all other groups. ARA supplementation increased brain ARA compared with all other groups but did not affect brain DHA. Combined supplementation increased brain DHA levels but did not affect brain ARA levels compared with the control. Pigs fed ARA or ARA+DHA exhibited more activity than those fed CON or DHA. Diet-dependent differences in activity suggested pigs fed ARA had the lowest percent time asleep, while those fed DHA had the highest. No differences were observed for immune or myelination outcomes. Conclusion: Supplementation with ARA and DHA did not differentially affect immune responses, but ARA levels in RBC and PFC were reduced when DHA was provided without ARA. Supplementation of either ARA or DHA alone induced differences in time spent asleep, and ARA inclusion increased general activity. Therefore, the current data support the combined supplementation with both ARA and DHA in infant formula and raise questions regarding the safety and nutritional suitability of ARA or DHA supplementation individually.
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Breastfeeding is universally recommended as the optimal choice of infant feeding and consequently human milk has been extensively investigated to unravel its unique nutrient profile. The human milk lipid composition is unique and supplies specifically long-chain polyunsaturated fatty acids (LC-PUFAs), in particular, arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3). Arachidonic acid (ARA) is the most predominant long-chain polyunsaturated fatty acid in human milk, albeit at low concentrations as compared to other fatty acids. It occurs predominantly in the triglyceride form and to a lesser extent as milk fat globule membrane phospholipids. Human milk ARA levels are modulated by dietary intake as demonstrated by animal and human studies and consequently vary dependent on dietary habits among mothers and regions across the globe. ARA serves as a precursor to eicosanoids and endocannabinoids that also occur in human milk. A review of scientific and clinical studies reveals that ARA plays an important role in physiological development and its related functions during early life nutrition. Therefore, ARA is an important nutrient during infancy and childhood and, as such, appropriate attention is required regarding its nutritional status and presence in the infant diet. Data are emerging indicating considerable genetic variation in encoding for desaturases and other essential fatty acid metabolic enzymes that may influence the ARA level as well as other LC-PUFAs. Human milk from well-nourished mothers has adequate levels of both ARA and DHA to support nutritional and developmental needs of infants. In case breastfeeding is not possible and infant formula is being fed, experts recommend that both ARA and DHA are added at levels present in human milk.
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Ácido Araquidônico/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Fenômenos Fisiológicos da Nutrição do Lactente , Leite Humano/metabolismo , Animais , Feminino , Humanos , Lactente , Recém-NascidoRESUMO
Optimized nutrition during the first 1000 days (from conception through the 2nd birthday) is critical for healthy development and a healthy life for the newborn. Pregnancy and the postpartum period are accompanied by physiological changes, increased energy needs, and changing requirements in the nutrients critical for optimal growth and development. Infants and toddlers also experience physiological changes and have specific nutritional needs. Food and nutrition experts can provide women of childbearing age with adequate dietary advice to optimize nutrition, as well as guidance on selecting appropriate dietary supplements. Considering the approaching 2020-2025 Dietary Guidelines for Americans (DGA) will be making specific recommendations for children, it is important to provide accurate scientific information to support health influencers in the field of nutrition. The purpose of this review is to summarize the nutrition and supplementation literature for the first 1000 days; to highlight nutritional and knowledge gaps; and to educate nutrition influencers to provide thoughtful guidance to mothers and families. Optimal nutrition during pregnancy through early childhood is critical for supporting a healthy life. Nutrition influencers, such as dietitians, obstetricians/gynecologists, and other relevant health professionals, should continue guiding supplement and food intake and work closely with expectant families and nutrition gatekeepers.
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Suplementos Nutricionais , Necessidades Nutricionais , Pré-Escolar , Feminino , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lactente , Recém-Nascido , Fenômenos Fisiológicos da Nutrição Materna , Política Nutricional , Gravidez , Cuidado Pré-NatalRESUMO
The relationship between seafood eaten during pregnancy and neurocognition in offspring has been the subject of considerable scientific study for over 25 years. Evaluation of this question led two scientific advisory committees to the Dietary Guidelines for Americans (DGAC), the Food and Agriculture Organization of the United Nations with the World Health Organization (FAO/WHO), Health Canada, the European Food Safety Authority (EFSA), and the U.S. Food and Drug Administration (FDA) to conclude through 2014 that seafood consumed by pregnant women is likely to benefit the neurocognitive development of their children. The evidence they reviewed included between four and ten studies of seafood consumption during pregnancy that reported beneficial associations. In contrast there are now 29 seafood consumption studies available describing over 100,000 mothers-child pairs and 15 studies describing over 25,000 children who ate seafood. A systematic review of these studies using Nutrition Evaluation Systematic Review methodology is warranted to determine whether recent research corroborates, builds on, or significantly alters the previous conclusions. Studies that evaluate the integrated effects of seafood as a complete food more directly and completely evaluate impacts on neurocognition as compared to studies that evaluate individual nutritients or toxicological constituents in isolation. Here we address how the findings could add to our understanding of whether seafood consumed during pregnancy and early childhood affects neurocognition, including whether such effects are clinically meaningful, lasting, related to amounts consumed, and affected by any neurotoxicants that may be present, particularly mercury, which is present at varying levels in essentially all seafood. We provide the history, context and rationale for reexamining these questions in light of currently available data.
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Ácidos Graxos Ômega-3/farmacologia , Processos Mentais/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Pré-Natal/efeitos dos fármacos , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Saúde da Criança , Feminino , Humanos , Política Nutricional , Gravidez , Alimentos MarinhosRESUMO
The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cognitive impairment and decline of gait speed in older adults. Therefore, we tested the hypothesis that low plasma LPC are associated with impaired skeletal muscle mitochondrial oxidative capacity. Skeletal muscle mitochondrial oxidative capacity was measured using in vivo phosphorus magnetic resonance spectroscopy (31 P-MRS) in 385 participants (256 women, 129 men), aged 24-97 years (mean 72.5) in the Baltimore Longitudinal Study of Aging. Postexercise recovery rate of phosphocreatine (PCr), kPCr , was used as a biomarker of mitochondrial oxidative capacity. Plasma LPC were measured using liquid chromatography-tandem mass spectrometry. Adults in the highest quartile of kPCr had higher plasma LPC 16:0 (p = 0.04), 16:1 (p = 0.004), 17:0 (p = 0.01), 18:1 (p = 0.0002), 18:2 (p = 0.002), and 20:3 (p = 0.0007), but not 18:0 (p = 0.07), 20:4 (p = 0.09) compared with those in the lower three quartiles in multivariable linear regression models adjusting for age, sex, and height. Multiple machine-learning algorithms showed an area under the receiver operating characteristic curve of 0.638 (95% confidence interval, 0.554, 0.723) comparing six LPC in adults in the lower three quartiles of kPCr with the highest quartile. Low plasma LPC are associated with impaired mitochondrial oxidative capacity in adults.
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Envelhecimento/metabolismo , Lisofosfatidilcolinas/sangue , Mitocôndrias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Baltimore , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mitocôndrias/patologia , Músculo Esquelético/metabolismo , Estresse OxidativoRESUMO
Background: Gait speed is an important measure of lower extremity physical performance in older adults and is predictive of disability and mortality. The biological pathways involved in the decline of lower extremity physical performance are not well understood. We used a targeted metabolomics approach to identify plasma metabolites predictive of change in gait speed over time. Methods: Gait speed was measured at baseline and over median follow-up of 50.5 months in 504 adults, aged ≥50 years, who had two or more study visits in the Baltimore Longitudinal Study of Aging (BLSA). Plasma metabolites were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates). Results: Of 148 plasma metabolites (amino acids, biogenic amines, hexoses, glycerophospholipids) measured, eight were significantly associated with gait speed at baseline, independent of age and sex: hexoses (r = -0.148, p < .001), [sphingomyelin (SM) 16:1 (r = -0.091, p = .0009), SM 18:0 (r = -0.085, p = .002), SM 18:1 (r = -0.128, p < .0001], phosphatidylcholine aa 32:3 (r = -0.088, p = .001), lysophosphatidylcholine (LPC) 17:0 (r = 0.083, p = .003), LPC 18:1 (r = 0.089, p = .001), and LPC 18:2 (r = 0.104, p < .0001). Adjusting for baseline age, sex, and chronic diseases, baseline plasma LPC 18:2 was an independent predictor of the rate of change of gait speed over subsequent follow-up (p = .003). No other plasma metabolites were significantly associated longitudinal changes of gait speed over time. Conclusions: Low plasma LPC 18:2, which has previously been shown to predict impaired glucose tolerance, insulin resistance, type 2 diabetes, coronary artery disease, and memory impairment, is an independent predictor of decline in gait speed in older adults.
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Envelhecimento/fisiologia , Marcha/fisiologia , Avaliação Geriátrica/métodos , Lisofosfatidilcolinas/sangue , Metabolômica/métodos , Sarcopenia/fisiopatologia , Velocidade de Caminhada/fisiologia , Idoso , Baltimore/epidemiologia , Biomarcadores/sangue , Estudos Transversais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Estudos Retrospectivos , Sarcopenia/sangue , Sarcopenia/epidemiologia , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
Context and Objectives: Glucose metabolism becomes progressively impaired with older age. Fasting glucose and insulin resistance are risk factors for premature death and other adverse outcomes. We aimed to identifying plasma metabolites associated with altered glucose metabolism and insulin resistance in older community-dwelling adults. Participants and Methods: A targeted metabolomics approach was used to identify plasma metabolites associated with impaired fasting plasma glucose, 2-hour plasma glucose on oral glucose tolerance testing, and homeostatic model assessment insulin resistance (HOMA-IR) in 472 participants who participated in the Baltimore Longitudinal Study of Aging, with a mean (SD) age of 70.7 (9.9) years. Results: We measured 143 plasma metabolites. In ordinal logistic regression analyses, using a false discovery rate of 5% and adjusting for potential confounders, we found that alanine, glutamic acid, and proline were significantly associated with increased odds of abnormal fasting plasma glucose. Phosphatidylcholine (diacyl C34:4, alkyl-acyl C32:1, C32:2, C34:2, C34:3, and C36:3) was associated with decreased odds of abnormal fasting plasma glucose. Glutamic and acid phosphatidylcholine alkyl-acyl C34:2 were associated with increased and decreased odds of 2-hour plasma glucose, respectively. Glutamic acid was associated with increased odds of higher tertiles of HOMA-IR. Glycine; phosphatidylcholine (diacyl C32:0, alkyl-acyl C32:1, C32:2, C34:1, C34:2, C34:3, C36:2, C36:3, C40:5, C40:6, C42:3, C42:4, and C42:5); sphingomyelin C16:0, C24:1, and C26:1; and lysophosphatidylcholine C18:1 were associated with decreased odds of abnormal HOMA-IR. Conclusions: Targeted metabolomics identified four plasma amino acids and 16 plasma lipid species, primarily containing polyunsaturated fatty acids, that were associated with abnormal glucose metabolism and insulin resistance in older adults.
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Aminoácidos/sangue , Glicemia/metabolismo , Resistência à Insulina/fisiologia , Lipídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Ácido Glutâmico/sangue , Glicina/sangue , Humanos , Estudos Longitudinais , Lisofosfatidilcolinas/sangue , Masculino , Metabolômica , Pessoa de Meia-Idade , Razão de Chances , Fosfatidilcolinas/sangue , Esfingomielinas/sangueRESUMO
This study focused on the effect of polyunsaturated fatty acids (PUFAs) during the lactation period of delta-6-desaturase knockout (D6D-KO) mice using an artificial rearing method. Newborn pups of D6D-KO male mice were separated from their dams within 48h and were fed artificial milk. Six formulations of milk were used: Control (Cont) milk (3.9% α-linolenic acid and 18% linoleic acid), + 1.3% arachidonic acid (ARA), + 1.2% docosahexaenoic acid (DHA), + 1.3% eicosapentaenoic acid (EPA), + 1.1% ARA + 1.3% DHA, and + 1.3% ARA + 1.3% EPA. After weaning, the mice were fed pelleted diets containing a similar fatty acid composition as during lactation. Brain function was measured using a behavioral approach including motor activity and the Morris water maze test at 9 weeks of age. The body weight of the KO Cont group was significantly lower than that of the wild-type (WT) group; however, the ARA, ARA+DHA and ARA+EPA groups were similar to the WT group. In the Morris water maze test, the DHA and ARA+DHA groups demonstrated learning and memory performance similar to the WT group; however, the Cont group exhibited quite poor learning performance. Interestingly, the ARA, EPA and ARA+EPA groups showed intermediate performance between the Cont and WT groups. These results suggested that the 18-C essential fatty acids linoleic and α-linolenic were not sufficient to support optimal growth and neural performance. ARA was the most critical long-chain PUFA for supporting body growth. In addition, DHA was clearly essential for brain function. Taken together, these results indicate that the combination of DHA and ARA is essential for optimal growth and development in early life.
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Encéfalo/efeitos dos fármacos , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Insaturados/administração & dosagem , Atividade Motora/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Ácido Araquidônico/administração & dosagem , Peso Corporal/efeitos dos fármacos , Peso Corporal/genética , Encéfalo/crescimento & desenvolvimento , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Ácidos Graxos Dessaturases/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Knockout , Atividade Motora/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismoRESUMO
Background: Stunting affects â¼25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood.Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting.Design: We measured 677 serum metabolites using liquid chromatography-tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12-59 mo, of whom 62% were stunted.Results: A low height-for-age z score (HAZ) was associated with lower serum concentrations of 1) ω-3 (n-3) and ω-6 (n-6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a role in brain development, 3) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and 4) γ-glutamyl amino acids, which represent an altered γ-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure.Conclusions: This metabolomics study shows a cross-sectional association between stunting and low serum ω-3 and ω-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for ß-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. This trial was registered at www.controlled-trials.com as ISRCTN14597012.
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Estatura , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Transtornos do Crescimento/sangue , Estado Nutricional , População Rural , Carnitina/sangue , Desenvolvimento Infantil , Pré-Escolar , Estudos Transversais , Metabolismo Energético , Exposição Ambiental/efeitos adversos , Feminino , Glutationa/sangue , Transtornos do Crescimento/etiologia , Humanos , Lactente , Metabolismo dos Lipídeos , Malaui , Masculino , Redes e Vias Metabólicas , Neurotransmissores/sangue , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
Although the literature on the contribution of DHA and arachidonic acid (ARA) to fundamental metabolic functions in brain, immune and cardiovascular systems is extensive, there is a lack of consensus on the need for explicit recommendations on dietary intake for both DHA and ARA during the early years of life. This review takes a public health perspective with the objective of ensuring that recommendations protect the most vulnerable children worldwide. Most studies on the effects of DHA and ARA in early life have been undertaken in high-income countries and this is reflected in policy recommendations. Although breast milk is considered the gold standard and always contains DHA and ARA, there are proposals that infant formulas, especially follow-on formulas, do not need to be supplemented with these fatty acids. Complementary foods frequently have low concentrations of ARA and DHA and this is most significant in low-income countries where availability is also limited. Recent evidence shows that in developing countries, intakes of DHA and ARA during the age period 6-36 months are low and this relates to low national income. It is concluded that a continuum of DHA and ARA intake needs to be maintained during early life, a critical period of infant growth and development. For both infant and follow-on formulas, DHA and ARA should be mandatory at levels that are equivalent to breast milk. An optional recommendation may be limited to countries that can demonstrate evidence of adequate intakes of DHA and ARA during early life.
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Ácido Araquidônico/administração & dosagem , Gorduras na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Saúde Pública , Recomendações Nutricionais , Pré-Escolar , Países em Desenvolvimento , Humanos , Lactente , Fórmulas Infantis/química , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Leite Humano/química , PobrezaRESUMO
BACKGROUND: In developing countries, dietary intakes of arachidonic acid (ARA) and docosahexaenoic acid (DHA) in early life are lower than current recommended levels. This review specifically focusses on the contribution that complementary feeding makes to ARA and DHA intakes in medium- to low-income countries. The aims of the review are (1) to determine the availability of ARA and DHA food sources in developing countries, (2) to estimate the contribution of complementary feeding to dietary intakes of ARA and DHA in infants aged 6-36 months, and (3) to relate the dietary ARA and DHA intake data to key socioeconomic and health indicators. SUMMARY: The primary dietary data was collected by the Food and Agriculture Organisation (FAO) using Food Balance Sheets, and fatty acid composition was based on the Australian food composition tables. There is evidence of wide variation in per capita dietary intake for both DHA and ARA food sources, with low intakes of meat and seafood products being highly prevalent in most low-income countries. In children aged 6-36 months, the supply of ARA and DHA from the longer duration of breastfeeding in low-income countries is counterbalanced by the exceptionally low provision of ARA and DHA from complementary foods. The lowest tertile for ARA intake is associated with higher percentages of childhood stunting, birth rate, infant mortality, and longer duration of breast feeding. Key Message: In developing countries, intakes of DHA and ARA from complementary foods are low, and public health organisations need to adopt pragmatic strategies that will ensure that there is a nutritional safety net for the most vulnerable infants.
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Ácido Araquidônico/provisão & distribuição , Países em Desenvolvimento , Ácidos Docosa-Hexaenoicos/provisão & distribuição , Ingestão de Alimentos , Fenômenos Fisiológicos da Nutrição do Lactente , Ácido Araquidônico/análise , Aleitamento Materno/estatística & dados numéricos , Pré-Escolar , Ácidos Docosa-Hexaenoicos/análise , Feminino , Análise de Alimentos , Humanos , Lactente , Masculino , Necessidades Nutricionais , Fatores de TempoRESUMO
The essentiality of arachidonic acid (ARA) and docosahexaenoic acid (DHA) for growth and brain function using delta-6-desaturase knockout (D6D-KO) mice and a novel artificial rearing method was investigated. Newborn male wild type (WT) and homozygous D6D-KO pups were separated from their dams within 48h and fed artificial milk containing α-linolenic acid and linoleic acid (Cont), or supplemented with ARA, DHA or both (ARA+DHA). After weaning, each group was fed diets similar to artificial milk in fatty acid composition for 7 weeks. KO-Cont showed a lower body weight than WT-Cont. When ARA was added to the control diet, (KO-ARA and KO-ARA+DHA diets) the body weight gain was restored. The KO-DHA group was initially similar to the WT groups for the first 6 weeks, but afterwards their body weight was significantly lower. Brain weight in the 10 week old KO-ARA+DHA group was significantly higher within the KO dietary groups. Motor activity of the KO-ARA and KO-ARA+DHA groups was elevated relative to the KO-Cont group but the KO-ARA+DHA group exhibited similar activity to the WT-Cont group. In the motor coordination ability test, the KO-Cont group performed significantly worse compared with the WT-Cont group. KO-ARA mice showed decreased motor coordination in spite of their increased motor activity. The best performance was observed in only KO-ARA+DHA mice. These experiments demonstrated that supplementation with only ARA or only DHA was insufficient for optimal development. ARA was essential for normal growth within the lactation period. In conclusion, only the combination of preformed ARA and DHA was capable of improving the dysfunction caused by D6D deficiency.
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Ácido Araquidônico/administração & dosagem , Encéfalo/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Graxos Dessaturases/genética , Técnicas de Inativação de Genes , Animais , Animais Recém-Nascidos , Ácido Araquidônico/farmacologia , Peso Corporal/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Ácidos Docosa-Hexaenoicos/farmacologia , Lactação , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Aumento de PesoRESUMO
This study investigated the role of ethanol-inducible cytochrome P450-2E1 (CYP2E1) in enhancing CYP2E1 and other P450 proteins in extracellular vesicles (EVs) from alcohol-exposed rodents and human patients with alcoholism and their effects on oxidative hepatocyte injury. Female Fischer rats and wild-type or Cyp2e1-null mice were exposed to three oral doses of binge ethanol or dextrose control at 12-hour intervals. Plasma EV and hepatic proteins from alcohol-exposed rodents, patients with alcoholism, and their respective controls were isolated and characterized. The number of EVs and the amounts of EV CYP2E1, CYP2A, CYP1A1/2, and CYP4B proteins were markedly elevated in both patients with alcoholism and alcohol-exposed rats and mice. The number of EVs and EV P450 proteins were significantly reduced in ethanol-exposed rats fed a diet containing polyunsaturated fatty acids. The increased number of EVs and EV CYP2E1 and other P450 isoforms in alcohol-exposed wild types were significantly reduced in the corresponding Cyp2e1-null mice. EV CYP2E1 amounts depended on increased oxidative and endoplasmic reticulum (ER) stress because their levels were decreased by cotreatment with the antioxidant N-acetylcysteine or the CYP2E1 inhibitor chlormethiazole but increased by ER stress-inducer thapsigargin, which was blocked by 4-phenylbutyric acid. Furthermore, cell death rates were elevated when primary hepatocytes or human hepatoma cells were exposed to EVs from alcohol-exposed rodents and patients with alcoholism, demonstrating that EVs from alcohol-exposed rats and patients with alcoholism are functional and can promote cell death by activating the apoptosis signaling pathway, including phospho-c-Jun N-terminal kinase, proapoptotic Bax, and activated caspase-3. Conclusion: CYP2E1 has an important role in elevating EV CYP2E1 and other P450 isoforms through increased oxidative and ER stress. Elevated EV-CYP2E1 detected after withdrawal from alcohol or exposure to the CYP2E1 inducer pyrazole can be a potential biomarker for liver injury. (Hepatology Communications 2017;1:675-690).
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This study explores dog plasma and brain fatty acid composition achieved after long-term supplementation at high DHA doses. A 90% concentrate of DHA Ethyl Ester (DHA-EE) administered by oral gavage to Beagle dogs at doses of 100, 500, 1000, and 2000mg/kg bw/day for 8 weeks resulted in DHA increases in both plasma and brain. In a subsequent 9-month study, DHA-EE was administered at 150, 1000 and 2000mg/kg bw/day. Plasma DHA increased between 150 and 1000mg/kg bw/day but not between 1000 and 2000mg/kg bw/day and there were increases from Day 1to 92 but not between days 92 and 273. Doses >500mg/kg bw/day in the 8-week and all doses in the 9-month study resulted in DHA increases in the brain. The dose of 150mg/k gbw/day is sufficient to achieve maximal brain concentrations if DHA is administered chronically. For shorter than 6 months of supplementation, higher doses are required.
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Química Encefálica , Ácidos Docosa-Hexaenoicos/análise , Plasma/química , Administração Oral , Animais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Cães , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , MasculinoRESUMO
Human studies and some animal work have shown more docosahexaenoic acid (DHA) and arachidonic acid (ARA) was accumulated or converted from precursors in females compared to males. This study explored in-depth the effect of gender on fatty acid composition and polyunsaturated fatty acid metabolism in rats fed one of two well-defined diets containing 10% total fat. One diet contained 15% of linoleic acid (LA) and 3% of α-linolenic acid (ALA) of the total fatty acids (LA+ALA diet), while the other diet contained 15% LA and 0.05% ALA (LA diet). At the age of 20 weeks, all animals were orally administered a single dose of a mixture of deuterium-labeled LA and ALA. Caudal venous blood was then drawn at 0, 2, 4, 8, 12, 24, 48, 96 and 168h. The concentrations of the deuterated precursors and their metabolites in plasma total lipids were quantified by GC/MS negative chemical ionization. Endogenous fatty acids were quantified by GC/FID analysis. When expressed as the percentage of oral dosage, female rats accumulated more precursors and more products, deuterated DHA and deuterated n-6 docosapentaenoic acid (2H5-DPAn-6), in plasma than did male rats in both the LA+ALA diet and the LA diet. For the endogenous non-labeled PUFA, greater concentrations of DHA and DPAn-6 were similarly observed in female rats compared to males within each diet. A lower concentration of non-labeled ARA was observed only in female rats fed the LA+ALA diet. In summary, greater endogenous and exogenous DHA and DPAn-6 was observed in female rat plasma and this was independent of dietary ALA status.
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Gorduras na Dieta/administração & dosagem , Ácidos Graxos Insaturados/análise , Ácidos Graxos Insaturados/metabolismo , Animais , Ácidos Graxos/administração & dosagem , Feminino , Ácidos Linoleicos/administração & dosagem , Masculino , Estado Nutricional , Ratos , Caracteres Sexuais , Ácido alfa-Linolênico/administração & dosagemRESUMO
BACKGROUND/AIMS: There are only few data on dietary arachidonic acid (ARA) and docosahexaenoic acid (DHA) intake in infants from developing countries, and current global recommendations on intake during early life may not reflect the needs of the world's most vulnerable infants. The aim of the study was to provide estimates of intake of ARA and DHA in infants and young children aged 6-36 months who live in developing countries. METHODS: FAO Food Balance Sheets and fatty acid composition data from Australian food composition tables were utilized to generate mean per capita intake estimates for DHA and ARA in developing countries. The median daily intake of DHA and ARA in children age 6-36 months in each country was determined by combining the fatty acid composition of breast milk and complementary foods with the estimated intakes being weighted according to median duration of any breastfeeding. RESULTS: The median daily dietary intake for ARA and DHA across 76 developing countries was 64.0 and 48.9 mg/day, respectively. The lowest complementary food intake of ARA and DHA was present in countries with the lowest gross national income and highest birth rates. CONCLUSION: Global recommendations on ARA and DHA in early life need to reflect the specific needs of infants and families living in low income countries, and country-specific food policies should address gaps between recommended and achieved intakes.
Assuntos
Ácido Araquidônico/administração & dosagem , Aleitamento Materno , Ácidos Docosa-Hexaenoicos/administração & dosagem , Alimentos Infantis , Necessidades Nutricionais , Pré-Escolar , Países em Desenvolvimento , Gorduras Insaturadas na Dieta/administração & dosagem , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Masculino , Leite Humano/química , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND/AIM: For international recommendations on docosahexaenoic acid (DHA) and arachidonic acid (ARA) dietary intake to be valid, there needs to be a greater understanding of dietary patterns across both the developed and developing world. The aim of this investigation was to provide a global overview of dietary intake of DHA and ARA. METHODS: Food balance sheets from the Food and Agriculture Organisation Statistics Division and fatty acid composition data from Australian food composition tables in Nutrient Tables 2010 were utilised to generate median per capita intake estimates for DHA and ARA in 175 countries worldwide. RESULTS: Estimated dietary intake per capita for DHA and ARA in 47 developed and 128 developing countries demonstrated that 48% of the 175 countries have an ARA intake of <150 mg/day and 64% have a dietary DHA intake of <200 mg/day. There was a direct relationship between dietary ARA and DHA intake and the per capita gross national income of the country. Regional analysis showed the lowest ARA and DHA dietary intake in Sub-Saharan Africa and Central and Southern Asian populations. CONCLUSIONS: This study demonstrates there are many populations worldwide that have ARA and DHA intake that do not reflect current international recommendations, and the public health consequences of this global inadequacy need to be urgently considered.
Assuntos
Ácido Araquidônico/administração & dosagem , Dieta Saudável , Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Saúde Global , Modelos Econômicos , Cooperação do Paciente , Adulto , Criança , Bases de Dados Factuais , Países Desenvolvidos , Países em Desenvolvimento , Dieta/economia , Abastecimento de Alimentos/economia , Produto Interno Bruto , Humanos , Nações Unidas , Populações VulneráveisRESUMO
Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were systematically identified in order to create a global map identifying countries and regions with different blood levels. Included studies were those of healthy adults, published in 1980 or later. A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including plasma total lipids (33%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA+DHA in erythrocyte equivalents. Regions with high EPA+DHA blood levels (>8%) included the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (≤4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. The present review reveals considerable variability in blood levels of EPA+DHA and the very low to low range of blood EPA+DHA for most of the world may increase global risk for chronic disease.