RESUMO
Modern western diets have been associated with a reduced proportion of dietary omega-3 fatty acids leading to decreased levels of DHA (docosahexaenoic acid) in the brain. Low DHA content has been associated with altered development of visual acuity in infants and also with an altered time course of synapse elimination and plasticity in subcortical visual nuclei in rodents. Microglia has an active role in normal developmental processes such as circuitry refinement and plasticity, and its activation status can be modulated by omega-3 (ω3) and omega-6 (ω6) essential fatty acids. In the present study, we investigated the impact of dietary restriction of DHA (ω3-), through the chronic administration of a coconut-based diet as the only fat source. This dietary protocol resulted in a reduction in DHA content in the retina and superior colliculus (SC) and in a neuroinflammatory outcome during the development of the rodent visual system. The ω3- group showed changes in microglial morphology in the retina and SC and a corresponding altered pattern of pro-inflammatory cytokine expression. Early and late fish oil protocols supplementation were able to restore DHA levels. The early supplementation also decreased neuroinflammatory markers in the visual system. The present study indicates that a chronic dietary restriction of omega-3 fatty acids and the resulting deficits in DHA content, commonly observed in Western diets, interferes with the microglial profile leading to an inflamed microenvironment which may underlie a disruption of synapse elimination, altered topographical organization, abnormal plasticity, and duration of critical periods during brain development.
Assuntos
Ácidos Graxos Ômega-3/metabolismo , Inflamação/etiologia , Visão Ocular/fisiologia , Animais , Animais Recém-Nascidos , Dieta , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Óleos de Peixe/uso terapêutico , Microglia , Doenças Neuroinflamatórias/etiologia , Ratos , Retina/crescimento & desenvolvimento , Retina/metabolismo , Colículos Superiores/crescimento & desenvolvimento , Colículos Superiores/metabolismo , Acuidade VisualRESUMO
Intermittent food restriction (IFR) is used mainly for weight loss; however, its effects on adipose tissue are not known when alternating with an obesogenic diet. To demonstrate its effects on morphological dynamics of fat deposits, female Wistar rats were distributed into groups: standard control (ST-C), with commercial diet; DIO control (DIO-C), with a diet that induces obesity (DIO) during the first and last 15 d, replaced by a standard diet for thirty intermediate days; standard restricted (ST-R), with standard diet during the first and last 15 d, with six cycles of IFR at 50 % of ST-C; and DIO restricted (DIO-R), in DIO during the first and last 15 d, with six cycles of IFR at 50 % of DIO-C. At 105 d of life, white adipose tissue (WAT) and brown adipose tissue (BAT) deposits were collected, weighed and histology performed. The DIO-R group showed higher total food intake (DIO-R 10 768·0 (SEM 357·52) kJ/g v. DIO-C 8868·6 (SEM 249·25) kJ/g, P < 0·0001), energy efficiency during RAI (DIO-R 2·26 (SEM 0·05) g/kJ v. DIO-C 0·70 (SEM 0·03) g/kJ, P < 0·0001) and WAT (DIO-R 5·65 (SEM 0·30) g/100 g v. DIO-C 4·56 (SEM 0·30) g/100 g) than their respective control. Furthermore, IFR groups presented hypertrophy of WAT and BAT, as well as fibrosis in BAT. Thus, IFR can establish prospective resistance to weight loss by favouring changes in adipose tissue morphology, increased energy intake and efficiency. Finally, the DIO diet before and after IFR aggravates the damages caused by the restriction.
Assuntos
Tecido Adiposo Marrom , Tecido Adiposo Branco/crescimento & desenvolvimento , Jejum , Comportamento Alimentar , Tecido Adiposo Marrom/crescimento & desenvolvimento , Animais , Feminino , Estudos Prospectivos , Ratos , Ratos Wistar , Redução de PesoRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease affecting up to 25% of the population worldwide. n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) have been associated with improved clinical parameters of NAFLD. Our purpose was to conduct a pilot study to evaluate the effects of n-3 PUFA supplementation in a randomized, double-blind, placebo-controlled clinical study performed on NAFLD individuals diagnosed by ultrasound. Patients received n-3 PUFA (n = 13) or placebo (n = 11) supplementation for six months. Circulating miR-122 expression (determined by quantitative real time-polymerase chain reaction (qRT-PCR), liver fibrosis (FibroScan®), red blood cells (RBC) fatty acids (gas chromatography), and biochemical tests were performed at baseline and after intervention. After the intervention, in the n-3 PUFA group, docosahexaenoic acid (DHA) and omega index increased significantly in RBC (p = 0.022 and p = 0.012, respectively), in addition to a significant reduction in alkaline phosphatase (ALP) (p = 0.002) and liver fibrosis (p = 0.039). However, there was no change in the expression of circulating miR-122 in both groups. Our results showed that omega-3 PUFA were incorporated in erythrocytes after six months of fish oil supplementary intake, and that n-3 PUFA were effective in reducing ALP and liver fibrosis without altering the expression of circulating miR-122 in individuals with NAFLD.
Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Óleos de Peixe/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/terapia , Idoso , Fosfatase Alcalina/sangue , Ácidos Docosa-Hexaenoicos/sangue , Método Duplo-Cego , Esquema de Medicação , Ácido Eicosapentaenoico/sangue , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Projetos Piloto , Fatores de Tempo , Resultado do TratamentoRESUMO
Changes in lipid metabolism occur during the development and progression non-alcoholic fatty liver disease (NAFLD). However, the fatty acid (FA) profile in red blood cells (RBC) from patients with liver fibrosis remains unexplored. Thus, the goal of this study was to evaluate the fatty acid profile in RBC, dietary lipid intake and insulin resistance indicators in patients with NAFLD, according to the degree of hepatic fibrosis. Using elastography, patients were classified with (n = 52) and without (n = 37) advanced liver fibrosis. The fatty acid profile in RBC was analyzed using gas chromatography and the lipid intake was evaluated through a 24-h dietary recall. Subjects with advanced liver fibrosis had higher levels of palmitic, stearic and oleic acid and total monounsaturated fatty acid (MUFA) and insulin (p < 0.05), and lower levels of elongase very long chain fatty acids protein-6 and the delta-5-desaturase enzymatic activity (p < 0.05). These results suggest a lack of regulation of enzymes related to FA metabolism in patients with advanced fibrosis.
Assuntos
Eritrócitos/química , Insulina/sangue , Cirrose Hepática/etiologia , Hepatopatia Gordurosa não Alcoólica/sangue , Ácido Palmítico/sangue , Acetiltransferases/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dessaturase de Ácido Graxo Delta-5 , Registros de Dieta , Gorduras na Dieta/análise , Técnicas de Imagem por Elasticidade , Ácidos Graxos Dessaturases/sangue , Elongases de Ácidos Graxos , Ácidos Graxos Monoinsaturados/sangue , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Ácido Oleico/sangue , Ácidos Esteáricos/sangueRESUMO
ABSTRACT Objective To analyze erythrocyte fatty acid composition and its association with serum cytokine levels in pediatric cystic fibrosis patients. Methods A cross-sectional study was performed at a reference center in Rio de Janeiro, Brazil. We have included all pediatric patients aged 5-19 years with confirmed cystic fibrosis diagnosis. Erythrocyte fatty acid composition and serum cytokine (TNF-α, IL-1β, IL-6 and IL-8) and C-reactive protein levels were measured. The cut-off point to determine essential fatty acids deficiency was the linoleic acid concentration of <21%. Results Twenty-six children (<10 years old) and thirty-one adolescents were studied. Most patients were female and heterozygous for DF508 mutation and suffered from exocrine pancreatic insufficiency. Both children and adolescents had lower linoleic acid concentration (<21%). TNF-α was the only pro-inflammatory marker whose levels were increased; the increase was greater in children. An association between fatty acid composition in erythrocytes and cytokines IL-1β and IL-6 was observed (p<0.05). Conclusion The pediatric cystic fibrosis patients studied presented a deficiency of essential fatty acids, and an association between fatty acid profile in erythrocytes and serum pro-inflammatory cytokines was observed. These findings highlight the importance of this type of assessment that may open new possibilities for studying pathophysiology and treating cystic fibrosis patients, such as the dietary supplementation with n-3 fatty acids (eicosapentaenoic and docosahexaenoic acids). However, further longitudinal studies are needed for better clarification of the imbalance in lipid metabolism and inflammation in cystic fibrosis
RESUMO Objetivo Analisar a composição dos ácidos graxos nos eritrócitos e sua associação com os níveis séricos de citocinas em pacientes pediátricos com fibrose cística. Métodos Estudo transversal, realizado em um centro de referência no Rio de Janeiro/Brasil. Foram incluídos todos os pacientes pediátricos com diagnóstico confirmado de fibrose cística, entre cinco e 19 anos de idade. Foram analisadas a composição de ácidos graxos nos eritrócitos, as citocinas séricas (TNFα, IL-1, IL-6 e IL-8) e a proteína C reativa. O ponto de corte para determinar a deficiência de ácidos graxos essenciais foi a concentração de ácido linoleico <21%. Resultados Foram estudadas 26 crianças (<10 anos) e 31 adolescentes, sendo a maioria do sexo feminino, heterozigoto para a mutação DF508 e com insuficiência pancreática exócrina. Nas crianças e nos adolescentes as concentrações de ácido graxo linoleico eram baixas (<21%). O TNF-α foi o único marcador pró-inflamatório cujas concentrações estavam aumentadas, principalmente nas crianças. Uma associação entre a composição de ácidos graxos nos eritrócitos e as citocinas IL-1β e IL-6 foi observada (p<0,05). Conclusão Os pacientes pediátricos estudados apresentaram deficiência de ácidos graxos essenciais e foi observada associação entre o perfil de ácidos graxos nos eritrócitos com as citocinas pró-inflamatórias séricas. Os achados destacam a importância deste tipo de avaliação sobre a fisiopatologia e o tratamento de pacientes com fibrose cística, como a suplementação com ácidos graxos n-3 (eicosapentaenoico e docosahexaenoico). No entanto são necessários mais estudos longitudinais no esclarecimento entre o desequilíbrio do metabolismo lipídico e a inflamação na fibrose cística.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Fibrose Cística , Insuficiência Pancreática Exócrina , Ácidos Graxos Essenciais , Criança , Estudos Transversais , Citocinas , Adolescente , Eritrócitos , Ácidos GraxosRESUMO
Adolescent pregnancy increases risk of adverse perinatal outcomes. Placental delivery of long-chain polyunsaturated fatty acids (LCPUFA) is essential for fetal growth and development. In this pilot study, we aimed to assess maternal and fetal status of fatty acids (FA) measured at birth and the expression of key genes involved in FA uptake, transport and metabolism in the placenta of fifteen adolescents and fifteen adults. FA were quantified by gas-liquid chromatography. Placental expression of FA transporters was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and peroxisome proliferator-activated receptor gamma (PPARγ) was quantified by Western Blot. Adolescents had lower docosahexaenoic acid (DHA, 22:6 n-3) and total n-3 FA levels in maternal erythrocytes and placenta, but these were not different in fetal erythrocytes. Arachidonic acid (AA, 20:4 n-6) concentration was increased in placenta but lower in fetal circulation. Plasma membrane fatty acid binding protein (FABPpm) and fatty acid transport protein (FATP) 4 mRNA expressions were not different, however FATP1, fatty acid translocase (FAT/CD36) and fatty acid binding protein 3 (FABP3) mRNA and PPARγ protein levels were decreased in placenta of adolescents. Despite significant downregulation of FATP1, CD36 and FABP3, there was only a modest decrease in LCPUFA (10%) and AA (12%) and no difference in DHA content in cord blood, suggesting that FA transfer to the fetus was partially protected by other factors in adolescents from this cohort.
Assuntos
Ácidos Graxos Insaturados/sangue , Placenta/metabolismo , Circulação Placentária , Gravidez na Adolescência , Adolescente , Adulto , Fatores Etários , Transporte Biológico , Western Blotting , Estudos Transversais , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , PPAR gama/metabolismo , Projetos Piloto , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemRESUMO
OBJECTIVE: This cross-sectional study aimed to evaluate the association between leptin, insulin and adiponectin levels and anthropometric measurements of term newborns of adolescent and adult mothers. STUDY DESIGN: Umbilical cord plasma samples were obtained from 80 healthy term neonates (40 from teenagers and 40 from adult mothers) and adiponectin, insulin and leptin concentrations were measured. RESULTS: Cord plasma adiponectin levels were higher in the boys from adult mothers than in the boys of the adolescent (p < 0.05), while plasma leptin levels in the boys of the adults were significantly lower (p < 0.05) than those of girls from both groups. Univariate correlation analysis showed that leptin umbilical cord plasma levels were positively associated with birth weight in neonates from adolescents and adults. Multiple linear regression analysis revealed that leptin levels showed significant positive predictor for birth weight specifically in the adult mother. CONCLUSION: Gestational age, but not adipokines, showed to be a significant positive predictor factor of birth weight in adolescent pregnancy.
Assuntos
Adiponectina/sangue , Peso ao Nascer , Sangue Fetal/química , Insulina/sangue , Leptina/sangue , Adolescente , Adulto , Fatores Etários , Estatura , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Idade Materna , Análise Multivariada , Gravidez , Fatores SexuaisRESUMO
The quality of dietary lipids in the maternal diet can programme the offspring to diseases in later life. We investigated whether the maternal intake of palm oil or interesterified fat, substitutes for trans-unsaturated fatty acids (FA), induces metabolic changes in the adult offspring. During pregnancy and lactation, C57BL/6 female mice received normolipidic diets containing partially hydrogenated vegetable fat rich in trans-unsaturated fatty acids (TG), palm oil (PG), interesterified fat (IG) or soyabean oil (CG). After weaning, male offspring from all groups received the control diet until day 110. Plasma glucose and TAG and liver FA profiles were ascertained. Liver mitochondrial function was accessed with high-resolution respirometry by measuring VO2, fluorimetry for detection of hydrogen peroxide (H2O2) production and mitochondrial Ca2+ uptake. The results showed that the IG offspring presented a 20 % increase in plasma glucose and both the IG and TG offspring presented a 2- and 1·9-fold increase in TAG, respectively, when compared with CG offspring. Liver MUFA and PUFA contents decreased in the TG and IG offspring when compared with CG offspring. Liver MUFA content also decreased in the PG offspring. These modifications in FA composition possibly affected liver mitochondrial function, as respiration was impaired in the TG offspring and H2O2 production was higher in the IG offspring. In addition, mitochondrial Ca2+ retention capacity was reduced by approximately 40 and 55 % in the TG and IG offspring, respectively. In conclusion, maternal consumption of trans-unsaturated and interesterified fat affected offspring health by compromising mitochondrial bioenergetics and lipid metabolism in the liver.
Assuntos
Metabolismo Energético , Ácidos Graxos/efeitos adversos , Lactação , Fígado/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Mitocôndrias/metabolismo , Ácidos Graxos trans/efeitos adversos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Glicemia/metabolismo , Cálcio/metabolismo , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Peróxido de Hidrogênio/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Consumo de Oxigênio , Óleos de Plantas , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Respiração , Ácidos Graxos trans/metabolismo , Triglicerídeos/sangueRESUMO
OBJECTIVE: To assess progress towards the elimination of trans-fatty acids (TFA) in foods after the 2008 Pan American Health Organization (PAHO) recommendation of virtual elimination of TFA in Latin America. DESIGN: A descriptive, comparative analysis of foods that were likely to contain TFA and were commonly consumed in four cities in Latin America. SETTING: San José (Costa Rica), Mexico City (Mexico), Rio de Janeiro (Brazil), Buenos Aires (Argentina). SUBJECTS: Foods from each city were sampled in 2011; TFA content was analysed using GC. TFA of selected foods was also monitored in 2016. RESULTS: In 2011-2016, there was a significant decrease in the content of TFA in the sampled foods across all sites, particularly in Buenos Aires (from 12·6-34·8 % range in 2011-2012 to nearly 0 % in 2015-2016). All sample products met the recommended levels of TFA content set by the PAHO. TFA were replaced with a mixture of saturated and unsaturated fats. CONCLUSIONS: Our results indicate a virtual elimination of TFA from major food sources in the cities studied. This could be due to a combination of factors, including recommendations by national and global public health authorities, voluntary and/or mandatory food reformulation made by the food industry.
Assuntos
Abastecimento de Alimentos , Implementação de Plano de Saúde , Ácidos Graxos trans/efeitos adversos , Saúde da População Urbana , Argentina , Brasil , Costa Rica , Inquéritos sobre Dietas , Análise de Alimentos , Abastecimento de Alimentos/normas , Indústria de Processamento de Alimentos/tendências , Fidelidade a Diretrizes/tendências , Humanos , Colaboração Intersetorial , México , Política Nutricional , Organização Pan-Americana da Saúde , Análise Espaço-Temporal , Ácidos Graxos trans/análiseRESUMO
We investigated whether maternal intake of normolipidic diets with distinct fatty acid (FA) compositions alters the lipidic profile and influences the inflammatory status of the adult offsprings׳ brains. C57BL/6 female mice during pregnancy and lactation received diets containing either soybean oil (CG), partially hydrogenated vegetable fat rich in trans-fatty acids (TG), palm oil (PG), or interesterified fat (IG). After weaning, male offspring from all groups received control diet. The FA profile was measured in the offspring׳s brains at post-natal days 21 and 90. Brain functional capillary density as well as leukocyte-endothelial interactions in the cerebral post-capillary venules was assessed by intravital fluorescence microscopy at post-natal day 90. Inflammation signaling was evaluated through toll-like receptor 4 (TLR4) content in brain of the adult offspring. In the 21-day old offspring, the brains of the TG showed higher levels of trans FA and reduced levels of linoleic acid (LA) and total n-6 polyunsaturated fatty acids (PUFA). At post-natal day 90, TG and IG groups showed reduced levels of eicosapentaenoic acid (EPA) and total n-3 PUFA tended to be lower compared to CG. The offspring׳s brains exhibited an altered microcirculation with increased leukocyte rolling in groups TG, PG and IG and in TG group increased leukocyte adhesion. The TLR4 content of TG, IG and PG groups only tended to increase (23%; 20% and 35%, respectively). Maternal consumption of trans FA, palm oil or interesterified fat during pregnancy and lactation can trigger the initial steps of inflammatory pathways in the brain of offspring in adulthood.