RESUMO
BACKGROUND: Inflammation and vaso-occlusion play key roles in Sickle Cell Disease (SCD) pathophysiology. Lipoxygenase products of the omega-3 fatty acids (O3FAs), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, are potent anti-inflammatory mediators modulating pain. O3FAs decrease episodes of vaso-occlusion in SCD. METHODS: We assessed erythrocyte fatty acid composition in two major cell membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine, in children with SCD HbSS-disease (nâ¯=â¯38) and age/race-matched HbAA-controls (nâ¯=â¯18). Ratio of pro-inflammatory arachidonic acid (AA) to anti-inflammatory DHA and EPA (FA-Ratio), and its relationship to hs-CRP were evaluated. RESULTS: FA-Ratios were increased in both phosphatidylcholine and phosphatidylethanolamine in HbSS compared to controls. Correlations were noted in HbSS subjects between hs-CRP and FA-Ratios (pâ¯=â¯0.011). FA-Ratios increased with age (pâ¯=â¯0.0007) due to an increase in pro-inflammatory AA with a concomitant decrease in anti-inflammatory DHA. CONCLUSIONS: Findings demonstrate relative deficiencies in HbSS of the anti-inflammatory precursor fatty acids DHA and EPA, which correlates positively with hs-CRP.
Assuntos
Anemia Falciforme/sangue , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Ômega-3/sangue , Inflamação/sangue , Adolescente , Anemia Falciforme/diagnóstico , Ácido Araquidônico/sangue , Criança , Pré-Escolar , Eritrócitos/metabolismo , Humanos , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Fatores de RiscoRESUMO
Preterm infants require fortification of human milk (HM) with essential fatty acids (FA) to ensure adequate post-natal development. As part of a larger randomized controlled study, we investigated FA metabolism in a subset of 47 clinically stable preterm infants (birth weight ≤1500 g or gestational age ≤32 weeks). Infants were randomized to receive HM supplemented with either a new HM fortifier (nHMF; n = 26) containing 12.5 g medium-chain FA (MCFA), 958 mg linoleic acid (LA), 417 mg α-linolenic acid (ALA), and 157 mg docosahexaenoic acid (DHA) per 100 g of powder (in compliance with the latest guidelines) or a fat-free HMF (cHMF; n = 21). Plasma phospholipid (PL) and triacylglycerol (TAG), and red blood cell phosphatidylcholine (RBC-PC) and phosphatidylethanolamine (RBC-PE) FA profiles were assessed before and after 21 days of feeding. In the nHMF group, significantly increased levels of n-9 monounsaturated fatty acids were observed, formed most likely by elongation and desaturation of dietary saturated fatty acids present in HM. ALA fortification increased ALA assimilation into plasma TAG. Similarly, DHA fortification enriched the DHA content in RBC-PE, which, in this compartment, was not associated with lower arachidonic acid levels as observed in plasma TAG and phospholipids. RBC-PE, a reliable indicator of FA metabolism and accretion, was the most sensitive compartment in this study.
Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Alimentos Fortificados/análise , Fórmulas Infantis/química , Recém-Nascido Prematuro/sangue , Metabolismo dos Lipídeos , Triglicerídeos/sangue , Ácido Araquidônico/sangue , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Eritrócitos/metabolismo , Ácidos Graxos Essenciais/administração & dosagem , Ácidos Graxos Essenciais/sangue , Ácidos Graxos Monoinsaturados/sangue , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Ácido Linoleico/administração & dosagem , Ácido Linoleico/sangue , Masculino , Leite Humano , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Pós , Triglicerídeos/administração & dosagem , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/sangueRESUMO
Little is known about arachidonic acid (ARA) and docosahexaenoic acid (DHA) requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers ( n = 133) age 13.4 ± 0.9 months (mean ± standard deviation), randomized to receive a DHA (200 mg/day) and ARA (200 mg/day) supplement (supplement) or a corn oil supplement (control) until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) cognitive and language composites and Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC), phosphatidylethanolamine (PE), and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21-9.00), B (95% CI), p = 0.045) in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10-17.94), p < 0.001) and girls (11.19 (4.69-17.68), p = 0.001). These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months.
Assuntos
Ácido Araquidônico/administração & dosagem , Desenvolvimento Infantil , Ácidos Docosa-Hexaenoicos/administração & dosagem , Fatores Etários , Ácido Araquidônico/efeitos adversos , Ácido Araquidônico/sangue , Colúmbia Britânica , Linguagem Infantil , Pré-Escolar , Cognição , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/efeitos adversos , Ácidos Docosa-Hexaenoicos/sangue , Método Duplo-Cego , Eritrócitos/metabolismo , Feminino , Humanos , Lactente , Inteligência , Masculino , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Estudos Prospectivos , Desempenho Psicomotor , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Docosahexaenoic (C22:6) and arachidonic acid (C20:4) are long-chain polyunsaturated fatty acids (LC-PUFA), essential to fetal development, and preferentially transported by plasma phospholipids. OBJECTIVE: To characterize fetal and maternal plasma phospholipid changes during gestation, and to investigate whether LC-PUFA phospholipid profiles are associated with bronchopulmonary dysplasia (BPD). DESIGN: Cord plasma and parturient serum from N = 108 pregnancies [24-42 week postmenstrual age (PMA)] were collected. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were analyzed with tandem mass spectrometry. PMA-associated changes were quantified, and break point analyses served to describe nonlinear changes during gestation. RESULTS: PC and PE were lower in cord than in parturient samples. In parturients, PC decreased until 33 week PMA, but then re-increased, whereas in cord plasma, concentrations linearly decreased. Fetal PC and PC sub-group values correlated with maternal values. C20:4-PC was twofold higher in cord than in maternal samples throughout gestation. C22:6-PC values, however, exceeded maternal values only beyond 33 week PMA. Consequently, early preterm C20:4-PC-to-C22:6-PC ratio largely exceeded term infant values. In infants born before 28 week PMA, a low C20:4-PC-to-C22:6-PC ratio was associated with BPD severity. CONCLUSIONS: Fetal plasma LC-PUFA-PC composition correlates with maternal values. Fetal C20:4-PC exceeds maternal values throughout gestation, whereas C22:6-PC exceeds maternal values only beyond 33 week PMA, resulting in a low fetal C20:4-PC/C22:6-PC ratio only toward end gestation. A low C20:4-PC/C22:6-PC ratio before 28 week PMA is associated with BPD severity. These data point to a concept of PMA-adjusted ARA and DHA supplementation and, potentially, cord plasma phospholipid analysis for BPD prediction.
Assuntos
Displasia Broncopulmonar/sangue , Displasia Broncopulmonar/diagnóstico , Sangue Fetal/química , Feto/metabolismo , Fosfolipídeos/sangue , Ácido Araquidônico/sangue , Cromatografia Líquida , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Graxos Insaturados/sangue , Feminino , Humanos , Lactente , Recém-Nascido Prematuro/sangue , Modelos Lineares , Fenômenos Fisiológicos da Nutrição Materna , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Espectrometria de Massas em TandemRESUMO
n-3 Long-chain PUFA (n-3 LC-PUFA), particularly EPA and DHA, play a key role in the maintenance of brain functions such as learning and memory that are impaired during ageing. Ageing is also associated with changes in the DHA content of brain membranes that could contribute to memory impairment. Limited studies have investigated the effects of ageing and n-3 LC-PUFA supplementation on both blood and brain fatty acid compositions. Therefore, we assessed the relationship between fatty acid contents in plasma and erythrocyte membranes and those in the hippocampus, striatum and cerebral cortex during ageing, and after a 5-month period of EPA/DHA supplementation in rats. In the blood, ageing was associated with an increase in plasma DHA content, whereas the DHA content remained stable in erythrocyte membranes. In the brain, ageing was associated with a decrease in DHA content, which was both region-specific and phospholipid class-specific. In EPA/DHA-supplemented aged rats, DHA contents were increased both in the blood and brain compared with the control rats. The present results demonstrated that n-3 LC-PUFA level in the plasma was not an accurate biomarker of brain DHA status during ageing. Moreover, we highlighted a positive relationship between the DHA levels in erythrocyte phosphatidylethanolamine (PE) and those in the hippocampus and prefrontal cortex in EPA/DHA-supplemented aged rats. Within the framework of preventive dietary supplementation to delay brain ageing, these results suggest the possibility of using erythrocyte PE DHA content as a reliable biomarker of DHA status in specific brain regions.
Assuntos
Envelhecimento/sangue , Envelhecimento/metabolismo , Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/sangue , Envelhecimento/psicologia , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Córtex Cerebral/metabolismo , Corpo Estriado/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/metabolismo , Membrana Eritrocítica/efeitos dos fármacos , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Hipocampo/metabolismo , Masculino , Memória/fisiologia , Fosfatidilcolinas/sangue , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/sangue , Fosfatidiletanolaminas/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND: The present study aimed to assess the dietary fat intake and blood fatty acid status of healthy Norwegian men and women living in Bergen whose habitual diet is known to be high in long-chain omega-3 fat. METHODS: Healthy men (n = 41) and women (n = 40) aged 20-50 years who were regular blood donors completed 7-day food diaries and their nutrient intake was analysed by Norwegian food database software, kbs, version 4.9 (kostberegningssystem; University of Oslo, Oslo, Norway). Blood samples were obtained before blood donation and assessed for the fatty acid composition of plasma triglycerides and cholesterol esters, phosphatidylcholine, and red cell phosphatidylcholine and phosphatidylethanolamine. RESULTS: There was no difference in dietary fat intake between men and women. Total and saturated fat intakes exceeded the upper limits of the recommendations of the National Nutrition Council of Norway. Although polyunsaturated fat intake was close to the lower limit of the recommended level, the intake varied greatly among individuals, partly as a result of the use of supplementary fish oil. Moreover, the proportional fatty acid composition of plasma and red cell lipids was similar between men and women. Enrichment of docosahexaenoic acid in red cell phosphatidylethanolamine was found in fish oil users. CONCLUSIONS: The results of the present study provide a snapshot of the current nutritional status of healthy Norwegian adults. Moreover, the detailed blood fatty acid composition of men and women whose habitual diet constitutes high long-chain polyunsaturated omega-3 fat as well as saturated fat could be used as reference value for population studies.
Assuntos
Gorduras na Dieta/administração & dosagem , Ácidos Graxos/sangue , Comportamento Alimentar , Estado Nutricional , Adulto , Ésteres do Colesterol/sangue , Ingestão de Energia , Ácidos Graxos/administração & dosagem , Feminino , Óleos de Peixe/administração & dosagem , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Triglicerídeos/sangue , Adulto JovemRESUMO
BACKGROUND: Phosphatidylcholine (PC) produced via the S-adenosylmethionine-dependent phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway is enriched with docosahexaenoic acid (DHA). DHA plays a critical role in fetal development and is linked to health endpoints in adulthood. It is unknown whether choline, which can serve as a source of S-adenosylmethionine methyl groups, influences PC-DHA or the PC:PE ratio in pregnant and nonpregnant women. OBJECTIVE: This study tested whether choline intake affects indicators of choline-related lipid metabolism, including erythrocyte and plasma PC-DHA and PC:PE ratios, in pregnant women in the third trimester and nonpregnant women. DESIGN: Pregnant (n = 26) and nonpregnant (n = 21) women consumed 480 or 930 mg choline/d and a daily DHA supplement for 12 wk. Blood was collected at baseline and at the midpoint and end of the study. PC-DHA was analyzed as the proportion of total PC fatty acids. RESULTS: Pregnant women had greater (P = 0.002) PC-DHA concentrations than did nonpregnant women at baseline. The proportion of erythrocyte and plasma PC-DHA increased (P ≤ 0.002) in pregnant and nonpregnant women regardless of choline intake. However, in nonpregnant women, consumption of 930 mg choline/d led to greater (P < 0.001) erythrocyte PC-DHA and a more rapid increase (P < 0.001) in plasma PC-DHA. Lower (P = 0.001-0.024) erythrocyte and plasma PC:PE in pregnant women was not modified by choline intake. CONCLUSIONS: A higher choline intake may increase PEMT activity, resulting in greater PC-DHA enrichment of the PC molecule in nonpregnant women. Increased production of PC-DHA during pregnancy indicates elevated PEMT activity and a higher demand for methyl donors. This trial was registered at clinicaltrials.gov as NCT01127022.
Assuntos
Colina/farmacologia , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipotrópicos/farmacologia , Fosfatidilcolinas/sangue , Gravidez/sangue , Eritrócitos/metabolismo , Feminino , Humanos , Fosfatidiletanolamina N-Metiltransferase/metabolismo , Fosfatidiletanolaminas/sangue , Gravidez/metabolismo , Terceiro Trimestre da GravidezRESUMO
BACKGROUND: Many disorders with plasmalogen deficiency have been reported. Replenishment or replacement of tissue plasmalogens of these disorders would be beneficial to the patients with these disorders, but effects of dietary plasmalogen on mammals have not been reported. METHODS: Plasmalogens were purified from chicken skin. The purified plasmalogens consisted of 96.4% ethanolamine plasmalogen (PlsEtn), 2.4% choline plasmalogen (PlsCho) and 0.5% sphingomyelin (SM). A diet containing 0.1% the purified plasmalogens (PlsEtn diet) was given to rats. Relative composition of phospholipids was measured by a high performance liquid chromatography (HPLC) method that can separate intact plasmalogens and all other phospholipid classes by a single chromatographic run. RESULTS: The PlsEtn diet given to Zucker diabetic fatty (ZDF) rats for 4 weeks caused decreases of plasma cholesterol and plasma phospholipid as compared to control diet. The other routine laboratory tests of plasma including triacylglycerol, glucose, liver and renal functions, albumin, and body weight were not different. Relative compositions of erythrocyte PlsEtn and phosphatidylethanolamine (PE) increased, and that of phosphatidylcholine (PC) decreased in PlsEtn diet group. The PlsEtn diet given to normal rats for 9 weeks again caused decrease of plasma cholesterol and phospholipid, and it induced increase of relative composition of PlsEtn of the erythrocyte membrane. The other routine laboratory tests of plasma and body weight were not different. CONCLUSIONS: Dietary PlsEtn increases relative composition of PlsEtn of erythrocyte membranes in normal and ZDF rats, and it causes decreases of plasma cholesterol and plasma phospholipids. Dietary PlsEtn for 9 weeks seemingly causes no adverse effect to health of normal rats.
Assuntos
Membrana Eritrocítica/metabolismo , Plasmalogênios/administração & dosagem , Plasmalogênios/sangue , Animais , Colesterol/sangue , Suplementos Nutricionais , Masculino , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Fosfolipídeos/sangue , Ratos , Ratos ZuckerRESUMO
INTRODUCTION: Docosahexaenoic acid (DHA) and DHA-containing ethanolamine plasmalogens (PlsEtn) are decreased in the brain, liver and the circulation in Alzheimer's disease. Decreased supply of plasmalogen precursors to the brain by the liver, as a result of peroxisomal deficits is a process that probably starts early in the AD disease process. To overcome this metabolic compromise, we have designed an orally bioavailable DHA-containing ether lipid precursor of plasmalogens. PPI-1011 is an alkyl-diacyl plasmalogen precursor with palmitic acid at sn-1, DHA at sn-2 and lipoic acid at sn-3. This study outlines the oral pharmacokinetics of this precursor and its conversion to PlsEtn and phosphatidylethanolamines (PtdEtn). METHODS: Rabbits were dosed orally with PPI-1011 in hard gelatin capsules for time-course and dose response studies. Incorporation into PlsEtn and PtdEtn was monitored by LC-MS/MS. Metabolism of released lipoic acid was monitored by GC-MS. To monitor the metabolic fate of different components of PPI-1011, we labeled the sn-1 palmitic acid, sn-2 DHA and glycerol backbone with (13)C and monitored their metabolic fates by LC-MS/MS. RESULTS: PPI-1011 was not detected in plasma suggesting rapid release of sn-3 lipoic acid via gut lipases. This conclusion was supported by peak levels of lipoic acid metabolites in the plasma 3 hours after dosing. While PPI-1011 did not gain access to the plasma, it increased circulating levels of DHA-containing PlsEtn and PtdEtn. Labeling experiments demonstrated that the PtdEtn increases resulted from increased availability of DHA released via remodeling at sn-2 of phospholipids derived from PPI-1011. This release of DHA peaked at 6 hrs while increases in phospholipids peaked at 12 hr. Increases in circulating PlsEtn were more complex. Labeling experiments demonstrated that increases in the target PlsEtn, 16:0/22:6, consisted of 2 pools. In one pool, the intact precursor received a sn-3 phosphoethanolamine group and desaturation at sn-1 to generate the target plasmalogen. The second pool, like the PtdEtn, resulted from increased availability of DHA released during remodeling of sn-2. In the case of sn-1 18:0 and 18:1 plasmalogens with [(13)C(3)]DHA at sn-2, labeling was the result of increased availability of [(13)C(3)]DHA from lipid remodeling. Isotope and repeated dosing (2 weeks) experiments also demonstrated that plasmalogens and/or plasmalogen precursors derived from PPI-1011 are able to cross both the blood-retinal and blood-brain barriers. CONCLUSIONS: Our data demonstrate that PPI-1011, an ether lipid precursor of plasmalogens is orally bioavailable in the rabbit, augmenting the circulating levels of unesterified DHA and DHA-containing PlsEtn and PtdEtn. Other ethanolamine plasmalogens were generated from the precursor via lipid remodeling (de-acylation/re-acylation reactions at sn-2) and phosphatidylethanolamines were generated via de-alkylation/re-acylation reactions at sn-1. Repeated oral dosing for 2 weeks with PPI-1011 resulted in dose-dependent increases in circulating DHA and DHA-containing plasmalogens. These products and/or precursors were also able to cross the blood-retinal and blood-brain barriers.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Diglicerídeos/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Caproatos/sangue , Diglicerídeos/farmacocinética , Ácidos Docosa-Hexaenoicos/sangue , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Fosfatidiletanolaminas/sangue , Plasmalogênios/sangue , Coelhos , Distribuição TecidualRESUMO
N-acylphosphatidylethanolamines (NAPEs) are a relatively abundant group of plasma lipids of unknown physiological significance. Here, we show that NAPEs are secreted into circulation from the small intestine in response to ingested fat and that systemic administration of the most abundant circulating NAPE, at physiologic doses, decreases food intake in rats without causing conditioned taste aversion. Furthermore, (14)C-radiolabeled NAPE enters the brain and is particularly concentrated in the hypothalamus, and intracerebroventricular infusions of nanomolar amounts of NAPE reduce food intake, collectively suggesting that its effects may be mediated through direct interactions with the central nervous system. Finally, chronic NAPE infusion results in a reduction of both food intake and body weight, suggesting that NAPE and long-acting NAPE analogs may be novel therapeutic targets for the treatment of obesity.
Assuntos
Regulação do Apetite , Fosfatidiletanolaminas/fisiologia , Amidas , Animais , Peso Corporal , Gorduras na Dieta/metabolismo , Endocanabinoides , Etanolaminas , Hipotálamo/metabolismo , Intestino Delgado/metabolismo , Camundongos , Camundongos Obesos , Atividade Motora , Obesidade/metabolismo , Ácidos Palmíticos/metabolismo , Fosfatidiletanolaminas/sangue , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Espectrometria de Massas em TandemRESUMO
In previous studies, we found that homozygous sickle cell (HbSS) patients, compared with their healthy (HbAA) counterparts, had reduced levels of the omega-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, in red cells, platelets, and mononuclear cells. These differences were not due to lower intake of the two fatty acids. We have investigated whether reduced antioxidant status in the patients could help explain the observed phenomenon. Blood specimens previously obtained for fatty acid study from Nigerian (26 HbSS and 30 HbAA) and British (30 HbSS, 9 sickle cell-hemoglobin C/HbSC, and 15 HbAA) subjects were analyzed for antioxidant status. The Nigerian HbSS patients compared with the controls had lower plasma retinol, alpha-tocopherol, and beta-carotene concentrations (p < 0.005) and reduced activity of red cell Cu/Zn-superoxide dismutase (Cu/Zn-SOD) (p < 0.05). Similarly, the British HbSS group had reduced concentrations of plasma alpha-tocopherol (p < 0.005), and activities of red cell Cu/Zn-superoxide dismutase (p < 0.05) and Se-glutathione peroxidase (Se-GPx) (p < 0.005) than the controls. In addition, the British patients in comparison with those who had HbSC, a mild form of the disease, had lower alpha-tocopherol than that of the HbAA controls (p < 0.005). In the British sickle cell patients, there was a positive correlation between red cell ethanolamine phosphoglyceride (EPG) DHA and Cu/Zn-SOD activity (r = 0.700, p < 0.05), choline phosphoglyceride (CPG) DHA and Se-GPx activity (r = 0.605, p < 0.05), and CPG EPA and Se-GPx activity (r = 0.558, p > 0.05). Similarly, the percent DHA in red cell EPG was positively related with the activity of Se-GPx in the patients with HbSC (r = 0.674, p < 0.05). These findings suggest that the lower levels of membrane EPA and DHA in blood cells of the HbSS patients could be due to peroxidation resulting from a compromised antioxidant competence.
Assuntos
Anemia Falciforme/sangue , Antioxidantes/metabolismo , Adolescente , Adulto , Idoso , Análise de Variância , Criança , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Glutationa Peroxidase/sangue , Humanos , Pessoa de Meia-Idade , Nigéria , Estresse Oxidativo , Fosfatidiletanolaminas/sangue , Superóxido Dismutase/sangue , Reino Unido , Vitamina A/sangue , Adulto Jovem , alfa-Tocoferol/sangue , beta Caroteno/sangueRESUMO
Peroxidized phospholipid-mediated cytotoxity, the abnormal increase in the levels of phosphatidylcholine hydroperoxide (PCOOH) found in the plasma of type 2 diabetic patients, is involved in the pathophysiology of many diseases. PCOOH accumulation may be related to Amadori-glycated phosphatidylethanolamine (deoxy-D-fructosyl PE, or Amadori-PE) because Amadori-PE causes oxidative stress. However, the occurrence of lipid glycation products, including Amadori-PE, in vivo remains unclear. We developed a method to analyze Amadori-PE by using quadrupole/linear ion-trap mass spectrometry, the Applied Biosystems 4000 Q TRAP. We found that pyridoxals could easily be condensed with PE before the glucose-PE reaction occurred. The PE-pyridoxal 5'-phosphate adduct was detectable in human red blood cells, and the increased plasma Amadori-PE concentration in streptozotocin-induced diabetic rats was decreased by dietary supplementation with pyridoxal 5'-phosphate. Therefore, it is likely that pyridoxal 5'-phosphate acts as a lipid glycation inhibitor in vivo, and this may contribute to diabetes prevention.
Assuntos
Diabetes Mellitus/sangue , Fosfatidiletanolaminas/sangue , Cromatografia Líquida , Produtos Finais de Glicação Avançada/sangue , Glicosilação/efeitos dos fármacos , Humanos , Espectrometria de Massas , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/isolamento & purificação , Fosfato de Piridoxal/sangue , Fosfato de Piridoxal/farmacologia , Valores de ReferênciaRESUMO
UNLABELLED: The objective of this study was to investigate the effect of docosahexaenoic acid (DHA) supplementation on blood and intestinal DHA levels and lung function in mild/moderately affected adult CF patients with the DeltaF508 genotype. BACKGROUND: Cystic Fibrosis (CF) patients often present with plasma fatty acid levels indicating low levels of linoleic (18:2n-6) and docosahexaenoic (22:6n-3) acids and an increased level of arachidonic acid (20:4n-6). Improved dietary fat intake or reducing fat malabsorption with pancreatic enzymes has failed to normalize this biochemical deficiency of DHA. METHODS: Five CF patients, aged 18-43, received 70 mg of DHA/kg body weight/d for six weeks. At baseline and at six weeks a physical exam, lung function, 3-day dietary intake, duodenal mucosal biopsy and blood sample were assessed. The blood was analyzed for plasma vitamin A, D and E levels, liver function tests, clinical chemistry (CBC, differential and electrolytes). Plasma and red blood cell fatty acid levels were also analyzed. At three weeks, assessment included a physical exam, lung function test and fasting blood sample (vitamin levels, liver function and clinical chemistry only). RESULTS: Pre- and post-measurements were compared for the four subjects who completed the study. An increase in DHA content (% w/w) was observed in all phospholipid fractions of plasma, red blood cell and mucosal samples. No significant differences in vitamin levels, liver function or lung function were observed. CONCLUSIONS: The study proves the concept that an increase in tissue DHA levels in CF patients can be achieved by supplementing for six weeks with 70 mg/kg/d DHA.
Assuntos
Fibrose Cística/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Duodeno/metabolismo , Ácidos Graxos/metabolismo , Administração Oral , Adolescente , Adulto , Cápsulas , Fibrose Cística/sangue , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Eritrócitos/metabolismo , Ácidos Graxos/sangue , Feminino , Genótipo , Humanos , Mucosa Intestinal/metabolismo , Masculino , Mutação , Fosfatidilcolinas/sangue , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/sangue , Fosfatidiletanolaminas/metabolismoRESUMO
Peroxidized phospholipid-mediated cytotoxity is involved in the pathophysiology of a number of diseases [i.e., the abnormal increase of phosphatidylcholine hydroperoxide (PCOOH) found in the plasma of type 2 diabetic patients]. The PCOOH accumulation may relate to Amadori-glycated phosphatidylethanolamine (deoxy-D-fructosyl PE, or Amadori-PE), because Amadori-PE causes oxidative stress. However, lipid glycation inhibitor has not been discovered yet because of the lack of a lipid glycation model useful for inhibitor screening. We optimized and developed a lipid glycation model considering various reaction conditions (glucose concentration, temperature, buffer type, and pH) between PE and glucose. Using the developed model, various protein glycation inhibitors (aminoguanidine, pyridoxamine, and carnosine), antioxidants (ascorbic acid, alpha-tocopherol, quercetin, and rutin), and other food compounds (L-lysine, L-cysteine, pyridoxine, pyridoxal, and pyridoxal 5'-phosphate) were evaluated for their antiglycative properties. Pyridoxal 5'-phosphate and pyridoxal (vitamin B(6) derivatives) were the most effective antiglycative compounds. These pyridoxals could easily be condensed with PE before the glucose/PE reaction occurred. Because PE-pyridoxal 5'-phosphate adduct was detectable in human red blood cells and the increased plasma Amadori-PE concentration in streptozotocin-induced diabetic rats was decreased by dietary supplementation of pyridoxal 5'-phosphate, it is likely that pyridoxal 5'-phosphate acts as a lipid glycation inhibitor in vivo, which possibly contributes to diabetes prevention.
Assuntos
Glicolipídeos/metabolismo , Glicosilação/efeitos dos fármacos , Fosfatidiletanolaminas/metabolismo , Fosfato de Piridoxal/fisiologia , Adulto , Animais , Colesterol/sangue , Diabetes Mellitus Experimental/metabolismo , Dieta , Glicolipídeos/antagonistas & inibidores , Humanos , Masculino , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/antagonistas & inibidores , Fosfatidiletanolaminas/sangue , Piridoxal/análogos & derivados , Piridoxal/sangue , Piridoxal/farmacologia , Ratos , Triglicerídeos/sangueRESUMO
Gestational diabetes mellitus (GDM) is a transient metabolic disorder that is a strong predictor of type 2 diabetes and cardiovascular disease. Previously, GDM was associated with reduced red cell long-chain omega-6 and omega-3 fatty acids in population (British) with high intake of total and saturated fat. The aim of the study was to examine blood fatty acids status of GDM patients (n=12) and normoglycaemic women (control, n=12) from South Korea where typical diet retains high omega-3 fat with low total fat intake. Subjects were matched for BMI and gestation week. Blood obtained at delivery were analyzed for plasma triacylglycerols (TG), phosphatidylcholine (PC), sphingomyelin (SM), and red cell PC, phosphatidylethanolamine (PE) and SM fatty acids. GDM patients had lower total saturated fatty acids (SFA) in the plasma TG (p<0.05) and PC (p<0.0001), and higher omega-6 and omega-3 metabolites in the plasma PC (p<0.05) than the controls. Conversely, the red cell PC and PE of the GDM contained higher proportions of palmitic (p<0.05) and SFA (p<0.05) but lower arachidonic (p<0.05) and docosahexaenoic (p>0.05) acids compared with the controls. Interestingly, red cell PC arachidonic acid level was comparable between Korean and British women whereas docosahexaenoic acid level decreased in the order of Korean control (5.5+/-0.9)>Korean GDM (3.5+/-2.1)=British control (3.9+/-2.9)>British GDM (2.8+/-2.3) (p<0.05). The similarity in the plasma and red cell fatty acids profile between Korean and British cohort suggests that the reduced membrane arachidonic and docosahexaenoic acids in GDM might be attributed to the effect of the disease itself regardless of ethnicity, obesity, or diet.
Assuntos
Diabetes Gestacional/sangue , Ácidos Graxos Insaturados/sangue , Adulto , Estudos de Coortes , Dieta , Gorduras Insaturadas na Dieta/administração & dosagem , Eritrócitos/química , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Insaturados/análise , Feminino , Humanos , Coreia (Geográfico) , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Projetos Piloto , Gravidez , Esfingomielinas/sangue , Triglicerídeos/sangue , Reino UnidoRESUMO
Sickle cell disease (SCD) is a group of inherited blood disorders in which clinical illness results from the presence of erythrocytes with sickled haemoglobin (HbS). Blood vessel occlusion is a fundamental pathological process in SCD. Sickle cell haemoglobin C (HbSC) disease and sickle cell anaemia (HbSS) share some pathophysiology and clinical manifestations. However, the former is generally less severe. Erythrocytes of HbSC patients have longer life span, reduced haemolysis, and lower propensity to adhere to vascular endothelium than those of their HbSS counterparts. The structure and function of erythrocytes are strongly modulated by membrane long chain polyunsaturated fatty acids (LCPUFA). We have tested the possibility that HbSC and HbSS patients have different membrane fatty acid composition consistent with the difference in their clinical severity. Steady-state patients, 9 HbSC and 28 HbSS, and 15 HbAA were studied. The HbSC patients had a higher level of linoleic (LA, P<0.05) and docosahexaenoic (DHA, P<0.05) acids, and lower arachidonic acid (AA, P<0.01) and AA/eicosapentaenoic acid (EPA) ratio (P<0.05) in erythrocyte choline phosphoglycerides (CPG) compared with the HbSS group. Similarly, the level of EPA was higher and AA/EPA ratio (P<0.01) lower in serine phosphoglycerides of the HbSC patients. In contrast to the HbSC, the HbSS group had lower levels of EPA (P<0.001), DHA (P<0.05), total n-3 metabolites and total n-3 fatty acids (P<0.001) in erythrocyte CPG compared with the healthy HbAA controls. Moreover, the HbSS patients with disease complications compared with those without complications had reduced DHA and total n-3 fatty acids (P<0.005) in erythrocyte CPG. The abnormalities in erythrocyte in LCPUFA which is manifested by an increase in AA and a decrease in EPA and DHA in HbSS relative to HbSC disease observed in this study are consistent with the contrast in clinical severity between the two entities.
Assuntos
Anemia Falciforme/sangue , Membrana Eritrocítica/química , Ácidos Graxos Ômega-3/sangue , Doença da Hemoglobina SC/sangue , Adulto , Idoso , Anemia Falciforme/complicações , Eritrócitos/química , Ácidos Graxos Insaturados/análise , Ácidos Graxos Insaturados/sangue , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Fosfatidilserinas/sangue , Triglicerídeos/sangueRESUMO
The effects of high dietary levels of phosphatidylethanolamine (PE) on plasma concentrations of homocysteine (tHcy) have not previously been studied. Eighteen mink (Mustela vison) studied were fed one of three diets during a 25 d period in a parallel-group design. The compared diets had 0, 17 and 67 % extracted lipids from natural gas-utilising bacteria (LNGB), which were rich in PE. The group with 0 % LNGB was fed a diet of 100 % soyabean oil (SB diet). Phospholipids are the main lipid components in LNGB and Methylococcus capsulatus is the main bacteria (90 %). The fasting plasma concentration of tHcy was significantly higher when the mink consumed the diet with 67 % LNGB than when they consumed the SB diet (P=0.039). A significantly lower glutathione peroxidase activity was observed in mink consuming the 17 % LNGB diet or the 67 % LNGB diet than was observed in mink fed the SB diet. The lack of significant differences in the level of plasma PE due to the diets indicates that most of the PE from the 67 % LNGB diet was converted to phosphatidylcholine (PC) in the liver. It has previously been hypothesised that phosphatidylethanolamine N-methyltransferase is an important source of tHcy. The present results indicate that plasma tHcy is at least partly regulated by phospholipid methylation from PE to PC. This methylation reaction is a regulator of physiological importance.
Assuntos
Dieta , Homocisteína/sangue , Vison/sangue , Fosfatidiletanolaminas/administração & dosagem , Óleo de Soja/administração & dosagem , Ração Animal , Animais , Metabolismo Energético , Glutationa Peroxidase/metabolismo , Fígado/metabolismo , Masculino , Methylococcus capsulatus/metabolismo , Fosfatidiletanolaminas/sangue , Fosfolipídeos/administração & dosagemRESUMO
This study investigates the relationship between changes in plasma sodium and changes in amino acid levels in a patient with post-traumatic sepsis and prolonged critical illness. Ninety-two consecutive measurements were performed at regular intervals over a period of many weeks; these consisted in the determination of full amino-acidograms, plasma sodium and complementary variables. A unique, highly significant inverse correlation between taurine and plasma sodium was found (r(2) = 0.48, p < 0.001). All other amino acids were unrelated, or much more weakly related, to sodium. Taurine was also strongly and directly related to phosphoethanolamine, glutamate and aspartate. Changes in sodium and in levels of these amino acids explained up to 86% of the variability of taurine. Besides, levels of these amino acids maintained a high degree of co-variation, remaining reciprocally related one to each other, directly, with r(2) ranging between 0.33 and 0.59 (p < 0.001 for all). There were similar findings for beta-alanine, which however was measured inconsistently. These data provide gross clinical evidence of a specific link binding plasma sodium and taurine levels, and may be consistent with occurrence of opposite and interdependent shifts of sodium and taurine between intravascular and extravascular space, to maintain osmoregulation. Co-variation of taurine with the other amino acids may be related to the same phenomenon, and/or to similarities in transport systems and chemical structure, or true metabolic interactions.
Assuntos
Ácido Aspártico/sangue , Estado Terminal , Ácido Glutâmico/sangue , Sódio/sangue , Taurina/sangue , Humanos , Fosfatidiletanolaminas/sangueRESUMO
OBJECTIVE: To evaluate changes in the fatty acid composition of red blood cell phospholipids in breast-fed infants compared with those in infants fed with different formulas (conventional, omega -6-enriched formula, omega -6- and omega -3-enriched formula and nucleotide-enriched formula). METHODS: Thirty-seven healthy term infants were randomly assigned to one of five different feeding groups. Weight, length, head circumference, and arm circumference were assessed at 7 and 60 days of age. The fatty acid composition of the infants' red blood cell phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were analyzed at these ages. RESULTS: The anthropometric variables studied showed no changes among the different groups. At 60 days old, arachidonic acid concentration (20:4 omega -6) was lower in non-omega -6 enriched formula-fed groups compared with that in the breast-milk fed group (4.03, 3.68 and 5.15 vs 7.20 g/100 g of fatty acids). Docosahexaenoic acid concentration (22:6omega -3) in both PC and PE clearly decreased in the non-omega -3 formula-fed groups compared with that in the breast-milk fed group (PC: 0.72 vs 2.82 g/100 g of fatty acids and PE: 5.15 vs 7.73 g/100 g of fatty acids). CONCLUSIONS: This study demonstrates differences in the fatty acid composition of red blood cell phospholipids between breast-milk fed infants and those fed with any of the artificial formulas available on the Spanish market. These data provide evidence of the influence of diet on certain essential fatty acids in the body.
Assuntos
Ácidos Graxos Insaturados/sangue , Fenômenos Fisiológicos da Nutrição do Lactente/fisiologia , Leite Humano/metabolismo , Antropometria , Ácido Araquidônico/sangue , Ácidos Docosa-Hexaenoicos/sangue , Humanos , Lactente , Recém-Nascido , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , EspanhaRESUMO
Nutritional management of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is based on the avoidance of fasting and substitution of medium-chain triglycerides for long- and very long-chain triglycerides. We report two cases of this disease, which developed omega-6 essential fatty acid deficiency after three and five months from the beginning of nutritional therapy (SHS product: Monogen). This alteration could be especially dangerous in these patients owing to their possible susceptibility to the development of pigmentary retinopathy. The incorporation of linoleic acid as 3-4% of total caloric intake supported as soybean oil ameliorates this deficiency. We wish to remark on this early complication in the nutritional management of VLCAD deficiency and the possibility of rescue by the incorporation of soybean oil into the diet.