Phosphatidylethanolamine DHA Research Articles

Synergistic effect of lecithins for tocopherols: formation and antioxidant effect of the phosphatidylethanolamine—l-ascorbic acid condensate

Ternary mixtures of lecithins, vitamin C and vitamin E are powerful antioxidants for the stabilization of polyunsaturated (n-3 fatty acid) oils. In this study, the chemistry of the antioxidant synergistic effect was investigated in ethyl linoleate (EL) containing α-tocopherol (α-Toc) or in linoleate rich vegetable oils at 110 °C using mixtures of phosphatidylethanolamine (PE) and either l-ascorbic acid (AA) or l-dehydroascorbic acid (DHA). The highest stabilization effects in EL were similar in both systems and were found in the molar mixtures of PE and AA or DHA. The thermal formation of reaction products between PE and AA (PE–AA) or DHA (PE–DHA) were investigated by HPTLC/ESI-MS. When α-tocopherylquinone (α-TQ) was used instead of α-Toc, nearly the same antioxidant effect was observed in the EL system. It was shown that molar mixtures of PE and AA, or PE and DHA, can regenerate α-TQ to α-Toc at elevated temperatures. PE–AA was synthesized and tested as antioxidants in EL containing α-Toc and in vegetable oils at room temperature. An improved stabilization was observed with the synthesized derivative compared to the physical mixture of the compounds, which demonstrated that PE–AA is a potential new antioxidant. A mechanism for the synergistic action between PE, AA and α-Toc through an acid-catalysed regeneration of α-TQ is suggested. PE–AA is an active apolar antioxidant, which is involved in the reduction of α-TQ.

Erythrocyte DHA level as a biomarker of DHA status in specific brain regions of n-3 long-chain PUFA-supplemented aged rats.

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.

Manipulation of the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in rotifersBrachionusNevada andBrachionusCayman

Rotifer cultures of Brachionus Nevada and Cayman were grown semi-continuously, fed live Rhodmonas baltica algae, and cultures were diluted daily (20% day−1). The enrichment diets Marol E (triacylglycerol-rich) and PL (cod roe emulsion, phospholipid-rich) were added to both cultures (Nevada 40 ng ind−1 day−1 and Cayman 25 ng ind−1 day−1, respectively). After 4 days of enrichment (dilution rate: 20% day−1), Cayman rotifers–fed Marol E had comparable (P > 0.05) quantitative amounts of DHA (docosahexaenoic acid, 22:6n-3) to natural harvested copepods, which were analysed for comparison, and the Cayman strain had generally more efficient incorporation of HUFAs (highly unsaturated fatty acids) than the Nevada strain. However, the percentage DHA of the total fatty acids in copepods were much higher than in enriched rotifers (P < 0.05). The PC-DHA (DHA in phosphatidylcholine) and PE-DHA (DHA in phosphatidylethanolamine) levels of copepods were up to 50%, which was highly unlikely for rotifers to reach. The increase of DHA in total phospholipids of rotifers was mainly due to an increase of DHA in PC, whereas the PE-DHA was only weakly affected by dietary lipids. The per cent PC-DHA levels in rotifers were positively related to the total dietary DHA levels (P < 0.0001), independent of the PC-DHA content in the diets.

NGF blocks polyunsaturated fatty acids biosynthesis in n − 3 fatty acid-supplemented PC12 cells

Regulation of polyunsaturated fatty acid (PUFA) biosynthesis in proliferating and NGF-differentiated PC12 pheochromocytoma cells deficient in n−3 docosahexaenoic acid (DHA 22:6n−3) was studied. A dose- and time-dependent increase in eicosapentaenoic acid (EPA, 20:5n−3), docosapentaenoic acid (DPA, 22:5n−3) and DHA in phosphatidylethanolamine (PtdEtn) and phosphatidylserine (PtdSer) glycerophospholipids (GPL) via the elongation/desaturation pathway following alpha-linolenic acid (ALA, 18:3n−3) supplements was observed. That was accompanied by a marked reduction of eicosatrienoic acid (Mead acid 20:3n−9), an index of PUFA deficiency. EPA supplements were equally effective converted to 22:5n−3 and 22:6n−3. On the other hand, supplements of linoleic acid (LNA, 18:2n−6) were not effectively converted into higher n−6 PUFA intermediates nor did they impair elongation/desaturation of ALA. Co-supplements of DHA along with ALA did not interfere with 20:5n−3 biosynthesis but reduced further elongation to 22-hydrocarbon PUFA intermediates. A marked decrease in the newly synthesized 22:5n−3 and 22:6n−3 following ALA or EPA supplements was observed after nerve growth factor (NGF)-induced differentiation. NGF also inhibited the last step in 22:5n−6 formation from LNA. These results emphasize the importance of overcoming n−3 PUFA deficiency and raise the possibility that growth factor regulation of the last step in PUFA biosynthesis may constitute an important feature of neuronal phenotype acquisition.

Plasma and Brain Fatty Acid Profiles in Mild Cognitive Impairment and Alzheimer's Disease

Alzheimer's disease (AD) is generally associated with lower omega-3 fatty acid intake from fish but despite numerous studies, it is still unclear whether there are differences in omega-3 fatty acids in plasma or brain. In matched plasma and brain samples provided by the Memory and Aging Project, fatty acid profiles were quantified in several plasma lipid classes and in three brain cortical regions. Fatty acid data were expressed as % composition and as concentrations (mg/dL for plasma or mg/g for brain). Differences in plasma fatty acid profiles between AD, mild cognitive impairment (MCI), and those with no cognitive impairment (NCI) were most apparent in the plasma free fatty acids (lower oleic acid isomers and omega-6 fatty acids in AD) and phospholipids (lower omega-3 fatty acids in AD). In brain, % DHA was lower only in phosphatidylserine of mid-frontal cortex and superior temporal cortex in AD compared to NCI (-14% and -12%, respectively; both p < 0.05). The only significant correlation between plasma and brain fatty acids was between % DHA in plasma total lipids and % DHA in phosphatidylethanolamine of the angular gyrus, but only in the NCI group (+0.77, p < 0.05). We conclude that AD is associated with altered plasma status of both DHA and other fatty acids unrelated to DHA, and that the lipid class-dependent nature of these differences reflects a combination of differences in intake and metabolism.

The effect of maternal T1DM on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidyethanolamine in infants during early life

The risk for type 1 diabetes (T1DM) in children of mothers with T1DM is different to that in children of fathers with T1DM. Fatty acid (FA) intake, in particular EPA and DHA, has been associated with T1DM risk and has been suggested to be inadequate in infants of diabetic mothers. We asked, therefore, whether EPA and DHA FA nutritional status in offspring of mothers with T1DM could contribute to their reduced T1DM risk. BABYDIET follows children with increased genetic and familial risk for T1DM from birth to age 3 years. FA nutritional state was assessed by determining the erythrocyte membrane phosphatidylethanolamine (PE) and phosphatidylcholine (PC) composition in children of T1DM mothers and children of T1DM fathers or with T1DM siblings participating in the BABYDIET study. Samples for determination of erythrocyte membrane FA composition were collected at ages 3 and 12 months in 48 and 49 infants, respectively. FA measurements were adjusted for breastfeeding duration, FA supplementation, and gluten exposure. 3-months-old children of T1DM mothers and T1DM fathers/sibs had similar levels of PC DHA and EPA (DHA 1.53+/-0.23 vs. 1.65+/-0.11 wt.%; EPA 0.15+/-0.02 vs. 0.21+/-0.03 wt.%) and PE DHA and EPA (DHA 7.54+/-0.37 vs. 7.92+/-0.38 wt.%; EPA 0.53+/-0.06 vs. 0.61+/-0.04 wt.%). No differences were also observed after stratification for breastfeeding. At age 12 months, a minor reduction of PE DHA was observed in children of T1DM mothers. Expected higher levels for DHA and EPA in fully breastfed children and in children of mothers taking fish oil supplementation were observed at 3 months in all children. Other differences included increased levels of the major saturated FA 16:0 in 3-months-old infants from T1DM mothers (PC 35.45+/-0.35 vs. 33.89+/-0.26 wt.%, mean +/- SEM, P(corr)=0.005; PE 16.13+/-0.39 vs. 14.93+/-0.24 wt.%, P(corr)=0.05). Although FA status was not identical in children from T1DM mothers and from T1DM fathers, maternal T1DM was not associated with changes in offspring's EPA and DHA incorporation into erythrocyte membrane.

Dietary Fatty Acid Composition in Pregnancy Alters Neurite Membrane Fatty Acids and Dopamine in Newborn Rat Brain

The importance of maternal dietary fatty acids on arachidonic acid [AA; 20:4(n-6)] and docosahexaenoic acid [DHA; 22:6(n-3)] in fetal brain nerve growth cone membranes and monoaminergic neurotransmitters was investigated. Rats were fed purified diets containing 20 g/100 g safflower oil with 74.3% 18:2(n-6), 0.2% 18:3(n-3), soybean oil with 55.4% 18:2(n-6), 7.7% 18:3(n-3) or high fish oil with 24.6% 22:6(n-3) through gestation. Tissue for rats within a litter were pooled at birth, brain growth cone membranes prepared and phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) fatty acids quantified by gas-liquid chromatography. Dopamine, serotonin, and the metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxyindolacetic acid were quantified by HPLC. Growth cone membranes from offspring of rats fed safflower oil had significantly lower, and offspring of rats fed high 22:6(n-3) fish oil had significantly higher 22:6(n-3) in PE, PS and PI than the soybean oil group. The growth cone membrane PC, PE and PS 20:4(n-6) was significantly lower in the fish oil than in the soybean or safflower oil groups. Serotonin concentration was significantly higher in brain of offspring in the safflower oil compared with the soybean oil group. The newborn brain dopamine was inversely related to PE DHA and PS DHA (P < 0.001), but positively related to PC AA (P < 0.05). These studies show that maternal dietary fatty acids may alter fetal brain growth cone (n-6) and (n-3) fatty acids, and neurotransmitters involved in neurite extension, target finding and synaptogenesis. The functional importance, however, is not known at this time.

Comparison of the fatty acid composition of total lipids and phospholipids in breast milk from Japanese women

Fatty acid (FA) composition of total lipids (TL) and phospholipids (PL) in breast milk obtained from 20 normal delivery healthy women in Tokyo, Japan was analyzed. Total lipids were extracted from the samples and then PL, consisting of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (Sph) and phosphatidylinositol (PI), were separated by two-dimensional thin-layer chromatography. The FA composition of TL and PL was analyzed by gas liquid-chromatography. Compared with previous reports, the contents of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in TL from Japanese women were higher than those from Chinese and Canadian women, which may be caused by different dietary habits and food types consumed by those populations. The contents of arachidonic acid (AA; 20:4n-6), EPA and DHA in PE and PI were much higher than those in PC. In addition, no significant correlation of EPA or DHA content was found between TL and PL. The findings indicate that PL especially PE and PI in human milk may be a source of EPA and DHA for infants in the rapid developmental stage. These results should be considered in infant formula production.

Visual Acuity and Fatty Acid Status of Term Infants Fed Human Milk and Formulas with and without Docosahexaenoate and Arachidonate from Egg Yolk Lecithin1

Preterm infants fed formulas with docosahexaenoic acid (DHA, 22:6n-3) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid. In term infants several nonrandomized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity, but the evidence for a cause-and-effect relationship is mixed. In the present study, term infants were randomly assigned to a standard term formula (n = 20) or the same formula with egg yolk lecithin to provide DHA (0.1%) and arachidonic acid (AA, 20:4n-6, 0.43%) (n = 19) at levels reported in milk of American women. A third group of infants was breast fed for > or = 3 mo (n = 19). Grating visual acuity (Teller Acuity Card procedure) and plasma and red blood cell (RBC) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) DHA and AA were determined at corrected ages of 2, 4, 6, 9 (acuity only), and 12 mo past term = 40 wk postmenstrual age (PMA). At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed standard formula. As in preterm infants, the increase was transient. Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants, but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond. Despite normal intrauterine accumulation of DHA and AA, infants fed formula with 2% linolenic acid and 0.1% DHA had better 2-mo visual acuity than infants fed formula with 2% linolenic acid.

Red blood cell membrane phosphatidylethanolamine fatty acid content in various forms of retinitis pigmentosa

In order to test the hypothesis that retinitis pigmentosa (RP) is associated with fatty acid abnormalities within cell membrane phospholipids, red blood cell membrane (RBC) phosphatidylethanolamine (PE) fatty acid content (% of total fatty acids) was measured using high performance liquid chromatography and capillary column gas chromatography in 155 patients from separate families with different genetic types of RP and 101 normal subjects. After controlling for the effects of age and sex, patients with all genetic forms of RP had significantly (P < 0.001) reduced mean RBC PE 22:6 omega 3 (n-3) (docosahexaenoic acid, DHA) content, and significantly (P < 0.001) elevated mean RBC PE dimethyl acetal (DMA) forms of 16:0, 18:0, and 18:1 omega 9 (n-9) as compared with normal subjects. RBC PE content of 22:5 omega 3 (n-3) (a precursor to DHA) and 18:2 omega 6 (n-6) (the major dietary essential fatty acid) were not significantly different in RP than in controls. Analysis by genetic types of RP showed that the mean RBC PE DHA percentages were significantly reduced by 24%, 14%, 30%, and 17%, respectively, in dominant, recessive, X-linked, and isolate forms of RP. The relative amounts of plasmalogens as indicated by DMA forms of 16:0 and 18:0 were significantly (P < 0.01) increased in dominant (by 33% and 25%), recessive (by 36% and 25%), and isolate cases (by 32% and 26%) of RP as compared with normal subjects. No such differences were seen in X-linked cases versus controls. Our data indicate that RBC PE DHA content is decreased in all genetic types of RP patients as compared to control subjects, and that RBC PE plasmalogens are increased in dominant, recessive, and isolate forms of RP. These data raise the possibility that membrane phospholipid fatty acid abnormalities may contribute to the pathogenesis of RP.