Fetal baboons convert 18:3n-3 to 22:6n-3 in vivo. A stable isotope tracer study

Using [13C]-tracers and direct fetal doses, we show for the first time that the fetal primate converts alpha-linolenic acid (18:3) to docosahexaenoic acid (22:6) in vivo, and we estimate the relative bioefficacy of the two substrates for brain 22:6 accretion. Pregnant female baboons consumed a diet free of long chain polyunsaturates (LCP), with n-6/n-3 ratio of 10/1. In the third trimester of pregnancy (normal gestation = 182 days), they were instrumented with chronic indwelling catheters in the maternal femoral artery and the fetal jugular artery. Doses of either [U-13C]-18:3 (18:3*, n = 3) or [U-13C]-22:6 (22:6*, n = 2) were administered directly to the fetus. Blood was collected from fetus and mother, and the fetus was taken by cesarean section when electromyographic activity indicated that parturition was imminent. Fetal liver, brain, retina, and retinal pigment epithelium (RPE) were collected, and (13)C fatty acids determined. In 18:3*- dosed animals, labeled n-3 LCP were detected in fetal plasma at 1 day post-dose and peaked at 2;-3 days; brain 22:6* was constant at 3, 5, and 9 days post-dose, at 0.57 +/- 0.03 percent of dose (%Dose). In 22:6*- dosed animals, brain 22:6* was similar at 3 and 9 days post-dose (4.64 +/- 0.43%Dose). From these data, we estimate that preformed 22:6 in the fetal bloodstream is 8-fold more efficacious for brain 22:6 accretion than is 18:3. Retina 22:6* was stable at about 0.0008%Dose from 3 to 9 days in 18:3-dosed animals, but RPE 22:6* dropped over the period; brain results were consistent with these observations. Liver showed about 0.5%Dose in 22:6* and in intermediary n-3 fatty acid metabolites 20:5* and 22:5* at 3 days post-dose, and declined afterward. Back-transfer of labeled fatty acids to the maternal bloodstream was measurable but not sufficient to compromise the quantitative conversion data in fetuses. We conclude 1) primate fetuses have the capacity to convert 18:3 to 22:6 in vivo; 2) fetal brain 22:6* as %Dose plateaus by 3 days post-dose; 3) fetal plasma 22:6 is about 8-fold more effective as a substrate for brain 22:6 accretion compared with 18:3; and 4) the fetal liver is likely to be an important site of 18:3 to 22:6 conversion.     

Significant utilization of dietary arachidonic acid is for brain adrenic acid in baboon neonates

Dietary arachidonic acid (20:4n-6) utilization in-vivo for carbon recycling into de-novo lipogenesis and conversion to n-6 long chain polyunsaturates was investigated in baboon neonates using [U-(13)C]20:4n-6. Neonates consuming a formula typical of human milk received a single oral dose of [(13)C]arachidonic acid in sn-2 position of either triglyceride or phosphatidylcholine at 18-19 days of postnatal life. Neonate brain, retina, liver, and plasma were obtained 10 days later (28-29 days of life). Low isotopic enrichment (0.27-1.0%Total label) was detected in dihomo-gamma-linolenic acid (20:3n-6) in all tissues, but label incorporation into saturates or monounsaturates was not detected. In neonate brain and retina, 16% and 11% of total label was recovered in 22:4n-6, respectively. The relative contribution of dietary fatty acids to postnatal brain 22:4n-6 accretion can be estimated for dietary 20:4n-6 and preformed 22:4n-6 as 17% and 8%, respectively, corresponding to efficiencies of 0.48% and 0.54% of dietary levels, respectively. These results demonstrate in term baboon neonates that in vivo 1) 20:4n-6 was retroconverted to 20:3n-6, 2) 20:4n-6 did not contribute significantly to de novo lipogenesis of saturates and monounsaturates, and 3) the preformed 20:4n-6 contribution to brain 22:4n-6 accumulation was quantitatively a significant metabolic fate for dietary 20:4n-6.     

The effect of dietary supplementation with linoleic acid to late gestation ewes on the fatty acid composition of maternal and fetal plasma and tissues and the synthetic capacity of the placenta for 2-series prostaglandins

Linoleic acid (18:2n-6) is metabolised to arachidonic acid (20:4n-6), the precursor for 2-series prostaglandins (PGs). Increased consumption of 18:2n-6 during pregnancy may thus modify PG synthesis during labour. We have investigated whether increased 18:2n-6 composition during gestation altered the fatty acid consumption and PG synthesis of maternal and fetal tissues in the sheep. Ewes were fed a control diet or a diet providing 40% more 18:2n-6 from 96 days gestation. Half of each group received dexamethasone on day 136 to up-regulate the PG synthetic pathways promoting parturition. Maternal and fetal tissues were collected at 138 days. The 18:2n-6 diet significantly increased the 20:4n-6 content of maternal plasma, fetal plasma and allantochorion (51-81%) phosphatidylcholine, and fetal liver (40%) and maternal caruncular endometrium (57%) phosphatidylethanolamine. Increased 18:2n-6 intake increased production of PGF(2alpha) and PGE(2) in all placental tissues (maternal caruncular and intercaruncular endometrium and fetal allantochorion) by 23-98%, whereas dexamethasone increased it by 32-142%. This suggests that consumption of an 18:2n-6-enriched diet in late pregnancy enhanced placental PG production by increasing the supply of 20:4n-6. Variations in the extent to which the diet altered the polyunsaturated fatty acid (PUFA) content of the different tissues indicated complex interactions between nutrient availability and metabolic adaptation.     

Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes during pregnancy in mice

We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from day 3 prior to conception till day 15 of pregnancy. We concentrated on DHA, AA, Mead acid, and EFA-index [(omega-3+omega-6)/(omega-7+omega-9)] in maternal erythrocytes, maternal brain, and fetal brain. It was found that erythrocyte EFA/LCP sensitively reflects declining EFA/LCP status in pregnancy, although this decline was not apparent in maternal brain. Differences in erythrocyte EFA/LCP coincided with larger differences in fetal brain EFA/LCP as compared to EFA/LCP in maternal brain. Both maternal and fetal brains were affected by short-term EFA/LCP intake, but the developing fetal brain proved most sensitive. The inverse relationship between fetal brain AA and DHA suggests the need of a maternal dietary DHA/AA balance, at least in mice.     

Metabolic conversion of intra-amniotically-injected deuterium-labeled essential fatty acids by fetal rats following maternal n-3 fatty acid deficiency

Accumulation of polyunsaturated fatty acids (PUFA) in the fetal brain is accomplished predominantly via a highly selective flow of docosahexaenoic acid (22:6n-3, DHA) and arachidonic acid (20:4n-6, AA) through the placenta. Little is known regarding the endogenous capability of the fetus to generate its own DHA and AA from lower homologues such as linolenic (18:3n-3, ALA) and linoleic (18:2n-6, LA) acids, respectively. Deuterium-labeled d5-ALA and d5-LA at millimolar concentrations were injected directly into the amniotic fluid in order to investigate maternal-independent metabolic conversion of the stable isotopes in brain and liver of the fetus near delivery. After 48 h under adequate maternal diet, the levels of d5-ALA metabolites in the fetal brain and fetal liver were 45 ± 2.2 pmol/mg and 86 ± 4 pmol/mg of which 79% and 63.6% were comprised of d5-DHA. At this time point, incorporation of d5-LA metabolites was 103 ± 5 pmol/mg and 772 ± 46 pmol/mg for brain and liver, of which 50% and 30% were comprised of d5-AA. Following sustained maternal dietary ALA deficiency, the levels of total d5-ALA derived metabolites in the fetal brain and fetal liver were increased to 231 pmol/mg and 696 pmol/mg of which 71% and 26% were comprised of d5-DHA. From the time course and relative rates of d5-ALA precursor displacement by d5-DHA in cellular phosphoglycerides, it is concluded that the fetal rat brain can generate its own DHA from its d5-ALA precursors particularly under dietary stress.     

Maternal and umbilical fatty acid status in relation to maternal diet

The aim of this study was to describe the dietary fat intake during pregnancy and to study the relationship between the intake of polyunsaturated fatty acids (PUFAs) and the fatty acid composition of maternal and umbilical plasma phospholipids (PLs) and cholesterol esters (CEs) at delivery. In addition, the contribution of food groups to the intake of total fat and fatty acids in the diet was quantified.Maternal and umbilical blood samples were collected at delivery from 30 healthy pregnant women. The women completed a food frequency questionnaire during the first and third trimesters. The total fat intake during pregnancy is 85 (SD 24) g/day. The mean intake of saturated fatty acids (SFAs) is 33.4 g/day, of monounsaturated fatty acids (MUFAs) 28.6 g/day and of PUFA 15.2 g/day. Major sources of fat, MUFA and PUFA are fats, oils and sauces. Major sources of SFA are meat and poultry followed by cheese and eggs. Meat and poultry contribute the most to the intake of 20:4n-6 whereas fish is the major source of 20:5n-3 (EPA) and 22:6n-3 (docosahexaenoic acid (DHA)) in the diet. Linoleic acid, EPA and DHA (w%) in PL of maternal plasma are positively related to the intake of these fatty acids during pregnancy. No association is found between the maternal intake of the two parent essential fatty acids (18:2n-6 and 18:3n-3) and their fraction in umbilical PL or CE. EPA and the sum of n-6 fatty acids (w%) in umbilical plasma PL are positively correlated with the dietary intake of these fatty acids.     

Dietary alpha linolenic acid in pregnant mice and during weaning increases brain docosahexaenoic acid and improves recognition memory in the offspring

Docosahexaenoic acid (DHA) is critical for normal brain development and function. DHA is in danger of being significantly reduced in the human food supply, and the question of whether its metabolic precursor, the essential n-3 alpha linolenic acid (ALA) during pregnancy, can support fetal brain DHA levels for optimal neurodevelopment, is fundamental.Female mice were fed either ALA-enriched or Control diet during pregnancy and lactation. The direct effect of maternal dietary ALA on lipids was analyzed in liver, red blood cells, brain and brain vasculature, together with genes of fatty acid metabolism and transport in three-week-old offspring. The long-term effect of maternal dietary ALA on brain fatty acids and memory was studied in 19-week-old offspring.Three-week-old ALA offspring showed higher levels of n-3 fatty acids in liver, red blood cell, blood-brain barrier (BBB) vasculature and brain parenchyma, DHA enrichment in brain phospholipids and higher gene and protein expression of the DHA transporter, major facilitator superfamily domain containing 2a, compared to Controls. 19-week-old ALA offspring showed higher brain DHA levels and better memory performance than Controls.The increased brain DHA levels induced by maternal dietary ALA during pregnancy-lactation, together with the up-regulated levels of major facilitator superfamily domain containing 2a, may indicate a mode for greater DHA uptake with long-term impact on better memory in ALA offspring.     

Polyunsaturated fatty acid biosynthesis from [1-14C]20:3 n-6 acid in rat cultured Sertoli cells. Linoleic acid effect

Primary culture is a suitable system to study lipid metabolism and polyunsaturated fatty acid biosynthesis. Sertoli cell-enriched preparations were used to determine the fatty acid composition after 5 and 7 days in culture (serum free) as well as the uptake and metabolism of [1-14C]eicosa-8,11,14-trienoic acid. The addition of unlabeled linoleic acid (0.2 and 2.0 microg/ml) was also evaluated. Fatty acid methyl esters derived from cellular lipids were analyzed by gas liquid chromatography and radiochromatography. After 5 days in culture, cells had significantly less 18:2, 20:4, 22:5 and 24:5 and more 18:3, 20:3, 22:4 and 24:4 n-6 fatty acids than non-cultured cells. On day 7, an additional increment in 22:4 n-6 and a decrease in linoleic, gamma-linoleic and 24:4 n-6 fatty acids were observed. The presence of linoleic acid (low dose) produced a significant decrease in saturated and monounsaturated acids and an increase in 18:2, 20:4 and 22:5 n-6 fatty acids. At a high concentration almost all fatty acids belonging to 18:2 n-6 increased significantly. The drop in 20:4 n-6/20:3 n-6 ratio was considered as an indirect evidence of a Delta 5 desaturase activity depression. This assumption was corroborated by studying the transformation of [1-14C]eicosa-8,11,14-trienoic acid into 20:4, 22:4, 22:5, 24:4 and 24:5 n-6 fatty acids. We conclude that Sertoli cells after 7 days in culture evidenced changes in the fatty acid profile similar to those described under fat deprivation. The addition of linoleic acid reverted this pattern and indicated that the Delta 5 desaturase activity is a limiting step in the polyunsaturated fatty acid biosynthesis.     

Maternal dietary fat alters amniotic fluid and fetal intestinal membrane essential n-6 and n-3 fatty acids in the rat

We investigated whether maternal fat intake alters amniotic fluid and fetal intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% alpha-linolenic acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n-6) levels in the n-3-deficient group than in the control group (DHA: 1.29 +/- 0.10 and 6.29 +/- 0.33 g/100 g fatty acid; DPA: 4.01 +/- 0.35 and 0.73 +/- 0.15 g/100 g fatty acid, respectively); these differences in DHA and DPA were present in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal intestines in the n-3-deficient group had significantly higher LA, arachidonic acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty acid ratio was 4.9 +/- 0.2 and 32.2 +/- 2.1 in PC and 2.4 +/- 0.03 and 17.1 +/- 0.21 in PE in n-3-deficient and control group intestines, respectively. We demonstrate that maternal dietary fat influences amniotic fluid and fetal intestinal membrane structural lipid essential fatty acids. Maternal dietary fat can influence tissue composition by manipulation of amniotic fluid that is swallowed by the fetus or by transport across the placenta.     

Formula alpha-linolenic (18:3(n - 3)) and linoleic (18:2(n - 6)) acid influence neonatal piglet liver and brain saturated fatty acids, as well as docosahexaenoic acid (22:6(n - 3)).

Saturated fatty acids can be synthesized de novo and play a role in determining properties of structural membranes. The effect of dietary essential fatty acids, linoleic acid (18:2(n - 6)) and alpha-linolenic acid (18:3(n - 3)), on the saturated fatty acid content of membrane phospholipid has not previously been considered in newborn nutrition. The studies report the effect of low (1% fatty acids) or high (4%) formula 18:3(n - 3) with low (16%) or high (30-35%) formula 18:2(n - 6) on the saturated and unsaturated fatty acid composition of liver and brain structural lipid of piglets fed formula from birth for 15 days. A significant inverse relationship between the formula % 18:3(n - 3), but not 18:2(n - 6), and the liver phospholipid palmitic acid (16:0) was found. This may indicate a possible effect of dietary 18:3(n - 3) on de novo synthesis of 16:0 and requires further investigation. Monounsaturated fatty acids in both liver and brain were significantly lower in response to high 18:3(n - 3) and to high 18:2(n - 6) plus low 18:1(n - 9) in the formula. Liver phospholipid and brain total lipid % docosahexaenoic acid (22:6(n - 3)) were significantly higher when formula containing 4% rather than 1% 18:3(n - 3) was fed, suggesting that 1% 18:3(n - 3) may limit tissue (n - 3) fatty acid accretion. These results suggest that future studies of essential fatty acid requirements, specifically 18:3(n - 3), should consider possible influences on the saturated fatty acids which also play a functional role in tissue structural lipids.     

Alpha-tocopherol and gamma-tocopherol attenuate ethanol-induced changes in membrane fatty acid composition in embryonic chick brains

BACKGROUND: This project investigated whether or not EtOH-induced reductions in the levels of long-chain polyunsaturated membrane fatty acids could be attenuated by exogenous exposure to either alpha-tocopherol, gamma-tocopherol, or diallyl sulfide (DAS). METHODS: At 0 days of development, fertile chicken eggs were injected with a single dose of either saline supplemented with various concentrations of EtOH, alpha- or gamma-tocopherol and EtOH, or DAS and EtOH. At 18 days of development, brains were isolated and subjected to membrane analyses. RESULTS: When exposed to EtOH, concentrations ranging from 0-60.50 microm/Kg egg, dose-dependent decreases in the levels of brain 18:0, 18:1 (n-9), 18:2 (n-6), 18:3 (n-3), and 20:4 (n-6) were observed. These ethanol-induced changes in membrane fatty acid composition correlated with ethanol-induced reductions in brain mass, brain protein levels, acetylcholine esterase (AChE) activities and correlated with increased lipid hydroperoxide levels. Exposure to either 2.5 microm alpha-tocopherol/Kg egg and 6.050 mm EtOH/Kg egg, or 2.5 microm alpha-tocopherol/ Kg egg and 6.050 mm EtOH/Kg egg attenuated EtOH-induced changes in membrane fatty acid composition, brain mass, brain protein levels, AChE activities, and lipid hydroperoxide levels. Embryonic exposure to the cytochrome p450-2E1 inhibitor, diallyl sulfide (DAS), also attenuated EtOH-induced decreases in long-chain, unsaturated membrane fatty acids. However, embryonic exposure to DAS promoted abnormally low brain mass. CONCLUSION: EtOH-induced reductions in the levels of brain long-chain polyunsaturated fatty acid are caused by lipid peroxidation.     

Fatty acid composition of phospholipids and cholesteryl esters in maternal serum in the early puerperium

The fatty acid composition of serum phospholipids (PL) and cholesteryl esters (CE) in 26 healthy pregnant women at the end of term and 1 and 3 days after delivery was analysed in order to determine whether the maternal serum fatty acid composition changes in the early puerperium. The composition of the saturated fatty acids significantly changes in the PL fraction: 16:0 decreased and 18:0 increased. Both 20:4n-6 and 20:5 n-3 significantly increased after parturition in serum PL while 22:6n-3 remained constant at the three sampling time points. The sum of HUFA was slightly higher 3 days postpartum compared to the prepartum data. The essential fatty acid index significantly increased after delivery. In the CE fraction too differences occurred during puerperium: 18:2n-6 and 20:4n-6 increased and 18:1n-9 decreased after parturition. The sum of the n-3 fatty acids in CE remained unaltered. The EFA index significantly improved both in PL as in CE after delivery.In conclusion, the previously reported changes in the fatty acid composition of PL and CE during normal pregnancy diminish shortly after delivery. In fact, very soon after delivery the maternal fatty acid composition returns to more normal values.     

Effect of fat free diet during the last week of pregnancy upon the linoleic and arachidonic acid content of fetal organ lipids and placenta lipids of the rat

Pregnant Wistar rats were fed a fatfree diet from day 16--22 of pregnancy. On day 22, the fatty acid components of cholesterol esters, triglycerides, free fatty acids and phospholipids of maternal (brain, muscle, serum, white adipose tissue, liver) and fetal (brain, carcass, serum, liver) tissues, including the placenta, were examined gaschromatographically for the participation of linoleic and arachidonic acid. In all fetal and maternal organs the linoleic acid levels in the fatty acid patterns were strongly reduced. The alterations nearly always involved all the lipid fractions of a tissue and were mostly equal within a tissue. The strongest decreases of linoleic acid occurred in the placenta, and the weakest, in the lipids of maternal muscle and maternal adipose tissue. The linoleic acid alterations were principally similar in fetal and the corresponding maternal tissues, while being less pronounced in case of maternal muscle. The participation of arachidonic acid in the fatty acid pattern is completely retained in the lipids of fetal organs, and is even enhanced in those of the placenta.     

Expression of mRNAs for alpha-fetoprotein (AFP) and albumin and incorporation of AFP and docosahexaenoic acid in baboon fetuses.

alpha-Fetoprotein and albumin, two members of a multigene family, reversibly bind fatty acids with high affinity. The origin of alpha-fetoprotein (AFP) and albumin present in fetal tissues other than the liver and yolk sac is a subject of controversy. In this work, we have searched for the presence of the albumin and AFP mRNA molecules in different fetal organs of the baboon (Papio cinocephalus), using a highly sensitive gel-blot hybridization assay with human albumin and AFP cDNA probes. Large amounts of albumin and AFP mRNA molecules were found in the fetal liver; significant quantities were also present in the gastrointestinal tract and in the kidney. No detectable levels were found in the other tissues examined (brain, skin, spleen, pancreas, muscle, heart, thymus, placenta, and amnion). After injection of radiolabeled AFP into pregnant baboons, all fetal tissues took up the protein. White adipose tissue, kidney, intestine, lung, liver, and cerebral cortex showed a great uptake of exogenous AFP. [14C]Docosahexaenoic acid (22:6, n-3), injected at the same time, was actively transferred from the maternal compartment across the placenta and incorporated into cellular lipids by all fetal tissues and particularly by liver (around 70% of total incorporation). The levels of [14C]docosahexaenoic acid per gram of tissue increased in the order: maternal blood less than placenta less than fetal liver, indicating a selective accumulation of this fatty acid by the fetus. These results indicate that intracellular AFP in non-hepatic tissues of the developing baboon is, for the most part, of plasma origin.     

Lower fetal status of docosahexaenoic acid, arachidonic acid and essential fatty acids is associated with less favorable neonatal neurological condition

Long-chain polyunsaturated fatty acids, notably arachidonic (AA) and docosahexaenoic (DHA) acids are abundant in brain and may be conditionally essential in fetal life. We investigated umbilical artery (UA) and vein (UV) fatty acid compositions and early neonatal neurological condition in 317 term infants. Neurological condition was summarized as a clinical classification and a 'neurological optimality score' (NOS). Neurologically abnormal infants (n=27) had lower UV DHA and essential fatty acid (EFA) status. NOS correlated positively with AA (UV), and EFA (UV) and DHA status (UV and UA) and negatively with 18:2omega6 and omega9 (UV), and 20:3omega9, omega7 and C18 trans fatty acids (UV and UA). UV DHA, AA, saturated fatty acids, gestational age and obstetrical optimality score explained 16.2% of the NOS variance. Early postnatal neurological condition seems negatively influenced by lower fetal DHA, AA and EFA status. C18 trans fatty acids and 18:2omega6 may exert negative effects by impairment of LCP status.     

Effects of ambient temperature on lipid and fatty acid composition in the oviparous lizards, Phrynocephalus przewalskii

This study was designed to assess the effect of ambient temperature on lipid content, lipid classes and fatty acid compositions of heart, liver, muscle and brain in oviparous lizards, Phrynocephalus przewalskii, caught in the desert area of China. Significant differences could be observed in the contents of the total lipid and fatty acid compositions among different temperatures (4, 25 and 38 degrees C). The study showed that liver and muscle were principal sites of lipid storage. Triacylglycerol (TAG) mainly deposited in the liver, while phospholipids (PL) was identified as the predominant lipid class in the muscle and brain. Palmitic and stearic acid generally occupied the higher proportion in saturated fatty acids (SFA), while monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) consisted mainly of 16:1n-7, 18:1n-9, 18:2n-6, 18:3n-3, 20:4n-6 and 22:6n-3 regardless of tissue and temperature. These predominant fatty acids proportion fluctuations caused by temperature affected directly the ratio of unsaturated to saturated fatty acids. There was a tendency to increase the degree of unsaturation in the fatty acids of TAG and PL as environmental temperature dropped from 38 to 4 degrees C, although the different extent in different tissues. These results suggested that lipid characteristics of P. przewalskii tissues examined were influenced by ambient temperature.     

Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys

Rhesus monkeys given pre- and postnatal diets deficient in n-3 essential fatty acids develop low levels of docosahexaenoic acid (22:6 n-3, DHA) in the cerebral cortex and retina and impaired visual function. This highly polyunsaturated fatty acid is an important component of retinal photoreceptors and brain synaptic membranes. To study the turnover of polyunsaturated fatty acids in the brain and the reversibility of n-3 fatty acid deficiency, we fed five deficient juvenile rhesus monkeys a fish oil diet rich in DHA and other n-3 fatty acids for up to 129 weeks. The results of serial biopsy samples of the cerebral cortex indicated that the changes of brain fatty acid composition began as early as 1 week after fish oil feeding and stabilized at 12 weeks. The DHA content of the phosphatidylethanolamine of the frontal cortex increased progressively from 3.9 +/- 1.2 to 28.4 +/- 1.7 percent of total fatty acids. The n-6 fatty acid, 22:5, abnormally high in the cerebral cortex of n-3 deficient monkeys, decreased reciprocally from 16.2 +/- 3.1 to 1.6 +/- 0.4%. The half-life (t 1/2) of DHA in brain phosphatidylethanolamine was estimated to be 21 days. The fatty acids of other phospholipids in the brain (phosphatidylcholine, -serine, and -inositol) showed similar changes. The DHA content of plasma and erythrocyte phospholipids also increased greatly, with estimated half-lives of 29 and 21 days, respectively. We conclude that monkey cerebral cortex with an abnormal fatty acid composition produced by dietary n-3 fatty acid deficiency has a remarkable capacity to change its fatty acid content after dietary fish oil, both to increase 22:6 n-3 and to decrease 22:5 n-6 fatty acids. The biochemical evidence of n-3 fatty acid deficiency was completely corrected. These data imply a greater lability of the fatty acids of the phospholipids of the cerebral cortex than has been hitherto appreciated.     

Low linoleic acid may facilitate Δ6 desaturase activity and docosahexaenoic acid accretion in human fetal development

The n-3 and n-6 fatty acids are transferred across the placenta with consistently higher 22:6n-3 and lower 18:2n-6 in fetal than maternal plasma. This study sought to determine whether maternal and fetal cord blood red blood cell (RBC) phospholipid fatty acids show similar saturation with 22:6n-3, and also addressed the relationship between 18:2n-6 and Δ6 desaturase product/precursor ratios for 97 mothers and newborns. Despite higher fetal than maternal plasma phospholipid 22:6n-3, the maternal and fetal RBC phospholipid 22:6n-3 showed similar curvilinear relationships to the plasma phospholipid 22:6n-3. Risk of failure to achieve high RBC phospholipid 22:6n-3 increased sharply below a plasma phospholipid 22:6n-3 of 6.5g/100g fatty acids. Higher maternal and fetal 18:2n-6 was associated with lower RBC phospholipid 22:6n-3/22:5n-3, 22:5n-6/22:4n-6 and 18:3n-6/18:2n-6. These findings suggest low placental transfer of 18:2n-6 may be a specific mechanism to prevent inhibition of fetal Δ6 desaturase and facilitate fetal cellular phospholipid 22:6n-3 accretion.     

Intestinal responsiveness to experimental colitis in young rats is altered by maternal diet

Increasing evidence suggests that fetal and neonatal nutrition impacts later health. Aims of the present study were to determine the effect of maternal dietary fat composition on intestinal phospholipid fatty acids and responsiveness to experimental colitis in suckling rat pups. Female rats were fed isocaloric diets varying only in fat composition throughout gestation and lactation. The oils used were high (8%) in n-3 [canola oil (18:3n-3)], n-6 (72%) [safflower oil (18:2n-6)], or n-9 (78%) [high oleic acid safflower oil (18:1n-9)] fatty acids, n = 6/group. Colitis was induced on postnatal day 15 by intrarectal 2,4-dinitrobenzene sulfonic acid (DNBS) administration with vehicle (50% ethanol) and procedure (0.9% saline) controls. Jejunal and colonic phospholipids and milk fatty acids were determined. The distal colon was assessed for macroscopic damage, histology, and MPO activity. The 18:2n-6 maternal diet increased n-6 fatty acids, whereas the 18:3n-3 diet increased n-3 fatty acids in milk and pup jejunal and colonic phospholipids. Maternal diet, milk, and pup intestinal n-6-to-n-3 fatty acid ratios increased significantly in order: high 18:3n-3 < high 18:1n-9 < high 18:2n-6. DNBS administration in pups in the high 18:2n-6 group led to severe colitis with higher colonic damage scores and MPO activity than in the 18:1n-9 and 18:3n-3 groups. High maternal dietary 18:3n-3 intake was associated with colonic damage scores and MPO activity, which were not significantly different from ethanol controls. We demonstrate that maternal dietary fat influences the composition of intestinal lipids and responsiveness to experimental colitis in nursing offspring.     

The lipid composition of two species of serrasalmid fish in relation to dietary polyunsaturated fatty acids

The lipid composition of two species of Serrasalmid fish with different natural feeding habits were compared in relation to the polyunsaturated fatty acids (PUFA) supplied in their diets. Mylossoma aureum , a herbivorous piranha, was maintained on oatmeal flakes in which : 2(n-6) and : 3(n-3) were the only PUFA and accounted for 40–8 and 1.2%, respectively of dietary fatty acids. Serrasalmus nattereri , the carnivorous red piranha, was fed mosquito larvae containing .0-33.4% of their total fatty acids as : 2(n-6)+18 : 3(n-3) and 4.9-8.5% as 20 : 4(n-6)+20 : 5(n-3). The two species had similar lipid class compositions in liver, brain, viscera and carcass, except that lipids from M. aureum were generally richer in triacylglycerols. In both species, visceral and carcass lipid contained high levels of triacylglycerols whose principal PUFA was : 2(n-6). In M. aureum the major PUFA in liver total lipid and triacylglycerols was : 2(n-6) whilst the major PUFA in liver phospholipids were : 4(n-6) and : 5(n-6), with : 6(n-3) being a minor component. The level of : 6(n-3) in ethanolamine glycerophospholipids was significantly greater in brain than liver of M. aureum. Although absent from dietary lipid, : 6(n-3) was the major PUFA in phosphatidylcholine and ethanolamine glycerophospholipids from both the liver and brain of S, nattereri . In both species, the ratio of (n-6)/(n-3)PUFA was consistently lower in tissue lipids than in dietary lipids. The results are consistent with (i) the herbivorous M. aureum converting dietary C18 PUFA to their C20 and C22 homologues, (ii) the carnivorous S, nattereri forming : 6(n-3) from either 18:3(n-3) or 20: 5(n-3) and (iii) both species selectively desaturating and elongating (n-3) rather than (n-6) PUFA.