n-6 and n-3 Long-chain polyunsaturated fatty acids in the erythrocyte membrane of Brazilian preterm and term neonates and their mothers at delivery

Placental transfer of the long-chain polyunsaturated fatty acids (LCPUFA) arachidonic (AA) and docosahexaenoic (DHA) acids is selectively high to maintain accretion to fetal tissues, especially the brain. The objectives of the present study were to investigate the essential fatty acid (EFA) and LCPUFA status at birth of preterm and term Brazilian infants and their mothers, from a population of characteristically low intake of n-3 LCPUFA, and to evaluate the association between fetal and maternal status, by the determination of the fatty acid composition of the erythrocyte membrane. Blood samples from umbilical cord of preterm (26-36 weeks of gestation; n = 30) and term (37-42 weeks of gestation; n = 30) infants and the corresponding maternal venous blood were collected at delivery. The LCPUFA composition of the erythrocyte membrane and DHA status were similar for mothers of preterm and term infants. Neonatal AA was higher (P < 0.01) whereas its precursor 18:2n-6 was lower (P < 0.01) than maternal levels, as expected. There was no difference in LCPUFA erythrocyte composition between preterm and term infants, except for DHA. Term infants presented a worse DHA status than preterm infants (P < 0.01) and than their mothers (P < 0.01) at delivery. There was a negative correlation of neonatal DHA with maternal AA and a positive correlation between neonatal AA and maternal AA and 18:2n-6 only at term. These results suggest that the persistent low DHA maternal status, together with the comparatively better AA and 18:2n-6 status, might have affected maternal-fetal transfer of DHA when gestation was completed up to term, and possibly contributed to the worse DHA status of term neonates compared with the preterm neonates.     

Evolutionary modifications of human milk composition: evidence from long-chain polyunsaturated fatty acid composition of anthropoid milks

Brain growth in mammals is associated with increased accretion of long-chain polyunsaturated fatty acids (LCPUFA) in brain phospholipids. The period of maximum accumulation is during the brain growth spurt. Humans have a perinatal brain growth spurt, selectively accumulating docosahexaenoic acid (DHA) and other LCPUFA from the third trimester through the second year of life. The emphasis on rapid postnatal brain growth and LCPUFA transfer during lactation has led to the suggestion that human milk LCPUFA composition may be unique. Our study tests this hypothesis by determining fatty acid composition for 11 species of captive anthropoids (n = 53; Callithrix jacchus, Cebus apella, Gorilla gorilla, Hylobates lar, Leontopithecus rosalia, Macaca mulatta, Pan troglodytes, Pan paniscus, Pongo pygmaeus, Saimiri boliviensis, and Symphalangus syndactylus). Results are compared to previously published data on five species of wild anthropoids (n = 28; Alouatta paliatta, Callithrix jacchus, Gorilla beringei, Leontopithecus rosalia, and Macaca sinica) and human milk fatty acid profiles. Milk LCPUFA profiles of captive anthropoids (consuming diets with a preformed source of DHA) are similar to milk from women on a Western diet, and those of wild anthropoids are similar to milk from vegan women. Collectively, the range of DHA percent composition values from nonhuman anthropoid milks (0.03–1.1) is nearly identical to that from a cross-cultural analysis of human milk (0.06–1.4). Humans do not appear to be unique in their ability to secrete LCPUFA in milk but may be unique in their access to dietary LCPUFA.     

Biochemical effects of supplemented long-chain polyunsaturated fatty acids in hyperphenylalaninemia

Hyperphenylalaninemic (HPA) children display low levels of long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), in circulating lipids and erythrocytes. We have investigated the effects on the blood fatty acid status and lipid picture of a balanced supplementation with LCPUFA in HPA children through a double-blind, placebo-controlled trial. A total of 20 well-controlled HPA, school-age children were randomized to receive through a 12-month trial fat capsules supplying either 26% fatty acid as LCPUFA (including 4.6%gamma -linolenic acid, 7.4% arachidonic acid, AA, 5.5% eicosapentaenoic acid and 8% DHA) or placebo (olive oil). The study supplementation was administered in order to provide 0.3-0.5% of the individual daily energy requirements as LCPUFA. Reference data were obtained from healthy children of comparable age. Among HPA children (whose DHA status was poor at baseline), those supplemented with LCPUFA showed an increase of around 100% in the baseline DHA levels in plasma phospholipids and erythrocytes. No changes of AA levels were observed. Blood lipid levels did not significantly change. A balanced supplementation with LCPUFA in treated HPA children may improve the DHA status without adversely affecting the AA status.     

Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition

We investigated whether supplementation with arachidonic acid (20:4 omega 6; AA), or a combination of AA and docosahexaenoic acid (22:6 omega 3; DHA) would affect human milk polyunsaturated fatty acid (PUFA) composition. Ten women were daily supplemented with 300 mg AA, eight with 300 mg AA, 110 mg eicosapentaenoic acid (20:5 omega 3; EPA) and 400 mg DHA, for one week and eight women served as unsupplemented controls. Milk samples were collected on days 0, 1 and 7. The fatty acid composition of the milk was analyzed by capillary gas chromatography with flame ionisation detection. Supplementation with AA alone had no effect on breastmilk AA, but tended to reduce EPA and DHA levels. Administration of a combination of AA, EPA and DHA tended to increase both milk AA and long chain PUFA (LCPUFA)omega 3 content. A larger simultaneous increase of milk AA, DHA and EPA than observed in the present study can probably be accomplished by the use of a combination of a lower LCPUFA omega 6/LCPUFA omega 3 ratio and higher AA, EPA and DHA dosages.     

Habitual fish consumption does not prevent a decrease in LCPUFA status in pregnant women (the Seychelles Child Development Nutrition Study)

Information on the status of long-chain polyunsaturated fatty acids (LCPUFAs) in pregnancy and breast milk in very high fish-eating populations is limited. The aim of this study was to examine dietary intake and changes in fatty acid status in a population of pregnant women in the Republic of Seychelles. Serum docosahexaenoic acid (DHA) decreased significantly between 28-week gestation and delivery (n=196). DHA status did not correlate significantly with length of gestation and was not associated with self-reported fish intake, which was high at 527 g/week. In breast milk, the ratio of DHA to arachidonic acid (AA) was consistent with those observed in other high fish-eating populations. Overall the data suggest that high exposure to LCPUFAs from habitual fish consumption does not prevent the documented decrease in LCPUFA status in pregnancy that occurs as a result of foetal accretion in the third trimester of pregnancy.     

Formula feeding potentiates docosahexaenoic and arachidonic acid biosynthesis in term and preterm baboon neonates

Infant formulas supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) are now available in the United States; however, little is known about the factors that affect biosynthesis. Baboon neonates were assigned to one of four treatments: term, breast-fed; term, formula-fed; preterm (155 of 182 days gestation), formula-fed; and preterm, formula+DHA/ARA-fed. Standard formula had no DHA/ARA; supplemented formula had 0.61%wt DHA (0.3% of calories) and 1.21%wt ARA (0.6% of calories), and baboon breast milk contained 0.68 +/- 0.22%wt DHA and 0.62 +/- 0.12%wt ARA. At 14 days adjusted age, neonates received a combined oral dose of [U-13C]alpha-linolenic acid (LNA*) and [U-13C]linoleic acid (LA*), and tissues were analyzed 14 days after dose. Brain accretion of linolenic acid-derived DHA was approximately 3-fold greater for the formula groups than for the breast-fed group, and dietary DHA partially attenuated excess DHA synthesis among preterms. A similar, significant pattern was found in other organs. Brain linoleic acid-derived ARA accretion was significantly greater in the unsupplemented term group but not in the preterm groups compared with the breast-fed group. These data show that formula potentiates the biosynthesis/accretion of DHA/ARA in term and preterm neonates compared with breast-fed neonates and that the inclusion of DHA/ARA in preterm formula partially restores DHA/ARA biosynthesis to lower, breast-fed levels. Current formula DHA concentrations are inadequate to normalize long-chain polyunsaturated fatty acids synthesis to that of breast-fed levels.     

Alpha-linolenic acid and its conversion to longer chain n−3 fatty acids: Benefits for human health and a role in maintaining tissue n−3 fatty acid levels

There is little doubt regarding the essential nature of alpha-linolenic acid (ALA), yet the capacity of dietary ALA to maintain adequate tissue levels of long chain n−3 fatty acids remains quite controversial. This simple point remains highly debated despite evidence that removal of dietary ALA promotes n−3 fatty acid inadequacy, including that of docosahexaenoic acid (DHA), and that many experiments demonstrate that dietary inclusion of ALA raises n−3 tissue fatty acid content, including DHA. Herein we propose, based upon our previous work and that of others, that ALA is elongated and desaturated in a tissue-dependent manner. One important concept is to recognize that ALA, like many other fatty acids, rapidly undergoes β-oxidation and that the carbons are conserved and reused for synthesis of other products including cholesterol and fatty acids. This process and the differences between utilization of dietary DHA or liver-derived DHA as compared to ALA have led to the dogma that ALA is not a useful fatty acid for maintaining tissue long chain n−3 fatty acids, including DHA. Herein, we propose that indeed dietary ALA is a crucial dietary source of n−3 fatty acids and its dietary inclusion is critical for maintaining tissue long chain n−3 levels.     

Correlations between blood and tissue omega-3 LCPUFA status following dietary ALA intervention in rats

The aim of this study was to assess relationships between the fatty acid contents of plasma and erythrocyte phospholipids and those in liver, heart, brain, kidney and quadriceps muscle in rats. To obtain a wide range of tissue omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFA) we subjected weanling rats to dietary treatment with the n-3 LCPUFA precursor, alpha linolenic acid (ALA, 18:3 n-3) for 3 weeks. With the exception of the brain, we found strong and consistent correlations between the total n-3 LCPUFA fatty acid content of both plasma and erythrocyte phospholipids with fatty acid levels in all tissues. The relationships between eicosapentaenoic acid (EPA, 20:5 n-3) and docosapentaenoic acid (DPA, 22:5 n-3) content in both blood fractions with levels in liver, kidney, heart and quadriceps muscle phospholipids were stronger than those for docosahexaenoic acid (DHA, 22:6 n-3). The strong correlations between the EPA+DHA (the Omega-3 Index), total n-3 LCPUFA and total n-3 PUFA contents in both plasma and erythrocyte phospholipids and tissues investigated in this study suggest that, under a wide range of n-3 LCPUFA values, plasma and erythrocyte n-3 fatty acid content reflect not only dietary PUFA intakes but also accumulation of endogenously synthesised n-3 LCPUFA, and thus can be used as a reliable surrogate for assessing n-3 status in key peripheral tissues.     

Arachidonic Acid and Docosahexaenoic Acid Suppress Osteoclast Formation and Activity in Human CD14+ Monocytes,In vitro

An unbalanced diet can have adverse effects on health. Long chain polyunsaturated fatty acids (LCPUFAs) have been the focus of research owing to their necessity of inclusion in a healthy diet. However, the effects of LCPUFAs on human osteoclast formation and function have not been explored before. A human CD14+ monocyte differentiation model was used to elucidate the effects of an ω-3 LCPUFA, docosahexaenoic acid (DHA), and an ω-6 LCPUFA, arachidonic acid (AA), on osteoclast formation and activity. CD14+ monocytes were isolated from peripheral blood of healthy donors and stimulated with macrophage colony stimulating factor and receptor activator of nuclear factor kappa-B ligand to generate osteoclasts. Data from this study revealed that both the LCPUFAs decreased osteoclast formation potential of CD14+ monocytes in a dose-dependent manner when treated at an early stage of differentiation. Moreover, when exposed at a late stage of osteoclast differentiation AA and DHA impaired the bone resorptive potential of mature osteoclasts without affecting osteoclast numbers. AA and DHA abrogated vitronectin receptor expression in differentiating as well as mature osteoclasts. In contrast, the degree of inhibition for calcitonin receptor expression varied between the LCPUFAs with only AA causing inhibition during osteoclast differentiation. Furthermore, AA and DHA down regulated the expression of key osteoclast-specific genes in differentiating as well as mature osteoclasts. This study demonstrates for the first time that LCPUFAs can modulate osteoclast formation and function in a human primary osteoclast cell line.     

Abnormality of erythrocyte membrane n-3 long chain polyunsaturated fatty acids in sickle cell haemoglobin C (HbSC) disease is not as remarkable as in sickle cell anaemia (HbSS)

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.     

Effects of long-chain polyunsaturated fatty acid supplementation on neurodevelopment in childhood: A review of human studies

Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA) are critical for infant and childhood brain development, but levels of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are often low in the Western diet. Increasing evidence from both epidemiological and intervention studies, reviewed here, indicates that DHA supplementation, during pregnancy, lactation, or childhood plays an important role in childhood neurodevelopment. Arachidonic acid (ARA) is also important for infant growth and development. Several studies have demonstrated positive associations between blood DHA levels and improvements on tests of cognitive and visual function in healthy children. Controlled trials also have shown that supplementation with DHA and EPA may help in the management of childhood psychiatric disorders, and improve visual and motor functions in children with phenylketonuria. In all studies, DHA and EPA supplementation is typically well tolerated. Further research is needed to determine optimal doses for efficacy at different developmental ages. The potential long-term benefits of early LCPUFA supplementation also require consideration.     

Arachidonic Acid-metabolizing Cytochrome P450 Enzymes Are Targets of ω-3 Fatty Acids

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect against cardiovascular disease by largely unknown mechanisms. We tested the hypothesis that EPA and DHA may compete with arachidonic acid (AA) for the conversion by cytochrome P450 (CYP) enzymes, resulting in the formation of alternative, physiologically active, metabolites. Renal and hepatic microsomes, as well as various CYP isoforms, displayed equal or elevated activities when metabolizing EPA or DHA instead of AA. CYP2C/2J isoforms converting AA to epoxyeicosatrienoic acids (EETs) preferentially epoxidized the ω-3 double bond and thereby produced 17,18-epoxyeicosatetraenoic (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) from EPA and DHA. We found that these ω-3 epoxides are highly active as antiarrhythmic agents, suppressing the Ca²⁺-induced increased rate of spontaneous beating of neonatal rat cardiomyocytes, at low nanomolar concentrations. CYP4A/4F isoforms ω-hydroxylating AA were less regioselective toward EPA and DHA, catalyzing predominantly ω- and ω minus 1 hydroxylation. Rats given dietary EPA/DHA supplementation exhibited substantial replacement of AA by EPA and DHA in membrane phospholipids in plasma, heart, kidney, liver, lung, and pancreas, with less pronounced changes in the brain. The changes in fatty acids were accompanied by concomitant changes in endogenous CYP metabolite profiles (e.g. altering the EET/EEQ/EDP ratio from 87:0:13 to 27:18:55 in the heart). These results demonstrate that CYP enzymes efficiently convert EPA and DHA to novel epoxy and hydroxy metabolites that could mediate some of the beneficial cardiovascular effects of dietary ω-3 fatty acids.     

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.     

Content of polyunsaturated fatty acids (PUFAs) in serum and liver of rats fed restricted diets supplemented with vitamins B2, B6 and folic acid

The aim of study was to investigate an influence of nutritional deficiency and dietary addition of vit. B(2), B(6) and folic acid on PUFAs content in rats' serum and liver. Limitation of consumption full value diet to 50% of its previously determined daily consumption, enriched with m/a vitamins, significant decreased of linoleic (LA) and alpha-linolenic (ALA) acids as well as distinctly increased arachidonic (AA) and docosahexaenoic (DHA) acids content in serum in 30th day. In 60th day lower content of AA and DHA fatty acids was found. Nutrition with such diet, lasting 90 days caused decrease of LA content and increase of AA. Diet limitation to its 30% of daily consumption decreased of eicosapentaenoic acid (EPA) and DHA in the 30th day, while AA and DHA content was increased in the 60th day. Distinct decrease of AA content and increase of EPA content were found in the 90th day of experiment. Use of diets, with limited consumption to 50% caused increase of LA and ALA acids content while AA and DHA acids content were significantly decreased in the liver, in 90th day. Limited consumption supplemented diet to 30% caused in liver significant decrease of LA and increase of EPA acids content.     

Influence of an increased intake of linoleic acid on the incorporation of dietary (n-3) fatty acids in phospholipids and on prostanoid synthesis in rat tissues.

We investigated whether the amount of dietary linoleic acid (LA) (as corn oil) influences the incorporation of dietary eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in tissue phospholipids and the prostanoid biosynthesis. Rats were fed four different levels of corn oil (at a total dietary fat level of either 2.5%, 5%, 10% or 20%); at each corn oil level, two groups of rats were supplemented with either EPA and DHA (200 mg/day) during 6 weeks, and compared with a group receiving oleic acid. The phospholipid fatty acid composition of liver, kidney and aorta showed, as expected, that the incorporation of EPA was highly suppressed by increasing the content of dietary linoleic acid in the diets. On the other hand, DHA was almost unaffected by the amounts of (n - 6) fatty acids in the diets. These results indicate that EPA levels but not DHA levels in tissue phospholipids were influenced by the competing dietary (n - 6) fatty acids. The tissue arachidonate content was similar under the various dietary linoleic acid conditions, but feeding EPA or DHA lowers the AA content. Moreover, the amount of dietary linoleic acid did not significantly influence the prostaglandin E2 (PGE2) production in stimulated aortic rings. However, PGE2 synthesis was significantly decreased in the groups treated with either EPA or DHA. Thromboxane B2 levels in serum followed a similar pattern. It is suggested that an increase of dietary (n - 3) PUFAs is more efficient to reduce (n - 6) eicosanoid formation than a decrease of dietary (n - 6) fatty acids.     

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.     

No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis

A deficiency of essential fatty acids (EFA) is frequently described in cystic fibrosis (CF), but whether this is a primary consequence of altered EFA metabolism or a secondary phenomenon is unclear. It was suggested that defective long-chain polyunsaturated fatty acid (LCPUFA) synthesis contributes to the CF phenotype. To establish whether cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction affects LCPUFA synthesis, we quantified EFA metabolism in cftr-/-CAM and cftr+/+CAM mice. Effects of intestinal phenotype, diet, age, and genetic background on EFA status were evaluated in cftr-/-CAM mice, DeltaF508/DeltaF508 mice, and littermate controls. EFA metabolism was measured by 13C stable isotope methodology in vivo. EFA status was determined by gas chromatography in tissues of cftr-/-CAM mice, DeltaF508/DeltaF508 mice, littermate controls, and C57Bl/6 wild types fed chow or liquid diet. After enteral administration of [13C]EFA, arachidonic acid (AA) and docosahexaenoic acid (DHA) were equally 13C-enriched in cftr-/-CAM and cftr+/+CAM mice, indicating similar EFA elongation/desaturation rates. LA, ALA, AA, and DHA concentrations were equal in pancreas, lung, and jejunum of chow-fed cftr-/-CAM and DeltaF508/DeltaF508 mice and controls. LCPUFA levels were also equal in liquid diet-weaned cftr-/-CAM mice and littermate controls, but consistently higher than in age- and diet-matched C57Bl/6 wild types. We conclude that cftr-/-CAM mice adequately absorb and metabolize EFA, indicating that CFTR dysfunction does not impair LCPUFA synthesis. A membrane EFA imbalance is not inextricably linked to the CF genotype. EFA status in murine CF models is strongly determined by genetic background.     

The effects of a diet rich in docosahexaenoic acid on organ and vascular fatty acid composition in spontaneously hypertensive rats

Previous research has shown that dietary docosahexaenoic acid (DHA) attenuates the development of high blood pressure in young spontaneously hypertensive rats (SHR). The purpose of this study was to investigate the effects of dietary DHA on organ and vascular fatty acid composition in SHR. Given the important structural and functional role of fatty acids in cell membranes, alterations in fatty acid composition may contribute to the antihypertensive effect of DHA. SHR were fed a purified diet containing either a corn/soybean oil mixture (CSO, control) or a DHA-enriched oil for 6 weeks. The DHA diet markedly increased the levels of DHA in the aorta, renal artery, plasma, liver, heart, kidney, and lung by 5-, 15-, 7-, 6-, 3.8-, 3.5-, and 8.8-fold (P<0.001), respectively. The levels of eicosapentaenoic acid were also increased while there was a concomitant reduction in arachidonic and adrenic acids. Therefore, dietary DHA increases the incorporation of omega-3 polyunsaturated fatty acids in specific organs and vascular tissue in SHR at the expense of omega-6 polyunsaturated fatty acids.     

Unraveling lipid metabolism with microarrays: effects of arachidonate and docosahexaenoate acid on murine hepatic and hippocampal gene expression

Introduction  

The functions, actions, and regulation of polyunsaturated fatty acids (PUFAs) are just now beginning to be unraveled, in large due to modern molecular techniques. In the present work, mice were fed diets rich in either arachidonic acid (AA, n6), docosahexaenoic acid (DHA, n3), or the combination (AA+DHA). Both liver and hippocampus tissue were then analyzed through a combined gene expression-, lipid-, and behavioral- profiling strategy in order to annotate the molecular functions and targets of dietary PUFA.