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.     

Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids

The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07–17.1 en%) and ALA (0.02–12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1–3 en% ALA and 1–2 en% LA but was suppressed to basal levels (～2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%).     

Higher plasma n-3 fatty acid status in the moderately healthy elderly in southern Québec: Higher fish intake or aging-related change in n-3 fatty acid metabolism?

The elderly reportedly have a significantly higher % of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma and red cell lipids. However, these observations are from a few small studies and the health status of the elderly in these studies is for the most part unclear. Since the elderly are susceptible to cardiovascular and neurological illnesses that seem to be related in part to lower intake of n-3 fatty acids it seems paradoxical that their blood levels of EPA and DHA would be higher than in young adults. We report here plasma fatty acid profiles and their response to supplementation with two types of fish oils from several of our recent studies in the moderately healthy elderly. We define the moderately healthy elderly as those who were in good physical condition, had no cognitive decline and, if present, in whom hypothyroidism, hyperlipidemia and/or hypertension were well-controlled. As shown previously, we confirm the higher % EPA and % total n-3 fatty acids (but not DHA) in fasting plasma and extend these findings to include higher plasma concentrations (mg/L) of n-3 fatty acids as well. The EPA-predominant supplement raised DHA only in the young, whereas the DHA-predominant supplement raised EPA more in the young than in the elderly. The moderately healthy elderly clearly have higher plasma n-3 fatty acids but whether this reflects differences in intake versus aging-related changes in n-3 fatty acid metabolism remains to be elucidated.     

Omega-3 fatty acid deficiency increases constitutive pro-inflammatory cytokine production in rats: Relationship with central serotonin turnover

Omega-3 (n-3) fatty acid deficiency, elevated inflammatory signaling, and central serotonin (5-HT) turnover have separately been implicated in the pathophysiology of major depressive disorder (MDD). In the present study we investigated the interrelationship between n-3 fatty acid status, pro-inflammatory signaling activity, and central 5-HT turnover in vivo. Rats were fed diets with or without the n-3 fatty acid precursor α-linolenic acid (ALA) during perinatal development (E0-P100), and a subset of rats fed the ALA− diet were switched to the ALA+ diet post-weaning (P21-P100, repletion). In adulthood (P100), plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) levels were measured. Additionally, indices of liver n-6 fatty acid biosynthesis, erythrocyte fatty acid composition, and regional brain monoamine turnover were determined. Indices of liver delta-6 desaturase activity were up-regulated in n-3-deficient rats, and were associated with greater erythrocyte membrane arachidonic acid (AA, 20:4 n-6) composition. Plasma IL-6 (p=0.001), TNFα (p=0.02), and CRP (p=0.001) concentrations were significantly greater in n-3-deficient rats relative to controls. The 5-HIAA/5-HT ratio was significantly greater in frontal cortex, hypothalamus, and ventral striatum of n-3-deficient rats relative to controls. Changes in membrane n-3 and n-6 fatty acid composition, elevations in plasma IL-6 and TNFα, and increased central 5-HT turnover were all prevented by normalization of n-3 fatty acid status. Erythrocyte docosahexaenoic acid (DHA, 22:6 n-3) was inversely correlated, and AA and the AA/DHA and AA/eicosapentaenoic acid ratios were positively correlated, with plasma IL-6, TNFα, and CRP levels. Plasma IL-6 levels were positively correlated with 5-HIAA/5-HT ratios in all brain regions. These preclinical data provide evidence for a functional link between n-3 fatty acid deficiency, elevated peripheral inflammatory signaling, and increased central 5-HT turnover.     

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.     

Rat heart cannot synthesize docosahexaenoic acid from circulating alpha-linolenic acid because it lacks elongase-2

The extent to which the heart can convert alpha-linolenic acid (alpha-LNA, 18:3n-3) to longer chain n-3 PUFAs is not known. Conversion rates can be measured in vivo using radiolabeled alpha-LNA and a kinetic fatty acid model. [1-(14)C]alpha-LNA was infused intravenously for 5 min in unanesthetized rats that had been fed an n-3 PUFA-adequate [4.6% alpha-LNA, no docosahexaenoic acid (DHA, 22:6n-3)] or n-3 PUFA-deficient diet (0.2% alpha-LNA, nor DHA) for 15 weeks after weaning. Arterial plasma was sampled, as was the heart after high-energy microwaving. Rates of conversion of alpha-LNA to longer chain n-3 PUFAs were low, and DHA was not synthesized at all in the heart. Most alpha-LNA within the heart had been beta-oxidized. In deprived compared with adequate rats, DHA concentrations in plasma and heart were both reduced by >90%, whereas heart and plasma levels of docosapentaenoic acid (DPAn-6, 22:5n-6) were elevated. Dietary deprivation did not affect cardiac mRNA levels of elongase-5 or desaturases Delta6 and Delta5, but elongase-2 mRNA could not be detected. In summary, the rat heart does not synthesize DHA from alpha-LNA, owing to the absence of elongase-2, but must obtain its DHA entirely from plasma. Dietary n-3 PUFA deprivation markedly reduces heart DHA and increases heart DPAn-6, which may make the heart vulnerable to different insults.     

Increased risk of postpartum depressive symptoms is associated with slower normalization after pregnancy of the functional docosahexaenoic acid status

Observational studies suggest an association between a low docosahexaenoic acid (DHA, 22:6n-3) status after pregnancy and the occurrence of postpartum depression. However, a comparison of the actual biochemical plasma DHA status among women with and without postpartum depression has not been reported yet. The contents of DHA and of its status indicator n-6 docosapentaenoic acid (n-6DPA, 22:5n-6) were measured in the plasma phospholipids of 112 women at delivery and 32 weeks postpartum. At this latter time point, the Edinburgh Postnatal Depression Scale (EPDS) questionnaire was completed to measure postpartum depression retrospectively. The EPDS cutoff score of 10 was used to define 'possibly depressed' (EPDS score > or =10) and non-depressed women (EPDS score <10). Odds ratios (OR) were calculated using a multiple logistic regression analysis with the EPDS cutoff score as dependent and fatty acid concentrations and ratio's as explanatory variables, while controlling for different covariables. The results demonstrated that the postpartum increase of the functional DHA status, expressed as the ratio DHA/n-6DPA, was significantly lower in the 'possibly depressed' group compared to the non-depressed group (2.34+/-5.56 versus 4.86+/-5.41, respectively; OR=0.88, P=0.03). Lactating women were not more predisposed than non-lactating women were to develop depressive symptoms. From this observation it seems that the availability of DHA in the postpartum period is less in women developing depressive symptoms. Although further studies are needed for confirmation, increasing the dietary DHA intake during pregnancy and postpartum, seems prudent.     

Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration

Docosahexaenoic acid (DHA), an n-3 fatty acid, is rapidly deposited during the period of rapid brain development. The influence of n-3 fatty acid deficiency on learning performance in adult rats over two generations was investigated. Rats were fed either an n-3 fatty acid-adequate (n-3 Adq) or -deficient (n-3 Def) diet for three generations (F1-F3). Levels of total brain n-3 fatty acids were reduced in the n-3 Def group by 83 and 87% in the F2 and F3 generations, respectively. In the Morris water maze, the n-3 Def group showed a longer escape latency and delayed acquisition of this task compared with the n-3 Adq group in both generations. The acquisition and memory levels of the n-3 Def group in the F3 generation seemed to be lower than that of the F2 generation. The 22:5n-6/22:6n-3 ratio in the frontal cortex and dams' milk was markedly increased in the n-3 Def group, and this ratio was significantly higher in the F3 generation compared with the F2 generation. These results suggest that learning and cognitive behavior are related to brain DHA status, which, in turn, is related to the levels of the milk/dietary n-3 fatty acids.     

Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates

To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.     

The effect of supplementation with docosahexaenoic and arachidonic acid derived from single cell oils on plasma and erythrocyte fatty acids of pregnant women in the second trimester

This study was performed to investigate whether supplementation of docosahexaenoic acid (DHA) and arachidonic acid (AA) to pregnant women would enhance their DHA levels, both in plasma and in erythrocyte phospholipids, without reducing the content of n-6 long-chain ployenes (LCP) usually seen when DHA is supplemented alone. Healthy pregnant women, in the second trimester, were randomly assigned to either the control group (n=12) or the intervention group (n=12). The control group received no supplements and the intervention group received daily during 4 weeks encapsulated algae-derived DHA oil (0.57 g DHA/day) and fungal-derived AA oil (0.26 g AA/day). The fatty acid compositions of plasma and erythrocyte phospholipids were determined in weekly-collected blood samples. DHA and n-6 LCP levels of the control group were unchanged after 4 weeks. Compared to the control group, DHA levels in plasma an erythrocytes of the intervention group increased significantly. No significant reductions were found in the levels of AA and total n-6 LCP. The supplement proved to be effective in increasing the DHA levels in both plasma and erythrocyte without a concomitant decline of the n-6 LCP.     

Polyunsaturated fatty acids in maternal plasma and in breast milk

In order to explain processes underlying the transfer of fatty acids from the maternal compartment into human milk, the lipid content and the fatty acid composition of maternal plasma and milk have been analyzed in breastfeeding mothers at 1 day and 3 months of lactation.The rise in milk lipids occurring during the study period was concomitant with a fall in plasma total fat content, mainly due to the decrease of triglycerides. Significant correlations between plasma and milk fatty acids at the two time points were observed only for linoleic (LA, 18:2 n-6) and (alpha;-linolenic acid (alpha LNA, 18:3 n-3), while for arachidonic (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) correlations were found only at one day and 3 months, respectively.These data suggest that levels of the n-6 and n-3 18C polyunsaturated fatty acids in milk are closely dependent on their concentrations in maternal plasma, in turn related with the dietary intake, while the accumulation of AA and DHA in milk is the result of a sequence of transfer and metabolic processes.     

Dairy fat blends high in α-linolenic acid are superior to n-3 fatty-acid-enriched palm oil blends for increasing DHA levels in the brains of young rats

Achieving an appropriate docosahexaenoic acid (DHA) status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how different dietary fat matrices improved DHA content in the brains of both male and female rats. Forty rats of each gender were born from dams fed over gestation and lactation with a low α-linolenic acid (ALA) diet (0.4% of fatty acids) and subjected for 6 weeks after weaning to a palm oil blend-based diet (10% by weight) that provided either 1.5% ALA or 1.5% ALA and 0.12% DHA with 0.4% arachidonic acid or to an anhydrous dairy fat blend that provided 1.5% or 2.3% ALA. Fatty acids in the plasma, red blood cells (RBCs) and whole brain were determined by gas chromatography. The 1.5% ALA dairy fat was superior to both the 1.5% ALA palm oil blends for increasing brain DHA (14.4% increase, P<.05), and the 2.3% ALA dairy blend exhibited a further increase that could be ascribed to both an ALA increase and n-6/n-3 ratio decrease. Females had significantly higher brain DHA due to a gender-to-diet interaction, with dairy fats attenuating the gender effect. Brain DHA was predicted with a better accuracy by some plasma and RBC fatty acids when used in combination (R² of 0.6) than when used individually (R²=0.47 for RBC n-3 docosapentaenoic acid at best). In conclusion, dairy fat blends enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of postweaning rats. Human applications are worth considering.     

α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans

Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long-chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets, which are rich in linoleic acid (LA), show that supplemental ALA raises EPA and DPA status in the blood and in breast milk. However, ALA or EPA dietary supplements have little effect on blood or breast milk DHA levels, whereas consumption of preformed DHA is effective in raising blood DHA levels. Addition of ALA to the diets of formula-fed infants does raise DHA, but no level of ALA tested raises DHA to levels achievable with preformed DHA at intakes similar to typical human milk DHA supply. The DHA status of infants and adults consuming preformed DHA in their diets is, on average, greater than that of people who do not consume DHA. With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors.     

Altered essential fatty acid metabolism and composition in rat liver, plasma, heart and brain after microalgal DHA addition to the diet

To investigate the effect of docosahexaenoic acid (DHA) without other highly unsaturated fatty acids (HUFA) on n-3 and n-6 essential fatty acid (EFA) metabolism and fatty acid composition in mammals, a stable isotope tracer technique was used in adult rats fed diets with or without 1.3% of algal DHA in a base diet containing 15% of linoleic acid and 3% of alpha-linolenic acid over 8 weeks. The rats were administered orally a mixed oil containing 48 mg/kg body weight of deuterated linoleic and alpha-linolenic acids and euthanized at 4, 8, 24, 96, 168, 240, 360 and 600 h after administration of the isotopes. Fatty acid compositions and the concentrations of deuterated precursors and their respective metabolites were determined in rat liver, plasma, heart and brain as a function of time. DHA, docosapentaenoic acid and eicosapentaenoic acid in the n-3 EFA family were significantly increased in all organs tested in the DHA-fed group, ranging from 5% to 200% greater in comparison with the control group. The accumulation of the metabolites, deuterated-DHA and deuterated-docosapentaenoic acid n-6 was greatly decreased by 1.5- to 2.5-fold in the dietary DHA group. In summary, feeding preformed DHA led to a marked increase in n-3 HUFA content of rat organs at the expense of n-6 HUFA and also prevented the accumulation of newly synthesized deuterated end products. This is the first study which has isolated the effects of DHA on the de novo metabolism on both the n-6 and n-3 EFA pathways.     

Plasma fatty acids of neonates born to mothers with and without gestational diabetes

Women with gestational diabetes mellitus (GDM) and their neonates have lower levels of arachidonic (AA) and docosahexaenoic (DHA) acids in red cell membranes. It is not clear if this abnormality is restricted to red cells or is a generalised problem. We have investigated plasma fatty acids of neonates (venous cord) of GDM (n=37), and non-diabetic (n=31) women. The GDMs had lower levels of dihomogamma-linolenic (20:3n-6, DHGLA) acid, summation operator n-6 metabolites, DHA and summation operator n-3 metabolites (p<0.05) in choline phosphoglycerides (CPG). They also had lower levels of AA (-4.5%), adrenic acid (22:4n-6, -13%), osbond acid (22:5n-6, -7%) and summation operator n-6 (-2.5%). There was a similar pattern in triglycerides (TG) and cholesterol esters (CE). Mead acid, a marker of generalised shortage of derived and parent essential fatty acids, was higher in CPG and TG of the GDM group by 73% and 76%. The adrenic/osbond acid (22:4n-6/22:5n-6) ratio, a biochemical marker of DHA insufficiency, was reduced in CPG (-4.5%), TG (-63%) and CE (-75%) of the GDM group. These findings, which are consistent with the previous red cell data, suggest that the neuro-visual and vascular development and function of the offspring of GDM women may be adversely affected if the levels of AA and DHA are compromised further by other factors, pre- or post-natally. Studies are required to elucidate the underlying mechanism for the reduction of the two fatty acids and to evaluate the developmental and health implications.     

Omega-3 fatty acids and rodent behavior

This paper reviews the role of the n-3 fatty acids in the regulation of cognitive functions, locomotor and exploratory activity and emotional status in rodents. There are disparate data on the performance of n-3 fatty acid deficient animals in the open field test and elevated plus maze. Results obtained in our laboratory indicated slower habituation to the open field in deficient mice, which affects total locomotor and exploratory parameters. We also observed no change in plus maze performance of deficient mice under low-stress but elevated anxiety under high-stress conditions. There is some evidence of elevated aggression and increased immobility time in the forced swimming test caused by n-3 fatty acid deficiency in rodents. Effects of n-3 fatty acid deficiency and supplementation on learning in several tests such as the Morris water maze, two odor olfactory discriminations, radial arm maze performance and avoidance tasks are reviewed in detail. There is some evidence of an enhanced vulnerability to stress of n-3 fatty acid deficient animals and this factor can influence performance in a variety of tests. Thus, behavioral tasks that involve a higher level of stress may better differentiate behavioral effects related to brain docosahexaenoic acid (DHA) status. It is suggested that a fruitful area for future investigations of functional alterations related to brain DHA status will be the delineation of the factors underlying changes in performance in behavioral tasks. The possible role of non-cognitive factors like emotionality and attention in the impaired performance of n-3 fatty acid deficient animals also requires further investigation.     

A modified <Emphasis Type="Italic">n</Emphasis>–3 fatty acid desaturase gene from <Emphasis Type="Italic">Caenorhabditis briggsae</Emphasis> produced high proportion of DHA and DPA in transgenic mice

The functions of polyunsaturated fatty acids (PUFAs) have been widely investigated. In mammals, levels of n-3 PUFAs are relatively low compared to those of n-6 PUFAs. Either a lack of n-3 PUFAs or an excess of n-6 PUFAs could potentially cause health problems in humans. Hence, methods to increase the amount of n-3 PUFAs in diet have been intensely sought. In this study, we demonstrated that the n-3 fatty acid desaturase gene (sFat-1) synthesized from revised and optimized codons based on roundworm Caenorhabditis briggsae genomic gene for enhanced expression in mammals was successfully expressed in Chinese hamster ovary (CHO) cells and significantly elevated cellular n-3 PUFA contents. We generated sFat-1 transgenic mice by introducing mammal expression vector DNAs containing the sFat-1 gene into regular mice through the method of microinjection. Fatty acid compositions were then altered and the levels of docosahexaenoic acid (DHA, 22:6n-3) and docosapentaenoic acid (DPA, 22:5n-3) were greatly increased in these transgenic mice. Various types of tissues in the transgenic mice produced many types of n-3 PUFAs, such as alpha-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), DPA, and DHA, for example, muscle tissues of the transgenic mice contained 12.2% DHA, 2.0% DPA, and 23.1% total n-3 PUFAs. These research results demonstrated that the synthesized sFat-1 gene with modified and optimized codons from C. briggsae possess functional activity and greater capability of producing n-3 PUFAs, especially DHA and DPA, in transgenic mice.     

Physiological effects of a fish oil supplement on captive juvenile tuatara (Sphenodon punctatus)

Tuatara (Sphenodon, Order Sphenodontia) are rare New Zealand reptiles whose conservation involves captive breeding. Wild tuatara eat seabirds, which contain high levels of the long-chain n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These fatty acids are absent from the captive diet, and consequently, plasma fatty acid composition of wild and captive tuatara differs. This study investigated the effects of incorporating EPA and DHA into the diet of captive juvenile tuatara (Sphenodon punctatus) in an attempt to replicate the plasma fatty acid composition of wild tuatara. Tuatara receiving a fish oil supplement containing EPA and DHA showed overall changes in their plasma fatty acid composition. Phospholipid EPA and DHA increased markedly, reaching 10.0% and 5.9 mol%, respectively, by 18 mo (cf. 相似文献   

Mechanical Force and Cytoplasmic Ca2+ Activate Yeast TRPY1 in Parallel

Diets supplemented with n-3 polyunsaturated fatty acids can promote lipid peroxidation and the propagation of oxygen radicals. These effects can be prevented by taurine, a functional ingredient with antioxidant properties. Here, we examined whether there is a correlation between transepithelial taurine transport, on the one hand, and membrane fatty acid composition and peroxidation in intestinal Caco-2 cells, on the other. Differentiated Caco-2 cells were maintained for 10 days, from the day of confluence, in control conditions or in a medium enriched with docosahexaenoic acid (DHA, 100 μmol/l), taurine (10 mmol/l) or DHA plus taurine. Incubation of the monolayers in a medium enriched with DHA increased the incorporation of this fatty acid into the brush-border membrane, at the expense of total n-6 fatty acids (C20:2n-6, C20:3n-6 and C22:4n-6). This was paralleled by increased membrane lipid peroxidation, which was partially limited by the addition of taurine. Transepithelial taurine transport was estimated from taurine uptake and efflux kinetic parameters at apical and basolateral domains. Cell incubation with DHA increased basolateral taurine uptake through an increase in V _max, whereas incubation with taurine downregulated basolateral uptake as occurred for apical taurine transporter. Moreover, addition of DHA reduced the apical downregulation effect exerted on taurine transport by taurine incubation. Our results suggest that the oxidative status of epithelial cells regulates taurine transport, thus satisfying antioxidant cellular requirements.     

Biochemical and biological functions of docosahexaenoic acid in the nervous system: modulation by ethanol

Docosahexaenoic acid (DHA, 22:6n-3), an n-3 fatty acid highly concentrated in the central nervous system, is essential for proper neuronal and retinal function. While a high level of DHA is generally maintained in neuronal membranes, inadequate supply of n-3 fatty acid or ethanol exposure leads to a significant loss of DHA in neuronal cells. The roles of DHA in neuronal signaling have been emerging. In this review, biological, biochemical and molecular mechanisms supporting the essential function of DHA in neuronal survival and development are described in relation to n-3 fatty acid depleting conditions.