Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids

We studied the effects of a diet chronically deficient in alpha-linolenic acid, the precursor of long-chain n-3 polyunsaturated fatty acids, on dopaminergic neurotransmission in the shell region of the nucleus accumbens of rats. In vivo microdialysis experiments showed increased basal levels of dopamine and decreased basal levels of metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in awake rats from the deficient group compared to controls. The release of dopamine under KCl stimulation was similar in both dietary groups. By contrast, the release of dopamine from the vesicular storage pool under tyramine stimulation was 90% lower in the deficient than in the control rats. Autoradiographic studies in the same cerebral region revealed a 60% reduction in the vesicular monoamine transporter sites in the deficient group. Dopamine D(2) receptors were 35% increased in these rats compared to controls, whereas no change occurred for D(1) receptors and membrane dopamine transporters. These results demonstrated that chronic n-3 polyunsaturated fatty acid deficiency modifies several factors of dopaminergic neurotransmission in the nucleus accumbens. These findings are in agreement with the changes in dopaminergic neurotransmission already observed in the frontal cortex, and with the behavioral disturbances described in these deficient rats.     

α-Linolenic Acid Dietary Deficiency Alters Age-Related Changes of Dopaminergic and Serotoninergic Neurotransmission in the Rat Frontal Cortex

Abstract: The effects of α-linolenic acid diet deficiency on rat dopaminergic and serotoninergic neurotransmission systems were investigated in the frontal cortex, striatum, and cerebellum of male rats 2, 6, 12, and 24 months of age. The diet deficiency induced a severe decrease in the 22:6n-3 fatty acid levels in all regions and a compensatory increase in n-6 fatty acid levels. A recovery in the levels of 22:6n-3 was observed in deficient rats between 2 and 12 months of age; however, this recovery was lower in frontal cortex than in striatum and cerebellum. In the striatum and the cerebellum, dopaminergic and serotoninergic receptor densities and endogenous dopamine and serotonin levels were affected by aging regardless of the diet. In contrast, a 40–75% lower level of endogenous dopamine in the frontal cortex occurred in deficient rats according to age. The deficiency also induced an 18–46% increase in serotonin 5-HT₂ receptor density in the frontal cortex during aging, without variation in endogenous serotonin level, and a 10% reduction in density of dopaminergic D₂ receptors. Monoamine oxidase-A and -B activities showed specific age-related variations but regardless of the diet. Our results suggest that a chronically α-linolenic-deficient diet specifically affects the monoaminergic systems in the frontal cortex.     

Dietary n-6 PUFA deprivation for 15 weeks reduces arachidonic acid concentrations while increasing n-3 PUFA concentrations in organs of post-weaning male rats

Few studies have examined effects of feeding animals a diet deficient in n-6 polyunsaturated fatty acids (PUFAs) but with an adequate amount of n-3 PUFAs. To do this, we fed post-weaning male rats a control n-6 and n-3 PUFA adequate diet and an n-6 deficient diet for 15 weeks, and measured stable lipid and fatty acid concentrations in different organs. The deficient diet contained nutritionally essential linoleic acid (LA,18:2n-6) as 2.3% of total fatty acids (10% of the recommended minimum LA requirement for rodents) but no arachidonic acid (AA, 20:4n-6), and an adequate amount (4.8% of total fatty acids) of α-linolenic acid (18:3n-3). The deficient compared with adequate diet did not significantly affect body weight, but decreased testis weight by 10%. AA concentration was decreased significantly in serum (− 86%), brain (− 27%), liver (− 68%), heart (− 39%), testis (− 25%), and epididymal adipose tissue (− 77%). Eicosapentaenoic (20:5n-3) and docosahexaenoic acid (22:6n-3) concentrations were increased in all but adipose tissue, and the total monounsaturated fatty acid concentration was increased in all organs. The concentration of 20:3n-9, a marker of LA deficiency, was increased by the deficient diet, and serum concentrations of triacylglycerol, total cholesterol and total phospholipid were reduced. In summary, 15 weeks of dietary n-6 PUFA deficiency with n-3 PUFA adequacy significantly reduced n-6 PUFA concentrations in different organs of male rats, while increasing n-3 PUFA and monounsaturated fatty acid concentrations. This rat model could be used to study metabolic, functional and behavioral effects of dietary n-6 PUFA deficiency.     

Susceptibility to kainate-induced seizures under dietary zinc deficiency

Zinc homeostasis in the brain is altered by dietary zinc deficiency, and its alteration may be associated with the etiology and manifestation of epileptic seizures. In the present study, susceptibility to kainate-induced seizures was enhanced in mice fed a zinc-deficient diet for 4 weeks. When Timm's stain was performed to estimate zinc concentrations in synaptic vesicles, Timm's stain in the brain was attenuated in the zinc-deficient mice. In rats fed the zinc-deficient diet for 4 weeks, susceptibility to kainate-induced seizures was also enhanced. When the release of zinc and neurotransmitters in the hippocampal extracellular fluid of the zinc-deficient rats was studied using in vivo microdialysis, the zinc concentration in the perfusate was less than 50% of that of the control rats and the increased levels of zinc by treatment with kainate were lower than the basal level in control rats, suggesting that vesicular zinc is responsive to dietary zinc deficiency. The levels of glutamate in the perfusate of the zinc-deficient rats were more increased than in the control rats, whereas the levels of GABA in the perfusate were not at all increased in the zinc-deficient rats, unlike in the control rats. The present results demonstrate an enhanced release of glutamate associated with a decrease in GABA concentrations as a possible mechanism for the increased seizure susceptibility under zinc deficiency.     

Reversibility of n-3 fatty acid deficiency-induced changes in dopaminergic neurotransmission in rats: critical role of developmental stage

Previous investigations have shown that the lipid composition of cerebral membranes and dopaminergic neurotransmission are changed under chronic alpha-linolenic acid diet deficiency in the rat. This study investigated whether these changes could be reversed and if the stage of brain maturation might play a role in the recovery process. The effects of reversion on the fatty acid (FA) composition and dopaminergic neurotransmission were studied in brain regions known to be affected by such deficiency (i.e., the prefrontal cortex and nucleus accumbens) in 2-month-old animals. Dopamine release under pharmacological stimulation was studied using a dual-probe microdialysis method. Vesicular monoamine transporters were studied using quantitative autoradiography. The reversal diet, with adequate levels of n-6 and n-3 polyunsaturated fatty acids (PUFAs), was given to deficient rats at different stages of development (0, 7, 14, or 21 days of age). The results showed that when given during the lactating period, this diet was able to restore both the FA composition of brain membranes and the parameters of dopaminergic neurotransmission studied. However, when given from weaning, it allowed partial recovery of biochemical parameters but no recovery of neurochemical factors. The occurrence of profound n-3 PUFA deficiency during the lactating period could therefore be an environmental insult leading to irreversible damage to specific brain functions.     

Activities of liver microsomal fatty acid desaturases in zinc-deficient rats force-fed diets with a coconut oil/safflower oil mixture of linseed oil

The present study was conducted to investigate the effect of zinc deficiency on fatty acid desaturation in rats fed two different types of dietary fat, a mixture of coconut oil and safflower oil (7∶1, w/w, “coconut oil diet”) or linseed oil (“linseed oil diet”). In order to ensure an adequate food intake, all rats were force-fed by gastric tube. Zinc deficiency caused statistical significant reducion of Δ9-desaturase activity in liver microsomes of rats fed coconut oil diet and tendencial reduction (p<0.15) in rats fed linseed oil diet compared with control rats fed diets with the same type of fat. In agreement with this effect, zinc deficiency in the rats fed both types of dietary fat increased the ratio between total saturated and total monounsaturated fatty in liver phospholipids and liver microsomes. Zinc deficient rats on the coconut oil diet had unchanged Δ6-desaturase activity with linoleic acid as substrate and lowered activity with α-linolenic acid as substrate. In contrast, zinc deficient rats on the linseed oil diet had increased Δ6-desaturase activity with linoleic acid as substrate and unchanged activity with α-linolenic acid. Because linoleic acid is the main substrate for Δ6-desaturase in the rats fed coconut oil diet, and α-linolenic acid is the main substrate in the rats fed linseed oil diet, it is concluded that in vivo Δ6-desaturation was not changed by zinc deficiency in the rats fed both types of dietary fat. Activity of Δ5-desaturase was also not changed by zinc deficiency in the rats fed both dietary fats. Levels of fatty acids in liver phospholipids and microsomes derived by Δ4-, Δ5-, and Δ6-desaturation were not consistently changed by zinc deficiency in the rats fed both types of dietary fat. Thus, the enzyme studies and also fatty acid composition data of liver phospholipids and microsomes indicate that zinc deficiency does not considerably disturb desaturation of linoleic and α-linolenic acid. Therefore, it is suggested that similarities between deficiencies of zinc and essential fatty acids described in literature are not due to disturbed desaturation of linoleic acid in zinc deficiency. The present study also indicates that zinc deficiency enhances incorporation of eicosapentaenoic acid into phosphatidylcholine of rats fed diets with large amounts ofn-3 polyunsaturated fatty acids.     

Effect of a diet-induced n-3 PUFA depletion on cholinergic parameters in the rat hippocampus

Because brain membranes contain large amounts of docosahexaenoic acid (DHA, 22:6n-3), and as (n-3) PUFA dietary deficiency can lead to impaired attention, learning, and memory performance in rodents, we have examined the influence of an (n-3) PUFA-deprived diet on the central cholinergic neurotransmission system. We have focused on several cholinergic neurochemical parameters in the frontal cortex and hippocampus of rats fed an (n-3) PUFA-deficient diet, compared with rats fed a control diet. The (n-3) PUFA deficiency resulted in changes in the membrane phospholipid compositions of both brain regions, with a dramatic loss (62-77%) of DHA. However, the cholinergic pathway was only modified in the hippocampus and not in the frontal cortex. The basal acetylcholine (ACh) release in the hippocampus of deficient rats was significantly (72%) higher than in controls, whereas the KCl-induced release was lower (34%). The (n-3) PUFA deprivation also caused a 10% reduction in muscarinic receptor binding. In contrast, acetylcholinesterase activity and the vesicular ACh transporter in both brain regions were unchanged. Thus, we evidenced that an (n-3) PUFA-deficient diet can affect cholinergic neurotransmission, probably via changes in the phospholipid PUFA composition.     

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.     

Effects of Iron Deficiency on Serotonin Uptake In Vitro by Rat Brain Synaptic Vesicles

Abstract: The effects of moderate and severe degrees of iron deficiency on brain and liver nonhaem iron levels and 5-hydroxytryptamine (serotonin; 5-HT) uptake by synaptic vesicles in vitro were investigated in experimental rats. Data obtained suggested that in both moderate and severe forms of iron deficiency, 5-HT uptake by brain synaptic vesicles is decreased and is accompanied by a reduction in brain and liver nonhaem iron levels. On repletion with iron for 4 weeks, the deficient group of rats showed a normalisation of 5-HT uptake by synaptic vesicles and liver nonhaem iron content, whereas the brain nonhaem iron concentration still showed a significant deficit. The data thus suggest that changes in the uptake of 5-HT by brain synaptic vesicles that accompany iron depletion and repletion are more rapid than changes in the total nonhaem iron concentration in the brain. The observation that 5-HT uptake by brain synaptic vesicles is decreased in iron deficiency suggests a probable role for iron in 5-HT storage in rat brain.     

Recovery of brain docosahexaenoate leads to recovery of spatial task performance

Infants fed vegetable oil-based formulas may have poorer visual function, lower cognitive scores and acquire learning tasks more slowly in comparison with those breast fed or those fed formulas supplemented with docosahexaenoate. The aim of the present study was to determine the reversibility of losses in brain function associated with the loss of brain DHA. Rats were fed very low or adequate levels of n-3 fatty acids through three generations. The n-3 fatty acid deficient animals of the F3 generation were then given an n-3 adequate diet containing alpha-linolenic and docosahexaenoic acids (DHA) at birth, weaning (3 weeks) or young adulthood (7 weeks). The spatial task performance of these animals returned to the n-3 adequate diet was then compared using the Morris water at two different ages, at 9 or 13 weeks. Our results indicate that animals repleted since birth or at weaning were able to achieve nearly the same level of brain DHA and spatial task performance as animals maintained for three generations on an n-3 adequate diet. In the case of young adult animals, the degree of DHA and behavioral performance recovery depended upon the duration of dietary repletion with substantial recovery in animals after 6 weeks but little recovery of function after two weeks. The significance of these findings is that they indicate that at least some of the adverse effects of DHA deficiency during neurodevelopment may be reversible with an n-3 fatty acid supplemented diet.     

Specific phospholipid fatty acid composition of brain regions in mice. Effects of n-3 polyunsaturated fatty acid deficiency and phospholipid supplementation

This study examined the effects of dietary alpha-linolenic acid deficiency followed or not by supplementation with phospholipids rich in n;-3 polyunsaturated fatty acid (PUFA) on the fatty acid composition of total phospholipids in 11 brain regions. Three weeks before mating, mice were fed a semisynthetic diet containing both linoleic and alpha-linolenic acid or deficient in alpha-linolenic acid. Pups were fed the same diet as their dams. At the age of 7 weeks, a part of the deficient group were supplemented with n;-3 polyunsaturated fatty acids (PUFA) from either egg yolk or pig brain phospholipids for 2 months. Saturated and monounsaturated fatty acid levels varied among brain regions and were not significantly affected by the diet. In control mice, the level of 22:6 n-3 was significantly higher in the frontal cortex compared to all regions. alpha-Linolenic acid deficiency decreased the level of 22:6 n-3 and was compensated by an increase in 22:5 n-6 in all regions. However, the brain regions were affected differently. After the pituitary gland, the frontal cortex, and the striatum were the most markedly affected with 40% reduction of 22:6 n-3. Supplementation with egg yolk or cerebral phospholipids in deficient mice restored a normal fatty acid composition in brain regions except for the frontal cortex. There was a regional distribution of the fatty acids in the brain and the impact of deficiency in alpha-linolenic acid was region-specific. Dietary egg yolk or cerebral phospholipids are an effective source of n-3 PUFA for the recovery of altered fatty acid composition induced by a diet deficient in n-3 PUFA.     

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%).     

Differences in serotonergic neurotransmission between rats displaying high or low anxiety/depression-like behaviour: effects of chronic paroxetine treatment

Disturbances in serotonergic neurotransmission have been suggested to be closely interlinked with hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) system, and are likely to be involved in the pathophysiology of anxiety disorders and major depression. We therefore investigated markers of serotonergic transmission and their modulation by chronic paroxetine in rats selectively bred for high (HAB) or low (LAB) anxiety-related behaviour, both under basal conditions and in response to emotional stress. Hippocampal serotonin 1 A (5-HT1A) receptor mRNA expression was reduced in HAB rats, whereas 5-HT concentrations in hippocampal microdialysates did not differ between HAB and LAB rats under basal conditions. In the hippocampus, overall expression of serotonin transporter binding sites was increased in HAB compared with LAB rats. Exposure to emotional stress failed to increase intrahippocampal 5-HT release in HAB rats whereas LAB rats displayed a physiological, albeit small rise. Chronic paroxetine treatment markedly increased the stress-induced rise in hippocampal 5-HT in HAB, but not LAB rats. This effect may be (at least in part) related to a greater down-regulation of hippocampal serotonin transporter binding sites by paroxetine in HABs compared with LABs, while 5-HT1A receptor expression remained unaffected in this brain area. The findings indicate reduced hippocampal serotonergic transmission in HAB rats as compared with LAB rats, which is evident both at the presynaptic (5-HT release) and the postsynaptic (5-HT1A receptor) level. Chronic paroxetine enhanced the presynaptic responsivity in HAB rats, but not LAB rats, pointing to a preferential efficacy of paroxetine in rats with enhanced anxiety/depression-related behaviour.     

Early effect of myo-inositol deficiency on fatty acid synthetic enzymes of rat liver

Young rats (100 g) were fed either a purified myo-inositol-deficient balanced diet or a control diet containing 0.5% by weight myo-inositol, ad libitum, for up to 2 weeks following a 48 h fast. Weight gain was the same for animals in both groups. Liver triacylglycerol levels in the deficient animals were 1.8-, 3.5- and 3.0-fold higher than the corresponding levels in the control animals after 4, 8 and 14 days of feeding, respectively. In the myo-inositol-deficient group the specific activities of liver fatty acid synthetase and acetyl-CoA carboxylase were elevated 1.5-2.0-fold over controls, reaching a maximum after 3-4 days of feeding. Subsequently, activities declined to control levels. Rates of fatty acid synthetase synthesis in the deficient group, as measured by [3H]leucine incorporation into immunoprecipitable fatty acid synthetase polypeptide, were significantly higher (1.5-2.0-fold) than controls after 12-18 h of feeding and then declined to control levels by 1 day. No difference was noted between groups in either the rate of total, soluble liver protein synthesis or the half-life of fatty acid synthetase over this time period. These results suggest that the liver lipodystrophy observed during myo-inositol deficiency in rats may be due in part to elevated levels of lipogenic enzymes in this tissue in the early stage of the deficiency.     

Dietary n-3 polyunsaturated fatty acid deprivation together with early maternal separation increases anxiety and vulnerability to stress in adult rats

Low concentrations of n-3 polyunsaturated fatty acid (PUFA) and chronic stress are implicated in susceptibility to mood disorders. We have investigated the combined effects of chronic n-3 PUFA dietary deficiency and early maternal separation (MS) stress on the reactivity to stressful situations of rats as adults. Pups fed a control or an n-3 PUFA deficient diet were daily separated for two weeks before weaning They were all tested at 3 month-old to determine their anxiety, and their ability to learn two aversive tasks differing in the control they could exert on the situation: auditory fear conditioning and brightness avoidance discrimination. Neither the n-3 PUFA-deficient diet nor MS alone significantly affected behavior. But n-3 PUFA-deficient rats that had been separated were more anxious and fearful in inescapable situations, while their ability to cope with an aversive avoidance task remained unaffected. These results support the notion that PUFA-unbalanced diet, together with stress, may be a determinant risk factor in emotional disorders.     

Synergistic effects of stress and omega-3 fatty acid deprivation on emotional response and brain lipid composition in adult rats

The aim was to determine the consequences of multi-generational n-3 polyunsaturated fatty acids (PUFA) deficiency on emotional response in rats subjected to maternal separation (MS) as chronic early life stress. Pups fed a control or an n-3 PUFA deficient diet were daily separated for 2 weeks before weaning. In adult rats, reward response was assessed by sucrose consumption and reactivity to novelty using openfield test. Both n-3 PUFA deficiency and MS increased reward response and impulsivity. Moreover, nutritional deficiency and stress acted in synergy to elevate sucrose intake by 80%, compared to control conditions. n-3 PUFA deprivation induced a depletion of docosahexanoeic acid of brain membranes by 70% compensated by increase in 22:5 n-6 and arachidonic acid (AA) levels. The diet-induced AA increase was, however, significantly higher in MS rats. This suggests that n-3 PUFA deficit could be an environmental risk increasing vulnerability to depressive-like response induced by chronic stress.     

Diets high in monounsaturated and polyunsaturated fatty acids decrease fatty acid synthase protein levels in adipose tissue but do not alter other markers of adipose function and inflammation in diet-induced obese rats

This study investigates the effects of monounsaturated and polyunsaturated fatty acids from different fat sources (High Oleic Canola, Canola, Canola–Flaxseed (3:1 blend), Safflower, or Soybean Oil, or a Lard-based diet) on adipose tissue function and markers of inflammation in Obese Prone rats fed high-fat (55% energy) diets for 12 weeks. Adipose tissue fatty acid composition reflected the dietary fatty acid profiles. Protein levels of fatty acid synthase, but not mRNA levels, were lower in adipose tissue of all groups compared to the Lard group. Adiponectin and fatty acid receptors GPR41 and GPR43 protein levels were also altered, but other metabolic and inflammatory mediators in adipose tissue and serum were unchanged among groups. Overall, rats fed vegetable oil- or lard-based high-fat diets appear to be largely resistant to major phenotypic changes when the dietary fat composition is altered, providing little support for the importance of specific fatty acid profiles in the context of a high-fat diet.     

Docosahexaenoic acid synthesis from alpha-linolenic acid by rat brain is unaffected by dietary n-3 PUFA deprivation

Rates of conversion of alpha-linolenic acid (alpha-LNA, 18:3n-3) to docosahexaenoic acid (DHA, 22:6n-3) by the mammalian brain and the brain's ability to upregulate these rates during dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) are unknown. To answer these questions, we measured conversion coefficients and rates in post-weaning rats fed an n-3 PUFA deficient (0.2% alpha-LNA of total fatty acids, no DHA) or adequate (4.6% alpha-LNA, no DHA) diet for 15 weeks. Unanesthetized rats in each group were infused intravenously with [1-(14)C]alpha-LNA, and their arterial plasma and microwaved brains collected at 5 minutes were analyzed. The deficient compared with adequate diet reduced brain DHA by 37% and increased brain arachidonic (20:4n-6) and docosapentaenoic (22:5n-6) acids. Only 1% of plasma [1-(14)C]alpha-LNA entering brain was converted to DHA with the adequate diet, and conversion coefficients of alpha-LNA to DHA were unchanged by the deficient diet. In summary, the brain's ability to synthesize DHA from alpha-LNA is very low and is not altered by n-3 PUFA deprivation. Because the liver's reported ability is much higher, and can be upregulated by the deficient diet, DHA converted by the liver from circulating alphaLNA is the source of the brain's DHA when DHA is not in the diet.     

Phospholipid hydroperoxide glutathione peroxidase activity and vitamin E level in the liver microsomal membrane: effects of age and dietary alpha-linolenic acid deficiency

Age and diet-induced variations of phospholipid hydroperoxide glutathione peroxidase (PHGPx) activity and alpha-tocopherol concentration in the liver microsomal membrane were studied in male Wistar rats fed a semipurified diet either balanced in n-6 and n-3 polyunsaturated fatty acids (PUFA) (Control) or deprived of alpha-linolenic acid, i.e. n-3 PUFA (Deficient) over two generations. The animals were studied at the age of 6 months (adult) or 24 months (old). Both PHGPx activity and vitamin E level were significantly higher in 24-month old rats as compared to 6-month old rats. By contrast, the thiobarbituric acid reactive substances (TBARS) following stimulated in vitro peroxidation of membrane lipids were markedly lower (P < 0.01) with aging. The fatty acid composition of microsomal membrane phospholipids (PL) was also considerably modified by age. In particular, the levels of arachidonic acid and total n-6 PUFA were lower (P < 0.001) whereas n-3 PUFA levels were higher (P < 0.001) in most PL main classes. The alpha-linolenic acid deficiency markedly influenced these age-related changes. The higher PHGPx activity in the old rats as compared to the adult rats was only significant in those fed the control diet. In the 6-month old rats (but not in the 24-month old rats), the deficient diet led to a higher membrane vitamin E level and to lower TBARS production than the control diet. The results suggest that the nature of dietary PUFA may influence the age-related variations in this pair of membrane antioxidants and also in the fatty acid composition of microsomes.