Workshop on DHA as a Required Nutrient: Can the rat liver maintain normal brain DHA metabolism in the absence of dietary DHA?

Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Building 9, Room 1S128, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Prostaglandins Leukotrienes and Essential Fatty Acids (Impact Factor: 2.35). 07/2009; 81(2-3):119-23. DOI: 10.1016/j.plefa.2009.05.021
Source: PubMed


Docosahexaenoic acid (DHA) is required for normal brain function. The concentration of DHA in the brain depends on both diet and liver metabolism.
To determine rat brain DHA concentration and consumption in relation to dietary n-3 (omega-3) polyunsaturated fatty acid (PUFA) content and liver secretion of DHA derived from circulating alpha-linolenic acid (alpha-LNA).
Following weaning, male rats were fed for 15 weeks either: (1) a diet with a high DHA and alpha-LNA content, (2) an n-3 PUFA "adequate" diet containing 4.6% alpha-LNA but no DHA, or (3) an n-3 PUFA "deficient" diet containing 0.2% alpha-LNA and no DHA. Brain DHA consumption rates were measured following intravenous infusion in unanesthetized rats of [1-14C]DHA, whereas liver and brain DHA synthesis rates were measured by infusing [1-14C]alpha-LNA.
Brain DHA concentrations equaled 17.6, 11.4 and 7.14 microm/g in rats on diets 1, 2 and 3, respectively. With each diet, the rate of brain DHA synthesis from alpha-LNA was much less than the brain DHA consumption rate, whereas the liver synthesis-secretion rate was 5-10 fold higher. Higher elongase 2 and 5 and desaturase Delta5 and Delta6 activities in liver than in brain accounted for the higher liver DHA synthesis rates. Furthermore, these enzymes were transcriptionally upregulated in liver but not in brain of rats fed the deficient diet.
While DHA is essential to normal brain function, this need might be covered by dietary alpha-LNA when liver metabolic conversion machinery is intact and the diet has a high alpha-LNA content.

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Available from: Miki Igarashi, Jul 08, 2014
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    • "flaxseed, canola, and soybean oils) might be a more suitable approach. However, tracer studies have shown that the rate of conversion of ALA to DHA is low in humans (1 - 5%) [16-18], but has been reported to be efficient in rats [19,20]. A recent study in rats showed that by decreasing linoleic acid (LA; 18:2n-6) in the background diet and by keeping the total dietary polyunsaturated fatty acid (PUFA) intake low it is possible to enhance the DHA status of rats fed diets containing only ALA as a source of n-3 FA [21]. "
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    ABSTRACT: Background We recently showed that a combined deficiency of iron (ID) and n-3 fatty acids (n-3 FAD) in rats disrupts brain monoamine metabolism and produces greater memory deficits than ID or n-3 FAD alone. Providing these double-deficient rats with either iron (Fe) or preformed docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) alone affected brain monoamine pathways differently from combined repletion and even exacerbated cognitive deficits associated with double-deficiency. Iron is a co-factor of the enzymes responsible for the conversion of alpha-linolenic acid (ALA) to EPA and DHA, thus, the provision of ALA with Fe might be more effective in restoring brain EPA and DHA and improving cognition in double-deficient rats than ALA alone. Methods In this study we examined whether providing double-deficient rats with ALA and Fe, alone or in combination, can correct deficits in monoamine metabolism and cognition associated with double-deficiency. Using a 2 × 2 design, male rats with concurrent ID and n-3 FAD were fed an Fe + ALA, Fe + n-3 FAD, ID + ALA, or ID + n-3 FAD diet for 5 weeks (postnatal day 56–91). Biochemical measures, and spatial working and reference memory (using the Morris water maze) were compared to age-matched controls. Results In the hippocampus, we found a significant Fe × ALA interaction on DHA: Compared to the group receiving ALA alone, DHA was significantly higher in the Fe + ALA group. In the brain, we found significant antagonistic Fe × ALA interactions on serotonin concentrations. Provision of ALA alone impaired working memory compared with age-matched controls, while in the reference memory task ALA provided with Fe significantly improved performance. Conclusion These results indicate that providing either iron or ALA alone to double-deficient rats affects serotonin pathways and cognitive performance differently from combined provision. This may be partly explained by the enhancing effect of Fe on the conversion of ALA to EPA and DHA.
    Lipids in Health and Disease 06/2014; 13(1):97. DOI:10.1186/1476-511X-13-97 · 2.22 Impact Factor
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    • "Dietary supplementation with 10 and 40 mg/kg/day of DHA for 30 days results in significantly increased DHA serum levels of 123 and 175% over baseline respectively (Bailes and Mills, 2010). DHA concentrations of 17.6, 11.4, and 7.14 μmol/g are found in the brains of rats on diets with high DHA and α-LNA content, an n-3 PUFA adequate diet containing 4.6% α-LNA but no DHA,or an n-3 PUFA deficient diet containing 0.2% α-LNA and no DHA, respectively (Rapoport and Igarashi, 2009). "
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    ABSTRACT: Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the brain and a structural component of neuronal membranes. Changes in DHA content of neuronal membranes lead to functional changes in the activity of receptors and other proteins which might be associated with synaptic function. Accumulating evidence suggests the beneficial effects of dietary DHA supplementation on neurotransmission. This article reviews the beneficial effects of DHA on the brain; uptake, incorporation and release of DHA at synapses, effects of DHA on synapses, effects of DHA on neurotransmitters, DHA metabolites, and changes in DHA with age. Further studies to better understand the metabolome of DHA could result in more effective use of this molecule for treatment of neurodegenerative or neuropsychiatric diseases.
    Biomolecules and Therapeutics 03/2012; 20(2):152-157. DOI:10.4062/biomolther.2012.20.2.152 · 1.73 Impact Factor
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    • "In older adults, conversion of α-linolenic acid to DHA is quite limited, with better yields for EPA.123 There is doubt that conversion, occurring chiefly in the liver, under the best of circumstances, can alone furnish sufficient DHA for optimal neurologic health.124 Therefore, these omega-3 PUFA requirements should be met by using the long chains themselves, EPA and DHA, rather than through plant sources rich in α-linolenic acid, the most popular being flax. "
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    ABSTRACT: Progressive destruction of neurons that produce dopamine in the basal ganglia of the brain, particularly the substantia nigra, is a hallmark of Parkinson's disease. The syndrome of the Parkinsonian phenotype is caused by many etiologies, involving multiple contributing mechanisms. Characteristic findings are pathologic inclusions called Lewy bodies, which are protein aggregates inside nerve cells. Environmental insults are linked with the disease, and a number of associated genes have also been identified. Neuroinflammation, microglia activation, oxidative stress, and mitochondrial dysfunction are central processes producing nerve damage. In addition, protein misfolding, driven by accumulation and condensation of α-synuclein, compounded by inadequate elimination of defective protein through the ubiquitin- proteasome system, promote apoptosis. Current pharmacologic therapy is palliative rather than disease- modifying, and typically becomes unsatisfactory over time. Coenzyme Q10 and creatine, two agents involved in energy production, may be disease-modifying, and able to produce sufficient beneficial pathophysiologic changes in preclinical studies to warrant large studies now in progress. Use of long-chain omega-3 fatty acids and vitamin D in PD are also topics of current interest.
    Clinical Pharmacology: Advances and Applications 09/2010; 2(1):185-98. DOI:10.2147/CPAA.S12082
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