Science.gov

Sample records for acid epa docosahexaenoic

  1. Docosahexaenoic acid and lactation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Docosahexaenoic acid (DHA) is an important component of membrane phospholipids in the retina, and brain, and accumulates rapidly in these tissues during early infancy. DHA is present in human milk, but the amount varies considerably and is largely dependent on maternal diet. This article reviews dat...

  2. Docosahexaenoic Acid (DHA) But Not Eicosapentaenoic Acid (EPA) Reverses Trans-10, Cis-12 Conjugated Linoleic Acid Induced Insulin Resistance in Mice1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: t10, c12-Conjugated linoleic acid (CLA) induces insulin resistance and fatty liver in mice which can be reversed by fish oils. We determined if it is eicospentaenoic acid (20:5n-3, EPA) or docoshexaenoic acid (22:6n-3, DHA) that reverses these adverse effects of CLA. Research Design and M...

  3. Unesterified docosahexaenoic acid is protective in neuroinflammation

    PubMed Central

    Orr, Sarah K; Palumbo, Sara; Bosetti, Francesca; Mount, Howard T; Kang, Jing X; E, Carol; Greenwood; Ma, David WL; Serhan, Charles N; Bazinet, Richard P

    2014-01-01

    Docosahexaenoic acid (22:6n-3) is the major brain n-3 polyunsaturated fatty acid and it is possible that docosahexaenoic acid is anti-inflammatory in the brain as it is known to be in other tissues. Using a combination of models including the fat-1 transgenic mouse, chronic dietary n-3 PUFA modulation in transgenic and wildtype mice, and acute direct brain infusion, we demonstrated that unesterified docosahexaenoic acid attenuates neuroinflammation initiated by intracerebroventricular lipopolysaccharide. Hippocampal neuroinflammation was assessed by gene expression and immunohistochemistry. Further, docosahexaenoic acid protected against lipopolysaccharide-induced neuronal loss. Acute intracerebroventricular infusion of unesterified docosahexaenoic acid or its 12/15-lipoxygenase product and precursor to protectins and resolvins, 17S-hydroperoxy-docosahexaenoic acid, mimics anti-neuroinflammatory aspects of chronically increased unesterified docosahexaenoic acid. LCMS/MS revealed that neuroprotectin D1 and several other docosahexaenoic acid-derived specialized pro-resolving mediators are present in the hippocampus. Acute icv infusion of 17S-hydroperoxydocosahexaenoic acid increases hippocampal neuroprotectin D1 levels concomitant to attenuating neuroinflammation. These results show that unesterified docosahexaenoic acid is protective in a lipopolysaccharide-initiated mouse model of acute neuroinflammation, at least in part, via its conversion to specialized pro-resolving mediators; these docosahexaenoic acid stores may provide novel targets for the prevention and treatment(s) of neurological disorders with a neuroinflammatory component. PMID:23919613

  4. Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammation and cardiovascular disease (CVD). Our aim was to assess the effect of a six-week supplementation with either olive oil, EPA, or DHA on gene expression in peripheral blood mononuclear cells (...

  5. Docosahexaenoic acid in neural signaling systems.

    PubMed

    Crawford, Michael A

    2006-01-01

    Docosahexaenoic acid has been conserved in neural signalling systems in the cephalopods, fish, amphibian, reptiles, birds, mammals, primates and humans. This extreme conservation, despite wide genomic changes over 500 million years, testifies to a uniqueness of this molecule in the brain. The brain selectively incorporates docosahexaenoic acid and its rate of incorporation into the developing brain has been shown to be greater than ten times more efficient than its synthesis from the omega 3 fatty acids of land plant origin. Data has now been published demonstrating a significant influence of dietary omega 3 fatty acids on neural gene expression. As docosahexaenoic acid is the only omega 3 fatty acid in the brain, it is likely that it is the ligand involved. The selective uptake, requirement for function and stimulation of gene expression would have conferred an advantage to a primate which separated from the chimpanzees in the forests and woodlands and sought a different ecological niche. In view of the paucity of docosahexaenoic acid in the land food chain it is likely that the advantage would have been gained from a lacustrine or marine coastal habitat with access to food rich in docosahexaenoic acid and the accessory micronutrients, such as iodine, zinc, copper, manganese and selenium, of importance in brain development and protection against peroxidation. Land agricultural development has, in recent time, come to dominate the human food chain. The decline in use and availability of aquatic resources is not considered important by Langdon (2006) as he considers the resource was not needed for human evolution and can be replaced from the terrestrial food chain. This notion is not supported by the biochemistry nor the molecular biology. He misses the point that the shoreline hypothesis is not just dependent on docosahexaenoic acid but also on the other accessory nutrients specifically required by the brain. Moreover he neglects the basic principle of Darwinian

  6. Lipid encapsulated docosahexaenoic acid methyl ester

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Encapsulation of structurally sensitive compounds within a solid lipid matrix provides a barrier to prooxidant compounds and effectively limits the extent of oxidative degradation. Encapsulated docosahexaenoic acid (DHA) methyl ester was examined as a model compound for functional foods and feeds. S...

  7. High-oleic ready-to-use therapeutic food maintains docosahexaenoic acid status in severe malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ready-to-use therapeutic food (RUTF) is the preferred treatment for uncomplicated severe acute malnutrition. It contains large amounts of linoleic acid and little a-linolenic acid, which may reduce the availability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the recovering child...

  8. Synthesis of docosahexaenoic acid from eicosapentaenoic acid in retina neurons protects photoreceptors from oxidative stress.

    PubMed

    Simón, María Victoria; Agnolazza, Daniela L; German, Olga Lorena; Garelli, Andrés; Politi, Luis E; Agbaga, Martin-Paul; Anderson, Robert E; Rotstein, Nora P

    2016-03-01

    Oxidative stress is involved in activating photoreceptor death in several retinal degenerations. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, protects cultured retina photoreceptors from apoptosis induced by oxidative stress and promotes photoreceptor differentiation. Here, we investigated whether eicosapentaenoic acid (EPA), a metabolic precursor to DHA, had similar effects and whether retinal neurons could metabolize EPA to DHA. Adding EPA to rat retina neuronal cultures increased opsin expression and protected photoreceptors from apoptosis induced by the oxidants paraquat and hydrogen peroxide (H2 O2 ). Palmitic, oleic, and arachidonic acids had no protective effect, showing the specificity for DHA. We found that EPA supplementation significantly increased DHA percentage in retinal neurons, but not EPA percentage. Photoreceptors and glial cells expressed Δ6 desaturase (FADS2), which introduces the last double bond in DHA biosynthetic pathway. Pre-treatment of neuronal cultures with CP-24879 hydrochloride, a Δ5/Δ6 desaturase inhibitor, prevented EPA-induced increase in DHA percentage and completely blocked EPA protection and its effect on photoreceptor differentiation. These results suggest that EPA promoted photoreceptor differentiation and rescued photoreceptors from oxidative stress-induced apoptosis through its elongation and desaturation to DHA. Our data show, for the first time, that isolated retinal neurons can synthesize DHA in culture. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in retina photoreceptors, and its precursor, eicosapentaenoic acid (EPA) have multiple beneficial effects. Here, we show that retina neurons in vitro express the desaturase FADS2 and can synthesize DHA from EPA. Moreover, addition of EPA to these cultures protects photoreceptors from oxidative stress and promotes their differentiation through its metabolization to DHA. PMID:26662863

  9. Impact of Omega-6 Polyunsaturated Fatty Acid:Eicosapentaenoic acid (EPA)+Docosahexaenoic Acid (DHA) Ratios in LDL Receptor Knockout (LDLr-/-) Mice on Atherosclerotic Lesion Formation and Elicited Peritoneal Macrophage Inflamm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Very long chain omega-3 fatty acids have been associated with decreased risk of CVD. LDL receptor knockout mice were used to assess the effect of different omega-6:EPA+DHA ratios on atherosclerotic lesion formation and elicited peritoneal macrophage inflammatory response. Methods and R...

  10. Effects of Docosahexaenoic Acid on Neurotransmission

    PubMed Central

    Tanaka, Kazuhiro; Farooqui, Akhlaq A.; Siddiqi, Nikhat J.; Alhomida, Abdullah S.; Ong, Wei-Yi

    2012-01-01

    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. PMID:24116288

  11. Docosahexaenoic Acid and Cognition throughout the Lifespan

    PubMed Central

    Weiser, Michael J.; Butt, Christopher M.; Mohajeri, M. Hasan

    2016-01-01

    Docosahexaenoic acid (DHA) is the predominant omega-3 (n-3) polyunsaturated fatty acid (PUFA) found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action. PMID:26901223

  12. Reduction in Dietary Omega-6 Polyunsaturated Fatty Acids: Eicosapentaenoic Acid plus Docosahexaenoic Acid Ratio Minimizes Atherosclerotic Lesion Formation and Inflammatory Response in the LDL Receptor Null Mouse

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary very long chain omega-3 polyunsaturated fatty acids (PUFA) have been associated with reduced CVD risk. LDL receptor null mice (LDLr-/-) were used to assess different dietary ratios of omega-6 PUFA to eicosapentaenoic acid plus docosahexaenoic acid (omega-6:EPA+DHA) on atherogenesis and infl...

  13. Impact of different ratios of Omega-6 polyundaturated fatty acids to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) on atherosclerotic lesion formation and inflammatory factors in the LDL receptor knockout mouse

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to assess the effect of different ratios of omega-6 to EPA plus DHA on atherosclerotic lesion formation and plasma inflammatory markers in LDLr-/- mice. Mice (n=10/group) were fed the following diets for 32 weeks: high fat (20% w/w) without EPA and DHA (HF omega-6), and high fat wi...

  14. Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice

    PubMed Central

    Johnson, Matthew L; Lalia, Antigoni Z; Dasari, Surendra; Pallauf, Maximilian; Fitch, Mark; Hellerstein, Marc K; Lanza, Ian R

    2015-01-01

    Mitochondrial dysfunction is often observed in aging skeletal muscle and is implicated in age-related declines in physical function. Early evidence suggests that dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve mitochondrial function. Here, we show that 10 weeks of dietary eicosapentaenoic acid (EPA) supplementation partially attenuated the age-related decline in mitochondrial function in mice, but this effect was not observed with docosahexaenoic acid (DHA). The improvement in mitochondrial function with EPA occurred in the absence of any changes in mitochondrial abundance or biogenesis, which was evaluated from RNA sequencing, large-scale proteomics, and direct measurements of muscle mitochondrial protein synthesis rates. We find that EPA improves muscle protein quality, specifically by decreasing mitochondrial protein carbamylation, a post-translational modification that is driven by inflammation. These results demonstrate that EPA attenuated the age-related loss of mitochondrial function and improved mitochondrial protein quality through a mechanism that is likely linked with anti-inflammatory properties of n-3 PUFAs. Furthermore, we demonstrate that EPA and DHA exert some common biological effects (anticoagulation, anti-inflammatory, reduced FXR/RXR activation), but also exhibit many distinct biological effects, a finding that underscores the importance of evaluating the therapeutic potential of individual n-3 PUFAs. PMID:26010060

  15. Eicosapentaenoic and docosahexaenoic acids production by and okara-utilizing potential of thraustochytrids.

    PubMed

    Fan, K W; Chen, F; Jones, E B; Vrijmoed, L L

    2001-10-01

    Nine thraustochytrid strains isolated from subtropical mangroves were screened for their eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) production potential in a glucose yeast extract medium. Their ability to utilize okara (soymilk residue) for growth and EPA and DHA production was also evaluated. EPA yield was low in most strains, while DHA level was high on glucose yeast extract medium, producing 28.1-41.1% of total fatty acids, for all strains, with the exception of Ulkenia sp. KF13. The DHA yield of Schizochytrium mangrovei strains ranged from 747.7 to 2778.9 mg/l after 52 h of fermentation at 25 degrees C. All strains utilized okara as a substrate for growth, but DHA yield was lower when compared with fermentation in a glucose yeast extract medium. PMID:11687930

  16. Higher Plasma Docosahexaenoic Acid is Associated with Reduced Progression of Coronary-Artery Atherosclerosis in Women with Established Coronary Artery Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fish intake, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and in some cases alpha-linolenic acid (ALA), have been associated with reduced risk of cardiovascular events and death. The association between n-3 fatty acids in plasma lipids and progression of coronary-artery atherosclerosi...

  17. Eicosapentaenoic acid/docosahexaenoic acid 1:1 ratio improves histological alterations in obese rats with metabolic syndrome

    PubMed Central

    2014-01-01

    Background Marine polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been associated with improvement in the Metabolic Syndrome (MS). The aim of this study is to evaluate how three fish-oil diets with different eicosapentaenoic acid/docosahexaenoic acid ratios (EPA/DHA ratio) affect the histology of liver, kidney, adipose tissue and aorta in a preliminary morphological study. This work uses an animal model of metabolic syndrome in comparison with healthy animals in order to provide information about the best EPA:DHA ratio to prevent or to improve metabolic syndrome symptoms. Methods 35 Wistar rats, as a control, and 35 spontaneously hypertensive obese rats (SHROB) were fed for 13 weeks with 3 different suplemmentation of fish oil containing EPA and DHA ratios (1:1, 2:1 and 1:2, respectively). All samples were stained with haematoxylin/eosin stain, except aorta samples, which were stained also with Verhoeff and van Gieson’s stain. A histological study was carried out to evaluate changes. These changes were statistically analyzed using SPSS IBM 19 software. The quantitative data were expressed by mean ± SD and were compared among groups and treatments using ANOVA with post-hoc tests for parametric data and the U-Mann–Whitney for non-parametric data. Qualitative data were expressed in frequencies, and compared with contingency tables using χ2 statistics. Results EPA:DHA 1:1 treatment tended to improve the density and the wrinkling of elastic layers in SHROB rats. Only Wistar rats fed with EPA:DHA 1:1 treatment did not show mast cells in adipose tissue and has less kidney atrophy. In both strains EPA:DHA 1:1 treatment improved inflammation related parameters in liver and kidney. Conclusions EPA:DHA 1:1 treatment was the most beneficial treatment since improved many histological parameters in both groups of rats. PMID:24512213

  18. Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults.

    PubMed

    Stark, Ken D; Van Elswyk, Mary E; Higgins, M Roberta; Weatherford, Charli A; Salem, Norman

    2016-07-01

    Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were systematically identified in order to create a global map identifying countries and regions with different blood levels. Included studies were those of healthy adults, published in 1980 or later. A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including plasma total lipids (33%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA+DHA in erythrocyte equivalents. Regions with high EPA+DHA blood levels (>8%) included the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (≤4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. The present review reveals considerable variability in blood levels of EPA+DHA and the very low to low range of blood EPA+DHA for most of the world may increase global risk for chronic disease. PMID:27216485

  19. Associations of obesity with triglycerides and C-reactive protein are attenuated in adults with high red blood cell eicosapentaenoic and docosahexaenoic acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background:N-3 fatty acids are associated with favorable, and obesity with unfavorable, concentrations of chronic disease risk biomarkers.Objective:We examined whether high eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid intakes, measured as percentages of total red blood cell (RBC) fatty acid...

  20. The Evidence for α-Linolenic Acid and Cardiovascular Disease Benefits: Comparisons with Eicosapentaenoic Acid and Docosahexaenoic Acid12

    PubMed Central

    Fleming, Jennifer A.; Kris-Etherton, Penny M.

    2014-01-01

    Our understanding of the cardiovascular disease (CVD) benefits of α-linolenic acid (ALA, 18:3n–3) has advanced markedly during the past decade. It is now evident that ALA benefits CVD risk. The expansion of the ALA evidence base has occurred in parallel with ongoing research on eicosapentaenoic acid (EPA, 20:5n–3) and docosahexaenoic acid (DHA, 22:6n–3) and CVD. The available evidence enables comparisons to be made for ALA vs. EPA + DHA for CVD risk reduction. The epidemiologic evidence suggests comparable benefits of plant-based and marine-derived n–3 (omega-3) PUFAs. The clinical trial evidence for ALA is not as extensive; however, there have been CVD event benefits reported. Those that have been reported for EPA + DHA are stronger because only EPA + DHA differed between the treatment and control groups, whereas in the ALA studies there were diet differences beyond ALA between the treatment and control groups. Despite this, the evidence suggests many comparable CVD benefits of ALA vs. EPA + DHA. Thus, we believe that it is time to revisit what the contemporary dietary recommendation should be for ALA to decrease the risk of CVD. Our perspective is that increasing dietary ALA will decrease CVD risk; however, randomized controlled clinical trials are necessary to confirm this and to determine what the recommendation should be. With a stronger evidence base, the nutrition community will be better positioned to revise the dietary recommendation for ALA for CVD risk reduction. PMID:25398754

  1. The evidence for α-linolenic acid and cardiovascular disease benefits: Comparisons with eicosapentaenoic acid and docosahexaenoic acid.

    PubMed

    Fleming, Jennifer A; Kris-Etherton, Penny M

    2014-11-01

    Our understanding of the cardiovascular disease (CVD) benefits of α-linolenic acid (ALA, 18:3n-3) has advanced markedly during the past decade. It is now evident that ALA benefits CVD risk. The expansion of the ALA evidence base has occurred in parallel with ongoing research on eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) and CVD. The available evidence enables comparisons to be made for ALA vs. EPA + DHA for CVD risk reduction. The epidemiologic evidence suggests comparable benefits of plant-based and marine-derived n-3 (omega-3) PUFAs. The clinical trial evidence for ALA is not as extensive; however, there have been CVD event benefits reported. Those that have been reported for EPA + DHA are stronger because only EPA + DHA differed between the treatment and control groups, whereas in the ALA studies there were diet differences beyond ALA between the treatment and control groups. Despite this, the evidence suggests many comparable CVD benefits of ALA vs. EPA + DHA. Thus, we believe that it is time to revisit what the contemporary dietary recommendation should be for ALA to decrease the risk of CVD. Our perspective is that increasing dietary ALA will decrease CVD risk; however, randomized controlled clinical trials are necessary to confirm this and to determine what the recommendation should be. With a stronger evidence base, the nutrition community will be better positioned to revise the dietary recommendation for ALA for CVD risk reduction. PMID:25398754

  2. Canola engineered with a microalgal polyketide synthase-like system produces oil enriched in docosahexaenoic acid.

    PubMed

    Walsh, Terence A; Bevan, Scott A; Gachotte, Daniel J; Larsen, Cory M; Moskal, William A; Merlo, P A Owens; Sidorenko, Lyudmila V; Hampton, Ronnie E; Stoltz, Virginia; Pareddy, Dayakar; Anthony, Geny I; Bhaskar, Pudota B; Marri, Pradeep R; Clark, Lauren M; Chen, Wei; Adu-Peasah, Patrick S; Wensing, Steven T; Zirkle, Ross; Metz, James G

    2016-08-01

    Dietary omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), docosahexaenoic acid (DHA, C22:6) and eicosapentaenoic acid (EPA, C20:5) are usually derived from marine fish. Although production of both EPA and DHA has been engineered into land plants, including Arabidopsis, Camelina sativa and Brassica juncea, neither has been produced in commercially relevant amounts in a widely grown crop. We report expression of a microalgal polyketide synthase-like PUFA synthase system, comprising three multidomain polypeptides and an accessory enzyme, in canola (Brassica napus) seeds. This transgenic enzyme system is expressed in the cytoplasm, and synthesizes DHA and EPA de novo from malonyl-CoA without substantially altering plastidial fatty acid production. Furthermore, there is no significant impact of DHA and EPA production on seed yield in either the greenhouse or the field. Canola oil processed from field-grown grain contains 3.7% DHA and 0.7% EPA, and can provide more than 600 mg of omega-3 LC-PUFAs in a 14 g serving. PMID:27398790

  3. Eicosapentaenoic Acid Versus Docosahexaenoic Acid as Options for Vascular Risk Prevention: A Fish Story.

    PubMed

    Singh, Sarabjeet; Arora, Rohit R; Singh, Mukesh; Khosla, Sandeep

    2016-01-01

    Vascular inflammation is a key component involved in the process of arthrosclerosis, which in turn increases the risk for cardiovascular injury. In the last 10 years, there have been many trials that looked at omega-3 fatty acids as a way to reduce cardiovascular risk. These trials observed the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the traditional lipid panel and found that both EPA and DHA reduce triglyceride (TG) level and increase high-density lipoprotein cholesterol (HDL-C) levels but also increase the low-density lipoprotein cholesterol (LDL-C) levels. In the 2 more recent trials, the MARINE and ANCHOR, EPA was given as an adjunct therapy to high-risk patients and not only was the traditional lipids measured but also examined the vascular inflammatory biomarkers. The results of these 2 trials not only showed reduction in cardiovascular risk because of reduction in vascular inflammation and reduction in the lipid panel but also showed that one of the MARINE-derived omega-3 fatty acid is superior to the other. Data search for omega-3 fatty acids and cardiovascular risk was performed, and articles were selected for review from 2006 to date. The research studies were all double-blind randomized trials except for one, which was a single-blind and focused on the effects of omega-3 fatty acids on the entire lipid panel. The participants received DHA/EPA and compared with a placebo group on the effect seen in the lipid panel. The first 7 studies looked at the effects of omega-3 fatty acids on TG, LDL-C, and HDL-C; of the 7, 1 directly compared DHA and EPA, 2 focused on EPA, and 4 were directed towards DHA alone. The MARINE and ANCHOR trials were more recent and also looked at the same parameter but also monitored vascular inflammatory biomarkers and how they were affected by omega-3 fatty acids. A second data search was performed for vascular biomarkers and cardiovascular risk, and articles that focused on high-sensitivity C

  4. Eicosapentaenoic and Docosahexaenoic Acid-Enriched High Fat Diet Delays Skeletal Muscle Degradation in Mice.

    PubMed

    Soni, Nikul K; Ross, Alastair B; Scheers, Nathalie; Savolainen, Otto I; Nookaew, Intawat; Gabrielsson, Britt G; Sandberg, Ann-Sofie

    2016-01-01

    Low-grade chronic inflammatory conditions such as ageing, obesity and related metabolic disorders are associated with deterioration of skeletal muscle (SkM). Human studies have shown that marine fatty acids influence SkM function, though the underlying mechanisms of action are unknown. As a model of diet-induced obesity, we fed C57BL/6J mice either a high fat diet (HFD) with purified marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (HFD-ED), a HFD with corn oil, or normal mouse chow for 8 weeks; and used transcriptomics to identify the molecular effects of EPA and DHA on SkM. Consumption of ED-enriched HFD modulated SkM metabolism through increased gene expression of mitochondrial β-oxidation and slow-fiber type genes compared with HFD-corn oil fed mice. Furthermore, HFD-ED intake increased nuclear localization of nuclear factor of activated T-cells (Nfatc4) protein, which controls fiber-type composition. This data suggests a role for EPA and DHA in mitigating some of the molecular responses due to a HFD in SkM. Overall, the results suggest that increased consumption of the marine fatty acids EPA and DHA may aid in the prevention of molecular processes that lead to muscle deterioration commonly associated with obesity-induced low-grade inflammation. PMID:27598198

  5. Triploidy does not decrease contents of eicosapentaenoic and docosahexaenoic acids in filets of pink salmon Oncorhynchus gorbuscha.

    PubMed

    Gladyshev, Michail I; Artamonova, Valentina S; Makhrov, Alexander A; Sushchik, Nadezhda N; Kalachova, Galina S; Dgebuadze, Yury Y

    2017-02-01

    Triploid fish has become an important item of commercial aquaculture, but data on its fatty acid (FA) composition are still controversial, especially regarding essential polyunsaturated fatty acids, eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA). We studied FA composition and content of diploid and triploid pink salmon Oncorhynchus gorbuscha, reared in aquaculture in a bay of the White Sea (Russia). FA composition, measured as percentages of total FA of triploids and immature diploid females significantly differed from that of mature diploid fish. Specifically, mature diploids had higher percentage of EPA and DHA in their muscle tissue (filets) compared to that of triploids and immature diploid females. Nevertheless, the contents of EPA and DHA per mass of the filets in diploid and triploid specimens were similar. Thus, no special efforts are needed to improve EPA and DHA contents in filets of triploids. PMID:27596393

  6. Docosahexaenoic acid and eicosapentaenoic acid induce changes in the physical properties of a lipid bilayer model membrane.

    PubMed

    Onuki, Yoshinori; Morishita, Mariko; Chiba, Yoshiyuki; Tokiwa, Shinji; Takayama, Kozo

    2006-01-01

    We investigated the effect of fatty acids such as stearic acid (SA, 18:0), oleic acid (OA, 18:1), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6) on a dipalmitoylphosphatidylcholine (DPPC) bilayer by determining the phase transition temperature, fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH), and detergent insolubility. Treatment with unsaturated fatty acid broadened and shifted the phase transitions of the DPPC bilayer to a lower temperature. The phase transition temperature and the value of fluorescence anisotropy of DPH at 37 degrees C decreased progressively with increasing treatment amounts of unsaturated fatty acid. A large amount of the DPPC bilayer treated with unsaturated fatty acid was dissolved in Triton X-100, obtaining a low level of detergent insolubility. These modifications of the bilayer physical properties were most pronounced with DHA and EPA treatment. These data show that unsaturated fatty acids, particularly DHA and EPA, induce a marked change in the lipid bilayer structure. The composition of fatty acids in the DPPC bilayer was similar after treatment with various unsaturated fatty acids, suggesting that the different actions of unsaturated fatty acids are attributed to change in the molecular structure (e.g., kinked conformation by double bonds). We further explored the change in physical properties induced by fatty acids dispersed in a water-in-oil-in-water multiple emulsion and found that unsaturated fatty acids acted efficiently on the DPPC bilayer, even when incorporated in emulsion form. PMID:16394552

  7. Boundary of Phase Co-existence in Docosahexaenoic Acid System

    NASA Astrophysics Data System (ADS)

    Lor, Chai; Hirst, Linda S.

    2011-11-01

    Docosahexaenoic acid (DHA) is a highly polyunsaturated fatty acid (PUFA) that exhibits six double bonds in the hydrocarbon tail. It induces phase separation of the membrane into liquid order and liquid disorder in mixtures containing other lipids with more saturation and cholesterol. With the utilization of atomic force microscopy, phase co-existence is observed in lipid mixtures containing DHA on a single supported lipid bilayer. The boundary of phase co-existence with decreasing DHA concentration is explored. The elastic force, thickness, and roughness of the different phases are investigated.

  8. Implications for eicosapentaenoic acid- and docosahexaenoic acid-derived resolvins as therapeutics for arthritis.

    PubMed

    Souza, Patricia R; Norling, Lucy V

    2016-08-15

    Omega-3 polyunsaturated fatty acids are essential for health and are known to possess anti-inflammatory properties, improving cardiovascular health as well as benefiting inflammatory diseases. Indeed, dietary supplementation with omega-3 polyunsaturated fatty acids has proved efficacious in reducing joint pain, morning stiffness and nonsteroidal anti-inflammatory drugs usage in rheumatoid arthritis patients. However, the mechanisms by which omega-3 polyunsaturated fatty acids exert their beneficial effects have not been fully explored. Seminal discoveries by Serhan and colleagues have unveiled a novel class of bioactive lipid mediators that are enzymatically biosynthesized in vivo from omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), termed resolvins, protectins and maresins. These bioactive pro-resolving lipid mediators provide further rationale for the beneficial effects of fish-oil enriched diets. These endogenous lipid mediators are spatiotemporally biosynthesized to actively regulate resolution by acting on specific G protein-coupled receptors (GPCRs) to initiate anti-inflammatory and pro-resolving signals that terminate inflammation. In this review, we will discuss the mechanism of actions of these molecules, including their analgesic and bone-sparing properties making them ideal therapeutic agonists for the treatment of inflammatory diseases such as rheumatoid arthritis. PMID:26165764

  9. Impact of Docosahexaenoic Acid on Gene Expression during Osteoclastogenesis in Vitro—A Comprehensive Analysis

    PubMed Central

    Akiyama, Masako; Nakahama, Ken-ichi; Morita, Ikuo

    2013-01-01

    Polyunsaturated fatty acids (PUFAs), especially n-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are known to protect against inflammation-induced bone loss in chronic inflammatory diseases, such as rheumatoid arthritis, periodontitis and osteoporosis. We previously reported that DHA, not EPA, inhibited osteoclastogenesis induced by the receptor activator of nuclear factor-κB ligand (sRANKL) in vitro. In this study, we performed gene expression analysis using microarrays to identify genes affected by the DHA treatment during osteoclastogenesis. DHA strongly inhibited osteoclastogenesis at the late stage. Among the genes upregulated by the sRANKL treatment, 4779 genes were downregulated by DHA and upregulated by the EPA treatment. Gene ontology analysis identified sets of genes related to cell motility, cell adhesion, cell-cell signaling and cell morphogenesis. Quantitative PCR analysis confirmed that DC-STAMP, an essential gene for the cell fusion process in osteoclastogenesis, and other osteoclast-related genes, such as Siglec-15, Tspan7 and Mst1r, were inhibited by DHA. PMID:23945674

  10. Docosahexaenoic Acid and Adult Memory: A Systematic Review and Meta-Analysis

    PubMed Central

    Yurko-Mauro, Karin; Alexander, Dominik D.; Van Elswyk, Mary E.

    2015-01-01

    Introduction Subjective memory complaints are common with aging. Docosahexaenoic acid (DHA; 22:6 n-3) is a long-chain polyunsaturated fatty acid (LCPUFA) and an integral part of neural membrane phospholipids that impacts brain structure and function. Past research demonstrates a positive association between DHA plasma status/dietary intake and cognitive function. Objectives The current meta-analysis was designed to determine the effect of DHA intake, alone or combined with eicosapentaenoic acid (EPA; 20:5 n-3), on specific memory domains: episodic, working, and semantic in healthy adults aged 18 years and older. A secondary objective was to systematically review/summarize the related observational epidemiologic literature. Methods A systematic literature search of clinical trials and observational studies that examined the relationship between n-3 LCPUFA on memory outcomes in healthy adults was conducted in Ovid MEDLINE and EMBASE databases. Studies of subjects free of neurologic disease at baseline, with or without mild memory complaints (MMC), were included. Random effects meta-analyses were conducted to generate weighted group mean differences, standardized weighted group mean differences (Hedge’s g), z-scores, and p-values for heterogeneity comparing DHA/EPA to a placebo. A priori sub-group analyses were conducted to evaluate the effect of age at enrollment, dose level, and memory type tested. Results Episodic memory outcomes of adults with MMC were significantly (P<.004) improved with DHA/EPA supplementation. Regardless of cognitive status at baseline, > 1 g/day DHA/EPA improved episodic memory (P<.04). Semantic and working memory changes from baseline were significant with DHA but no between group differences were detected. Observational studies support a beneficial association between intake/blood levels of DHA/EPA and memory function in older adults. Conclusion DHA, alone or combined with EPA, contributes to improved memory function in older adults with

  11. Analysis of eicosapentaenoic and docosahexaenoic acid geometrical isomers formed during fish oil deodorization.

    PubMed

    Fournier, Véronique; Juanéda, Pierre; Destaillats, Frédéric; Dionisi, Fabiola; Lambelet, Pierre; Sébédio, Jean-Louis; Berdeaux, Olivier

    2006-09-29

    Addition of long-chain polyunsaturated fatty acids (LC-PUFAs) from marine oil into food products implies preliminary refining procedures of the oil which thermal process affects the integrity of LC-PUFAs. Deodorization, the major step involving high temperatures, is a common process used for the refining of edible fats and oils. The present study evaluates the effect of deodorization temperature on the formation of LC-PUFA geometrical isomers. Chemically isomerized eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were used as reference samples. Fish oil samples have been deodorized at 180, 220 and 250 degrees C for 3 h and pure EPA and DHA fatty acid methyl esters (FAMEs) were chemically isomerized using p-toluenesulfinic acid as catalyst. FAMEs prepared from fish oil were fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC). Geometrical isomers produced by both processes were fractionated by silver-ion thin-layer chromatography (Ag-TLC) and silver-ion high-performance liquid chromatography (Ag-HPLC). The FAME fractions were subsequently analyzed by gas chromatography (GC) on a 100 m highly polar cyanopropylpolysiloxane coated capillary column, CP-Sil 88. Our results show that thermally induced geometrical isomerization appears to be a directed reaction and some ethylenic double bond positions on the hydrocarbon chain are more prone to stereomutation. Only minor changes were observed in the EPA and DHA trans isomers content and distribution after deodorization at 180 degrees C. The analyses of EPA and DHA isomer fractions revealed that it is possible to quantify EPA geometrical isomers by GC using the described conditions. However, we notice that a mono-trans isomer of DHA, formed during both chemical and thermal treatments, co-elute with all-cis DHA. This feature should be taken into consideration for the quantification of DHA geometrical isomers. PMID:16893549

  12. Docosahexaenoic Acid Induces Apoptosis in Primary Chronic Lymphocytic Leukemia Cells

    PubMed Central

    Gyan, Emmanuel; Tournilhac, Olivier; Halty, Christelle; Veyrat-Masson, Richard; Akil, Saïda; Berger, Marc; Hérault, Olivier; Callanan, Mary; Bay, Jacques-Olivier

    2015-01-01

    Chronic lymphocytic leukemia is an indolent disorder with an increased infectious risk remaining one of the main causes of death. Development of therapies with higher safety profile is thus a challenging issue. Docosahexaenoic acid (DHA, 22:6) is an omega-3 fatty acid, a natural compound of normal cells, and has been shown to display antitumor potency in cancer. We evaluated the potential in vitro effect of DHA in primary CLL cells. DHA induces high level of in vitro apoptosis compared to oleic acid in a dose-dependent and time-dependent manner. Estimation of IC50 was only of 4.813 µM, which appears lower than those reported in solid cancers. DHA is highly active on CLL cells in vitro. This observation provides a rationale for further studies aiming to understand its mechanisms of action and its potent in vivo activity. PMID:26734128

  13. The effect of eicosapentaenoic and docosahexaenoic acid on protein synthesis and breakdown in murine C2C12 myotubes

    SciTech Connect

    Kamolrat, Torkamol; Gray, Stuart R.

    2013-03-22

    Highlights: ► EPA can enhance protein synthesis and retard protein breakdown in muscle cells. ► These effects were concurrent with increases in p70s6k and FOXO3a phosphorylation. ► EPA may be a useful tool in the treatment of muscle wasting conditions. -- Abstract: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been found to stimulate protein synthesis with little information regarding their effects on protein breakdown. Furthermore whether there are distinct effects of EPA and DHA remains to be established. The aim of the current study was to determine the distinct effects of EPA and DHA on protein synthesis, protein breakdown and signalling pathways in C2C12 myotubes. Fully differentiated C2C12 cells were incubated for 24 h with 0.1% ethanol (control), 50 μM EPA or 50 μM DHA prior to experimentation. After serum (4 h) and amino acid (1 h) starvation cells were stimulated with 2 mM L-leucine and protein synthesis measured using {sup 3}H-labelled phenylalanine. Protein breakdown was measured using {sup 3}H-labelled phenylalanine and signalling pathways (Akt, mTOR, p70S6k, 4EBP1, rps6 and FOXO3a) via Western blots. Data revealed that after incubation with EPA protein synthesis was 25% greater (P < 0.05) compared to control cells, with no effect of DHA. Protein breakdown was 22% (P < 0.05) lower, compared to control cells, after incubation with EPA, with no effect of DHA. Analysis of signalling pathways revealed that both EPA and DHA incubation increased (P < 0.05) p70s6k phosphorylation, EPA increased (P < 0.05) FOXO3a phosphorylation, with no alteration in other signalling proteins. The current study has demonstrated distinct effects of EPA and DHA on protein metabolism with EPA showing a greater ability to result in skeletal muscle protein accretion.

  14. Docosahexaenoic acid (22:6, n-3) is metabolized to lipoxygenase reaction products in the retina.

    PubMed

    Bazan, N G; Birkle, D L; Reddy, T S

    1984-12-14

    Docosahexaenoic acid (22:6, n-3), a major component of retinal phospholipids, is a substrate for active lipoxygenation in intact canine retinas incubated in vitro with [U-14C]docosahexaenoic acid. The major lipoxygenase reaction product was identified by high performance liquid chromatography and gas chromatography-mass spectrometry as 11-hydroxy-4,7,9-(trans)13,16,19 docosahexaenoic acid. Other mono- and di-hydroxy derivatives also were detected. The synthesis of these compounds was inhibited by the antioxidant and lipoxygenase inhibitor, nordihydroguaiaretic acid, but was not inhibited by indomethacin or esculetin. PMID:6240268

  15. Acute anti-fibrillating and defibrillating potential of atorvastatin, melatonin, eicosapentaenoic acid and docosahexaenoic acid demonstrated in isolated heart model.

    PubMed

    Benova, T; Knezl, V; Viczenczova, C; Bacova, B S; Radosinska, J; Tribulova, N

    2015-02-01

    Cardioprotective compounds such as atorvastatin, melatonin, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibit antiarrhythmic potential in clinical and/or experimental conditions but underlying mechanisms are poorly understood. We have previously shown that protection from ventricular fibrillation (VF) due to prolonged treatment with these compounds was linked with modulation of myocardial connexin-43, which is responsible for myocardial electrical coupling and synchronisation. To elucidate further the antiarrhythmic potential of atorvastatin, melatonin, EPA and DHA we aimed to explore their acute anti-fibrillating effects and defibrillating efficacy. Experiments were conducted on isolated perfused heart preparation of adult male and female hypertriglyceridemic (HTG) rats when using atorvastatin, EPA and DHA, while melatonin was examined in hearts of old male and female guinea pigs. VF inducibility was tested in hearts pre-treated for 10 min with atorvastatin, EPA or DHA (15 μmol) or melatonin (50 μmol) and compared with non-pre-treated hearts. Sustained VF was induced in all untreated HTG rat hearts. In contrast, its incidence was reduced to 30% and 60% by atorvastatin, 70% and 75% by EPA, 60% and 60% by DHA in male or female rat hearts respectively. Moreover, bolus (150 μmol) of EPA and DHA administered directly to the fibrillating heart restored sinus rhythm in 6 of 6 hearts and atorvastatin in 4 of 6 hearts. Threshold to induce sustained VF was 21.7 ± 3.8 mA in male and 38.3 ± 2.9 mA in female guinea pig hearts. However, sustained VF was not possible to induce even by the strongest (50 mA) stimulus in the heart pre-treated with melatonin regardless the sex. In conclusion, atorvastatin, melatonin, EPA and DHA exhibit clear cut acute anti-fibrillating efficacy. Findings challenge to investigate expression of connexin-43, especially its phosphorylated status associated with connexin channel function, in acute conditions. PMID:25716968

  16. Enhanced Production of Docosahexaenoic Acid in Mammalian Cells

    PubMed Central

    Zhu, Guiming; Jiang, Xudong; Ou, Qin; Zhang, Tao; Wang, Mingfu; Sun, Guozhi; Wang, Zhao; Sun, Jie; Ge, Tangdong

    2014-01-01

    Docosahexaenoic acid (DHA), one of the important polyunsaturated fatty acids (PUFA) with pharmaceutical and nutraceutical effects, may be obtained through diet or synthesized in vivo from dietary a-linolenic acid (ALA). However, the acumulation of DHA in human body or other mammals relies on the intake of high dose of DHA for a certain period of time, and the bioconversion of dietary ALA to DHA is very limited. Therefore the mammalian cells are not rich in DHA. Here, we report a new technology for increased prodution of DHA in mammalian cells. By using transient transfection method, Siganus canaliculatus Δ4 desaturase was heterologously expressed in chinese hamster ovary (CHO) cells, and simultaneously, mouse Δ6-desaturase and Δ5-desaturase were overexpressed. The results demonstrated that the overexpression of Δ6/Δ5-desaturases significantly enhanced the ability of transfected cells to convert the added ALA to docosapentaenoic acid (DPA) which in turn get converted into DHA directly and efficiently by the heterologously expressed Δ4 desaturase. This technology provides the basis for potential utility of these gene constructs in the creation of transgenic livestock for increased production of DHA/related products to meet the growing demand of this important PUFA. PMID:24788769

  17. Enhanced production of docosahexaenoic acid in mammalian cells.

    PubMed

    Zhu, Guiming; Jiang, Xudong; Ou, Qin; Zhang, Tao; Wang, Mingfu; Sun, Guozhi; Wang, Zhao; Sun, Jie; Ge, Tangdong

    2014-01-01

    Docosahexaenoic acid (DHA), one of the important polyunsaturated fatty acids (PUFA) with pharmaceutical and nutraceutical effects, may be obtained through diet or synthesized in vivo from dietary a-linolenic acid (ALA). However, the accumulation of DHA in human body or other mammals relies on the intake of high dose of DHA for a certain period of time, and the bioconversion of dietary ALA to DHA is very limited. Therefore the mammalian cells are not rich in DHA. Here, we report a new technology for increased production of DHA in mammalian cells. By using transient transfection method, Siganus canaliculatus Δ4 desaturase was heterologously expressed in chinese hamster ovary (CHO) cells, and simultaneously, mouse Δ6-desaturase and Δ5-desaturase were overexpressed. The results demonstrated that the overexpression of Δ6/Δ5-desaturases significantly enhanced the ability of transfected cells to convert the added ALA to docosapentaenoic acid (DPA) which in turn get converted into DHA directly and efficiently by the heterologously expressed Δ4 desaturase. This technology provides the basis for potential utility of these gene constructs in the creation of transgenic livestock for increased production of DHA/related products to meet the growing demand of this important PUFA. PMID:24788769

  18. Docosahexaenoic Acid Status in Pregnancy Determines the Maternal Docosahexaenoic Acid Status 3-, 6- and 12 Months Postpartum. Results from a Longitudinal Observational Study

    PubMed Central

    Markhus, Maria Wik; Rasinger, Josef Daniel; Malde, Marian Kjellevold; Frøyland, Livar; Skotheim, Siv; Braarud, Hanne Cecilie; Stormark, Kjell Morten; Graff, Ingvild Eide

    2015-01-01

    Background Essential fatty acid status as well as docosahexaenoic acid (DHA, 22:6n-3) declines during pregnancy and lactation. As a result, the DHA status may not be optimal for child development and may increase the risk for maternal postpartum depression. The objective of this study was to assess changes in the maternal fatty acid status from pregnancy to 12 months postpartum, and to study the impact of seafood consumption on the individual fatty acid status. Methods Blood samples and seafood consumption habits (gestation week 28, and three-, six- and 12 months postpartum) were collected in a longitudinal observational study of pregnant and postpartum women (n = 118). Multilevel linear modeling was used to assess both changes over time in the fatty acid status of red blood cells (RBC), and in the seafood consumption. Results Six fatty acids varied the most (>80%) across the four time points analyzed, including the derivative of the essential α-linoleic acid (ALA, 18:3n-3), DHA; the essential linoleic acid (LA, 18:2 n-6); and the LA derivative, arachidonic acid (AA, 20:4n-6). Over all, a large variation in individuals’ DHA- and AA status was observed; however, over the 15-month study period only small inter-individual differences in the longitudinal trajectory of DHA- and AA abundance in the RBC were detected. The median intake of seafood was lower than recommended. Regardless, the total weekly frequency of seafood and eicosapentaenoic acid (EPA, 20:5n-3)/DHA-supplement intake predicted the maternal level of DHA (μg/g RBC). Conclusion The period of depletion of the maternal DHA status during pregnancy and lactation, seem to turn to repletion from about six months postpartum towards one year after childbirth, irrespective of RBC concentration of DHA during pregnancy. Seafood and EPA/DHA-supplement intake predicted the DHA levels over time. Trial Registration www.helseforskning.etikkom.no 2009/570/REC, project number: 083.09 PMID:26331947

  19. Potential of spectroscopic techniques and chemometric analysis for rapid measurement of docosahexaenoic acid and eicosapentaenoic acid in algal oil.

    PubMed

    Wu, Di; He, Yong

    2014-09-01

    Developing rapid methods for measuring long-chain ω-3 (n-3) poly-unsaturated fatty acid (LCPUFA) contents has been a crucial request from the algal oil industry. In this study, four spectroscopy techniques, namely visible and short-wave near infra-red (Vis-SNIR), long-wave near infra-red (LNIR), mid-infra-red (MIR) and nuclear magnetic resonance (NMR) spectroscopy, were exploited for determining the docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) contents in algal oil. The best prediction for both DHA and EPA were achieved by NMR spectroscopy, in which the determination coefficients of cross-validation (rCV(2)) values were 0.963 and 0.967 for two LCPUFAs. The performances of Vis-SNIR and LNIR spectroscopy were also accepted. The variable selection was proved as an efficient and necessary step for the spectral analysis in this study. The results were promising and implied that spectroscopy techniques have a great potential for assessment of DHA and EPA in algal oil. PMID:24731319

  20. [Docosahexaenoic acid (DHA) in fetal development and in infant nutrition].

    PubMed

    Valenzuela, A; Nieto, M S

    2001-10-01

    Docosahexanoic acid (C22:6, DHA) is a highly unsaturated omega-3 fatty acid that forms part of the central nervous and visual system structures. DHA is synthesized from its precursor, alfa-linolenic acid, that is also a omega-3 fatty acid and can be obtained from vegetable oils. Marine organisms, specially fish, are good nutritional sources of DHA and eicosapentanoic acid (EPA), another omega-3 fatty acid that has a role in vascular homeostasis. DHA increases membrane fluidity, improving neurogenesis, synaptogenesis and the activity of retinal photoreceptors. The fetus, specially during the last trimester of pregnancy, has high DHA requirements. It is provided by the mother, since fetal DHA synthesis is negligible in this stage of development. Breast feeding provides DHA to the child, but most replacement artificial formulas do not provide this fatty acid. At the present moment, many products for infant nutrition contain DHA. PMID:11775350

  1. Mechanisms of Docosahexaenoic and Eicosapentaenoic Acid Loss from Pacific Saury and Comparison of Their Retention Rates after Various Cooking Methods.

    PubMed

    Cheung, Lennie K Y; Tomita, Haruo; Takemori, Toshikazu

    2016-08-01

    The docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) contents of Pacific saury (Cololabis saira), a fatty fish and staple of the Japanese diet, have been reported to decrease after cooking. This study compared the DHA and EPA contents remaining in saury after grilling, pan-frying or deep-frying to center temperatures of 75, 85, or 95 °C, and examined physical loss, lipid oxidation, and thermal degradation as mechanisms of DHA and EPA loss. Temperature changes inside the saury were monitored using thermocouples, while DHA and EPA contents, oxygen radical absorbance capacity, and measurements of lipid oxidation (that is, carbonyl value and thiobarbituric acid value) were determined chemically. Visualization of temperature distribution inside fish samples during cooking revealed large differences in heat transfer among cooking methods. True retention rates in grilled (DHA: 84 ± 15%; EPA: 87 ± 14%) and pan-fried samples (DHA: 85 ± 16%; EPA: 77 ± 17%) were significantly higher than deep-fried samples (DHA: 58 ± 17%; EPA: 51 ± 18%), but were not affected by final center temperatures despite differences in cooking times. Physical loss via cooking losses (grilling and pan-frying) or migration into frying oil (deep-frying) accounted for large quantities of DHA and EPA loss, while lipid oxidation and thermal degradation did not appear to be major mechanisms of loss. The antioxidant capacity of saury was not significantly affected by cooking treatments. The results of this study suggest that minimization of physical losses during cooking may increase DHA and EPA contents retained in cooked Pacific saury. PMID:27305642

  2. Formulation, Characterization and Optimization of Liposomes Containing Eicosapentaenoic and Docosahexaenoic Acids; A Methodology Approach

    PubMed Central

    Hadian, Zahra; Sahari, Mohammad Ali; Moghimi, Hamid Reza; Barzegar, Mohsen

    2014-01-01

    Omega-3 fatty acids (FAs) have been shown to prevent cardiovascular disease. The most commonly used omega-3 fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are highly vulnerable to oxidation and therefore, have short shelf life. Recent advances in nanoliposomes provided a biocompatible system for stabilizing omega-3 FAs. Several methods could be implemented to prepare nanoliposomes. To the best of our knowledge, the performances of these methods in preparation omega-3 FAs have not been examined. Nanoliposomes were prepared by thin film hydration followed by one of the following methods: 1- extrusion, ultrasonic irradiation; 2- bath sonication; 3- probe sonication; or 4- combined probe and bath sonication. The size of liposomes obtained from methods 1 to 4 were 99.7 ± 3.5, 381.2 ± 7.8, 90.1 ± 2.3, and 87.1 ± 4.10 nm with zeta potential being -42.4 ± 1.7, -36.3 ± 1.6, -43.8 ± 2.4, and 31.6 ± 1.9 mV, respectively. The encapsulation efficiency (EE) for DHA was 13.2 ± 1.1%, 26.7 ± 1.9%, 56.9 ± 5.2% and 51.8 ± 3.8% for methods 1 to 4, respectively. The corresponding levels for EPA were 6.5 ± 1.3%, 18.1 ± 2.3%, 38.6 ± 1.8%, and 38 ± 3.7%, respectively. The EE for DHA and EPA of liposomes for both methods 3 and 4 increased significantly (p<0.05). Propanal, as the major volatile product formed during liposomal preparations, amounts from 81.2 ± 4.1 to 118.8 ± 2.3 μg/Kg. The differential scanning calorimetry (DSC) study showed that DHA and EPA influence the phase transition temperature of small unilamellar vesicles (SUVs) of dipalmitoyl phosphatidyl choline (DPPC). Transmission electron microscopy (TEM) images of liposomes stained with uranyl acetate showed that the liposomes were spherical in shape and maintain high structural integrity. In conclusion, probe ultrasound of pre-formed liposomes facilitates significant loading of DHA and EPA into the nanoliposomal membrane. PMID:25237335

  3. Circulating Docosahexaenoic Acid Levels Are Associated with Fetal Insulin Sensitivity

    PubMed Central

    Zhao, Jin-Ping; Levy, Emile; Fraser, William D.; Julien, Pierre; Delvin, Edgard; Montoudis, Alain; Spahis, Schohraya; Garofalo, Carole; Nuyt, Anne Monique; Luo, Zhong-Cheng

    2014-01-01

    Background Arachidonic acid (AA; C20∶4 n-6) and docosahexaenoic acid (DHA; C22∶6 n-3) are important long-chain polyunsaturated fatty acids (LC-PUFA) in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally “programming” this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies. Methods and Principal Findings In a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation) and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration) and beta-cell function (proinsulin-to-insulin ratio) in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids) were lower comparing newborns of gestational diabetic (n = 24) vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01). Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = −0.37, P <0.0001). The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity. Conclusion Low circulating DHA levels are associated with compromised

  4. Docosahexaenoic acid and visual functioning in preterm infants: a review.

    PubMed

    Molloy, Carly; Doyle, Lex W; Makrides, Maria; Anderson, Peter J

    2012-12-01

    Preterm children are at risk for a number of visual impairments which can be important for a range of other more complex visuocognitive tasks reliant on visual information. Despite the relatively high incidence of visual impairments in this group there are no good predictors that would allow early identification of those at risk for adverse outcomes. Several lines of evidence suggest that docosahexaenoic acid (DHA) supplementation for preterm infants may improve outcomes in this area. For example, diets deficient in the long-chain polyunsaturated fatty acid DHA have been shown to reduce its concentration in the cerebral cortex and retina, which interferes with physiological processes important for cognition and visual functioning. Further, various studies with pregnant and lactating women, as well as formula-fed infants, have demonstrated a general trend that supplementation with dietary DHA is associated with better childhood outcomes on tests of visual and cognitive development over the first year of life. However, research to date has several methodological limitations, including concentrations of DHA supplementation that have been too low to emulate the in utero accretion of DHA, using single measures of visual acuity to make generalised assumptions about the entire visual system, and little attempt to match what we know about inadequate DHA and structural ramifications with how specific functions may be affected. The objective of this review is to consider the role of DHA in the context of visual processing with a specific emphasis on preterm infants and to illustrate how future research may benefit from marrying what we know about structural consequences to inadequate DHA with functional outcomes that likely have far-reaching ramifications. Factors worth considering for clinical neuropsychological evaluation are also discussed. PMID:23065239

  5. Differential effects of eicosapentaenoic and docosahexaenoic acids upon oxidant-stimulated release and uptake of arachidonic acid in human lymphoma U937 cells.

    PubMed

    Obajimi, Oluwakemi; Black, Kenneth D; MacDonald, Donald J; Boyle, Rose M; Glen, Iain; Ross, Brian M

    2005-08-01

    The use of n-3 polyunsaturated fatty acids, as found in fish-oil derived dietary supplements, as anti-inflammatory agents is supported by a variety of biochemical and physiological data. Recent studies investigating the therapeutic potential of long chain (>C20) n-3 fatty acids in mental illness have lead to the conclusion, however, that not all n-3 fatty acid types are equally efficacious. In particular eicosapentaeoic acid (EPA) appears to possess antidepressant and antipsychotic activity, while docosahexaenoic acid (DHA) does not, an effect suggested to be due to a differential ability to antagonize arachidonic acid (AA)-dependent cell signalling. In this study, we examine the effect of EPA and DHA supplementation upon uptake and release of arachidonic acid stimulated by tert-butyl hydroperoxide/Fe2+ in U937 cells. Oxidant-stimulated 3H-AA release from cells was enhanced by pre-treatment with EPA, DHA and AA, but not stearic or oleic acids for 18 days, with the order of effect magnitude being EPA > DHA = AA. Supplementation of cells for 1 day gave qualitatively similar results, although the effect magnitude was smaller. To determine whether enhanced release was due to decreased reuptake of AA, cells were cultured in the presence of 10 microM fatty acids. Pre-treatment of cells with EPA, and to a lesser extent AA, but not DHA, inhibited uptake of 3H-AA measured subsequent to the removal of unesterified fatty acids. This study suggests that, in U937 cells, EPA can alter the rate of uptake and release of AA from phospholipids in an exposure time-dependent manner, whereas DHA has no or little effect. Our results predict that EPA will have a more pronounced effect upon AA-dependent processes compared to DHA, and suggests that the relative amounts of EPA and DHA in fish oil supplements may modify their biochemical, and potentially, behavioural effects. PMID:15967385

  6. Docosahexaenoic Acid Modulates Invasion and Metastasis of Human Ovarian Cancer via Multiple Molecular Pathways

    PubMed Central

    Wang, Ying-Chun; Wu, Yi-Nan; Wang, Su-Li; Lin, Qing-Hua; He, Ming-Fang; Liu, Qiao-lin; Wang, Jin-Hua

    2016-01-01

    Objective We investigated the effect of docosahexaenoic acid (DHA) on the invasion and metastasis of ovarian cancer cells (A2780, HO8910, and SKOV-3). Methods Cytotoxicity assay was performed to determine the optimal doses of DHA in this experiment. The effects of DHA on invasion ability were assessed by invasion assay. The expressions of messenger RNA and/or proteins associated with invasion or metastasis were detected by quantitative Real Time-Polymerase Chain Reaction or Western blot. The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish. Results Docosahexaenoic acid and α-linolenic acid could reduce the cell vitalities in dose-dependent manner. However, DHA inhibited the invasion and metastasis of ovarian cancer cells, but α-linolenic acid did not (**P < 0.01). Docosahexaenoic acid could downregulate the expressions of WAVE3, vascular endothelial cell growth factor, and MMP-9, and upregulate KISS-1, TIMP-1, and PPAR-γ, which negatively correlated with cell invasion and metastasis (*P < 0.05). Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01). Conclusions Docosahexaenoic acid inhibited the invasion and metastasis of ovarian cancer cells in vitro and in vivo through the modulation of NF-κB signaling pathway, suggesting that DHA is a promising candidate for ovarian cancer therapy. PMID:27258728

  7. Omega-3 fatty acids protect renal functions by increasing docosahexaenoic acid-derived metabolite levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

    PubMed

    Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Al Mamun, Abdullah; Tanabe, Yoko; Iwamoto, Ryo; Arita, Makoto; Tsuchikura, Satoru; Shido, Osamu

    2014-01-01

    The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) protect against diabetic nephropathy by inhibiting inflammation. The aim of this study was to assess the effects of highly purified DHA and EPA or EPA only administration on renal function and renal eicosanoid and docosanoid levels in an animal model of metabolic syndrome, SHR.Cg-Lepr(cp)/NDmcr (SHRcp) rats. Male SHRcp rats were divided into 3 groups. Control (5% arabic gum), TAK-085 (300 mg/kg/day, containing 467 mg/g EPA and 365 mg/g DHA), or EPA (300 mg/kg/day) was orally administered for 20 weeks. The urinary albumin to creatinine ratio in the TAK-085-administered group was significantly lower than that in other groups. The glomerular sclerosis score in the TAK-085-administered group was significantly lower than that in the other groups. Although DHA levels were increased in total kidney fatty acids, the levels of nonesterified DHA were not significantly different among the 3 groups, whereas the levels of protectin D1, resolvin D1, and resolvin D2 were significantly increased in the TAK-085-administered group. The results show that the use of combination therapy with DHA and EPA in SHRcp rats improved or prevented renal failure associate with metabolic syndrome with decreasing triglyceride levels and increasing ω-3 PUFA lipid mediators. PMID:24642910

  8. The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer's disease: Acting separately or synergistically?

    PubMed

    Song, Cai; Shieh, Chu-Hsin; Wu, Yi-Shyuan; Kalueff, Allan; Gaikwad, Siddharth; Su, Kuan-Pin

    2016-04-01

    Omega-3 polyunsaturated fatty acids (n-3-PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may improve or prevent some psychiatric and neurodegenerative diseases in both experimental and clinical studies. As important membrane components, these PUFAs benefit brain health by modulating neuroimmune and apoptotic pathways, changing membrane function and/or competing with n-6 PUFAs, the precursors of inflammatory mediators. However, the exact role of each fatty acid in neuroimmune modulation and neurogenesis, the interaction between EPA and DHA, and the best EPA:DHA ratios for improving brain disorders, remain unclear. It is also unknown whether EPA, as a DHA precursor, acts directly or via DHA. Here, we discuss recent evidence of EPA and DHA effects in the treatment of major depression and Alzheimer's disease, as well as their potential synergistic action on anti-inflammatory, antioxidant and neurotrophic processes in the brain. We further analyze the cellular and molecular mechanisms by which EPA, DHA or their combination may benefit these diseases. We also outline the limitations of current studies and suggest new genetic models and novel approaches to overcome these limitations. Finally, we summarize future strategies for translational research in this field. PMID:26763196

  9. Dietary Crude Lecithin Increases Systemic Availability of Dietary Docosahexaenoic Acid with Combined Intake in Rats.

    PubMed

    van Wijk, Nick; Balvers, Martin; Cansev, Mehmet; Maher, Timothy J; Sijben, John W C; Broersen, Laus M

    2016-07-01

    Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined. PMID:27038174

  10. Inverse Association of Serum Docosahexaenoic Acid With Newly Diagnosed Hypertension

    PubMed Central

    Yang, Bo; Ding, Fang; Wang, Feng-Lei; Yu, Wei; Li, Duo

    2016-01-01

    Abstract Observational studies on circulating fatty acid (FA) and primary prevention of hypertension have yielded inconsistent results, and the association among the Chinese population is not fully clear. The aim of the study was to discern important FAs that can discriminate hypertensive patients from normotensive persons, and investigate associations between the important FAs and risk of hypertension. We conducted a case-control study nested within a community-based cohort of 2447 Chinese participants aged 35 to 79 years who completed a baseline assessment between October 2012 and April 2013. In all, 480 patients with newly diagnosed hypertension were identified at baseline and 480 normotensive individuals were randomly selected as matched normotensive controls. Controls were individually matched to cases by age (±2 y), sex, and recruitment center, with a 1:1 case-to-control ratio. Serum FA profile was compared between cases and controls by orthogonal partial least squares-discriminant analyses. Odds ratio (OR) with 95% confidence interval (CI) for newly diagnosed hypertension was estimated by a conditional logistical analysis. After adjustment for body mass index, education, profession, family history of hypertension, salt intake, heart rate, blood lipids, and fasting glucose levels, serum FA profile in hypertensive patients was typically characterized by higher 16:0 and 16:1n-7, and lower 18:2n-6 and 22:6n-3, compared with normotensive controls. Docosahexaenoic acid (22:6n-3) and palmitoleic acid (16:1n-7) were identified as the important FA contributing most to the intergroup separations. When comparing the highest and lowest quartile of FA composition, newly diagnosed hypertension was negatively associated with 22:6n-3 (OR 0.65; 95% CI, 0.45–0.93; P for trend = 0.02), but positively associated with 16:1n-7 (OR 2.14; 95% CI, 1.46–3.12; P for trend < 0.001). The associations remained pronounced after multiple adjustments and in further stratified

  11. The Omega-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid (DHA) Reverses Corticosterone-Induced Changes in Cortical Neurons

    PubMed Central

    Pusceddu, Matteo M.; Nolan, Yvonne M.; Green, Holly F.; Robertson, Ruairi C.; Stanton, Catherine; Kelly, Philip; Dinan, Timothy G.

    2016-01-01

    Background: Chronic exposure to the glucocorticoid hormone corticosterone exerts cellular stress-induced toxic effects that have been associated with neurodegenerative and psychiatric disorders. Docosahexaenoic acid is a polyunsaturated fatty acid that has been shown to be of benefit in stress-related disorders, putatively through protective action in neurons. Methods: We investigated the protective effect of docosahexaenoic acid against glucocorticoid hormone corticosterone-induced cellular changes in cortical cell cultures containing both astrocytes and neurons. Results: We found that glucocorticoid hormone corticosterone (100, 150, 200 μM) at different time points (48 and 72 hours) induced a dose- and time-dependent reduction in cellular viability as assessed by methyl thiazolyl tetrazolium. Moreover, glucocorticoid hormone corticosterone (200 μM, 72 hours) decreased the percentage composition of neurons while increasing the percentage of astrocytes as assessed by βIII-tubulin and glial fibrillary acidic protein immunostaining, respectively. In contrast, docosahexaenoic acid treatment (6 μM) increased docosahexaenoic acid content and attenuated glucocorticoid hormone corticosterone (200 μM)-induced cell death (72 hours) in cortical cultures. This translates into a capacity for docosahexaenoic acid to prevent neuronal death as well as astrocyte overgrowth following chronic exposure to glucocorticoid hormone corticosterone. Furthermore, docosahexaenoic acid (6 μM) reversed glucocorticoid hormone corticosterone-induced neuronal apoptosis as assessed by terminal deoxynucleotidyl transferase–mediated nick-end labeling and attenuated glucocorticoid hormone corticosterone-induced reductions in brain derived neurotrophic factor mRNA expression in these cultures. Finally, docosahexaenoic acid inhibited glucocorticoid hormone corticosterone-induced downregulation of glucocorticoid receptor expression on βIII- tubulin-positive neurons. Conclusions: This work

  12. Docosahexaenoic acid ester degradation measured by FTIR-ATR with correlation spectroscopy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly unsaturated fatty acids such as docosahexaenoic acid and linolenic acid are prone to oxidation with a resulting loss of bioactivity and generation of malodorous degradation compounds. Degradation proceeds by formation of the corresponding hydroperoxyl free radical with subsequent oxidative cl...

  13. n-3 fatty acids effectively improve the reference memory-related learning ability associated with increased brain docosahexaenoic acid-derived docosanoids in aged rats.

    PubMed

    Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Al Mamun, Abdullah; Inoue, Takayuki; Hossain, Shahdat; Arita, Makoto; Shido, Osamu

    2015-02-01

    We investigated whether a highly purified eicosapentaenoic acid (EPA) and a concentrated n-3 fatty acid formulation (prescription TAK-085) containing EPA and docosahexaenoic acid (DHA) ethyl ester could improve the learning ability of aged rats and whether this specific outcome had any relation with the brain levels of EPA-derived eicosanoids and DHA-derived docosanoids. The rats were tested for reference memory errors (RMEs) and working memory errors (WMEs) in an eight-arm radial maze. Fatty acid compositions were analyzed by GC, whereas brain eicosanoid/docosanoids were measured by LC-ESI-MS-MS-based analysis. The levels of lipid peroxides (LPOs) were measured by thiobarbituric acid reactive substances. The administration of TAK-085 at 300 mg·kg⁻¹day⁻¹ for 17 weeks reduced the number of RMEs in aged rats compared with that in the control rats. Both TAK-085 and EPA administration increased plasma EPA and DHA levels in aged rats, with concurrent increases in DHA and decreases in arachidonic acid in the corticohippocampal brain tissues. TAK-085 administration significantly increased the formation of EPA-derived 5-HETE and DHA-derived 7-, 10-, and 17-HDoHE, PD1, RvD1, and RvD2. ARA-derived PGE2, PGD2, and PGF2α significantly decreased in TAK-085-treated rats. DHA-derived mediators demonstrated a significantly negative correlation with the number of RMEs, whereas EPA-derived mediators did not exhibit any relationship. Furthermore, compared with the control rats, the levels of LPO in the plasma, cerebral cortex, and hippocampus were significantly reduced in TAK-085-treated rats. The findings of the present study suggest that long-term EPA+DHA administration may be a possible preventative strategy against age-related cognitive decline. PMID:25450447

  14. Grouping newly isolated docosahexaenoic acid-producing thraustochytrids based on their polyunsaturated fatty acid profiles and comparative analysis of 18S rRNA genes.

    PubMed

    Huang, Jianzhong; Aki, Tsunehiro; Yokochi, Toshihiro; Nakahara, Toro; Honda, Daiske; Kawamoto, Seiji; Shigeta, Seiko; Ono, Kazuhisa; Suzuki, Osamu

    2003-01-01

    Seven strains of marine microbes producing a significant amount of docosahexaenoic acid (DHA; C22:6, n-3) were screened from seawater collected in coastal areas of Japan and Fiji. They accumulate their respective intermediate fatty acids in addition to DHA. There are 5 kinds of polyunsaturated fatty acid (PUFA) profiles which can be described as (1) DHA/docosapentaenoic acid (DPA; C22:5, n-6), (2) DHA/DPA/eicosapentaenoic acid (EPA; C20:5, n-3), (3) DHA/EPA, (4) DHA/DPA/EPA/arachidonic acid (AA; C20:4, n-6), and (5) DHA/DPA/EPA/AA/docosatetraenoic acid (C22:4, n-6). These isolates are proved to be new thraustochytrids by their specific insertion sequences in the 18S rRNA genes. The phylogenetic tree constructed by molecular analysis of 18S rRNA genes from the isolates and typical thraustochytrids shows that strains with the same PUFA profile form each monophyletic cluster. These results suggest that the C20-22 PUFA profile may be applicable as an effective characteristic for grouping thraustochytrids. PMID:14730428

  15. [The influence of docosahexaenoic acid moiety on cytotoxic activity of 1,2,4-thiadiazole derivatives].

    PubMed

    Akimov, M G; Gretskaia, N M; Karnoukhova, V A; Serkov, I V; Proshin, A N; Shtratnikova, V Iu; Bezuglov, V V

    2014-01-01

    Among 3-(2-aminopropyl)-1,2,4-thiadiazole derivatives contatining substitution-ready secondary amino group and exhibiting cytotoxic towards rat C 6 glioma cells three compounds with LD 50 values ranged from 6 to 48 мM were chosen. For these compounds amides with docosahexaenoic acid were synthetised and their cytotoxic activity was studied. It was shown that, although docosahexaenoic acid itself was not toxic for C 6 glioma cells, its addition to the amino derivatives of 1,2,4-thiadiazole increased or decreased resultant cytotoxicity. The effect depended on the structure of 1,2,4-thiadiazole substituents. The obtained data show that the acylation of cytotoxic compounds with docosahexaenoic acid does not necessarily lead to the increase of their activity, but sometimes can inactivate a compound. This fact should be taken into account, especially in the case of anti-cancer drug development. PMID:25249531

  16. Supplementation of orange juice with docosahexaenoic acid improves plasma phospholipid DHA content of children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Docosahexaenoic acid (DHA) is a long-chain, polyunsaturated fatty acid that is important for brain and retinal development. Its principal dietary source in children is fish. Since many children have a low fish intake, there is concern that they do not receive adequate DHA. In older children, it may ...

  17. First-episode bipolar disorder is associated with erythrocyte membrane docosahexaenoic acid deficits: Dissociation from clinical response to lithium or quetiapine.

    PubMed

    McNamara, Robert K; Jandacek, Ronald; Tso, Patrick; Blom, Thomas J; Welge, Jeffrey A; Strawn, Jeffrey R; Adler, Caleb M; DelBello, Melissa P; Strakowski, Stephen M

    2015-12-15

    Deficits in long-chain omega-3 (LCn-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be associated with the pathophysiology of bipolar disorder. However, LCn-3 fatty acid status at the initial onset of mania and its association with treatment response are not known. Erythrocyte membrane fatty acid composition was determined in first-episode bipolar manic or mixed (n=40) and healthy (n=40) subjects. Mood symptom ratings were obtained with the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS). Erythrocyte fatty acid composition and clinical ratings were also determined within a sub-group of bipolar subjects following 8-week (n=19) or 52-week (n=11) open-label treatment with lithium or quetiapine. At baseline bipolar subjects exhibited significantly lower erythrocyte docosahexaenoic acid (DHA, 22:6n-3) composition compared with healthy subjects (-23%, p<0.0001). EPA (20:5n-3) and docosapentanoic acid (22:5n-3), and LCn-6 fatty acids including arachidonic acid were not different. Following 8- or 52-week treatment with lithium or quetiapine, YMRS and HDRS total scores decreased significantly whereas erythrocyte fatty acids including DHA did not change. These data indicate that selective erythrocyte DHA deficits coincide with the initial onset of manic symptoms, and reductions in mood symptoms following treatment are not mediated by changes in fatty acid status. PMID:26477955

  18. High oleic ready-to-use therapeutic food maintains docosahexaenoic acid status in severe malnutrition: a randomized, blinded trial

    PubMed Central

    Hsieh, Ji-Cheng; Liu, Lei; Zeilani, Mamane; Ickes, Scott; Trehan, Indi; Maleta, Ken; Craig, Christina; Thakwalakwa, Chrissie; Singh, Lauren; Brenna, J. Thomas; Manary, Mark J.

    2015-01-01

    Objective Ready-to-use therapeutic food (RUTF) is the preferred treatment for uncomplicated severe acute malnutrition. RUTF contains large amounts of linoleic acid and very little α-linolenic acid, which may reduce the availability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the recovering child. A novel high oleic RUTF (HO-RUTF) was developed with less linoleic acid to determine its effect on DHA and EPA status. Methods We conducted a prospective, randomized, double-blinded, clinical effectiveness trial treating rural Malawian children with severe acute malnutrition. Children were treated with either HO-RUTF or standard RUTF. Plasma phospholipid (PL) fatty acid status was measured upon enrollment and after 4 weeks and compared between the two intervention groups. Results Among the 141 children enrolled, 48/71 receiving HO-RUTF and 50/70 receiving RUTF recovered. Plasma PL samples were analyzed from 43 children consuming HO-RUTF and 35 children consuming RUTF. The change in DHA content during the first 4 weeks was +4% and −25% in the HO-RUTF and RUTF groups, respectively (P = 0.04). For EPA, the change in content was 63% and −24% in the HO-RUTF and RUTF groups (P < 0.001). For arachidonic acid, the change in content was −3% and 13% in the HO-RUTF and RUTF groups (P < 0.009). Conclusions The changes in DHA and EPA seen in the children treated with HO-RUTF warrant further investigation as they suggest HO-RUTF support improved PUFA status, necessary for neural development and recovery. PMID:25633498

  19. Effects of increasing docosahexaenoic acid intake in human healthy volunteers on lymphocyte activation and monocyte apoptosis

    PubMed Central

    Mebarek, Saïda; Ermak, Natalia; Benzaria, Amal; Vicca, Stéphanie; Dubois, Madeleine; Némoz, Georges; Laville, Martine; Lacour, Bernard; Véricel, Evelyne; Lagarde, Michel; Prigent, Annie-France

    2009-01-01

    Dietary intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However most human studies examined the combined effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate (TPA) plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL (oxLDL). Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800 and 1600mg) in a triacylglycerol form containing DHA as the only PUFA, for two weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400mg DHA/day. The TPA plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400mg DHA/day, with a maximum after 800mg intake, and was positively correlated (P<0.003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxLDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. OxLDL apoptotic effect was significantly attenuated after 400mg DHA/day and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxLDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis. PMID:18710607

  20. Effect of Docosahexaenoic Acid on Cell Cycle Pathways in Breast Cell Lines With Different Transformation Degree.

    PubMed

    Rescigno, Tania; Capasso, Anna; Tecce, Mario Felice

    2016-06-01

    n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), abundant in fish, have been shown to affect development and progression of some types of cancer, including breast cancer. The aim of our study was to further analyze and clarify the effects of these nutrients on the molecular mechanisms underlying breast cancer. Following treatments with DHA we examined cell viability, death, cell cycle, and some molecular effects in breast cell lines with different transformation, phenotypic, and biochemical characteristics (MCF-10A, MCF-7, SK-BR-3, ZR-75-1). These investigations showed that DHA is able to affect cell viability, proliferation, and cell cycle progression in a different way in each assayed breast cell line. The activation of ERK1/2 and STAT3 pathways and the expression and/or activation of molecules involved in cell cycle regulation such as p21(Waf1/Cip1) and p53, are very differently regulated by DHA treatments in each cell model. DHA selectively: (i) arrests non tumoral MCF-10A breast cells in G0 /G1 cycle phase, activating p21(Waf1/Cip1) , and p53, (ii) induces to death highly transformed breast cells SK-BR-3, reducing ERK1/2 and STAT3 phosphorylation and (iii) only slightly affects each analyzed process in MCF-7 breast cell line with transformation degree lower than SK-BR-3 cells. These findings suggest a more relevant inhibitory role of DHA within early development and late progression of breast cancer cell transformation and a variable effect in the other phases, depending on individual molecular properties and degree of malignancy of each clinical case. J. Cell. Physiol. 231: 1226-1236, 2016. © 2015 Wiley Periodicals, Inc. PMID:26480024

  1. Microbial Conversion and In Vitro and In Vivo Antifungal Assessment of Bioconverted Docosahexaenoic Acid (bDHA) Against Agricultural Plant Pathogenic Fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of this research is to develop potential antifungal agents through the microbial conversion of docosahexaenoic acid. Bioconverted docosahexaenoic acid (bDHA), obtained from the microbial conversion of docosahexaenoic acid by Pseudomonas aeruginosa PR3, was assessed for its in vitro and in ...

  2. From aquatic to terrestrial food webs: decrease of the docosahexaenoic acid/linoleic acid ratio.

    PubMed

    Koussoroplis, Apostolos-Manuel; Lemarchand, Charles; Bec, Alexandre; Desvilettes, Christian; Amblard, Christian; Fournier, Christine; Berny, Philippe; Bourdier, Gilles

    2008-05-01

    Fatty acid composition of the adipose tissue of six carnivorous mammalian species (European otter Lutra lutra, American mink Mustela vison, European Mink Mustela lutreola, European polecat Mustela putorius, stone marten Martes foina and European wild cat Felis silvestris) was studied. These species forage to differing degrees in aquatic and terrestrial food webs. Fatty acid analysis revealed significant differences in polyunsaturated fatty acid composition between species. More specifically, our results underline a gradual significant decrease in the docosahexaenoic acid (DHA)/linoleic acid (LNA) ratio of carnivore species as their dependence on aquatic food webs decreases. In conclusion, the use of the DHA/LNA ratio in long-term studies is proposed as a potential proxy of changes in foraging behaviour of semi-aquatic mammals. PMID:18335265

  3. Cognitive Findings of an Exploratory Trial of Docosahexaenoic Acid and Lutein in Older Women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low levels of docosahexaenoic acid (DHA) and low intake of foods rich in lutein may negatively affect cognitive function. DHA and lutein are concentrated in the brain. The objective of this study was to determine effects of supplemental DHA (800 mg/d) and/or lutein (12 mg/d) on cognitive function in...

  4. Docosahexaenoic acid supplementation improves fasting and postprandial plasma lipid profiles in hypertriglyceridemic men.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The effects of docosahexaenoic acid (DHA) on the concentrations of different subclasses of VLDL, LDL and HDL particles, and their mean diameters in fasting and postprandial plasma has not been studied. Objective: To determine the effects of DHA supplementation on the concentrations of a...

  5. Generation of Bioactive Oxylipins from Exogenously Added Arachidonic, Eicosapentaenoic and Docosahexaenoic Acid in Primary Human Brain Microvessel Endothelial Cells.

    PubMed

    Aukema, Harold M; Winter, Tanja; Ravandi, Amir; Dalvi, Siddhartha; Miller, Donald W; Hatch, Grant M

    2016-05-01

    The human blood-brain barrier (BBB) is the restrictive barrier between the brain parenchyma and the circulating blood and is formed in part by microvessel endothelial cells. The brain contains significant amounts of arachidonic acid (ARA), and docosahexaenoic acid (DHA), which potentially give rise to the generation of bioactive oxylipins. Oxylipins are oxygenated fatty acid metabolites that are involved in an assortment of biological functions regulating neurological health and disease. Since it is not known which oxylipins are generated by human brain microvessel endothelial cells (HBMECs), they were incubated for up to 30 min in the absence or presence of 0.1-mM ARA, eicosapentaenoic acid (EPA) or DHA bound to albumin (1:1 molar ratio), and the oxylipins generated were examined using high performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). Of 135 oxylipins screened in the media, 63 were present at >0.1 ng/mL at baseline, and 95 were present after incubation with fatty acid. Oxylipins were rapidly generated and reached maximum levels by 2-5 min. While ARA, EPA and DHA each stimulated the production of oxylipins derived from these fatty acids themselves, ARA also stimulated the production of oxylipins from endogenous 18- and 20-carbon fatty acids, including α-linolenic acid. Oxylipins generated by the lipoxygenase pathway predominated both in resting and stimulated states. Oxylipins formed via the cytochrome P450 pathway were formed primarily from DHA and EPA, but not ARA. These data indicate that HBMECs are capable of generating a plethora of bioactive lipids that have the potential to modulate BBB endothelial cell function. PMID:26439837

  6. Mechanisms by which docosahexaenoic acid and related fatty acids reduce colon cancer risk and inflammatory disorders of the intestine

    PubMed Central

    Chapkin, Robert S.; Seo, Jeongmin; McMurray, David N.; Lupton, Joanne R.

    2008-01-01

    A growing body of epidemiological, clinical, and experimental evidence has underscored both the pharmacological potential and the nutritional value of dietary fish oil enriched in very long chain n-3 PUFAs such as docosahexaenoic acid (DHA, 22:6, n-3) and eicosapentaenoic acid (EPA, 20:5, n-3). The broad health benefits of very long chain n-3 PUFAs and the pleiotropic effects of dietary fish oil and DHA have been proposed to involve alterations in membrane structure and function, eicosanoid metabolism, gene expression and the formation of lipid peroxidation products, although a comprehensive understanding of the mechanisms of action has yet to be elucidated. In this review, we present data demonstrating that DHA selectively modulates the subcellular localization of lipidated signaling proteins depending on their transport pathway, which may be universally applied to other lipidated protein trafficking. An interesting possibility raised by the current observations is that lipidated proteins may exhibit different subcellular distribution profiles in various tissues, which contain a distinct membrane lipid composition. In addition, the current findings clearly indicate that subcellular localization of proteins with a certain trafficking pathway can be subjected to selective regulation by dietary manipulation. This form of regulated plasma membrane targeting of a select subset of upstream signaling proteins may provide cells with the flexibility to coordinate the arrangement of signaling translators on the cell surface. Ultimately, this may allow organ systems such as the colon to optimally decode, respond, and adapt to the vagaries of an ever-changing extracellular environment. PMID:18346463

  7. Long-Chain Omega-3 Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid and Blood Pressure: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Van Elswyk, Mary; Alexander, Dominik D.

    2014-01-01

    BACKGROUND Although a large body of literature has been devoted to examining the relationship between eicosapentaenoic and docosahexaenoic acids (EPA+DHA) and blood pressure, past systematic reviews have been hampered by narrow inclusion criteria and a limited scope of analytical subgroups. In addition, no meta-analysis to date has captured the substantial volume of randomized controlled trials (RCTs) published in the past 2 years. The objective of this meta-analysis was to examine the effect of EPA+DHA, without upper dose limits and including food sources, on blood pressure in RCTs. METHODS Random-effects meta-analyses were used to generate weighted group mean differences and 95% confidence intervals (CIs) between the EPA+DHA group and the placebo group. Analyses were conducted for subgroups defined by key subject or study characteristics. RESULTS Seventy RCTs were included. Compared with placebo, EPA+DHA provision reduced systolic blood pressure (−1.52mm Hg; 95% confidence interval (CI) = −2.25 to −0.79) and diastolic blood pressure (−0.99mm Hg; 95% CI = −1.54 to −0.44) in the meta-analyses of all studies combined. The strongest effects of EPA+DHA were observed among untreated hypertensive subjects (systolic blood pressure = −4.51mm Hg, 95% CI = −6.12 to −2.83; diastolic blood pressure = −3.05mm Hg, 95% CI = −4.35 to −1.74), although blood pressure also was lowered among normotensive subjects (systolic blood pressure = −1.25mm Hg, 95% CI = −2.05 to −0.46; diastolic blood pressure = −0.62mm Hg, 95% CI = −1.22 to −0.02). CONCLUSIONS Overall, available evidence from RCTs indicates that provision of EPA+DHA reduces systolic blood pressure, while provision of ≥2 grams reduces diastolic blood pressure. PMID:24610882

  8. Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice.

    PubMed

    Suzuki-Kemuriyama, Noriko; Matsuzaka, Takashi; Kuba, Motoko; Ohno, Hiroshi; Han, Song-Iee; Takeuchi, Yoshinori; Isaka, Masaaki; Kobayashi, Kazuto; Iwasaki, Hitoshi; Yatoh, Shigeru; Suzuki, Hiroaki; Miyajima, Katsuhiro; Nakae, Dai; Yahagi, Naoya; Nakagawa, Yoshimi; Sone, Hirohito; Yamada, Nobuhiro; Shimano, Hitoshi

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, can progress to steatohepatitis (NASH) and advanced liver damage, such as that from liver cirrhosis and cancer. Recent studies have shown the benefits of consuming n-3 polyunsaturated fatty acids (PUFAs) for the treatment of NAFLD. In the present study, we investigated and compared the effects of the major n-3 PUFAs-eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6)-in preventing atherogenic high-fat (AHF) diet-induced NAFLD. Mice were fed the AHF diet supplemented with or without EPA or DHA for four weeks. Both EPA and DHA reduced the pathological features of AHF diet-induced NASH pathologies such as hepatic lobular inflammation and elevated serum transaminase activity. Intriguingly, EPA had a greater hepatic triacylglycerol (TG)-reducing effect than DHA. In contrast, DHA had a greater suppressive effect than EPA on AHF diet-induced hepatic inflammation and ROS generation, but no difference in fibrosis. Both EPA and DHA could be effective for treatment of NAFLD and NASH. Meanwhile, the two major n-3 polyunsaturated fatty acids might differ in a relative contribution to pathological intermediate steps towards liver fibrosis. PMID:27333187

  9. Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

    PubMed Central

    Suzuki-Kemuriyama, Noriko; Matsuzaka, Takashi; Kuba, Motoko; Ohno, Hiroshi; Han, Song-iee; Takeuchi, Yoshinori; Isaka, Masaaki; Kobayashi, Kazuto; Iwasaki, Hitoshi; Yatoh, Shigeru; Suzuki, Hiroaki; Miyajima, Katsuhiro; Nakae, Dai; Yahagi, Naoya; Nakagawa, Yoshimi; Sone, Hirohito; Yamada, Nobuhiro; Shimano, Hitoshi

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, can progress to steatohepatitis (NASH) and advanced liver damage, such as that from liver cirrhosis and cancer. Recent studies have shown the benefits of consuming n-3 polyunsaturated fatty acids (PUFAs) for the treatment of NAFLD. In the present study, we investigated and compared the effects of the major n-3 PUFAs—eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6)—in preventing atherogenic high-fat (AHF) diet-induced NAFLD. Mice were fed the AHF diet supplemented with or without EPA or DHA for four weeks. Both EPA and DHA reduced the pathological features of AHF diet-induced NASH pathologies such as hepatic lobular inflammation and elevated serum transaminase activity. Intriguingly, EPA had a greater hepatic triacylglycerol (TG)-reducing effect than DHA. In contrast, DHA had a greater suppressive effect than EPA on AHF diet-induced hepatic inflammation and ROS generation, but no difference in fibrosis. Both EPA and DHA could be effective for treatment of NAFLD and NASH. Meanwhile, the two major n-3 polyunsaturated fatty acids might differ in a relative contribution to pathological intermediate steps towards liver fibrosis. PMID:27333187

  10. Compared with Daily, Weekly n–3 PUFA Intake Affects the Incorporation of Eicosapentaenoic Acid and Docosahexaenoic Acid into Platelets and Mononuclear Cells in Humans123

    PubMed Central

    Browning, Lucy M.; Walker, Celia G.; Mander, Adrian P.; West, Annette L.; Gambell, Joanna; Madden, Jackie; Calder, Philip C.; Jebb, Susan A.

    2014-01-01

    Consumption of oily fish is sporadic, whereas controlled intervention studies of n–3 (ω-3) fatty acids usually provide capsules containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as a daily dose. This methodologic study explored whether there are differences in the short-, medium-, and long-term incorporation of EPA and DHA into blood plasma and cells with the provision of identical amounts of EPA and DHA, equivalent to 2 oily fish servings per week (or 6.54 g/wk EPA and DHA), either intermittently (i.e., 1 portion twice per week) or continuously (i.e., divided into daily amounts). The study was part of a randomized, double-blind controlled intervention lasting 12 mo, with participants stratified by age and sex. There were 5 intervention groups, 2 of which are reported here: the 2 intermittent portions (2I) and 2 continuous portions (2C) groups. EPA and DHA were measured in plasma phosphatidylcholine, platelets, and blood mononuclear cells (MNCs) at 9 time points. Sixty-five participants completed the study (2I group, n = 30, mean age of 49.2 y; 2C group, n = 35, mean age of 50.6 y). The incorporation pattern over the 12-mo intervention was different between the 2 groups in all samples (P < 0.0001, time × treatment interaction). At the end of the 12-mo intervention, the 2C group had higher EPA, DHA, and EPA + DHA in platelets (all P < 0.01) and higher EPA and EPA + DHA in MNCs (both P < 0.05) compared with the 2I group. No significant differences were shown for plasma phosphatidylcholine EPA (P = 0.1), DHA (P = 0.15), EPA + DHA (P = 0.07), or MNC DHA (P = 0.06). In conclusion, the pattern of consumption does affect the incorporation of EPA and DHA into cells used as biomarkers of intake. The differences identified here need to be considered in the design of studies and when extrapolating results from continuous capsule-based intervention studies to dietary guidelines for oily fish consumption. This trial was registered at www

  11. Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish1234

    PubMed Central

    Browning, Lucy M; Walker, Celia G; Mander, Adrian P; West, Annette L; Madden, Jackie; Gambell, Joanna M; Young, Stephen; Wang, Laura; Jebb, Susan A

    2012-01-01

    Background: Estimation of the intake of oily fish at a population level is difficult. The measurement of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in biological samples may provide a useful biomarker of intake. Objective: We identified the most appropriate biomarkers for the assessment of habitual oily fish intake and changes in intake by elucidating the dose- and time-dependent response of EPA and DHA incorporation into various biological samples that represent roles in fatty acid transport, function, and storage. Design: This was a double-blind, randomized, controlled intervention trial in 204 men and women that lasted 12 mo. EPA and DHA capsules were provided in a manner to reflect sporadic consumption of oily fish (ie, 1, 2, or 4 times/wk). EPA and DHA were assessed at 9 time points over 12 mo in 9 sample types (red blood cells, mononuclear cells, platelets, buccal cells, adipose tissue, plasma phosphatidylcholine, triglycerides, cholesteryl esters, and nonesterified fatty acids). Results: A dose response (P < 0.05) was observed for EPA and DHA in all pools except for red blood cell EPA (P = 0.057). EPA and DHA measures in plasma phosphatidylcholine and platelets were best for the discrimination between different intakes (P < 0.0001). The rate of incorporation varied between sample types, with the time to maximal incorporation ranging from days (plasma phosphatidylcholine) to months (mononuclear cells) to >12 mo (adipose tissue). Conclusions: Plasma phosphatidylcholine EPA plus DHA was identified as the most suitable biomarker of acute changes in EPA and DHA intake, and platelet and mononuclear cell EPA plus DHA were the most suitable biomarkers of habitual intake. This trial was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN48398526. PMID:22932281

  12. Docosahexaenoic acid (DHA) and docosapentaenoic acid (DPAn-6) algal oils reduce inflammatory mediators in human peripheral mononuclear cells in vitro and paw edema in vivo.

    PubMed

    Nauroth, Julie M; Liu, Ying Chun; Van Elswyk, Mary; Bell, Rebecca; Hall, Eileen Bailey; Chung, Gloria; Arterburn, Linda M

    2010-05-01

    The anti-inflammatory activity associated with fish oil has been ascribed to the long-chain polyunsaturated fatty acids (LC-PUFA), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Here we examined the anti-inflammatory effects of two DHA-rich algal oils, which contain little EPA, and determined the contribution of the constituent fatty acids, particularly DHA and docosapentaenoic acid (DPAn-6). In vitro, lipopolysaccharide (LPS)-stimulated Interleukin-1 beta (IL-1beta) and Tumor Necrosis Factor-alpha (TNF-alpha) secretion in human peripheral blood mononuclear cells (PBMC) was inhibited with apparent relative potencies of DPAn-6 (most potent) > DHA > EPA. In addition, DPAn-6 decreased intracellular levels of cyclooxygenase-2 (COX-2) and was a potent inhibitor of pro-inflammatory prostaglandin E2 (PGE2) production. DHA/DPAn-6-rich DHA-S (DHA-S) algal oil was more effective at reducing edema in rats than DHA-rich DHA-T (DHA-T), suggesting that DPAn-6 has anti-inflammatory properties. Further in vivo analyses demonstrated that feeding DPAn-6 alone, provided as an ethyl ester, reduced paw edema to an extent approaching that of indomethacin and enhanced the anti-inflammatory activity of DHA when given in combination. Together, these results demonstrate that DPAn-6 has anti-inflammatory activity and enhances the effect of DHA in vitro and in vivo. Thus, DHA-S algal oil may have potential for use in anti-inflammatory applications. PMID:20364438

  13. Krill oil supplementation increases plasma concentrations of eicosapentaenoic and docosahexaenoic acids in overweight and obese men and women.

    PubMed

    Maki, Kevin C; Reeves, Mathew S; Farmer, Mildred; Griinari, Mikko; Berge, Kjetil; Vik, Hogne; Hubacher, Rachel; Rains, Tia M

    2009-09-01

    Antarctic krill, also known as Euphausia superba, is a marine crustacean rich in both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety, tolerability, or selected metabolic parameters. In this randomized, double-blind parallel arm trial, overweight and obese men and women (N = 76) were randomly assigned to receive double-blind capsules containing 2 g/d of krill oil, menhaden oil, or control (olive) oil for 4 weeks. Results showed that plasma EPA and DHA concentrations increased significantly more (P < .001) in the krill oil (178.4 +/- 38.7 and 90.2 +/- 40.3 micromol/L, respectively) and menhaden oil (131.8 +/- 28.0 and 149.9 +/- 30.4 micromol/L, respectively) groups than in the control group (2.9 +/- 13.8 and -1.1 +/- 32.4 micromol/L, respectively). Systolic blood pressure declined significantly more (P < .05) in the menhaden oil (-2.2 +/- 2.0 mm Hg) group than in the control group (3.3 +/- 1.5 mm Hg), and the response in the krill oil group (-0.8 +/- 1.4 mm Hg) did not differ from the other 2 treatments. Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group (P < .006). No significant differences for other safety variables were noted, including adverse events. In conclusion, 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated, with no indication of adverse effects on safety parameters. PMID:19854375

  14. COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance.

    PubMed

    Poorani, R; Bhatt, Anant N; Dwarakanath, B S; Das, Undurti N

    2016-08-15

    Polyunsaturated fatty acids (PUFAs) are vital for normal growth and development and physiological function of various tissues in humans. PUFAs have immunomodulatory actions in addition to their ability to modulate inflammation, vascular reactivity, neurotransmission and stem cell biology. PUFAs and their metabolites possess both pro- and anti-inflammatory properties that underlie their actions and involvement in several diseases. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), possesses both cyclo-oxygenase (COX) and lipoxygenase (LOX) inhibitory action and enhances the production of anti-inflammatory lipoxin A4 {(called as epi-lipoxin A4, aspirin-triggered lipoxins (ATLs))}. In addition, at low doses aspirin may not interfere with the production of prostacyclin (PGI2). Both lipoxin A4 and PGI2 have vasodilator, platelet anti-aggregator and anti-inflammatory actions that may underlie the beneficial actions of aspirin. Paradoxically, other NSAIDs may not have the same actions as that of aspirin on PUFA metabolism. Similar anti-inflammatory compounds are formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the action of aspirin termed as resolvins (from EPA and DHA) and protectins and maresins from DHA. PUFAs: arachidonic acid (AA), EPA and DHA and their various products modulate not only inflammation and immune response but also possess actions on various genes, nuclear factors, cyclic AMP and GMP, G-protein coupled receptors (GPRs), hypothalamic neurotransmitters, hormones, cytokines and enzymes, and interact with nitric oxide, carbon monoxide, and hydrogen sulfide to regulate their formation and action and to form new compounds that have several biological actions. These pleiotropic actions of PUFAs and their metabolites may explain their ability to play a role in several physiological actions and diseases. The big challenge is to harness these actions to prevent and manage clinical conditions. PMID:26335394

  15. Fatty Acid Binding Protein 5 Modulates Docosahexaenoic Acid-Induced Recovery in Rats Undergoing Spinal Cord Injury.

    PubMed

    Figueroa, Johnny D; Serrano-Illan, Miguel; Licero, Jenniffer; Cordero, Kathia; Miranda, Jorge D; De Leon, Marino

    2016-08-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs) promote functional recovery in rats undergoing spinal cord injury (SCI). However, the precise molecular mechanism coupling n-3 PUFAs to neurorestorative responses is not well understood. The aim of the present study was to determine the spatiotemporal expression of fatty acid binding protein 5 (FABP5) after contusive SCI and to investigate whether this protein plays a role in n-3 PUFA-mediated functional recovery post-SCI. We found that SCI resulted in a robust spinal cord up-regulation in FABP5 mRNA levels (556 ± 187%) and protein expression (518 ± 195%), when compared to sham-operated rats, at 7 days post-injury (dpi). This upregulation coincided with significant alterations in the metabolism of fatty acids in the injured spinal cord, as revealed by metabolomics-based lipid analyses. In particular, we found increased levels of the n-3 series PUFAs, particularly docosahexaenoic acid (DHA; 22:6 n-3) and eicosapentaenoic acid (EPA; 20:5 n-3) at 7 dpi. Animals consuming a diet rich in DHA and EPA exhibited a significant upregulation in FABP5 mRNA levels at 7 dpi. Immunofluorescence showed low basal FABP5 immunoreactivity in spinal cord ventral gray matter NeuN(+) neurons of sham-operated rats. SCI resulted in a robust induction of FABP5 in glial (GFAP(+), APC(+), and NG2(+)) and precursor cells (DCX(+), nestin(+)). We found that continuous intrathecal administration of FABP5 silencing with small interfering RNA (2 μg) impaired spontaneous open-field locomotion post-SCI. Further, FABP5 siRNA administration hindered the beneficial effects of DHA to ameliorate functional recovery at 7 dpi. Altogether, our findings suggest that FABP5 may be an important player in the promotion of cellular uptake, transport, and/or metabolism of DHA post-SCI. Given the beneficial roles of n-3 PUFAs in ameliorating functional recovery, we propose that FABP5 is an important contributor to basic repair mechanisms in the

  16. Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats

    PubMed Central

    Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

    2015-01-01

    Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography–tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID:26485038

  17. Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats.

    PubMed

    Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

    2015-01-01

    Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography-tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID:26485038

  18. Endogenous Docosahexaenoic Acid (DHA) Prevents Aβ1-42 Oligomer-Induced Neuronal Injury.

    PubMed

    Tan, Yuan; Ren, Huixia; Shi, Zhe; Yao, Xiaoli; He, Chengwei; Kang, Jing-X; Wan, Jian-Bo; Li, Peng; Yuan, Ti-Fei; Su, Huanxing

    2016-07-01

    The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) or n-3 fatty acid has been associated with reduced risk of Alzheimer's disease (AD) in epidemiological reports. However, the underlying mechanism remains to be elucidated. Here, we report that exogenous DHA administration could protect neurons against Aβ oligomer-induced injury both in vitro and in vivo, partly through reducing the endoplasmic reticulum (ER) stress, and preventing cell apoptosis. In transgenic fat-1 mice with enriched ω-3 fatty acids, Aβ oligomers induced fewer neuronal losses, when compared to wild-type (WT) mice. We conclude that endogenous DHA are neuroprotective in pathogenesis processes of AD. PMID:26021747

  19. Plasma oxylipin profiling identifies polyunsaturated vicinal diols as responsive to arachidonic acid and docosahexaenoic acid intake in growing piglets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The dose-responsiveness of plasma oxylipins to incremental dietary intake of arachidonic (20:4n-6; ARA) and docosahexaenoic (22:6n-3; DHA) acid was determined in piglets. Piglets randomly received one of six formulas (n=8 per group) from day 3 to 27 postnatally. Diets contained varying ARA and DHA l...

  20. Plasma oxylipin profiling identifies polyunsaturated vicinal diols as responsive to arachidonic acid and docosahexaenoic acid intake in growing piglets.

    PubMed

    Bruins, Maaike J; Dane, Adrie D; Strassburg, Katrin; Vreeken, Rob J; Newman, John W; Salem, Norman; Tyburczy, Cynthia; Brenna, J Thomas

    2013-06-01

    The dose-responsiveness of plasma oxylipins to incremental dietary intake of arachidonic acid (20:4n-6; ARA) and docosahexaenoic acid (22:6n-3; DHA) was determined in piglets. Piglets randomly received one of six formulas (n = 8 per group) from days 3 to 27 postnatally. Diets contained incremental ARA or incremental DHA levels as follows (% fatty acid, ARA/DHA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D1) 0.66/0.33; and (D2) 0.67/0.62, resulting in incremental intake (g/kg BW/day) of ARA: 0.07 ± 0.01, 0.43 ± 0.03, 0.55 ± 0.03, and 0.82 ± 0.05 at constant DHA intake (0.82 ± 0.05), or incremental intake of DHA: 0.27 ± 0.02, 0.49 ± 0.03, and 0.81 ± 0.05 at constant ARA intake (0.54 ± 0.04). Plasma oxylipin concentrations and free plasma PUFA levels were determined at day 28 using LC-MS/MS. Incremental dietary ARA intake dose-dependently increased plasma ARA levels. In parallel, ARA intake dose-dependently increased ARA-derived diols 5,6- and 14,15-dihydroxyeicosatrienoic acid (DiHETrE) and linoleic acid-derived 12,13-dihydroxyoctadecenoic acid (DiHOME), downstream metabolites of cytochrome P450 expoxygenase (CYP). The ARA epoxide products from CYP are important in vascular homeostatic maintenance. Incremental DHA intake increased plasma DHA and most markedly raised the eicosapentaenoic acid (EPA) metabolite 17,18-dihydroxyeicosatetraenoic acid (DiHETE) and the DHA metabolite 19,20-dihydroxydocosapentaenoic acid (DiHDPE). In conclusion, increasing ARA and DHA intake dose-dependently influenced endogenous n-6 and n-3 oxylipin plasma concentrations in growing piglets, although the biological relevance of these findings remains to be determined. PMID:23543770

  1. Arachidonic acid needed in infant formula when docosahexaenoic acid is present.

    PubMed

    Brenna, J Thomas

    2016-05-01

    Recently, the European Food Safety Authority asserted that arachidonic acid (ARA) is an optional nutrient for the term infant even when docosahexaenoic acid (DHA) is present. The brief rationale is based on an explicit, widespread misapplication of the concept of "essential fatty acids" to linoleic acid that implies it is uniquely required as a nutrient per se. Linoleic acid prevents acute clinical symptoms caused by polyunsaturated fatty acid-deficient diets and is the major precursor for ARA in most human diets. Experimental diets with ARA as the sole n-6 similarly prevent symptoms but at a lower energy percentage than linoleic acid and show ARA is a precursor for linoleic acid. The absence of consistent evidence of ARA benefit from randomized controlled trials is apparently an issue as well. This review highlights basic and clinical research relevant to ARA requirements as an adjunct to DHA in infancy. ARA is a major structural central nervous system component, where it rapidly accumulates perinatally and is required for signaling. Tracer studies show that ARA-fed infants derive about half of their total body ARA from dietary preformed ARA. Clinically, of the 3 cohorts of term infants studied with designs isolating the effects of ARA (DHA-only vs DHA+ARA), none considered ARA-specific outcomes such as vascular or immune function; the study with the highest ARA level showed significant neurocognitive benefit. All breastfed term infants of adequately nourished mothers consume both DHA and ARA. The burden of proof to substantially deviate from the composition of breastmilk is greater than that available from inherently empirical human randomized controlled trial evidence. Infant formulas with DHA but without ARA risk harm from suppression of ARA-mediated metabolism manifest among the many unstudied functions of ARA. PMID:27013482

  2. Modification of Docosahexaenoic Acid Composition of Milk from Nursing Women Who Received Alpha Linolenic Acid from Chia Oil during Gestation and Nursing

    PubMed Central

    Valenzuela, Rodrigo; Bascuñán, Karla A.; Chamorro, Rodrigo; Barrera, Cynthia; Sandoval, Jorge; Puigrredon, Claudia; Parraguez, Gloria; Orellana, Paula; Gonzalez, Valeria; Valenzuela, Alfonso

    2015-01-01

    α-Linolenic acid (ALA) is the precursor of docosahexaenoic acid (DHA) in humans, which is fundamental for brain and visual function. Western diet provides low ALA and DHA, which is reflected in low DHA in maternal milk. Chia oil extracted from chia (Salvia hispanica L.), a plant native to some Latin American countries, is high in ALA (up to 60%) and thereby is an alternative to provide ALA with the aim to reduce DHA deficits. We evaluated the modification of the fatty acid profile of milk obtained from Chilean mothers who received chia oil during gestation and nursing. Forty healthy pregnant women (22–35 years old) tabulated for food consumption, were randomly separated into two groups: a control group with normal feeding (n = 21) and a chia group (n = 19), which received 16 mL chia oil daily from the third trimester of pregnancy until the first six months of nursing. The fatty acid profile of erythrocyte phospholipids, measured at six months of pregnancy, at time of delivery and at six months of nursing, and the fatty acid profile of the milk collected during the first six months of nursing were assessed by gas-chromatography. The chia group, compared to the control group, showed (i) a significant increase in ALA ingestion and a significant reduction of linoleic acid (LA) ingestion, no showing modification of arachidonic acid (AA), eicosapentaenoic acid (EPA) and DHA; (ii) a significant increase of erythrocyte ALA and EPA and a reduction of LA. AA and DHA were not modified; (iii) a increased milk content of ALA during the six months of nursing, whereas LA showed a decrease. AA and EPA were not modified, however DHA increased only during the first three months of nursing. Consumption of chia oil during the last trimester of pregnancy and the first three months of nursing transiently increases the milk content of DHA. PMID:26247968

  3. What is the relationship between gestational age and docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels?

    PubMed

    Baack, Michelle L; Puumala, Susan E; Messier, Stephen E; Pritchett, Deborah K; Harris, William S

    2015-09-01

    Long chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid (DHA) and arachidonic acid (ARA) are increasingly transferred from mother to fetus late in pregnancy. Infants born before this transfer is complete are at risk for deficiency. This study determines the relationship between gestational age (GA) and circulating LCPUFA levels to better understand the unique needs of premature infants born at various GAs. Whole blood was collected within the first 7 days of life from 60 preterm (≤34 weeks GA) and 30 term infants (≥38 weeks GA) and FA levels were analyzed. Since concurrent intravenous lipid emulsion can skew composition data, blood LCPUFA concentrations were also measured. Levels were compared among groups, and linear regression models were used to examine the association between FA composition and GA. Preterm infants had significantly lower DHA and ARA levels than term peers, and whether assessed as concentrations or compositions, both directly correlated with GA (p<0.0001). Moreover, FA comparisons suggest that premature infants have impaired synthesis of LCPUFAs from precursors and may require preformed DHA and ARA. This study confirms that essential FA status is strongly related to GA, and that those babies born the earliest are at the greatest risk of LCPUFA deficiency. PMID:26205427

  4. Docosahexaenoic acid-enriched fish oil attenuates kidney disease and prolongs median and maximal life span of autoimmune lupus-prone mice

    PubMed Central

    Halade, Ganesh V; Rahman, Md Mizanur; Bhattacharya, Arunabh; Barnes, Jeffery; Chandrasekar, Bysani; Fernandes, Gabriel

    2010-01-01

    The therapeutic efficacy of individual components of fish oils (FO) in various human inflammatory diseases still remains unresolved, possibly due to low levels of n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or lower ratio of DHA to EPA. Since FO enriched with DHA (FO-DHA) or EPA (FO-EPA) has become available recently, we investigated their efficacy on survival and inflammatory kidney disease in a well-established animal model of human Systemic Lupus Erythematosus (SLE). Results show for the first time that FO-DHA dramatically extends both the median (658 days) and maximal (848 days) lifespan of (NZB × NZW)F1 (B × W) mice. In contrast, FO-EPA fed mice had a median and maximal lifespan of ~384 and 500 days, respectively. Investigations into possible survival mechanisms revealed that FO-DHA (Vs. FO-EPA) lowers serum anti-dsDNA antibodies, IgG deposition in kidneys, and proteinuria. Further, FO-DHA lowered LPS-mediated increases in serum IL-18 levels and caspase-1-dependent cleavage of pro-IL-18 to mature IL-18 in kidneys. Moreover, FO-DHA suppressed LPS-mediated PI3K, Akt, and NF-κB activations in kidney. These data indicate that DHA, but not EPA, is the most potent n-3 fatty acid that suppresses glomerulonephritis and extends lifespan of SLE-prone short-lived B × W mice, possibly via inhibition of IL-18 induction and IL-18-dependent signaling. PMID:20368275

  5. Comparative metabolomics analysis of docosahexaenoic acid fermentation processes by Schizochytrium sp. under different oxygen availability conditions.

    PubMed

    Li, Juan; Ren, Lu-Jing; Sun, Guan-Nan; Qu, Liang; Huang, He

    2013-05-01

    The intracellular metabolic profile characterization of Schizochytrium sp. throughout docosahexaenoic acid fermentation was investigated using gas chromatography-mass spectrometry (GC-MS). Metabolite profiles originating from Schizochytrium sp. under normal and limited oxygen supply conditions were distinctive and distinguished by principal components analysis (PCA). A total of more than 60 intracellular metabolites were detected and quantified with the levels of some metabolites involved in central carbon metabolism varying throughout both processes. Both fermentation processes were differentiated into three main phases by principal components analysis. Potential biomarkers responsible for distinguishing the different fermentation phases were identified as glutamic acid, proline, glycine, alanine, and glucose. In addition, alanine, glutamic acid, glucose, inositol, ornithine, and galactose were found to make great contribution for dry cell weight and fatty acid composition during normal and limited oxygen supply fermentations. Furthermore, significantly higher levels of succinate and several amino acids in cells of limited oxygen supply fermentation revealed that they might play important roles in resisting oxygen deficiency and increasing DHA synthesis during the lipid accumulation. These findings provide novel insights into the metabolomic characteristics during docosahexaenoic acid fermentation processes by Schizochytrium sp. PMID:23586678

  6. Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid.

    PubMed

    Nguyen, Long N; Ma, Dongliang; Shui, Guanghou; Wong, Peiyan; Cazenave-Gassiot, Amaury; Zhang, Xiaodong; Wenk, Markus R; Goh, Eyleen L K; Silver, David L

    2014-05-22

    Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is essential for normal brain growth and cognitive function. Consistent with its importance in the brain, DHA is highly enriched in brain phospholipids. Despite being an abundant fatty acid in brain phospholipids, DHA cannot be de novo synthesized in brain and must be imported across the blood-brain barrier, but mechanisms for DHA uptake in brain have remained enigmatic. Here we identify a member of the major facilitator superfamily--Mfsd2a (previously an orphan transporter)--as the major transporter for DHA uptake into brain. Mfsd2a is found to be expressed exclusively in endothelium of the blood-brain barrier of micro-vessels. Lipidomic analysis indicates that Mfsd2a-deficient (Mfsd2a-knockout) mice show markedly reduced levels of DHA in brain accompanied by neuronal cell loss in hippocampus and cerebellum, as well as cognitive deficits and severe anxiety, and microcephaly. Unexpectedly, cell-based studies indicate that Mfsd2a transports DHA in the form of lysophosphatidylcholine (LPC), but not unesterified fatty acid, in a sodium-dependent manner. Notably, Mfsd2a transports common plasma LPCs carrying long-chain fatty acids such LPC oleate and LPC palmitate, but not LPCs with less than a 14-carbon acyl chain. Moreover, we determine that the phosphor-zwitterionic headgroup of LPC is critical for transport. Importantly, Mfsd2a-knockout mice have markedly reduced uptake of labelled LPC DHA, and other LPCs, from plasma into brain, demonstrating that Mfsd2a is required for brain uptake of DHA. Our findings reveal an unexpected essential physiological role of plasma-derived LPCs in brain growth and function. PMID:24828044

  7. Eicosapentaenoic Acid and Docosahexaenoic Acid in Whole Blood Are Differentially and Sex-Specifically Associated with Cardiometabolic Risk Markers in 8–11-Year-Old Danish Children

    PubMed Central

    Damsgaard, Camilla T.; Eidner, Maj B.; Stark, Ken D.; Hjorth, Mads F.; Sjödin, Anders; Andersen, Malene R.; Andersen, Rikke; Tetens, Inge; Astrup, Arne; Michaelsen, Kim F.; Lauritzen, Lotte

    2014-01-01

    n-3 long-chain polyunsaturated fatty acids improve cardiovascular risk markers in adults. These effects may differ between eicosapentaenoic acid (EPA, 20∶5n-3) and docosahexaenoic acid (DHA, 22∶6n-3), but we lack evidence in children. Using baseline data from the OPUS School Meal Study we 1) investigated associations between EPA and DHA in whole blood and early cardiometabolic risk markers in 713 children aged 8–11 years and 2) explored potential mediation through waist circumference and physical activity and potential dietary confounding. We collected data on parental education, pubertal stage, 7-day dietary records, physical activity by accelerometry and measured anthropometry, blood pressure, and heart rate. Blood samples were analyzed for whole blood fatty acid composition, cholesterols, triacylglycerol, insulin resistance by the homeostatic model of assessment (HOMA-IR), and inflammatory markers. Whole blood EPA was associated with a 2.7 mmHg (95% CI 0.4; 5.1) higher diastolic blood pressure per weight% EPA, but only in boys. Heart rate was negatively associated with both EPA and DHA status (P = 0.02 and P = 0.002, respectively). Whole blood EPA was negatively associated with triacylglycerol (P = 0.003) and positively with total cholesterol, low density and high density lipoprotein (HDL) cholesterol and HDL:triacylglycerol (all P<0.01) whereas DHA was negatively associated with insulin and HOMA-IR (P = 0.003) and tended to be negatively associated with a metabolic syndrome-score (P = 0.05). Adjustment for waist circumference and physical activity did not change the associations. The association between DHA and HOMA-IR was attenuated but remained after adjustment for fiber intake and none of the other associations were confounded by dietary fat, protein, fiber or energy intake. This study showed that EPA status was negatively associated with triacylglycerol and positively with cholesterols whereas DHA was negatively associated with

  8. Neonatal lamb vigour is improved by feeding docosahexaenoic acid in the form of algal biomass during late gestation.

    PubMed

    Pickard, R M; Beard, A P; Seal, C J; Edwards, S A

    2008-08-01

    To determine whether feeding a sustainable, algal source of docosahexaenoic acid (DHA) to sheep during late pregnancy would improve neonatal lamb vigour, 48 English mule ewes, of known conception date, were divided into four treatment groups. For the last 9 weeks of gestation, ewes received one of two dietary supplements: either a DHA-rich algal biomass providing 12 g DHA/ewe per day, or a control supplement based on vegetable oil. The four dietary treatment groups (n = 12) were: control supplement for the duration of the trial (C), DHA supplement from 9 to 6 weeks before parturition (3 week), DHA supplement from 9 to 3 weeks before parturition (6 week) and DHA supplement for the duration of the trial (9 week). Dietary supplements were fed alongside grass silage and commercial concentrate. There was a tendency for gestation length to be extended with increased duration of DHA supplementation (P = 0.08). After parturition, the concentrations of eicosapentaenoic acid (EPA) and DHA in ewe and lamb plasma and colostrum were elevated in line with increased periods of DHA supplementation. Lambs from the 6-week and 9-week groups stood significantly sooner after birth than lambs from the C group (P < 0.05). These data show that neonatal vigour may be improved by the supplementation of maternal diets with DHA-rich algal biomass and that this beneficial effect depends upon the timing and/or duration of DHA allocation. PMID:22443731

  9. Draft genome sequence of the docosahexaenoic acid producing thraustochytrid Aurantiochytrium sp. T66.

    PubMed

    Liu, Bin; Ertesvåg, Helga; Aasen, Inga Marie; Vadstein, Olav; Brautaset, Trygve; Heggeset, Tonje Marita Bjerkan

    2016-06-01

    Thraustochytrids are unicellular, marine protists, and there is a growing industrial interest in these organisms, particularly because some species, including strains belonging to the genus Aurantiochytrium, accumulate high levels of docosahexaenoic acid (DHA). Here, we report the draft genome sequence of Aurantiochytrium sp. T66 (ATCC PRA-276), with a size of 43 Mbp, and 11,683 predicted protein-coding sequences. The data has been deposited at DDBJ/EMBL/Genbank under the accession LNGJ00000000. The genome sequence will contribute new insight into DHA biosynthesis and regulation, providing a basis for metabolic engineering of thraustochytrids. PMID:27222814

  10. The effect of docosahexaenoic acid on t10, c12-conjugated linoleic acid-induced changes in fatty acid composition of mouse liver, adipose and muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Concomitant supplementation of 1.5% docosahexaenoic acid (22:6 n-3; DHA) with 0.5% t10, c12- conjugated linoleic acid (18:2 n-6; CLA) prevented the CLA-induced increase in expression of hepatic genes involved in fatty acid synthesis and the decrease in expression of genes involved in fat...

  11. Docosahexaenoic acid and palmitic acid reciprocally modulate monocyte activation in part through endoplasmic reticulum stress.

    PubMed

    Snodgrass, Ryan G; Huang, Shurong; Namgaladze, Dmitry; Jandali, Ola; Shao, Tiffany; Sama, Spandana; Brüne, Bernhard; Hwang, Daniel H

    2016-06-01

    Palmitic acid (C16:0) and TLR2 ligand induce, but docosahexaenoic acid (DHA) inhibits monocyte activation. C16:0 and TLR2 or TLR4 ligand induce certain ER stress markers; thus, we determined whether ER stress induced by these agonists is sufficient to induce monocyte activation, and whether the ER stress is inhibited by DHA which is known to inhibit C16:0- or ligand-induced TLR activation. Monocyte activation and ER stress were assessed by TLR/inflammasome-induced IL-1β production, and phosphorylation of IRE-1 and eIF2 and expression of CHOP, respectively in THP-1 cells. TLR2 ligand Pam3CSK4 induced phosphorylation of eIF2, but not phosphorylation of IRE-1 and CHOP expression. LPS also induced phosphorylation of both IRE-1 and eIF2 but not CHOP expression suggesting that TLR2 or TLR4 ligand, or C16:0 induces different ER stress responses. C16:0-, Pam3CSK4-, or LPS-induced IL-1β production was inhibited by 4-phenylbutyric acid, an inhibitor of ER stress suggesting that IL-1β production induced by these agonists is partly mediated through ER stress. Among two ER stress-inducing molecules, thapsigargin but not tunicamycin led to the expression of pro-IL-1β and secretion of IL-1β. Thus, not all types of ER stress are sufficient to induce inflammasome-mediated IL-1β secretion in monocytes. Although both C16:0 and thapsigargin-induced IL-1β secretion was inhibited by DHA, only C16:0-mediated ER stress was responsive to DHA. These findings suggest that the anti-inflammatory effects of DHA are at least in part mediated through modulating ER homeostasis and that the propensity of ER stress can be differentially modulated by the types of dietary fat we consume. PMID:27142735

  12. Effects of Pure Eicosapentaenoic and Docosahexaenoic Acids on Oxidative Stress, Inflammation and Body Fat Mass in Patients with Type 2 Diabetes

    PubMed Central

    Azizi-Soleiman, Fatemeh; Jazayeri, Shima; Eghtesadi, Shahryar; Rajab, Asadollah; Heidari, Iraj; Vafa, Mohammad R; Gohari, Mahmood R

    2013-01-01

    Background: N-3 Fatty acids reduce the risk of cardiovascular disease. Previous studies have shown that they may reduce inflammation, oxidative stress, and fat mass in patients with type 2 diabetes, but the results are inconclusive, due, in part, to type of omega-3 fatty acids used. The aim of this study was to determine the effects of pure eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), the two major omega-3 fatty acids, on inflammation, oxidative stress, and fat mass in patients with type 2 diabetes. Methods: Sixty patients with DM-II were randomly allocated to receive daily either ~1 gr EPA or ~1 gr DHA, or a canola oil as placebo for 12 weeks in a randomized triple-blind, placebo-controlled trial. Serum MDA, CRP, body weight, BMI, and fat mass were measured at baseline and after intervention. Results: Forty-five patients with a mean (±SD) age of 54.9 ± 8.2 years with BMI of 27.6 ± 4.1 kg/m2 and fasting blood glucose 96.0 ± 16.2 mg/dl completed the intervention. Neither EPA nor DHA had significant effects on serum FBS, C-reactive protein, body weight, BMI, and fat mass after intervention (P > 0.05). In addition, while MDA increased 18% in the placebo group (P = 0.009), it did not change in the EPA or DHA group (P > 0.05). Conclusions: Twelve weeks of supplementation with 1gr/d EPA or DHA prevent increasing oxidative stress without changing marker of inflammation. This study is the first report demonstrating that neither EPA nor DHA have effects on body fat mass in type 2 diabetic patients. PMID:24049619

  13. Docosahexaenoic acid status in females of reproductive age with maple syrup urine disease.

    PubMed

    Mazer, Laura M; Yi, Sarah H L; Singh, Rani H

    2010-04-01

    Individuals with maple syrup urine disease (MSUD) have impaired metabolism of branched-chain amino acids (BCAA) valine, isoleucine, and leucine. Life-long dietary therapy is recommended to restrict BCAA intake and thus prevent poor neurological outcomes and death. To maintain adequate nutritional status, the majority of protein and nutrients are derived from synthetic BCAA-free medical foods with variable fatty acid content. Given the restrictive diet and the importance of omega-3 fatty acids, particularly docosahexaenoic acid (DHA), in neurological development, this study evaluated the dietary and fatty acid status of females of reproductive age with MSUD attending a metabolic camp. Healthy controls of similar age and sex were selected from existing normal laboratory data. Total lipid fatty acid concentration in plasma and erythrocytes was analyzed using gas chromatography-mass spectroscopy. Participants with MSUD had normal to increased concentrations of plasma and erythrocyte alpha linolenic acid (ALA) but significantly lower concentrations of plasma and erythrocyte docosahexaenoic acid (DHA) as percent of total lipid fatty acids compared with controls (plasma DHA: MSUD 1.03 +/- 0.35, controls 2.87 +/- 1.08; P = 0.001; erythrocyte DHA: MSUD 2.58 +/- 0.58, controls 3.66 +/- 0.80; P = 0.011). Dietary records reflected negligible or no DHA intake over the 3-day period prior to the blood draw (range 0-2 mg). These results suggest females of reproductive age with MSUD have lower blood DHA concentrations than age-matched controls. In addition, the presence of ALA in medical foods and the background diet may not counter the lack of preformed DHA in the diet. The implications of these results warrant further investigation. PMID:20217236

  14. Docosahexaenoic acid and human brain development: evidence that a dietary supply is needed for optimal development.

    PubMed

    Brenna, J Thomas; Carlson, Susan E

    2014-12-01

    Humans evolved a uniquely large brain among terrestrial mammals. Brain and nervous tissue is rich in the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). Docosahexaenoic acid is required for lower and high order functions in humans because of understood and emerging molecular mechanisms. Among brain components that depend on dietary components, DHA is limiting because its synthesis from terrestrial plant food precursors is low but its utilization when consumed in diet is very efficient. Negligible DHA is found in terrestrial plants, but in contrast, DHA is plentiful at the shoreline where it is made by single-celled organisms and plants, and in the seas supports development of very large marine mammal brains. Modern human brains accumulate DHA up to age 18, most aggressively from about half-way through gestation to about two years of age. Studies in modern humans and non-human primates show that modern infants consuming infant formulas that include only DHA precursors have lower DHA levels than for those with a source of preformed DHA. Functional measures show that infants consuming preformed DHA have improved visual and cognitive function. Dietary preformed DHA in the breast milk of modern mothers supports many-fold greater breast milk DHA than is found in the breast milk of vegans, a phenomenon linked to consumption of shore-based foods. Most current evidence suggests that the DHA-rich human brain required an ample and sustained source of dietary DHA to reach its full potential. PMID:24780861

  15. Docosahexaenoic acid, an omega-3 polyunsaturated acid protects against indomethacin-induced gastric injury.

    PubMed

    Pineda-Peña, Elizabeth Arlen; Jiménez-Andrade, Juan Miguel; Castañeda-Hernández, Gilberto; Chávez-Piña, Aracely Evangelina

    2012-12-15

    Previous studies have shown gastroprotective effect of fish oil in several experimental models. However, the mechanisms and active compounds underlying this effect are not fully understood. Fish oil has several components; among them, one of the most studied is docosahexaenoic acid (DHA), which is an omega-3 long-chain polyunsaturated fatty acid. The aim of this study was to examine the gastroprotective effect of DHA as a pure compound in a rat model of indomethacin-induced gastric injury as well as elucidate some of the mechanism(s) behind DHA's gastroprotective effect. Indomethacin was orally administered to induce an acute gastric injury (3, 10 and 30mg/kg). Omeprazol (a proton pump inhibitor, 30mg/kg, p.o.) and DHA (3, 10, 30mg/kg, p.o.) were gavaged 30 and 120min, respectively, before indomethacin insult (30mg/kg p.o.). Three hours after indomethacin administration, rats were sacrificed, gastric injury was evaluated by determining the total damaged area. A sample of gastric tissue was harvested and processed to quantify prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) levels by enzyme-linked immunosorbent assay. Indomethacin produced gastric injury in dose-dependent manner. DHA protected against indomethacin-induced gastric damage, and this effect was comparable with omeprazol's gastroprotective effect. DHA did not reverse the indomethacin-induced reduction of PGE(2) gastric levels. In contrast, DHA partially prevented the indomethacin-induced increase in LTB(4) gastric levels. This is the first report demonstrating DHA's gastroprotective effect as a pure compound. Furthermore, the results reveal that the gastroprotective effect is mediated by a decrease in gastric LTB(4) levels in indomethacin-induced gastric damage. PMID:23063544

  16. Intrauterine, postpartum and adult relationships between arachidonic acid (AA) and docosahexaenoic acid (DHA).

    PubMed

    Kuipers, Remko S; Luxwolda, Martine F; Janneke Dijck-Brouwer, D A; Muskiet, Frits A J

    2011-11-01

    Erythrocyte (RBC) fatty acid compositions from populations with stable dietary habits but large variations in RBC-arachidonic (AA) and RBC-docosahexaenoic acid (DHA) provided us with insight into relationships between DHA and AA. It also enabled us to estimate the maternal RBC-DHA (mRBC-DHA) status that corresponded with no decrease in mRBC-DHA during pregnancy, or in infant (i) RBC-DHA or mRBC-DHA during the first 3 months postpartum (DHA-equilibrium) while exclusively breastfeeding. At delivery, iRBC-AA is uniformly high and independent of mRBC-AA. Infants born to mothers with low RBC-DHA exhibit higher, but infants born to mothers with high RBC-DHA exhibit lower RBC-DHA than their mothers. This switch from 'biomagnification' into 'bioattenuation' occurs at 6g% mRBC-DHA. At 6g%, mRBC-DHA is stable throughout pregnancy, corresponds with postpartum infant DHA-equilibrium of 6 and 0.4g% DHA in mature milk, but results in postpartum depletion of mRBC-DHA to 5g%. Postpartum maternal DHA-equilibrium is reached at 8g% mRBC-DHA, corresponding with 1g% DHA in mature milk and 7g% iRBC-DHA at delivery that increases to 8g% during lactation. This 8g% RBC-DHA concurs with the lowest risks of cardiovascular and psychiatric diseases in adults. RBC-data from 1866 infants, males and (non-)pregnant females indicated AA vs. DHA synergism at low RBC-DHA, but antagonism at high RBC-DHA. These data, together with high intakes of AA and DHA from our Paleolithic diet, suggest that bioattenuation of DHA during pregnancy and postnatal antagonism between AA and DHA are the physiological standard for humans across the life cycle. PMID:21561751

  17. The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

    PubMed Central

    Carlsson, Johan A.; Wold, Agnes E.; Sandberg, Ann-Sofie; Östman, Sofia M.

    2015-01-01

    Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells. PMID:26619195

  18. Docosahexaenoic acid modulates the enterocyte Caco-2 cell expression of MicroRNAs involved in lipid metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consumption of the long-chain omega-3 (n-3) polyunsaturated fatty acid docosahexaenoic acid (DHA) is associated with a reduced risk of cardiovascular disease and greater chemoprevention. However, the mechanisms underlying the biologic effects of DHA remain unknown. It is well known that microRNAs (m...

  19. [Importance of docosahexaenoic acid (DHA): Functions and recommendations for its ingestion in infants].

    PubMed

    Gil-Campos, M; Dalmau Serra, J

    2010-09-01

    Docosahexaenoic acid (DHA) is a n-3 polyunsaturated fatty acid with multiple functions, although these are still under study. The development of visual and neurological functions have been demonstrated in premature infants and neonates, however, its effects are still being studied in certain chronic neurological diseases, and inflammatory and metabolic disorders. The DHA requirements are not fixed but recommendations must be based on an intake similar to the composition of breastfeeding, and in older children and during pregnancy and lactation, to ensure consumption of oily fish at least twice a week. It is essential to recognise the need for supplementation of this fatty acid in some diseases that require restricted diet, and in metabolic alterations resulting in a deficiency, but also know the scientific evidence on the effects produced in different situations. This review updates this information to propose an adequate intake of DHA at different ages and in different diseases. PMID:20570579

  20. Evaluation of docosahexaenoic acid in a dog model of hypertension induced left ventricular hypertrophy.

    PubMed

    Stanley, William C; Cox, James W; Asemu, Girma; O'Connell, Kelly A; Dabkowski, Erinne R; Xu, Wenhong; Ribeiro, Rogerio F; Shekar, Kadambari C; Hoag, Stephen W; Rastogi, Sharad; Sabbah, Hani N; Daneault, Caroline; des Rosiers, Christine

    2013-12-01

    Marine n-3 polyunsaturated fatty acids alter cardiac phospholipids and prevent cardiac pathology in rodents subjected to pressure overload. This approach has not been evaluated in humans or large animals with hypertension-induced pathological hypertrophy. We evaluated docosahexaenoic acid (DHA) in old female dogs with hypertension caused by 16 weeks of aldosterone infusion. Aldosterone-induced hypertension resulted in concentric left ventricular (LV) hypertrophy and impaired diastolic function in placebo-treated dogs. DHA supplementation increased DHA and depleted arachidonic acid in cardiac phospholipids, but did not improve LV parameters compared to placebo. Surprisingly, DHA significantly increased serum aldosterone concentration and blood pressure compared to placebo. Cardiac mitochondrial yield was decreased in placebo-treated hypertensive dogs compared to normal animals, which was prevented by DHA. Extensive analysis of mitochondrial function found no differences between DHA and placebo groups. In conclusion, DHA did not favorably impact mitochondrial or LV function in aldosterone hypertensive dogs. PMID:24065618

  1. Fatty Acid-Binding Protein 5 Facilitates the Blood-Brain Barrier Transport of Docosahexaenoic Acid.

    PubMed

    Pan, Yijun; Scanlon, Martin J; Owada, Yuji; Yamamoto, Yui; Porter, Christopher J H; Nicolazzo, Joseph A

    2015-12-01

    The brain has a limited ability to synthesize the essential polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) from its omega-3 fatty acid precursors. Therefore, to maintain brain concentrations of this PUFA at physiological levels, plasma-derived DHA must be transported across the blood-brain barrier (BBB). While DHA is able to partition into the luminal membrane of brain endothelial cells, its low aqueous solubility likely limits its cytosolic transfer to the abluminal membrane, necessitating the requirement of an intracellular carrier protein to facilitate trafficking of this PUFA across the BBB. As the intracellular carrier protein fatty acid-binding protein 5 (FABP5) is expressed at the human BBB, the current study assessed the putative role of FABP5 in the brain endothelial cell uptake and BBB transport of DHA in vitro and in vivo, respectively. hFAPB5 was recombinantly expressed and purified from Escherichia coli C41(DE3) cells and the binding affinity of DHA to hFABP5 assessed using isothermal titration calorimetry. The impact of FABP5 siRNA on uptake of (14)C-DHA into immortalized human brain microvascular endothelial (hCMEC/D3) cells was assessed. An in situ transcardiac perfusion method was optimized in C57BL/6 mice and subsequently used to compare the BBB influx rate (Kin) of (14)C-DHA between FABP5-deficient (FABP5(-/-)) and wild-type (FABP5(+/+)) C57BL/6 mice. DHA bound to hFABP5 with an equilibrium dissociation constant of 155 ± 8 nM (mean ± SEM). FABP5 siRNA transfection decreased hCMEC/D3 mRNA and protein expression of FABP5 by 53.2 ± 5.5% and 44.8 ± 13.7%, respectively, which was associated with a 14.1 ± 2.7% reduction in (14)C-DHA cellular uptake. By using optimized conditions for the in situ transcardiac perfusion (a 1 min preperfusion (10 mL/min) followed by perfusion of (14)C-DHA (1 min)), the Kin of (14)C-DHA was 0.04 ± 0.01 mL/g/s. Relative to FABP5(+/+) mice, the Kin of (14)C-DHA decreased 36.7 ± 12.4% in FABP5(-/-) mice

  2. Docosahexaenoic Acid-Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties.

    PubMed

    Kuda, Ondrej; Brezinova, Marie; Rombaldova, Martina; Slavikova, Barbora; Posta, Martin; Beier, Petr; Janovska, Petra; Veleba, Jiri; Kopecky, Jan; Kudova, Eva; Pelikanova, Terezie; Kopecky, Jan

    2016-09-01

    White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids-lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans. PMID:27313314

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

    PubMed

    Dijck-Brouwer, D A Janneke; Hadders-Algra, Mijna; Bouwstra, Hylco; Decsi, Tamás; Boehm, Günther; Martini, Ingrid A; Boersma, E Rudy; Muskiet, Frits A J

    2005-01-01

    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. PMID:15589396

  4. Court date for EPA acid rain rule

    SciTech Connect

    Lobsenz, G.

    1994-03-04

    In an acid rain rulemaking that appears headed straight for the courtroom, the Environmental Protection Agency this week announced new limits on emissions of nitrogen oxides from coal-fired power plants. The regulations, announced March 1, are expected to achieve a 1.8 million ton per year reduction in power plant NOx emissions, which are considered a major contributor to acid rain. The agency issued companion regulations last year to cut power plant discharges of sulfur dioxide, the other major acid rain pollutant. The NOx rulemaking elicited contradictory responses from utility industry officials. One point of contention involves the agency's definition of low-NOx burner technology, a key regulatory determination. If a utility installs EPA-defined low-NOx burner technology and still cannot meet the new NOx limits, it can apply for a less stringent [open quotes]alternative emission limit.[close quotes] The other issue likely to be raised by industry officials involves the January 1995 compliance deadline for utilities included in Phase I of the NOx program. While EPA will allow individual utilities to seek a deadline extension until April 1996 in the event of operational difficulties, the agency rejected the industry's request for an across-the-board extension.

  5. Development of a real-time bioprocess monitoring method for docosahexaenoic acid production by Schizochytrium sp.

    PubMed

    Guo, Dong-Sheng; Ji, Xiao-Jun; Ren, Lu-Jing; Li, Gan-Lu; Yin, Feng-Wei; Huang, He

    2016-09-01

    Oxygen uptake rate (OUR) and respiratory quotient (RQ) are key respiratory parameters for docosahexaenoic acid (DHA) production by Schizochytrium sp. HX-308 under dissolved oxygen limited conditions. To investigate the relationship of OUR and RQ with culture status, three independent cultures with different aeration rates were performed in a 50L bioreactor. OUR was found to be positively correlated with the aeration rate, which reflected the oxygen supply level in each culture. The highest biomass, reaching 124.5g/L, was achieved under the highest OUR. DHA content was found to be highly correlated with the RQ value, and the highest DHA content (44.85% in total fatty acids, w/w) was achieved in the highest RQ level, which implies that the polyketide synthase pathway was more active. OUR and RQ, which reflect the physiological state of microorganisms, are suggested as synergistic real-time bioprocess monitoring parameters for DHA fermentation. PMID:27262097

  6. Isolation and characterization of a novel thraustochytrid-like microorganism that efficiently produces docosahexaenoic acid.

    PubMed

    Perveen, Zakia; Ando, Hitomi; Ueno, Akio; Ito, Yukiya; Yamamoto, Yusuke; Yamada, Yohko; Takagi, Tomoko; Kaneko, Takako; Kogame, Kazuhiro; Okuyama, Hidetoshi

    2006-02-01

    A thraustochytrid-like microorganism (strain 12B) was isolated from the mangrove area of Okinawa, Japan. On the basis of its ectoplasmic net structure and biflagellate zoospores we determined strain 12B to be a novel member of the phylum Labyrinthulomycota in the kingdom Protoctista. When grown on glucose/seawater at 28 degrees C, it had a lipid content of 58% with docosahexaenoic acid (DHA; 22:6 n-3) at 43% of the total fatty acids. It had a growth rate of 0.38 h(-1). The DHA production rate of 2.8 +/- 0.7 g l(-1) day(-1) is the highest value reported for any microorganism. PMID:16489498

  7. Production of Structured Triacylglycerols Containing Palmitic Acids at sn-2 Position and Docosahexaenoic Acids at sn-1, 3 Positions.

    PubMed

    Liu, Yanjun; Guo, Yongli; Sun, Zhaomin; Jie, Xu; Li, Zhaojie; Wang, Jingfeng; Wang, Yuming; Xue, Changhu

    2015-01-01

    Docosahexaenoic acid supplementation has been shown well-established health benefits that justify their use as functional ingredients in healthy foods and nutraceutical products. Structured triacylglycerols rich in 1,3-docosahexenoyl-2-palmitoyl-sn-glycerol were produced from algal oil (Schizochytrium sp) which was prepared by a two-step process. Novozym 435 lipase was used to produce tripalmitin. Tripalmitin was then used to produce the final structured triacylglycerol (STAG) through interesterification reactions using Lipozyme RM IM. The optimum conditions for the enzymatic reaction were a mole ratio of tripalmitin/fatty acid ethyl esters 1:9, 60°C, 10% enzyme load (wt % of substrates), 10 h; the enzymatic product contained 51.6% palmitic acid (PA), 30.13% docosahexaenoic acid (DHA, C22:6 n-3) and 5.33% docosapentanoic acid (DPA, C22:5 n-3), 12.15% oleic acid (OLA). This STAG can be used as a functional ingredient in dietary supplementation to provide the benefits of DHA. PMID:26521813

  8. Effects of Short-Term Docosahexaenoic Acid Supplementation on Markers of Inflammation after Eccentric Strength Exercise in Women.

    PubMed

    Corder, Katherine E; Newsham, Katherine R; McDaniel, Jennifer L; Ezekiel, Uthayashanker R; Weiss, Edward P

    2016-03-01

    facilitate better training adaptations and exercise adherence. Key pointsSeven days of 3000 mg/day supplementation with algae-derived docosahexaenoic acid (DHA) attenuates the delayed onset muscle soreness and stiffness, and protects against the loss of joint range of motion that is caused by strenuous eccentric exercise.This benefit was observed in women, and supports the findings from other studies that were conducted on men or a combination of men and womenThe benefits from algae-derived DHA appear to be similar to those reported in other studies that used a combination of DHA and eicosapentaenoic acid (EPA) derived from fish oilThe findings of better recovery from strenuous exercise with DHA supplementation, paired with other research which demonstrated that DHA and EPA protect against chronic diseases suggest that DHA is an attractive optionThese findings have relevance to athletic populations, in that DHA would be expected to facilitate recovery and allow for better performance during training and competition. However, DHA supplementation might also benefit non-athletic populations, such as individuals starting new exercise programs and patient populations that are prone to muscle soreness (e.g. physical therapy patients). PMID:26957941

  9. Effects of Short-Term Docosahexaenoic Acid Supplementation on Markers of Inflammation after Eccentric Strength Exercise in Women

    PubMed Central

    Corder, Katherine E.; Newsham, Katherine R.; McDaniel, Jennifer L.; Ezekiel, Uthayashanker R.; Weiss, Edward P.

    2016-01-01

    facilitate better training adaptations and exercise adherence. Key points Seven days of 3000 mg/day supplementation with algae-derived docosahexaenoic acid (DHA) attenuates the delayed onset muscle soreness and stiffness, and protects against the loss of joint range of motion that is caused by strenuous eccentric exercise. This benefit was observed in women, and supports the findings from other studies that were conducted on men or a combination of men and women The benefits from algae-derived DHA appear to be similar to those reported in other studies that used a combination of DHA and eicosapentaenoic acid (EPA) derived from fish oil The findings of better recovery from strenuous exercise with DHA supplementation, paired with other research which demonstrated that DHA and EPA protect against chronic diseases suggest that DHA is an attractive option These findings have relevance to athletic populations, in that DHA would be expected to facilitate recovery and allow for better performance during training and competition. However, DHA supplementation might also benefit non-athletic populations, such as individuals starting new exercise programs and patient populations that are prone to muscle soreness (e.g. physical therapy patients). PMID:26957941

  10. State acid rain permitting programs: A report from EPA

    SciTech Connect

    Miller, R.L.

    1995-12-31

    States and EPA are laying the groundwork for state acid rain permitting in Phase 2 of the Acid Rain Program. Early indications suggest a high degree of state compliance with the acid rain permitting requirements of the Acid Rain Program. Phase 2 acid rain permitting forms have been revised and are available on EPA`s Technology Transfer Network. EPA has developed a policy and rationale concerning submission of Phase 2 permit applications, as well as suggested state timing and methodology regarding adoption of 40 CFR Part 76, the NO{sub x} regulation.

  11. Genome Sequence of Schizochytrium sp. CCTCC M209059, an Effective Producer of Docosahexaenoic Acid-Rich Lipids

    PubMed Central

    Ji, Xiao-Jun; Mo, Kai-Qiang; Ren, Lu-Jing; Li, Gan-Lu; Huang, Jian-Zhong

    2015-01-01

    Schizochytrium is an effective species for producing omega-3 docosahexaenoic acid (DHA). Here, we report a genome sequence of Schizochytrium sp. CCTCC M209059, which has a genome size of 39.09 Mb. It will provide the genomic basis for further insights into the metabolic and regulatory mechanisms underlying the DHA formation. PMID:26251485

  12. DHA and EPA Content and Fatty Acid Profile of 39 Food Fishes from India

    PubMed Central

    Mahanty, Arabinda; Sankar, T. V.; Anandan, R.; Paul, B. N.; Sarma, Debajit; Syama Dayal, J.; Venkateshwarlu, G.; Mathew, Suseela; Karunakaran, D.; Chanda, Soumen; Shahi, Neetu; Das, Puspita; Das, Partha; Akhtar, Md Shahbaz; Vijayagopal, P.; Sridhar, N.

    2016-01-01

    Docosahexaenoic acid (DHA) is the principal constituent of a variety of cells especially the brain neurons and retinal cells and plays important role in fetal brain development, development of motor skills, and visual acuity in infants, lipid metabolism, and cognitive support and along with eicosapentaenoic acid (EPA) it plays important role in preventing atherosclerosis, dementia, rheumatoid arthritis, Alzheimer's disease, and so forth. Being an essential nutrient, it is to be obtained through diet and therefore searching for affordable sources of these ω-3 polyunsaturated fatty acids (PUFA) is important for consumer guidance and dietary counseling. Fish is an important source of PUFA and has unique advantage that there are many food fish species available and consumers have a wide choice owing to availability and affordability. The Indian subcontinent harbors a rich fish biodiversity which markedly varies in their nutrient composition. Here we report the DHA and EPA content and fatty acid profile of 39 important food fishes (including finfishes, shellfishes, and edible molluscs from both marine water and freshwater) from India. The study showed that fishes Tenualosa ilisha, Sardinella longiceps, Nemipterus japonicus, and Anabas testudineus are rich sources of DHA and EPA. Promotion of these species as DHA rich species would enhance their utility in public health nutrition. PMID:27579313

  13. DHA and EPA Content and Fatty Acid Profile of 39 Food Fishes from India.

    PubMed

    Mohanty, Bimal Prasanna; Ganguly, Satabdi; Mahanty, Arabinda; Sankar, T V; Anandan, R; Chakraborty, Kajal; Paul, B N; Sarma, Debajit; Syama Dayal, J; Venkateshwarlu, G; Mathew, Suseela; Asha, K K; Karunakaran, D; Mitra, Tandrima; Chanda, Soumen; Shahi, Neetu; Das, Puspita; Das, Partha; Akhtar, Md Shahbaz; Vijayagopal, P; Sridhar, N

    2016-01-01

    Docosahexaenoic acid (DHA) is the principal constituent of a variety of cells especially the brain neurons and retinal cells and plays important role in fetal brain development, development of motor skills, and visual acuity in infants, lipid metabolism, and cognitive support and along with eicosapentaenoic acid (EPA) it plays important role in preventing atherosclerosis, dementia, rheumatoid arthritis, Alzheimer's disease, and so forth. Being an essential nutrient, it is to be obtained through diet and therefore searching for affordable sources of these ω-3 polyunsaturated fatty acids (PUFA) is important for consumer guidance and dietary counseling. Fish is an important source of PUFA and has unique advantage that there are many food fish species available and consumers have a wide choice owing to availability and affordability. The Indian subcontinent harbors a rich fish biodiversity which markedly varies in their nutrient composition. Here we report the DHA and EPA content and fatty acid profile of 39 important food fishes (including finfishes, shellfishes, and edible molluscs from both marine water and freshwater) from India. The study showed that fishes Tenualosa ilisha, Sardinella longiceps, Nemipterus japonicus, and Anabas testudineus are rich sources of DHA and EPA. Promotion of these species as DHA rich species would enhance their utility in public health nutrition. PMID:27579313

  14. Raman Spectroscopic Imaging of Cholesterol and Docosahexaenoic Acid Distribution in the Retinal Rod Outer Segment

    PubMed Central

    Schultz, Zachary D.

    2011-01-01

    Raman vibrational spectroscopic imaging was performed on retinal rod cells isolated from bullfrogs (Rana catesbeiana). The Raman spectra enable determination of the lipid and protein rich rod outer segment (ROS) from the nucleus and inner segment of the cell. Peak fitting analysis of spectra obtained from individual rod photoreceptor cells show characteristic vibrational modes that can be associated with cholesterol and docosahexaenoic acid containing lipids. These results provide direct observations of biomolecular gradients in the rod photoreceptor cells, which, thus far, have been based on indirect detergent extracts and histochemical analysis with indicators such as filipin. The detected biomolecules are associated with regulation of the integral membrane protein rhodopsin, and methods capable direct observation of these biomolecules offer new routes to exploring their role in the regulation of cellular processes. PMID:21799539

  15. Biotechnological Production of Docosahexaenoic Acid Using Aurantiochytrium limacinum: Carbon Sources Comparison And Growth Characterization

    PubMed Central

    Abad, Sergi; Turon, Xavier

    2015-01-01

    Aurantiochytrium limacinum, a marine heterotrophic protist/microalga has shown interesting yields of docosahexaenoic acid (DHA) when cultured with different carbon sources: glucose, pure and crude glycerol. A complete study in a lab-scale fermenter allowed for the characterization and comparison of the growth kinetic parameters corresponding to each carbon source. Artificial Marine Medium (AMM) with glucose, pure and crude glycerol offered similar biomass yields. The net growth rates (0.10–0.12 h−1), biomass (0.7–0.8 g cells/g Substrate) and product (0.14–0.15 g DHA/g cells) yields, as well as DHA productivity were similar using the three carbon sources. Viable potential applications to valorize crude glycerol are envisioned to avoid an environmental problem due to the excess of byproduct. PMID:26690180

  16. Docosahexaenoic Acid Levels in Blood and Metabolic Syndrome in Obese Children: Is There a Link?

    PubMed Central

    Lassandro, Carlotta; Banderali, Giuseppe; Radaelli, Giovanni; Borghi, Elisa; Moretti, Francesca; Verduci, Elvira

    2015-01-01

    Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF) criteria has been suggested in children. Docosahexaenoic acid (DHA) has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure) and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome. PMID:26307979

  17. Modulation of prenatal stress via docosahexaenoic acid supplementation: implications for child mental health

    PubMed Central

    Hipwell, Alison E.

    2015-01-01

    Pregnant women living in poverty experience chronic and acute stressors that may lead to alterations in circulating glucocorticoids. Experimental evidence from animal models and correlational studies in humans support the hypothesis that prenatal exposure to high levels of glucocorticoids can negatively affect the developing fetus and later emotional and behavioral regulation in the offspring. In this integrative review, recent findings from research in psychiatry, obstetrics, and animal and human experimental studies on the role of docosahexaenoic acid in modulation of the stress response and brain development are discussed. The potential for an emerging field of nutritionally based perinatal preventive interventions for improving offspring mental health is described. Prenatal nutritional interventions may prove to be effective approaches to reducing common childhood mental disorders. PMID:26024539

  18. Identification of significant medium components that affect docosahexaenoic acid production by Schizochytrium sp. SW1

    NASA Astrophysics Data System (ADS)

    Manikan, Vidyah; Hamid, Aidil A.

    2013-11-01

    Central composite design (CCD) was employed to investigate the significance of glucose, yeast extract, MSG and sea salt in affecting the amount of docosahexaenoic acid (DHA) accumulated by a locally isolated strain of Schizochytrium. Design Expert software was used to construct a set of experiments where each medium component mentioned above was varied over three levels. Cultivation was carried out in 250mL flasks containing 50mL of medium, incubated at 30°C with 200 rpm agitation for 96 hours. ANOVA was conducted to identify the influential factors and the level of their significance where factors that scored a probability value of less than 0.05 were considered significant. The level of influence for each independent variable was also interpreted using perturbation whereas pattern of interaction between the factors were interpreted using interaction plots. This experiment revealed that yeast extract and monosodium glutamate have significant influence on DHA accumulation process by Schizochytrium sp. SW1.

  19. Incorporation of lutein and docosahexaenoic acid from dietary microalgae into the retina in quail.

    PubMed

    Schnebelen-Berthier, Coralie; Acar, Niyazi; Pouillart, Philippe; Thabuis, Clementine; Rodriguez, Bertrand; Depeint, Flore; Clerc, Elise; Mathiaud, Adeline; Bourdillon, Anne; Baert, Blandine; Bretillon, Lionel; Lecerf, Jean-Michel

    2015-03-01

    Lutein and docosahexaenoic acid (DHA) are associated with the prevention of age-related macular degeneration (AMD). Since microalgae are potent natural sources of these nutrients, their nutritional value should be evaluated based on the bioavailability of lutein and DHA for the retina via the plasmatic compartment. In this study, quail were fed for 5 months either with a diet supplemented or deprived with microalgae rich in lutein and DHA. In the microalgae-fed group, the retinal concentrations of lutein and zeaxanthin gradually increased whereas in plasma, these compounds started to increase from the first month of supplementation. We also observed a significant increase in retinal and plasmatic levels of DHA in the microalgae-fed group. In conclusion, the plasmatic and retinal contents of lutein and DHA were significantly increased in quail fed with lutein- and DHA-rich microalgae. Food fortification with microalgae may be an innovative way to increase lutein and DHA consumption in humans. PMID:25657100

  20. Identification of 14,20-dihydroxy-docosahexaenoic acid as a novel anti-inflammatory metabolite.

    PubMed

    Yokokura, Yoshiyuki; Isobe, Yosuke; Matsueda, Shinnosuke; Iwamoto, Ryo; Goto, Tomomi; Yoshioka, Takeshi; Urabe, Daisuke; Inoue, Masayuki; Arai, Hiroyuki; Arita, Makoto

    2014-12-01

    Docosahexaenoic acid (DHA) exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as D-series resolvins, protectin and maresin. Here, we analysed the lipids in inflammatory exudates using liquid chromatography-tandem mass spectrometry and identified a novel DHA metabolite, 14,20-dihydroxy-DHA (14,20-diHDHA) and showed that it is biosynthesized by eosinophils through the 12/15-lipoxygenase pathway. The chemical structure of the dominant 14,20-diHDHA isomer, which is endogenously biosynthesized by eosinophils, was identified as 14S,20R-diHDHA using chemically synthesized stereoisomers. Nanogram doses of 14,20-diHDHA displayed a potent anti-inflammatory action by limiting neutrophil infiltration in zymosan-induced peritonitis. The in vivo formation and potent anti-inflammatory action of 14,20-diHDHA may contribute to the protective effects of DHA. PMID:25012818

  1. Biotechnological Production of Docosahexaenoic Acid Using Aurantiochytrium limacinum: Carbon Sources Comparison And Growth Characterization.

    PubMed

    Abad, Sergi; Turon, Xavier

    2015-12-01

    Aurantiochytrium limacinum, a marine heterotrophic protist/microalga has shown interesting yields of docosahexaenoic acid (DHA) when cultured with different carbon sources: glucose, pure and crude glycerol. A complete study in a lab-scale fermenter allowed for the characterization and comparison of the growth kinetic parameters corresponding to each carbon source. Artificial Marine Medium (AMM) with glucose, pure and crude glycerol offered similar biomass yields. The net growth rates (0.10-0.12 h(-1)), biomass (0.7-0.8 g cells/g Substrate) and product (0.14-0.15 g DHA/g cells) yields, as well as DHA productivity were similar using the three carbon sources. Viable potential applications to valorize crude glycerol are envisioned to avoid an environmental problem due to the excess of byproduct. PMID:26690180

  2. Genetic and acute toxicological evaluation of an algal oil containing eicosapentaenoic acid (EPA) and palmitoleic acid.

    PubMed

    Collins, M L; Lynch, B; Barfield, W; Bull, A; Ryan, A S; Astwood, J D

    2014-10-01

    Algal strains of Nannochloropsis sp. were developed, optimized, cultivated and harvested to produce a unique composition of algal oil ethyl esters (Algal-EE) that are naturally high in eicosapentaenoic acid (EPA, 23-30%) and palmitoleic acid (20-25%), and contain no docosahexaenoic acid (DHA). Algal-EE was evaluated for mutagenic activity (Ames bacterial reverse mutation, in vitro mammalian chromosome aberration, in vivo micronucleus test) and for acute oral toxicity in Sprague-Dawley rats. In the acute toxicity study, rats received a single oral gavaged dose of Algal-EE (2000 mg/kg body weight). Clinical observations were made for 14 days before sacrifice on Day 15. Macroscopic evaluation involved the examination of all organs in the cranial, thoracic, and abdominal cavities. Algal-EE showed no evidence of mutagenicity, did not produce an increase in the frequency of structural chromosome aberrations, and did not cause an increase in the induction of micronucleated polychromatic erythrocytes. There were no macroscopic abnormalities. Algal-EE up to 2000 mg/kg body weight did not affect body weight, organ appearance or produce any toxic-related signs of morbidity. The acute median lethal dose (LD50) of Algal-EE was >2000 mg/kg body weight. Based on these assays, Algal-EE does not appear to have any genetic or acute oral toxicity. PMID:25057807

  3. Prospective Randomized Trial on Postoperative Administration of Diet Containing Eicosapentaenoic Acid, Docosahexaenoic Acid, Gamma-linolenic Acid, and Antioxidants in Head and Neck Cancer Surgery Patients with Free-flap Reconstruction

    PubMed Central

    Tsukahara, Kiyoaki; Motohashi, Ray; Sato, Hiroki; Endo, Minoru; Ueda, Yuri; Nakamura, Kazuhiro

    2014-01-01

    OBJECTIVES The purpose of this prospective, randomized study was to evaluate the effects of a diet containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), and antioxidants in head and neck cancer surgery patients with free-flap reconstruction. METHODS In this randomized, prospective study, 62 patients with head and neck cancers were assigned to receive a general control diet (Ensure® H; Abbott Japan, Tokyo, Japan) or the study diet (Oxepa®; Abbott Japan) containing EPA, DHA, GLA, and antioxidants (eg vitamins A, E, and C). The primary assessment item was the degree of postoperative inflammation, as assessed by measuring maximum body temperature and levels of C-reactive protein (CRP) and procalcitonin from the day of surgery to postoperative day 8. Secondary assessment items were lengths of stays in the intensive care unit (ICU) and hospital. RESULTS The control diet group (n = 32) and study diet group (n = 30) showed no significant difference in energy administered through diet. No significant differences in the parameters of the primary assessment item were noted. Length of stay in the ICU was significantly shorter for the control diet group than for the study diet group (P = 0.011). No significant difference in duration of hospitalization was seen between groups. CONCLUSION No usefulness of a diet containing EPA, DHA, GLA, and antioxidants was demonstrated. PMID:25368541

  4. Docosahexaenoic acid supplementation fully restores fertility and spermatogenesis in male delta-6 desaturase-null mice

    PubMed Central

    Roqueta-Rivera, Manuel; Stroud, Chad K.; Haschek, Wanda M.; Akare, Sandeep J.; Segre, Mariangela; Brush, Richard S.; Agbaga, Martin-Paul; Anderson, Robert E.; Hess, Rex A.; Nakamura, Manabu T.

    2010-01-01

    Delta-6 desaturase-null mice (−/−) are unable to synthesize highly unsaturated fatty acids (HUFAs): arachidonic acid (AA), docosahexaenoic acid (DHA), and n6-docosapentaenoic acid (DPAn6). The −/− males exhibit infertility and arrest of spermatogenesis at late spermiogenesis. To determine which HUFA is essential for spermiogenesis, a diet supplemented with either 0.2% (w/w) AA or DHA was fed to wild-type (+/+) and −/− males at weaning until 16 weeks of age (n = 3–5). A breeding success rate of DHA-supplemented −/− was comparable to +/+. DHA-fed −/− showed normal sperm counts and spermiogenesis. Dietary AA was less effective in restoring fertility, sperm count, and spermiogenesis than DHA. Testis fatty acid analysis showed restored DHA in DHA-fed −/−, but DPAn6 remained depleted. In AA-fed −/−, AA was restored at the +/+ level, and 22:4n6, an AA elongated product, accumulated in testis. Cholesta-3,5-diene was present in testis of +/+ and DHA-fed −/−, whereas it diminished in −/− and AA-fed −/−, suggesting impaired sterol metabolism in these groups. Expression of spermiogenesis marker genes was largely normal in all groups. In conclusion, DHA was capable of restoring all observed impairment in male reproduction, whereas 22:4n6 formed from dietary AA may act as an inferior substitute for DHA. PMID:19690334

  5. Relation between stable isotope ratios in human red blood cells and hair: implications for using the nitrogen isotope ratio of hair as a biomarker of eicosapentaenoic acid and docosahexaenoic acid1234

    PubMed Central

    Nash, Sarah H; Kristal, Alan R; Boyer, Bert B; King, Irena B; Metzgar, Jordan S

    2009-01-01

    Background: The nitrogen isotope ratio (expressed as δ15N) of red blood cells (RBCs) is highly correlated with the RBC long-chain ω−3 (n−3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in Yup'ik Eskimos. Because δ15N can also be measured in hair samples, it could provide a noninvasive, retrospective biomarker for EPA and DHA intakes. Objectives: We investigated the agreement between δ15N in hair and RBCs and then evaluated the relations between hair δ15N and RBC EPA and DHA. We also assessed the agreement in carbon isotope ratios (δ13C) between hair and RBCs, because δ13C has been proposed as a dietary biomarker in other populations. Design: We assessed relations between hair and RBC δ15N and δ13C in a community-based sample of 144 Yup'ik Eskimos and examined the correlations between δ15N and RBC EPA and DHA in a subset of these participants (n = 44). Results: We showed a 1:1 relation with good agreement between hair and RBC δ15N (r = 0.91) and δ13C (r = 0.87). Hair isotope ratios were greater than RBC ratios by 1.5‰ for δ15N and by 2.3‰ for δ13C. There were strong correlations between hair δ15N and RBC EPA and DHA (r = 0.83 and 0.84, respectively). Conclusions: These results support the use of hair δ15N values as a biomarker of EPA and DHA intakes. Because hair collection is noninvasive and the samples require no special processing, studies of EPA and DHA intakes in large populations could use biomarkers rather than self-reports to assess these fatty acids. PMID:19864410

  6. Docosahexaenoic Acid (DHA): An Ancient Nutrient for the Modern Human Brain

    PubMed Central

    Bradbury, Joanne

    2011-01-01

    Modern humans have evolved with a staple source of preformed docosahexaenoic acid (DHA) in the diet. An important turning point in human evolution was the discovery of high-quality, easily digested nutrients from coastal seafood and inland freshwater sources. Multi-generational exploitation of seafood by shore-based dwellers coincided with the rapid expansion of grey matter in the cerebral cortex, which characterizes the modern human brain. The DHA molecule has unique structural properties that appear to provide optimal conditions for a wide range of cell membrane functions. This has particular implications for grey matter, which is membrane-rich tissue. An important metabolic role for DHA has recently been identified as the precursor for resolvins and protectins. The rudimentary source of DHA is marine algae; therefore it is found concentrated in fish and marine oils. Unlike the photosynthetic cells in algae and higher plants, mammalian cells lack the specific enzymes required for the de novo synthesis of alpha-linolenic acid (ALA), the precursor for all omega-3 fatty acid syntheses. Endogenous synthesis of DHA from ALA in humans is much lower and more limited than previously assumed. The excessive consumption of omega-6 fatty acids in the modern Western diet further displaces DHA from membrane phospholipids. An emerging body of research is exploring a unique role for DHA in neurodevelopment and the prevention of neuropsychiatric and neurodegenerative disorders. DHA is increasingly being added back into the food supply as fish oil or algal oil supplementation. PMID:22254110

  7. IMAGING BRAIN SIGNAL TRANSDUCTION AND METABOLISM VIA ARACHIDONIC AND DOCOSAHEXAENOIC ACID IN ANIMALS AND HUMANS

    PubMed Central

    Basselin, Mireille; Ramadan, Epolia; Rapoport, Stanley I.

    2012-01-01

    The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A2 (PLA2) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M1,3,5, serotonergic 5-HT2A/2C, dopaminergic D2-like (D2, D3, D4) or glutamatergic N-methyl-D-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics. PMID:22178644

  8. The Relationship of Docosahexaenoic Acid (DHA) with Learning and Behavior in Healthy Children: A Review

    PubMed Central

    Kuratko, Connye N.; Barrett, Erin Cernkovich; Nelson, Edward B.; Norman, Salem

    2013-01-01

    Childhood is a period of brain growth and maturation. The long chain omega-3 fatty acid, docosahexaenoic acid (DHA), is a major lipid in the brain recognized as essential for normal brain function. In animals, low brain DHA results in impaired learning and behavior. In infants, DHA is important for optimal visual and cognitive development. The usual intake of DHA among toddlers and children is low and some studies show improvements in cognition and behavior as the result of supplementation with polyunsaturated fatty acids including DHA. The purpose of this review was to identify and evaluate current knowledge regarding the relationship of DHA with measures of learning and behavior in healthy school-age children. A systematic search of the literature identified 15 relevant publications for review. The search found studies which were diverse in purpose and design and without consistent conclusions regarding the treatment effect of DHA intake or biomarker status on specific cognitive tests. However, studies of brain activity reported benefits of DHA supplementation and over half of the studies reported a favorable role for DHA or long chain omega-3 fatty acids in at least one area of cognition or behavior. Studies also suggested an important role for DHA in school performance. PMID:23877090

  9. Thraustochytrids as production organisms for docosahexaenoic acid (DHA), squalene, and carotenoids.

    PubMed

    Aasen, Inga Marie; Ertesvåg, Helga; Heggeset, Tonje Marita Bjerkan; Liu, Bin; Brautaset, Trygve; Vadstein, Olav; Ellingsen, Trond E

    2016-05-01

    Thraustochytrids have been applied for industrial production of the omega-3 fatty acid docosahexaenoic (DHA) since the 1990s. During more than 20 years of research on this group of marine, heterotrophic microorganisms, considerable increases in DHA productivities have been obtained by process and medium optimization. Strains of thraustochytrids also produce high levels of squalene and carotenoids, two other commercially interesting compounds with a rapidly growing market potential, but where yet few studies on process optimization have been reported. Thraustochytrids use two pathways for fatty acid synthesis. The saturated fatty acids are produced by the standard fatty acid synthesis, while DHA is synthesized by a polyketide synthase. However, fundamental knowledge about the relationship between the two pathways is still lacking. In the present review, we extract main findings from the high number of reports on process optimization for DHA production and interpret these in the light of the current knowledge of DHA synthesis in thraustochytrids and lipid accumulation in oleaginous microorganisms in general. We also summarize published reports on squalene and carotenoid production and review the current status on strain improvement, which has been hampered by the yet very few published genome sequences and the lack of tools for gene transfer to the organisms. As more sequences now are becoming available, targets for strain improvement can be identified and open for a system-level metabolic engineering for improved productivities. PMID:27041691

  10. Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain.

    PubMed

    Bradbury, Joanne

    2011-05-01

    Modern humans have evolved with a staple source of preformed docosahexaenoic acid (DHA) in the diet. An important turning point in human evolution was the discovery of high-quality, easily digested nutrients from coastal seafood and inland freshwater sources. Multi-generational exploitation of seafood by shore-based dwellers coincided with the rapid expansion of grey matter in the cerebral cortex, which characterizes the modern human brain. The DHA molecule has unique structural properties that appear to provide optimal conditions for a wide range of cell membrane functions. This has particular implications for grey matter, which is membrane-rich tissue. An important metabolic role for DHA has recently been identified as the precursor for resolvins and protectins. The rudimentary source of DHA is marine algae; therefore it is found concentrated in fish and marine oils. Unlike the photosynthetic cells in algae and higher plants, mammalian cells lack the specific enzymes required for the de novo synthesis of alpha-linolenic acid (ALA), the precursor for all omega-3 fatty acid syntheses. Endogenous synthesis of DHA from ALA in humans is much lower and more limited than previously assumed. The excessive consumption of omega-6 fatty acids in the modern Western diet further displaces DHA from membrane phospholipids. An emerging body of research is exploring a unique role for DHA in neurodevelopment and the prevention of neuropsychiatric and neurodegenerative disorders. DHA is increasingly being added back into the food supply as fish oil or algal oil supplementation. PMID:22254110

  11. Beyond Building Better Brains: Bridging the Docosahexaenoic acid (DHA) Gap of Prematurity

    PubMed Central

    Harris, William

    2014-01-01

    Long chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid (DHA), are essential for normal vision and neurodevelopment. DHA accretion in utero occurs primarily in the last trimester of pregnancy to support rapid growth and brain development. Premature infants, born before this process is complete, are relatively deficient in this essential fatty acid. Very low birth weight (VLBW) infants remain deficient for a long period of time due to ineffective conversion from precursor fatty acids, lower fat stores, and a limited nutritional provision of DHA after birth. In addition to long- term visual and neurodevelopmental risks, VLBW infants have significant morbidity and mortality from diseases specific to premature birth, including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP). There is increasing evidence that DHA has protective benefits against these disease states. The aim of this article is to identify the unique needs of premature infants, review the current recommendations for LCPUFA provision in infants, and discuss the caveats and innovative new ways to overcome the DHA deficiency through postnatal supplementation, with the long term goal of improving morbidity and mortality in this at risk population. PMID:25357095

  12. Production of human milk fat analogue containing docosahexaenoic and arachidonic acids.

    PubMed

    Turan, Dilek; Sahin Yeşilçubuk, Neşe; Akoh, Casimir C

    2012-05-01

    Human milk fat (HMF) analogue containing docosahexaenoic acid (DHA) and arachidonic acid (ARA) at sn-1,3 positions and palmitic acid (PA) at sn-2 position was produced. Novozym 435 lipase was used to produce palmitic acid-enriched hazelnut oil (EHO). EHO was then used to produce the final structured lipid (SL) through interesterification reactions using Lipozyme RM IM. Reaction variables for 3 h reactions were temperature, substrate mole ratio, and ARASCO/DHASCO (A:D) ratio. After statistical analysis of DHA, ARA, total PA, and PA content at sn-2 position, a large-scale production was performed at 60 °C, 3:2 A:D ratio, and 1:0.1 substrate mole ratio. For the SL, those results were determined as 57.3 ± 0.4%, 2.7 ± 0.0%, 2.4 ± 0.1%, and 66.1 ± 2.2%, respectively. Tocopherol contents were 84, 19, 85, and 23 μg/g oil for α-, β-, γ-, and δ-tocopherol. Melting range of SL was narrower than that of EHO. Oxidative stability index (OSI) value of SL (0.80 h) was similar to that of EHO (0.88 h). This SL can be used in infant formulas to provide the benefits of ARA and DHA. PMID:22497589

  13. [Possible role of altered levels of plasma docosahexaenoic acid in the pathogenesis of retinitis pigmentosa. Preliminary results].

    PubMed

    Simonelli, F; Milone, A; Iura, A; Picardi, C; La Banca, A M; Cotticelli, L; Rinaldi, E

    1990-09-01

    Plasma samples obtained from Retinitis Pigmentosa (R.P.) patients and controls were assayed for docosahexaenoic acid (DXA), the major fatty acid in photoreceptor cells, in order to evaluate the possibility that abnormalities in PUFA metabolism could be involved in R.P. pathogenesis. Our preliminary results show levels of plasma DXA in dominantly inherited R.P. lower than in the recessive forms and controls. PMID:2149985

  14. Dietary arachidonic acid and docosahexaenoic acid regulate liver fatty acid desaturase (FADS) alternative transcript expression in suckling piglets.

    PubMed

    Wijendran, Vasuki; Downs, Ian; Srigley, Cynthia Tyburczy; Kothapalli, Kumar S D; Park, Woo Jung; Blank, Bryant S; Zimmer, J Paul; Butt, C M; Salem, Norman; Brenna, J Thomas

    2013-10-01

    Molecular regulation of fatty acid desaturase (Fads) gene expression by dietary arachidonic acid (ARA) and docosahexaenoic acid (DHA) during early post-natal period, when the demand for long chain polyunsaturated fatty acids (LC-PUFA) is very high, has not been well defined. The objective of the current study was to determine regulation of liver Fads1, Fads2 and Fads3 classical (CS) and alternative transcripts (AT) expression by dietary ARA and DHA, within the physiological range present in human breast milk, in suckling piglets. Piglets were fed one of six milk replacer formula diets (formula-reared groups, FR) with varying ARA and DHA content from days 3-28 of age. The ARA/DHA levels of the six formula diets were as follows (% total fatty acid, FA/FA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D2) 0.67/0.62; and (D1) 0.66/0.33. The control maternal-reared (MR) group remained with the dam. Fads1 expression was not significantly different between FR and MR groups. Fads2 expression was down-regulated significantly in diets with 1:1 ratio of ARA:DHA, compared to MR. Fads2 AT1 expression was highly correlated to Fads2 expression. Fads3 AT7 was the only Fads3 transcript sensitive to dietary LC-PUFA intake and was up-regulated in the formula diets with lowest ARA and DHA contents compared to MR. Thus, the present study provides evidence that the proportion of dietary ARA:DHA is a significant determinant of Fads2 expression and LC-PUFA metabolism during the early postnatal period. Further, the data suggest that Fads3 AT7 may have functional significance when dietary supply of ARA and DHA are low during early development. PMID:24075244

  15. Metabolic engineering of Pseudomonas putida for production of docosahexaenoic acid based on a myxobacterial PUFA synthase.

    PubMed

    Gemperlein, Katja; Zipf, Gregor; Bernauer, Hubert S; Müller, Rolf; Wenzel, Silke C

    2016-01-01

    Long-chain polyunsaturated fatty acids (LC-PUFAs) can be produced de novo via polyketide synthase-like enzymes known as PUFA synthases, which are encoded by pfa biosynthetic gene clusters originally discovered from marine microorganisms. Recently similar gene clusters were detected and characterized in terrestrial myxobacteria revealing several striking differences. As the identified myxobacterial producers are difficult to handle genetically and grow very slowly we aimed to establish heterologous expression platforms for myxobacterial PUFA synthases. Here we report the heterologous expression of the pfa gene cluster from Aetherobacter fasciculatus (SBSr002) in the phylogenetically distant model host bacteria Escherichia coli and Pseudomonas putida. The latter host turned out to be the more promising PUFA producer revealing higher production rates of n-6 docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). After several rounds of genetic engineering of expression plasmids combined with metabolic engineering of P. putida, DHA production yields were eventually increased more than threefold. Additionally, we applied synthetic biology approaches to redesign and construct artificial versions of the A. fasciculatus pfa gene cluster, which to the best of our knowledge represents the first example of a polyketide-like biosynthetic gene cluster modulated and synthesized for P. putida. Combination with the engineering efforts described above led to a further increase in LC-PUFA production yields. The established production platform based on synthetic DNA now sets the stage for flexible engineering of the complex PUFA synthase. PMID:26617065

  16. Essential role of docosahexaenoic acid towards development of a smarter brain.

    PubMed

    Gharami, Kusumika; Das, Moitreyi; Das, Sumantra

    2015-10-01

    Evolution of the high order brain function in humans can be attributed to intake of poly unsaturated fatty acids (PUFAs) of which the ω-3 fatty acid, docosahexaenoic acid (DHA) has special significance. DHA is abundantly present in the human brain and is an essential requirement in every step of brain development like neural cell proliferation, migration, differentiation, synaptogenesis etc. The multiple double bonds and unique structure allow DHA to impart special membrane characteristics for effective cell signaling. Evidences indicate that DHA accumulate in areas of the brain associated with learning and memory. Many development disorders like dyslexia, autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia etc. are causally related to decreased level of DHA. The review discusses the various reports of DHA in these areas for a better understanding of the role of DHA in overall brain development. Studies involving laboratory animals and clinical findings in cases as well as during trials have been taken into consideration. Additionally the currently available dietary source of DHA for supplementation as nutraceutics with general caution for overuse has been examined. PMID:26321578

  17. Dietary docosahexaenoic acid alleviates autistic-like behaviors resulting from maternal immune activation in mice.

    PubMed

    Weiser, Michael J; Mucha, Brittany; Denheyer, Heather; Atkinson, Devon; Schanz, Norman; Vassiliou, Evros; Benno, Robert H

    2016-03-01

    The prevalence of autism spectrum disorders over the last several decades has risen at an alarming rate. Factors such as broadened clinical definitions and increased parental age only partially account for this precipitous increase, suggesting that recent changes in environmental factors may also be responsible. One such factor could be the dramatic decrease in consumption of anti-inflammatory dietary omega-3 (n-3) polyunsaturated fatty acids (PUFAs) relative to the amount of pro-inflammatory omega-6 (n-6) PUFAs and saturated fats in the Western diet. Docosahexaenoic acid (DHA) is the principle n-3 PUFA found in neural tissue and is important for optimal brain development, especially during late gestation when DHA rapidly and preferentially accumulates in the brain. In this study, we tested whether supplementation of a low n-3 PUFA diet with DHA throughout development could improve measures related to autism in a mouse model of maternal immune activation. We found that dietary DHA protected offspring from the deleterious effects of gestational exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid on behavioral measures of autism and subsequent adulthood immune system reactivity. These data suggest that elevated dietary levels of DHA, especially during pregnancy and nursing, may help protect normal neurodevelopment from the potentially adverse consequences of environmental insults like maternal infection. PMID:26703213

  18. A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution.

    PubMed

    Crawford, Michael A; Broadhurst, C Leigh; Guest, Martin; Nagar, Atulya; Wang, Yiqun; Ghebremeskel, Kebreab; Schmidt, Walter F

    2013-01-01

    Six hundred million years ago, the fossil record displays the sudden appearance of intracellular detail and the 32 phyla. The "Cambrian Explosion" marks the onset of dominant aerobic life. Fossil intracellular structures are so similar to extant organisms that they were likely made with similar membrane lipids and proteins, which together provided for organisation and specialisation. While amino acids could be synthesised over 4 billion years ago, only oxidative metabolism allows for the synthesis of highly unsaturated fatty acids, thus producing novel lipid molecular species for specialised cell membranes. Docosahexaenoic acid (DHA) provided the core for the development of the photoreceptor, and conversion of photons into electricity stimulated the evolution of the nervous system and brain. Since then, DHA has been conserved as the principle acyl component of photoreceptor synaptic and neuronal signalling membranes in the cephalopods, fish, amphibian, reptiles, birds, mammals and humans. This extreme conservation in electrical signalling membranes despite great genomic change suggests it was DHA dictating to DNA rather than the generally accepted other way around. We offer a theoretical explanation based on the quantum mechanical properties of DHA for such extreme conservation. The unique molecular structure of DHA allows for quantum transfer and communication of π-electrons, which explains the precise depolarisation of retinal membranes and the cohesive, organised neural signalling which characterises higher intelligence. PMID:23206328

  19. Age-related changes in retinoic, docosahexaenoic and arachidonic acid modulation in nuclear lipid metabolism.

    PubMed

    Gaveglio, Virginia L; Pascual, Ana C; Giusto, Norma M; Pasquaré, Susana J

    2016-08-15

    The aim of this work was to study how age-related changes could modify several enzymatic activities that regulate lipid mediator levels in nuclei from rat cerebellum and how these changes are modulated by all-trans retinoic acid (RA), docosahexaenoic acid (DHA) and arachidonic acid (AA). The higher phosphatidate phosphohydrolase activity and lower diacylglycerol lipase (DAGL) activity observed in aged animals compared with adults could augment diacylglycerol (DAG) availability in the former. Additionally, monoacylglycerol (MAG) availability could be high due to an increase in lysophosphatidate phosphohydrolase (LPAPase) activity and a decrease in monocylglycerol lipase activity. Interestingly, RA, DHA and AA were observed to modulate these enzymatic activities and this modulation was found to change in aged rats. In adult nuclei, whereas RA led to high DAG and MAG production through inhibition of their hydrolytic enzymes, DHA and AA promoted high MAG production by LPAPase and DAGL stimulation. In contrast, in aged nuclei RA caused high MAG generation whereas DHA and AA diminished it through LPAPase activity modulation. These results demonstrate that aging promotes a different nuclear lipid metabolism as well as a different type of non-genomic regulation by RA, DHA and AA, which could be involved in nuclear signaling events. PMID:27355428

  20. High levels of retinal membrane docosahexaenoic acid increase susceptibility to stress-induced degeneration.

    PubMed

    Tanito, Masaki; Brush, Richard S; Elliott, Michael H; Wicker, Lea D; Henry, Kimberly R; Anderson, Robert E

    2009-05-01

    The fat-1 gene cloned from C. elegans encodes an n-3 fatty acid desaturase that converts n-6 to n-3 PUFA. Mice carrying the fat-1 transgene and wild-type controls were fed an n-3-deficient/n-6-enriched diet [fat-1- safflower oil (SFO) and wt-SFO, respectively]. Fatty acid profiles of rod outer segments (ROS), cerebellum, plasma, and liver demonstrated significantly lower n-6/n-3 ratios and higher docosahexaenoic acid (DHA) levels in fat-1-SFO compared with wt-SFO. When mice were exposed to light stress: 1) the outer nuclear layer (ONL) thickness was reduced; 2) amplitudes of the electroretinogram (ERG) were lower; 3) the number of apoptotic photoreceptor cells was greater; and 4) modification of retinal proteins by 4-hydroxyhexenal (4-HHE), an end-product of n-3 PUFA oxidation was increased in both fat-1-SFO and wt mice fed a regular lab chow diet compared with wt-SFO. The results indicate a positive correlation between the level of DHA, the degree of n-3 PUFA lipid peroxidation, and the vulnerability of the retina to photooxidative stress. In mice not exposed to intense light, the reduction in DHA resulted in reduced efficacy in phototransduction gain steps, while no differences in the retinal morphology or retinal biochemistry. These results highlight the dual roles of DHA in cellular physiology and pathology. PMID:19023138

  1. N-acyl amines of docosahexaenoic acid and other n–3 polyunsatured fatty acids – from fishy endocannabinoids to potential leads

    PubMed Central

    Meijerink, Jocelijn; Balvers, Michiel; Witkamp, Renger

    2013-01-01

    N–3 long-chain polyunsaturated fatty acids (n–3 LC-PUFAs), in particular α-linolenic acid (18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) are receiving much attention because of their presumed beneficial health effects. To explain these, a variety of mechanisms have been proposed, but their interactions with the endocannabinoid system have received relatively little attention so far. However, it has already been shown some time ago that consumption of n–3 LC-PUFAs not only affects the synthesis of prototypic endocannabinoids like anandamide but also stimulates the formation of specific n–3 LC-PUFA-derived conjugates with ethanolamine, dopamine, serotonin or other amines. Some of these fatty amides show overlapping biological activities with those of typical endocannabinoids, whereas others possess distinct and sometimes largely unknown receptor affinities and other properties. The ethanolamine and dopamine conjugates of DHA have been the most investigated thus far. These mediators may provide promising new leads to the field of inflammatory and neurological disorders and for other pharmacological applications, including their use as carrier molecules for neurotransmitters to target the brain. Furthermore, combinations of n–3 LC-PUFA-derived fatty acid amides, their precursors and FAAH inhibitors offer possibilities to optimise their effects in health and disease. Linked Articles This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-4 & http://dx.doi.org/10.1111/bph.2012.167.issue-8 PMID:23088259

  2. High contents of both docosahexaenoic and arachidonic acids in milk of women consuming fish from lake Kitangiri (Tanzania): targets for infant formulae close to our ancient diet?

    PubMed

    Kuipers, Remko S; Fokkema, M Rebecca; Smit, Ella N; van der Meulen, Jan; Boersma, E Rudy; Muskiet, Frits A J

    2005-04-01

    Current recommendations for arachidonic (AA) and docosahexaenoic (DHA) acids in infant formulae are based on milk of Western mothers. Validity may be questioned in view of the profound dietary changes in the past 100 years, as opposed to our slowly adapting genome. Hominin evolution occurred in the proximity of East-African freshwater lakes and rivers and early homo sapiens had higher intakes of AA and DHA from a predominantly lacustrine-based diet. In search of milk AA and DHA contents of our African ancestors, we investigated the milk of 29 lactating women living in Doromoni near lake Kitangiri (Tanzania). They consumed sunflower oil-fried local fish as only animal lipid sources, maize and local vegetables. AA and DHA contents of Doromoni milk may be close to that of early homo sapiens, because of the similarity of their life-long consumption of East-African lacustrine-based foods. Human milk fatty acid relationships from our historical worldwide database and the literature revealed that disparities between the Doromoni diet and the presumed ancient diet (i.e. higher carbohydrate and linoleic acid intakes) are unlikely to affect milk AA and DHA contents. Doromoni milk had high contents of AA (median 0.70 mol%), DHA (0.75) and eicosapentaenoic acid (EPA, 0.17), and low AA/DHA ratios (median 0.91; 0.55-2.61). This tracks down to consumption of fish with high AA and DHA contents, and AA/EPA ratios. We conclude that the milk AA, DHA and EPA contents of Doromoni women might provide us with clues to optimize infant formulae and perhaps the milk of Western women. PMID:15763440

  3. Docosahexaenoic Acid Induces Oxidative DNA Damage and Apoptosis, and Enhances the Chemosensitivity of Cancer Cells

    PubMed Central

    Song, Eun Ah; Kim, Hyeyoung

    2016-01-01

    The human diet contains low amounts of ω-3 polyunsaturated fatty acids (PUFAs) and high amounts of ω-6 PUFAs, which has been reported to contribute to the incidence of cancer. Epidemiological studies have shown that a high consumption of fish oil or ω-3 PUFAs reduced the risk of colon, pancreatic, and endometrial cancers. The ω-3 PUFA, docosahexaenoic acid (DHA), shows anticancer activity by inducing apoptosis of some human cancer cells without toxicity against normal cells. DHA induces oxidative stress and oxidative DNA adduct formation by depleting intracellular glutathione (GSH) and decreasing the mitochondrial function of cancer cells. Oxidative DNA damage and DNA strand breaks activate DNA damage responses to repair the damaged DNA. However, excessive DNA damage beyond the capacity of the DNA repair processes may initiate apoptotic signaling pathways and cell cycle arrest in cancer cells. DHA shows a variable inhibitory effect on cancer cell growth depending on the cells’ molecular properties and degree of malignancy. It has been shown to affect DNA repair processes including DNA-dependent protein kinases and mismatch repair in cancer cells. Moreover, DHA enhanced the efficacy of anticancer drugs by increasing drug uptake and suppressing survival pathways in cancer cells. In this review, DHA-induced oxidative DNA damage, apoptotic signaling, and enhancement of chemosensitivity in cancer cells will be discussed based on recent studies. PMID:27527148

  4. Docosahexaenoic acid modulates inflammatory and antineurogenic functions of activated microglial cells.

    PubMed

    Antonietta Ajmone-Cat, Maria; Lavinia Salvatori, Maria; De Simone, Roberta; Mancini, Melissa; Biagioni, Stefano; Bernardo, Antonietta; Cacci, Emanuele; Minghetti, Luisa

    2012-03-01

    The complex process of microglial activation encompasses several functional activation states associated either with neurotoxic/antineurogenic or with neurotrophic/proneurogenic properties, depending mainly on the extent of activation and the nature of the activating stimuli. Several studies have demonstrated that acute exposure to the prototypical activating agent lipopolysaccharide (LPS) confers antineurogenic properties upon microglial cells. Acutely activated microglia ortheir conditioned media (CM) reduce neural stem progenitor cell (NPC) survival and prevent NPC differentiation into neurons. The present study tested the hypothesis that docosahexaenoic acid (DHA), a long-chain polyunsatured fatty acid (L-PUFA) with potent immunomodulatory properties, could dampen microglial proinflammatory functions and modulate their antineurogenic effect. We demonstrate that DHA dose dependently inhibits the synthesis of inflammatory products in activated microglia without inducing an alternative antiinflammatory phenotype. Among the possible DHA mechanisms of action, we propose the inhibition of p38 MAPK phosphorylation and the activation of the nuclear receptor peroxisome proliferator activated receptor (PPAR)-γ. The attenuation of M1 proinflammatory phenotype has relevant consequences for the survival and differentiation of NPC, because DHA reverses the antineurogenic activities of conditioned media from LPS-activated microglia. Our study identifies new relevant potentially protective and proneurogenic functions of DHA, exerted through the modulation of microglial functions, that could be exploited to sustain or promote neuroregenerative processes in damaged/aged brain. PMID:22057807

  5. Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain

    PubMed Central

    Chen, Chuck T.; Kitson, Alex P.; Hopperton, Kathryn E.; Domenichiello, Anthony F.; Trépanier, Marc-Olivier; Lin, Lauren E.; Ermini, Leonardo; Post, Martin; Thies, Frank; Bazinet, Richard P.

    2015-01-01

    Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool as well as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. Furthermore, upon acute iv administration, although more radiolabeled lysophosphatidylcholine (LPC)-DHA enters the brain than NEFA-DHA, this is due to the longer plasma half-life and exposure to the brain. Direct comparison of the uptake rate of LPC-DHA and NEFA-DHA demonstrates that uptake of NEFA-DHA into the brain is 10-fold greater than LPC-DHA. In conclusion, plasma NEFA-DHA is the major plasma pool supplying the brain. PMID:26511533

  6. Docosahexaenoic Acid Induces Oxidative DNA Damage and Apoptosis, and Enhances the Chemosensitivity of Cancer Cells.

    PubMed

    Song, Eun Ah; Kim, Hyeyoung

    2016-01-01

    The human diet contains low amounts of ω-3 polyunsaturated fatty acids (PUFAs) and high amounts of ω-6 PUFAs, which has been reported to contribute to the incidence of cancer. Epidemiological studies have shown that a high consumption of fish oil or ω-3 PUFAs reduced the risk of colon, pancreatic, and endometrial cancers. The ω-3 PUFA, docosahexaenoic acid (DHA), shows anticancer activity by inducing apoptosis of some human cancer cells without toxicity against normal cells. DHA induces oxidative stress and oxidative DNA adduct formation by depleting intracellular glutathione (GSH) and decreasing the mitochondrial function of cancer cells. Oxidative DNA damage and DNA strand breaks activate DNA damage responses to repair the damaged DNA. However, excessive DNA damage beyond the capacity of the DNA repair processes may initiate apoptotic signaling pathways and cell cycle arrest in cancer cells. DHA shows a variable inhibitory effect on cancer cell growth depending on the cells' molecular properties and degree of malignancy. It has been shown to affect DNA repair processes including DNA-dependent protein kinases and mismatch repair in cancer cells. Moreover, DHA enhanced the efficacy of anticancer drugs by increasing drug uptake and suppressing survival pathways in cancer cells. In this review, DHA-induced oxidative DNA damage, apoptotic signaling, and enhancement of chemosensitivity in cancer cells will be discussed based on recent studies. PMID:27527148

  7. Docosahexaenoic acid conjugated near infrared flourescence probe for in vivo early tumor diagnosis

    NASA Astrophysics Data System (ADS)

    Li, Siwen; Cao, Jie; Qin, Jingyi; Zhang, Xin; Achilefu, Samuel; Qian, Zhiyu; Gu, Yueqing

    2013-02-01

    Docosahexaenoic acid(DHA) is an omega-3 C22 natural fatty acid with six cis double bonds and as a constituent of membranes used as a precursor for metabolic and biochemical path ways. In this manuscript,we describe the synthesis of near-infrared(NIR) flourescence ICG-Der-01 labeled DHA for in vitro and vivo tumor targeting.The structure of the probe was intensively characterized by UV and MS. The in vitro and vivo tumor targeting abilities of the DHA-based NIR probes were investigeted in MCF-7 cells and MCF-7 xenograft mice model differently by confocal microscopy and CCD camera. The cell cytotoxicity were tested in tumor cells MCF-7 .The results shows that the DHA-based NIR probes have high affinity with the tumor both in vitro and vivo.In addition ,we also found that the DHA-based NIR probes have the apparent cytotoxicity on MCF-7 cells .which demonstrated that DHA was conjugated with other antitumor drug could increase the abilities of antirumor efficacy .So DHA-ICG-Der-01 is a promising optical agent for diagnosis of tumors especially in their early stage.

  8. Docosahexaenoic acid triglyceride-based microemulsions with an added dendrimer - Structural considerations.

    PubMed

    Lidich, Nina; Francesca Ottaviani, M; Hoffman, Roy E; Aserin, Abraham; Garti, Nissim

    2016-12-01

    Omega fatty acids, mainly the triglyceride of docosahexaenoic acid (TG-DHA), are considered important nutraceuticals. These compounds are water-insoluble and their transport across membranes depends on their carriers. Dendrimers are known as drug carriers across cell membranes and also as permeation enhancers. The solubilization of TG-DHA and dendrimer into a microemulsion (ME) system serving as a carrier could be used for a targeted delivery in the future. The interactions between TG-DHA and second generation poly(propyleneimine) dendrimers (PPI-G2) and their effect on structural transitions of ME were explored along the water dilution line using electron paramagnetic resonance and pulsed-gradient spin-echo NMR along with other analytical techniques. The microviscosity, order parameter, and micropolarity of all studied systems decrease upon water dilution. Incorporation of TG-DHA reduces the microviscosity, order, and micropolarity, whereas PPI-G2 leads to an increase in these parameters. The effect of PPI-G2 is more pronounced at relative high contents (1 and 5wt%) where PPI-G2 interacts with the hydrophilic headgroups of the surfactants. In the macroscale, the effects of TG-DHA and PPI-G2 differ mostly in the bicontinuous region, where macroviscosity increases upon TG-DHA incorporation and decreases upon solubilization of 5wt% PPI-G2. From DSC measurements it was concluded that in the presence of TG-DHA the PPI-G2 is intercalated easily at the interface. PMID:27571688

  9. Thrombin-activated human platelets acutely generate oxidized docosahexaenoic-acid-containing phospholipids via 12-lipoxygenase.

    PubMed

    Morgan, Lloyd T; Thomas, Christopher P; Kühn, Hartmut; O'Donnell, Valerie B

    2010-10-01

    Arachidonate-containing oxidized phospholipids are acutely generated by 12-LOX (12-lipoxygenase) in agonist-activated platelets. In the present study, formation of structurally related lipids by oxidation of DHA (docosahexaenoic acid)-containing phospholipids is demonstrated using lipidomic approaches. Precursor scanning reverse-phase LC (liquid chromatography)-MS/MS (tandem MS) identified a new family of lipids that comprise phospholipid-esterified HDOHE (hydroxydocosahexaenoic acid). Two diacyl and two plasmalogen PEs (phosphatidylethanolamines) containing predominantly the 14-HDOHE positional isomer (18:0p/14-HDOHE-PE, 18:0a/14-HDOHE-PE, 16:0a/14-HDOHE-PE and 16:0p/14-HDOHE-PE) were structurally characterized using MS/MS and by comparison with biogenic standards. An involvement of 12-LOX was indicated as purified recombinant human 12-LOX also generated the 14-HDOHE isomer from DHA. Pharmacological studies using inhibitors and recombinant platelet 12-LOX indicate that they form via esterification of newly formed non-esterified HDOHE. HDOHE-PEs formed at significant rates (2-4 ng/4×10(7) cells) within 2-180 min of thrombin stimulation, and their formation was blocked by calcium chelation. In summary, a new family of oxidized phospholipid was identified in thrombin-activated human platelets. PMID:20653566

  10. Docosahexaenoic Acid Supplementation Early in Pregnancy May Prevent Deep Placentation Disorders

    PubMed Central

    Carvajal, Jorge A.

    2014-01-01

    Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction). Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called “deep placentation disorders”; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids) rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA) supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction. PMID:25019084

  11. Low-density lipoprotein-mediated delivery of docosahexaenoic acid selectively kills murine liver cancer cells

    PubMed Central

    Reynolds, Lacy; Mulik, Rohit S.; Wen, Xiaodong; Dilip, Archana; Corbin, Ian R.

    2014-01-01

    Aim The natural omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), has recently been credited for possessing anticancer properties. Herein, we investigate the cytotoxic actions of DHA-loaded low-density lipoprotein (LDL) nanoparticles in normal and liver cancer cells. Materials & methods LDL-DHA nanoparticles were prepared and subjected to extensive biophysical characterization. The therapeutic utility of LDL-DHA nanoparticles was evaluated in normal and malignant murine hepatocyte cell lines, TIB-73 and TIB-75, respectively. Results & discussion The engineered LDL-DHA nanoparticles possessed enhanced physical and oxidative stabilities over native LDL and free DHA. Dose–response studies showed that therapeutic doses of LDL-DHA nanoparticles that completely killed TIB-75 were innocuous to TIB-73. The selective induction of lipid peroxidation and reactive oxygen species in the cancer cells was shown to play a central role in LDL-DHA nanoparticle-mediated cytotoxicity. Conclusion In summary, these findings indicate that LDL-DHA nanoparticles show great promise as a selective anticancer agent against hepatocellular carcinoma. PMID:24397600

  12. Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival

    PubMed Central

    Rice, Dennis S.; Calandria, Jorgelina M.; Gordon, William C.; Jun, Bokkyoo; Zhou, Yongdong; Gelfman, Claire M.; Li, Songhua; Jin, Minghao; Knott, Eric J.; Chang, Bo; Abuin, Alex; Issa, Tawfik; Potter, David; Platt, Kenneth A.; Bazan, Nicolas G.

    2015-01-01

    The identification of pathways necessary for photoreceptor and retinal pigment epithelium (RPE) function is critical to uncover therapies for blindness. Here we report the discovery of adiponectin receptor 1 (AdipoR1) as a regulator of these cells’ functions. Docosahexaenoic acid (DHA) is avidly retained in photoreceptors, while mechanisms controlling DHA uptake and retention are unknown. Thus, we demonstrate that AdipoR1 ablation results in DHA reduction. In situ hybridization reveals photoreceptor and RPE cell AdipoR1 expression, blunted in AdipoR1−/− mice. We also find decreased photoreceptor-specific phosphatidylcholine containing very long-chain polyunsaturated fatty acids and severely attenuated electroretinograms. These changes precede progressive photoreceptor degeneration in AdipoR1−/− mice. RPE-rich eyecup cultures from AdipoR1−/− reveal impaired DHA uptake. AdipoR1 overexpression in RPE cells enhances DHA uptake, whereas AdipoR1 silencing has the opposite effect. These results establish AdipoR1 as a regulatory switch of DHA uptake, retention, conservation and elongation in photoreceptors and RPE, thus preserving photoreceptor cell integrity. PMID:25736573

  13. Dietary docosahexaenoic acid supplementation reduces SERCA Ca2+ transport efficiency in rat skeletal muscle.

    PubMed

    Fajardo, Val Andrew; Bombardier, Eric; Irvine, Thomas; Metherel, Adam H; Stark, Ken D; Duhamel, Todd; Rush, James W E; Green, Howard J; Tupling, A Russell

    2015-04-01

    Docosahexaenoic acid (DHA) can reduce the efficiency and increase the energy consumption of Na(+)/K(+)-ATPase pump and mitochondrial electron transport chain by promoting Na(+) and H(+) membrane permeability, respectively. In skeletal muscle, the sarco(endo) plasmic reticulum Ca(2+)-ATPase (SERCA) pumps are major contributors to resting metabolic rate. Whether DHA can affect SERCA efficiency remains unknown. Here, we examined the hypothesis that dietary supplementation with DHA would reduce Ca(2+) transport efficiency of the SERCA pumps in skeletal muscle. Total lipids were extracted from enriched sarcoplasmic reticulum (SR) membranes that were isolated from red vastus lateralis skeletal muscles of rats that were either fed a standard chow diet supplemented with soybean oil or supplemented with DHA for 8 weeks. The fatty acid composition of total SR membrane lipids and the major phospholipid species were determined using electrospray ionization mass spectrometry (ESI-MS). After 8 weeks of DHA supplementation, total SR DHA content was significantly elevated (control, 4.1 ± 1.0% vs. DHA, 9.9 ± 1.7%; weight percent of total fatty acids) while total arachidonic acid was reduced (control, 13.5 ± 0.4% vs. DHA-fed, 9.4 ± 0.2). Similar changes in these fatty acids were observed in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol, altogether indicating successful incorporation of DHA into the SR membranes post-diet. As hypothesized, DHA supplementation reduced SERCA Ca(2+) transport efficiency (control, 0.018 ± 0.0002 vs. DHA-fed, 0.014 ± 0.0009) possibly through enhanced SR Ca(2+) permeability (ionophore ratio: control, 2.8 ± 0.2 vs. DHA-fed, 2.2 ± 0.3). Collectively, our results suggest that DHA may promote skeletal muscle-based metabolism and thermogenesis through its influence on SERCA. PMID:25772907

  14. Efficient production of triacylglycerols rich in docosahexaenoic acid (DHA) by osmo-heterotrophic marine protists.

    PubMed

    Liu, Ying; Tang, Jie; Li, Jingjing; Daroch, Maurycy; Cheng, Jay J

    2014-12-01

    Thraustochytrids have recently emerged as a promising source for docosahexaenoic acid (DHA) production due to their high growth rate and oil content. In this study, two thraustochytrid isolates, Aurantiochytrium sp. PKU#SW7 and Thraustochytriidae sp. PKU#Mn16 were used for DHA production. Following growth parameters were optimized to maximize DHA production: temperature, pH, salinity, and glucose concentration. Both isolates achieved the highest DHA yield at the cultivation temperature of 28 °C, pH 6, 100 % seawater, and 2 % glucose. A DHA yield of 1.395 g/l and 1.426 g/l was achieved under the optimized culture conditions. Further investigation revealed that both isolates possess simple fatty acids profiles with palmitic acid and DHA as their dominant constituents, accounting for ∼79 % of total fatty acids. To date, very few studies have focused on the DHA distribution in various lipid fractions which is an important factor for identifying strains with a potential for industrial DHA production. In the present study, the lipids profiles of each strain both revealed that the majority of DHA was distributed in neutral lipids (NLs), and the DHA distribution in NLs of PKU#SW7 was exclusively in the form of triacylglycerols (TAGs) which suggest that PKU#SW7 could be utilized as an alternative source of DHA for dietary supplements. The fermentation process established for both strains also indicating that Aurantiochytrium sp. PKU#SW7 was more suitable for cultivation in fermenter. In addition, the high percentage of saturated fatty acids produced by the two thraustochytrids indicates their potential application in biodiesel production. Overall, our findings suggest that two thraustochytrid isolates are suitable candidates for biotechnological applications. PMID:25186147

  15. Production of lipids containing high levels of docosahexaenoic acid from empty palm fruit bunches by Aurantiochytrium sp. KRS101.

    PubMed

    Hong, Won-Kyung; Yu, Anna; Heo, Sun-Yeon; Oh, Baek-Rock; Kim, Chul Ho; Sohn, Jung-Hoon; Yang, Ji-Won; Kondo, Akihiko; Seo, Jeong-Woo

    2013-07-01

    The oleaginous microalga Aurantiochytrium sp. KRS101 was cultivated in enzymatic hydrolysates of alkali-pretreated empty palm fruit bunches (EFBs), without prior detoxification process. The maximal levels of lipid and docosahexaenoic acid synthesized were 12.5 and 5.4 g L⁻¹ after cultivation for 36 h. Similar lipid levels were also obtained via simultaneous saccharification and cultivation. The results suggested that EFB is a promising source for production of useful lipids by the microalgal strain. PMID:23053417

  16. Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations.

    PubMed

    Guesnet, Philippe; Alessandri, Jean-Marc

    2011-01-01

    The accretion of docosahexaenoic acid (DHA) in membranes of the central nervous system is required for the optimum development of retina and brain functions. DHA status is determined by the dietary intake of n-3 polyunsaturated fatty acids (PUFA), both the metabolic precursor α-linolenic acid (α-LNA) and DHA. Clinical studies have shown that feeding term or premature infants with formula low in total n-3 PUFA may alter the maturation of visual acuity. Moreover, feeding infants over the first 6 mon of life with formula containing adequate α-LNA, but no DHA, did not sustain the same cerebral accretion of DHA as that of breast-fed infants. Whether lower DHA accretion in brain of formula-fed term infants impairs neurophysiological performances is not clearly established. Contradictory data have been published, possibly owing to confounding factors such as maternal intakes and/or genetic variations in PUFA metabolism. Nevertheless, a large corpus of data is in favor of the recommendation of regular dietary intakes of DHA (during at least the first 6 mon of life) and suggest that DHA should be added in formulas at the level generally found in human milk (0.2-0.3 wt% of total fatty acids). The maternal intake of n-3 PUFA during pregnancy and lactation is also crucial, since the n-3 PUFA are provided during perinatal development through placental transfer and maternal milk, which determines the DHA status of the newborn and consequently impacts on post-natal development of brain and visual functions. Whether more clinical studies are needed to control and improve the impact of DHA maternal intakes on the progeny's neurodevelopment, several commissions recommended by precaution that DHA average intake for pregnant and lactating women should be of 200-300 mg/day. PMID:20478353

  17. Screening and characterization of Isochrysis strains and optimization of culture conditions for docosahexaenoic acid production.

    PubMed

    Liu, Jin; Sommerfeld, Milton; Hu, Qiang

    2013-06-01

    Isochrysis is a genus of marine unicellular microalgae that produces docosahexaenoic acid (DHA, C22:6), a very long chain polyunsaturated fatty acid (PUFA) of significant health and nutritional value. Mass cultivation of Isochrysis for DHA production for human consumption has not been established due to disappointing low DHA productivity obtained from commonly used Isochrysis strains. In this study, 19 natural Isochrysis strains were screened for DHA yields and the results showed that the cellular DHA content ranged from 6.8 to 17.0 % of total fatty acids with the highest DHA content occurring in the exponential growth phase. Isochrysis galbana #153180 exhibited the greatest DHA production potential and was selected for further investigation. The effects of different light intensities, forms, and concentrations of nitrogen, phosphorus, and salinity on growth and DHA production of I. galbana #153180 were studied in a bubble column photobioreactor (PBR). Under favorable culture conditions, I. galbana #153180 contained DHA up to 17.5 % of total fatty acids or 1.7 % of cell dry weight. I. galbana #153180 was further tested in outdoor flat-plate PBRs varying in light path length, starting cell density (SCD), and culture mode (batch versus semicontinuous). When optimized, record high biomass and DHA productivity of I. galbana #153180 of 0.72 g L(-1) day(-1) and 13.6 mg L(-1) day(-1), or 26.4 g m(-2) day(-1) and 547.7 mg m(-2) day(-1), respectively, were obtained, suggesting that I. galbana #153180 may be a desirable strain for commercial production of DHA. PMID:23423326

  18. Effect of docosahexaenoic acid and sardine oil diets on the ultrastructure of hepatocytes in adult mice.

    PubMed

    Tamura, M; Suzuki, H

    1995-08-01

    The influence of docosahexaenoic acid (DHA) on the ultrastructure of hepatocytes was studied. Adult male mice of Crj:CD-1 (ICR) strain were fed a fat-free purified diet supplemented with 5% (by weight) of purified DHA, refined sardine oil, and palm oil. The mice were fed the DHA diet or the palm oil diet for 7 days, and the sardine oil diet or the palm oil diet for one month. There were significant ultrastructural changes in the hepatocytes between the mice fed palm oil diet and the animals fed DHA and sardine oil diets. Many lipid droplets in the tissues of mice fed the palm oil diet were observed. Few lipid droplets were contained in the hepatocytes from the mice fed DHA and sardine oil diets, but electron-dense bodies were found in their tissues. These electron-dense bodies were mainly found near the region of the nucleus, blood sinusoids and bile canaliculi. These results suggest that the dense bodies found in the DHA and sardine oil diet groups may appear as a result of acceleration of lipid metabolism in the liver of mice. PMID:8676220

  19. Does docosahexaenoic acid supplementation in term infants enhance neurocognitive functioning in infancy?

    PubMed Central

    Heaton, Alexandra E.; Meldrum, Suzanne J.; Foster, Jonathan K.; Prescott, Susan L.; Simmer, Karen

    2013-01-01

    The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive functioning in term infants is controversial. Theoretical evidence, laboratory research and human epidemiological studies have convincingly demonstrated that DHA deficiency can negatively impact neurocognitive development. However, the results from randomized controlled trials (RCTs) of DHA supplementation in human term-born infants have been inconsistent. This article will (i) discuss the role of DHA in the human diet, (ii) explore the physiological mechanisms by which DHA plausibly influences neurocognitive capacity, and (iii) seek to characterize the optimal intake of DHA during infancy for neurocognitive functioning, based on existing research that has been undertaken in developed countries (specifically, within Australia). The major observational studies and RCTs that have examined dietary DHA in human infants and animals are presented, and we consider suggestions that DHA requirements vary across individuals according to genetic profile. It is important that the current evidence concerning DHA supplementation is carefully evaluated so that appropriate recommendations can be made and future directions of research can be strategically planned. PMID:24312040

  20. Development of a stepwise aeration control strategy for efficient docosahexaenoic acid production by Schizochytrium sp.

    PubMed

    Ren, Lu-Jing; Ji, Xiao-Jun; Huang, He; Qu, Liang; Feng, Yun; Tong, Qian-Qian; Ouyang, Ping-Kai

    2010-08-01

    The effect of aeration on the performance of docosahexaenoic acid (DHA) production by Schizochytrium sp. was investigated in a 1,500-L bioreactor using fed-batch fermentation. Six parameters, including specific growth rate, specific glucose consumption rate, specific lipid accumulation rate, cell yield coefficient, lipid yield coefficient, and DHA yield coefficient, were used to understand the relationship between aeration and the fermentation characteristics. Based on the information obtained from the parameters, a stepwise aeration control strategy was proposed. The aeration rate was controlled at 0.4 volume of air per volume of liquid per minute (vvm) for the first 24 h, then shifted to 0.6 vvm until 96 h, and then switched back to 0.4 vvm until the end of the fermentation. High cell density (71 g/L), high lipid content (35.75 g/L), and high DHA percentage (48.95%) were achieved by using this strategy, and DHA productivity reached 119 mg/L h, which was 11.21% over the best results obtained by constant aeration rate. PMID:20445973

  1. Curcumin and docosahexaenoic acid block insulin-induced colon carcinoma cell proliferation.

    PubMed

    Fenton, Jenifer I; McCaskey, Sarah J

    2013-03-01

    Diets high in fish and curcumin are associated with a decreased risk of CRC. Insulin resistance and obesity are associated with increased CRC risk and higher reoccurrence rates. We utilized cell culture to determine if dietary compounds could reduce insulin-induced cell proliferation comparing the response in normal and metastatic colon epithelial cells. We treated model normal murine colon epithelial cells (YAMC) and adenocarcinoma cells (MC38) with docosahexaenoic acid (DHA) or curcumin alone and then co-treatments of the diet-derived compound and insulin were combined. Cell proliferation was stimulated with insulin (1 ug/mL) to model insulin resistance in obesity. Despite the presence of insulin, proliferation was reduced in the MC38 cells treated with 10 μM curcumin (p<0.001) and 50 μM DHA (p<0.001). Insulin stimulated MAPK and MEK phosphorylation was inhibited by DHA and curcumin in MC38 cancer cells. Here we show that curcumin and DHA can block insulin-induced colon cancer cell proliferation in vitro via a MEK mediated mechanism. PMID:23266210

  2. CFD investigation of Schizochytrium sp. impeller configurations on cell growth and docosahexaenoic acid synthesis.

    PubMed

    Zhao, Xiaoyan; Ren, Lujing; Guo, Dongsheng; Wu, Wenjia; Ji, Xiaojun; Huang, He

    2016-08-01

    Effects of impeller configurations on docosahexaenoic acid production and flow characteristics were investigated by Schizochytrium sp. in a 15 L bioreactor. 6-straight blade disc turbine (6-SBDT), 6-arrowy-blade disc turbine (6-ABDT) and down-pumping propeller (DPP) were combined to form different impeller configurations. Simulated results showed that configuration SSA consisting of upper two 6-SBDT and one bottom 6-ABDT possessed the worst oxygen supply capacity. But it obtained the highest DHA percentage of 48.17 % and DHA yield of 21.42 g/L, indicating that it was beneficial for DHA synthesis and converting glucose to biomass and lipids. Configuration SAS consisting of one middle 6-ABDT and two 6-SBDT provided better mixing capacity, which resulted in the maximum glucose consumption rate of 2.86 g/L h and the highest biomass of 108.09 g/L. This study would improve insight into understanding the relationship between flow field and the physiology of Schizochytrium sp. for the scale-up of industrial DHA production. PMID:27102911

  3. Adaptive evolution of Schizochytrium sp. by continuous high oxygen stimulations to enhance docosahexaenoic acid synthesis.

    PubMed

    Sun, Xiao-Man; Ren, Lu-Jing; Ji, Xiao-Jun; Chen, Sheng-Lan; Guo, Dong-Sheng; Huang, He

    2016-07-01

    Adaptive laboratory evolution (ALE) is an effective method in changing the strain characteristics. Here, ALE with high oxygen as a selection pressure was applied to improve the production capacity of Schizochytrium sp. Results showed that cell dry weight (CDW) of endpoint strain was 32.4% higher than that of starting strain. But slight lipid accumulation impairment was observed. These major performance changes were accompanied with enhanced isocitrate dehydrogenase enzyme activity and reduced ATP:citrate lyase enzyme activity. And a serious decrease of 62.6% in SDHA 140rpm→170rpm was observed in the endpoint strain. To further study the docosahexaenoic acid (DHA) production ability of evolved strain, fed-batch strategy was applied and 84.34g/L of cell dry weight and 26.40g/L of DHA yield were observed. In addition, endpoint strain produced greatly less squalene than starting strain. This work demonstrated that ALE may be a promising tool in modifying microalga strains. PMID:27030957

  4. Intranasal microemulsion for targeted nose to brain delivery in neurocysticercosis: Role of docosahexaenoic acid.

    PubMed

    Shinde, Rajshree L; Bharkad, Gopal P; Devarajan, Padma V

    2015-10-01

    Intranasal Microemulsions (MEs) for nose to brain delivery of a novel combination of Albendazole sulfoxide (ABZ-SO) and Curcumin (CUR) for Neurocysticercosis (NCC), a brain infection are reported. MEs prepared by simple solution exhibited a globule size <20nm, negative zeta potential and good stability. The docosahexaenoic acid (DHA) ME revealed high and rapid ex vivo permeation of drugs through sheep nasal mucosa. Intranasal DHA ME resulted in high brain concentrations and 10.76 (ABZ-SO) and 3.24 (CUR) fold enhancement in brain area-under-the-curve (AUC) compared to intravenous DHA MEs at the same dose. Direct nose to brain transport (DTP) of >95% was seen for both drugs. High drug targeting efficiency (DTE) to the brain compared to Capmul ME and drug solution (P<0.05) suggested the role of DHA in aiding nose to brain delivery. Histopathology study confirmed no significant changes. High efficacy of ABZ-SO: CUR (100:10ng/mL) DHA ME in vitro on Taenia solium cysts was confirmed by complete ALP inhibition and disintegration of cysts at 96h. Considering that the brain concentration at 24h was 1400±160.1ng/g (ABZ-SO) and 120±35.2ng/g (CUR), the in vitro efficacy seen at a 10 fold lower concentration of the drugs strongly supports the assumption of clinical efficacy. The intranasal DHA ME is a promising delivery system for targeted nose to brain delivery. PMID:26318978

  5. Effects of culture conditions on growth and docosahexaenoic acid production from Schizochytrium limacinum

    NASA Astrophysics Data System (ADS)

    Zhu, Luying; Zhang, Xuecheng; Ren, Xueying; Zhu, Qinghua

    2008-02-01

    The effects of temperature, initial pH, salinity of culture medium, and carbon and nitrogen sources on growth and docosahexaenoic acid (C22: 6 n-3, DHA) production from Schizochytrium limacinum OUC88 were investigated in the present study. The results revealed that the optimal temperature, initial pH and salinity level of the medium for DHA production were 23°C, 7.0 and 18, respectively. Glucose was proved the best carbon source for the growth and DHA production from S. limacinum. Among the nitrogen sources tested, soybean cake hydrolysate, a cheap by-product, was found to be effective for the accumulation of DHA in S. limacinum cells. In addition, increasing the concentration of carbon sources in the medium caused a significant increase in cell biomass; however, accumulation of DHA in cells was mainly stimulated by the ratio of C/N in the medium. Under the optimal culture conditions, the maximum DHA yield achieved in flasks was 4.08 g L-1 after 5 d of cultivation.

  6. Preoperative serum docosahexaenoic acid level predicts prognosis of renal cell carcinoma

    PubMed Central

    TASAKI, SHINSUKE; HORIGUCHI, AKIO; ASANO, TAKAKO; KURODA, KENJI; SATO, AKINORI; ASAKUMA, JUNICHI; ITO, KEIICHI; ASANO, TOMOHIKO; ASAKURA, HIROTAKA

    2016-01-01

    The recent discovery and clinical development of targeted agents have expanded treatment options in metastatic renal cell carcinoma (RCC). However, metastatic RCC remains a lethal disease. Complete response is rare and treatment with targeted agents eventually fails in the majority of the patients. Therefore, there is a need for developing a prognostic tool and a novel therapeutic agent for RCC to improve the follow-up strategy after surgical treatment. Clinical data, including patient characteristics, serum fatty acid profile, clinicopathological parameters and clinical outcome, were obtained from 112 patients with RCC prior to surgical treatment. Preoperative fatty acid levels were grouped according to patient characteristics, such as performance status, body mass index or pathological parameters, and were analyzed using the Mann-Whitney U test. Cancer-specific survival in the high and low docosahexaenoic acid (DHA) level groups were compared using the Kaplan-Meier method. Cox proportional hazards models were applied to determine the independent prognostic factors associated with shortened cancer-specific survival. The serum DHA level in patients with metastasis was significantly lower compared with that in patients without metastasis (P=0.047). Low serum DHA level, presence of metastasis and cachexia were independent predictors of shortened cancer-specific survival in a multivariate Cox proportional hazard model (P=0.033, hazard ratio = 4.43). Patients with a serum DHA level below the median value exhibited significantly shorter cancer-specific survival compared with those with a higher serum DHA level (P=0.008). Thus, according to our results, the preoperative serum DHA level may be able to predict the surgical outcome of RCC. However, this finding requires validation by large-scale prospective studies. PMID:27330769

  7. Docosahexaenoic Acid Ameliorates Fructose-Induced Hepatic Steatosis Involving ER Stress Response in Primary Mouse Hepatocytes

    PubMed Central

    Zheng, Jinying; Peng, Chuan; Ai, Yanbiao; Wang, Heng; Xiao, Xiaoqiu; Li, Jibin

    2016-01-01

    The increase in fructose consumption is considered to be a risk factor for developing nonalcoholic fatty liver disease (NAFLD). We investigated the effects of docosahexaenoic acid (DHA) on hepatic lipid metabolism in fructose-treated primary mouse hepatocytes, and the changes of Endoplasmic reticulum (ER) stress pathways in response to DHA treatment. The hepatocytes were treated with fructose, DHA, fructose plus DHA, tunicamycin (TM) or fructose plus 4-phenylbutyric acid (PBA) for 24 h. Intracellular triglyceride (TG) accumulation was assessed by Oil Red O staining. The mRNA expression levels and protein levels related to lipid metabolism and ER stress response were determined by real-time PCR and Western blot. Fructose treatment led to obvious TG accumulation in primary hepatocytes through increasing expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), two key enzymes in hepatic de novo lipogenesis. DHA ameliorates fructose-induced TG accumulation by upregulating the expression of carnitine palmitoyltransferase 1A (CPT-1α) and acyl-CoA oxidase 1 (ACOX1). DHA treatment or pretreatment with the ER stress inhibitor PBA significantly decreased TG accumulation and reduced the expression of glucose-regulated protein 78 (GRP78), total inositol-requiring kinase 1 (IRE1α) and p-IRE1α. The present results suggest that DHA protects against high fructose-induced hepatocellular lipid accumulation. The current findings also suggest that alleviating the ER stress response seems to play a role in the prevention of fructose-induced hepatic steatosis by DHA. PMID:26805874

  8. Effect of docosahexaenoic acid monoacylglyceride on systemic hypertension and cardiovascular dysfunction.

    PubMed

    Morin, Caroline; Rousseau, Eric; Blier, Pierre U; Fortin, Samuel

    2015-07-01

    ω-3 Fatty acid supplementation has been associated with lower blood pressure. Cardiovascular diseases are also known to be linked directly to an increase in ω-6 and a reduction in ω-3 fatty acid levels in blood circulation and tissues. To determine the effect of docosahexaenoic acid monoglycerides (MAG-DHA) on blood pressure, lipid profiles, and vascular remodeling in rats fed a high-fat/high-carbohydrate (HFHC) diet. Studies were performed in male rats subjected to 8 wk of HFHC diet supplemented or not with 3 g/day MAG-DHA. After 8 wk of daily MAG-DHA treatment, rats in the HFHC + MAG-DHA group had lower arterial blood pressure and heart rate compared with the HFHC group. Moreover, MAG-DHA prevented the increase aortic wall thickness, whereas lipid analysis of aortic tissues revealed an increase in DHA/AA ratio correlated with the production of resolvin D2 and D3 metabolites. Histological analysis revealed that MAG-DHA prevented the development of LVH in the HFHC group. Serum lipid profile analysis further showed a decrease in total cholesterol (TC) and LDL, including very low-density lipoprotein (VLDL) and triglyceride (TG) levels, together with an increase in HDL levels after 8 wk of MAG-DHA treatment compared with the HFHC group. Furthermore, daily MAG-DHA treatment resulted in reduced proinflammatory marker levels such as CRP, IL-6, TNFα, and IL-1β. Altogether, these findings revealed that per os administration of MAG-DHA prevents HFHC-diet induced hypertension and LVH in rats. PMID:25910811

  9. Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid.

    PubMed

    Hachem, Mayssa; Géloën, Alain; Van, Amanda Lo; Foumaux, Baptiste; Fenart, Laurence; Gosselet, Fabien; Da Silva, Pedro; Breton, Gildas; Lagarde, Michel; Picq, Madeleine; Bernoud-Hubac, Nathalie

    2016-07-01

    Docosahexaenoic acid (DHA) is the main essential omega-3 fatty acid in brain tissues required for normal brain development and function. An alteration of brain DHA in neurodegenerative diseases such as Alzheimer's and Parkinson's is observed. Targeted intake of DHA to the brain could compensate for these deficiencies. Blood DHA is transported across the blood-brain barrier more efficiently when esterified at the sn-2 position of lyso-phosphatidylcholine. We used a structured phosphatidylcholine to mimic 2-docosahexaenoyl-lysoPC (lysoPC-DHA), named AceDoPC (1-acetyl,2-docosahexaenoyl-glycerophosphocholine), that may be considered as a stabilized form of the physiological lysoPC-DHA and that is neuroprotective in experimental ischemic stroke. The aim of the present study was to investigate whether AceDoPC is a relevant delivery form of DHA to the brain in comparison with other forms of the fatty acid. By combining in vitro and in vivo experiments, our findings report for the first time that AceDoPC is a privileged and specific carrier of DHA to the brain, when compared with DHA-containing PC and non-esterified DHA. We also show that AceDoPC was hydrolyzed, in part, into lysoPC-DHA. Ex vivo autoradiography of rat brain reveals that DHA from AceDoPC was localized in specific brain regions playing key roles in memory, thoughts, and cognitive functions. Finally, using molecular modeling approaches, we demonstrate that electrostatic and lipophilic potentials are distributed very similarly at the surfaces of AceDoPC and lysoPC-DHA. Our findings identify AceDoPC as an efficient way to specifically target DHA to the brain, which would allow potential preventive and therapeutic approaches for neurological diseases. PMID:26041661

  10. Docosahexaenoic acid reverses cyclosporin A-induced changes in membrane structure and function.

    PubMed

    Thakkar, R R; Wang, O L; Zerouga, M; Stillwell, W; Haq, A; Kissling, R; Pierce, W M; Smith, N B; Miller, F N; Ehringer, W D

    2000-04-01

    The use of a fish oil vehicle for cyclosporin A (CsA) can decrease the toxic effects of CsA but the mechanism is unclear. Here we examine the mechanism by which docosahexaenoic acid (DHA), a fish oil-derived polyunsaturated fatty acid, can alter the toxic effects of CsA on mouse organ function, endothelial macromolecular permeability, and membrane bilayer function. Mice given CsA and fish oil showed increased liver toxicity, kidney toxicity, incorporation of DHA, and evidence of oxidized fatty acids compared to control animals. We hypothesized that the toxic effects of CsA were primarily a result of membrane perturbation, which could be decreased if DHA were not oxidized. The presence of CsA (10 mol%) alone increased dipalmitoylphosphatidylcholine membrane permeability by seven fold over control (no CsA, no DHA). However, if non-oxidized DHA (15 mol%) and CsA were added to the membrane, the permeability returned to control levels. Interestingly, if the DHA was oxidized, the antagonistic effect of DHA on CsA was completely lost. While CsA alone increased endothelial permeability to albumin, the combination of non-oxidized DHA and CsA had no effect on endothelial macromolecular permeability. However the combination of oxidized DHA and CsA was no different than the effects of CsA only. CsA increased the fluorescence anisotropy of DPH in the liquid crystalline state of DPPC, while DHA decreased fluorescence anisotropy. However the combination of CsA and DHA was no different than DHA alone. We conclude that non-oxidized DHA can reverse the membrane perturbing effects of CsA, and the increases in endothelial macromolecular permeability, which may explain how fish oil is capable of decreasing the toxicity of CsA. PMID:10742598

  11. Cholesterol versus cholesterol sulfate: effects on properties of phospholipid bilayers containing docosahexaenoic acid.

    PubMed

    Schofield, M; Jenski, L J; Dumaual, A C; Stillwell, W

    1998-09-01

    The important omega-3 fatty acid docosahexaenoic acid (DHA) is present at high concentration in some membranes that also contain the unusual sterol cholesterol sulfate (CS). The association between these lipids and their effect on membrane structure is presented here. Differential scanning calorimetry (DSC), MC540 fluorescence, erythritol permeability, pressure/area isotherms on lipid monolayers and molecular modeling are used to compare the effect of CS and cholesterol on model phospholipid membranes. By DSC, CS decreases the main phase transition temperature and broadens the transitions of dipalmitolyphosphatidylcholine (DPPC), 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (18:0,18:1 PC) and 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0,22:6 PC) to a much larger extent than does cholesterol. In addition CS produces a three-component transition in 18:0,18:1 PC bilayers that is not seen with cholesterol. In a mixed phospholipid bilayer composed of 18:0,18:1 PC/18:0,22:6 PC (1:1, mol/mol), CS at 2.5 membrane mol% or more induces lateral phase separation while cholesterol does not. CS decreases lipid packing density and increases permeability of 18:0,18:1 PC and 18:0,22:6 PC bilayers to a much larger extent than cholesterol. CS disrupts oleic acid-containing bilayers more than those containing DHA. Molecular modeling confirms that the anionic sulfate moiety on CS renders this sterol more polar than cholesterol with the consequence that CS likely resides higher (extends further into the aqueous environment) in the bilayer. CS can therefore be preferentially accommodated into DHA-enriched bilayers where its tetracyclic ring system may fit into the delta 4 pocket of DHA, a location excluded to cholesterol. It is proposed that CS may in part replace the membrane function of cholesterol in DHA-rich membranes. PMID:9807808

  12. EPA'S CATALYST RESEARCH PROGRAM: ENVIRONMENTAL IMPACT OF SULFURIC ACID EMISSIONS

    EPA Science Inventory

    A sulfuric acid review conference sponsored by EPA's automotive Catalyst Research Program was held recently at Hendersonville, NC, for researchers whose work is funded by EPA. Emissions characterization research indicated that in-use catalyst-equipped vehicles emit low levels of ...

  13. Linoleic and docosahexaenoic acids in human milk have opposite relationships with cognitive test performance in a sample of 28 countries.

    PubMed

    Lassek, W D; Gaulin, S J C

    2014-11-01

    Polyunsaturated fatty acids play critical roles in brain development and function, and their levels in human breast milk closely reflect the long-term diet. The fatty acid contents of human milk samples from 28 countries were used to predict averaged 2009 and 2012 test scores in mathematics, reading, and science from the Program for International Student Assessment. All test scores were positively related to milk docosahexaenoic acid (r=0.48 to 0.55), and negatively related to linoleic acid (r=-0.28 to -0.56). Together, these two human milk fatty acids explained 46% to 48% of the variance in scores, with no improvement in predictive power when socioeconomic variables were added to the regression. The (log) ratio of linoleic to arachidonic acid was negatively related to scores (r=-0.45 to -0.48). Statistical effects were similar for the two sexes. In a separate US sample, estimated dietary linoleic was negatively related to the levels of all long-chain n-3 and n-6 plasma fatty acids. High levels of dietary linoleic may impair cognition by decreasing both docosahexaenoic and arachidonic acids in the brain. PMID:25172360

  14. Selective decrease of bis(monoacylglycero)phosphate content in macrophages by high supplementation with docosahexaenoic acid.

    PubMed

    Bouvier, Jérôme; Zemski Berry, Karin A; Hullin-Matsuda, Françoise; Makino, Asami; Michaud, Sabine; Geloën, Alain; Murphy, Robert C; Kobayashi, Toshihide; Lagarde, Michel; Delton-Vandenbroucke, Isabelle

    2009-02-01

    Bis(monoacylglycero)phosphate (BMP) is a unique phospholipid (PL) preferentially found in late endosomal membranes, where it forms specialized lipid domains. Recently, using cultured macrophages treated with anti-BMP antibody, we showed that BMP-rich domains are involved in cholesterol homeostasis. We had previously stressed the high propensity of BMP to accumulate docosahexaenoic acid (DHA), compared with other PUFAs. Because phosphatidylglycerol (PG) was reported as a precursor for BMP synthesis in RAW macrophages, we examined the effects of PG supplementation on both FA composition and amount of BMP in this cell line. Supplementation with dioleoyl-PG (18:1/18:1-PG) induced BMP accumulation, together with an increase of oleate proportion. Supplementation with high concentrations of didocosahexaenoyl-PG (22:6/22:6-PG) led to a marked enrichment of DHA in BMP, resulting in the formation of diDHA molecular species. However, the amount of BMP was selectively decreased. Similar effects were observed after supplementation with high concentrations of nonesterified DHA. Addition of vitamin E prevented the decrease of BMP and further increased its DHA content. Supplementation with 22:6/22:6-PG promoted BMP accumulation with an enhanced proportion of 22:6/22:6-BMP. DHA-rich BMP was significantly degraded after cell exposure to oxidant conditions, in contrast to oleic acid-rich BMP, which was not affected. Using a cell-free system, we showed that 22:6/22:6-BMP is highly oxidizable and partially protects cholesterol oxidation, compared with 18:1/18:1-BMP. Our data suggest that high DHA content in BMP led to specific degradation of this PL, possibly through the diDHA molecular species, which is very prone to peroxidation and, as such, a potential antioxidant in its immediate vicinity. PMID:18809971

  15. Diacylglycerol-containing docosahexaenoic acid in acyl chain modulates airway smooth muscle tone.

    PubMed

    Hichami, Aziz; Morin, Caroline; Rousseau, Eric; Khan, Naim A

    2005-10-01

    We synthesized and assessed the role of a diacylglycerol (DAG)-containing docosahexaenoic acid (DHA), that is, 1-stearoyl-2-docosahexaenoyl-sn-glycerol (SDHG), in the contraction of guinea pig airway smooth muscle (ASM). We compared its action with 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG) and 1,2-dioctanoyl-sn-glycerol (1,2-DiC8), a stable DAG analog. The three DAGs (SAG, SDHG, and 1,2-DiC8) induced reversible concentration-dependent contraction of ASM. SDHG induced higher guinea pig ASM contraction than did SAG and 1,2-DiC8. The effects of SDHG were blocked, to different extents, by nifedipine (L-type Ca2+ channel blocker). By employing GF-109203X (protein kinase C [PKC] inhibitor) and lanthanum (La3+), a nonselective cation channel blocker, we observed that SDHG evoked ASM contractile response via PKC-dependent and PKC-independent (but Ca2+-dependent) pathways. Interestingly, SAG exerted its action only by increasing [Ca2+]i and did not require PKC activation. To probe the implication of calcium mobilization, we employed thapsigargin (TG), which also induced ASM contraction in a calcium-dependent manner. SDHG and 1,2-DiC8, in a PKC-dependent manner, induced the phosphorylation of CPI-17 (myosin light chain phosphatase inhibitor of 17 kD). Furthermore, SAG and TG failed to phosphorylate CPI-17 in ASM cells. Our results suggest that different DAG species, produced during a dietary supplementation with fatty acids, could modulate the reactivity of airway smooth muscles in a PKC-dependent and -independent manner, and hence, may play a critical role in health and disease. PMID:15961724

  16. Oleic- and Docosahexaenoic Acid-Containing Phosphatidylethanolamines Differentially Phase Separate from Sphingomyelin

    PubMed Central

    Shaikh, Saame Raza; LoCascio, Daniel S.; Soni, Smita P.; Wassall, Stephen R.; Stillwell, William

    2009-01-01

    A central tenet of the lipid raft model is the existence of non-raft domains. In support of this view, we have established in model membranes that a phosphatidylethanolamine (PE)-containing docosahexaenoic acid (DHA) forms organizationally distinct non-raft domains in the presence of sphingomyelin (SM) and cholesterol (Chol). We have shown that formation of DHA-rich domains is driven by unfavorable molecular interactions between the rigid Chol molecule and the highly flexible DHA acyl chain. However, the molecular interactions between SM and the DHA-containing PE, which could also contribute to the formation of DHA-rich non-raft domains, have not been sufficiently investigated. To address this issue, we use differential scanning calorimetry (DSC) to study the phase behavior of mixtures of SM with either 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (16:0-22:6PE) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (16:0-18:1PE), an oleic acid (OA)-containing control, over a wide range of concentrations. Deconvolution of binary DSC scans shows that both 16:0-22:6PE and 16:0-18:1PE phase separate from SM. Analysis of transition temperatures and partial phase diagrams, constructed from the DSC scans for the first time, show that 16:0-22:6PE displays greater non-ideal mixing with SM compared to 16:0-18:1PE. Our findings support a model in which DHA- and OA-containing PEs differentially phase separate from SM over a wide range of molar ratios to initiate the formation of non-raft domains, which is greatly enhanced by DHA, but not OA, in the presence of cholesterol. PMID:19735642

  17. Docosahexaenoic acid counteracts attenuation of CD95-induced cell death by inorganic mercury

    SciTech Connect

    Gill, Randall; Lanni, Lydia; Jen, K.-L. Catherine; McCabe, Michael J.; Rosenspire, Allen

    2015-01-01

    In the United States the principal environmental exposure to mercury is through dietary consumption of sea food. Although the mechanism by which low levels of mercury affect the nervous system is not well established, epidemiological studies suggest that low level exposure of pregnant women to dietary mercury can adversely impact cognitive development in their children, but that Docosahexaenoic acid (DHA), the most prominent n-polyunsaturated fatty acid (n-PUFA) present in fish may counteract negative effects of mercury on the nervous system. Aside from effects on the nervous system, epidemiological and animal studies have also suggested that low level mercury exposure may be a risk factor for autoimmune disease. However unlike the nervous system where a mechanism linking mercury to impaired cognitive development remains elusive, we have previously suggested a potential mechanism linking low level mercury exposures to immune system dysfunction and autoimmunity. In the immune system it is well established that disruption of CD95 mediated apoptosis leads to autoimmune disease. We have previously shown in vitro as well as in vivo that in lymphocytes burdened with low levels of mercury, CD95 mediated cell death is impaired. In this report we now show that DHA counteracts the negative effect of mercury on CD95 signaling in T lymphocytes. T cells which have been pre-exposed to DHA are able to cleave pro-caspase 3 and efficiently signal programmed cell death through the CD95 signaling pathway, whether or not they are burdened with low levels of mercury. Thus DHA may lower the risk of autoimmune disease after low level mercury exposures. - Highlights: • Inorganic mercury (Hg{sup 2+}) interferes with CD95 mediated cell death in Jurkat T cells • DHA restores the ability of CD95 to signal cell death in Hg{sup 2+} intoxicated T cells • The restoration of CD95 mediated cell death by DHA is correlated with increased activation of Caspase 3.

  18. DOCOSAHEXAENOIC ACID PARTIALLY AMELIORATES DEFICITS IN SOCIAL BEHAVIOR AND ULTRASONIC VOCALIZATIONS CAUSED BY PRENATAL ETHANOL EXPOSURE

    PubMed Central

    Wellmann, Kristen A.; George, Finney; Brnouti, Fares; Mooney, Sandra M.

    2015-01-01

    Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long-Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10 g/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol’s damaging effects. PMID:25746516

  19. Role of Docosahexaenoic Acid Treatment in Improving Liver Histology in Pediatric Nonalcoholic Fatty Liver Disease

    PubMed Central

    Alisi, Anna; De Vito, Rita; Franchitto, Antonio; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

    2014-01-01

    Introduction Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of liver-related morbidity and mortality in children. Recently, we have reported the effects of docosahexaenoic acid (DHA), the major dietary long-chain polyunsaturated fatty acids, in children with NAFLD. DHA exerts a potent anti-inflammatory activity through the G protein-coupled receptor (GPR)120. Our aim was to investigate in pediatric NAFLD the mechanisms underlying the effects of DHA administration on histo-pathological aspects, GPR120 expression, hepatic progenitor cell activation and macrophage pool. Patients and Methods 20 children with untreated NAFLD were included. Children were treated with DHA for 18 months. Liver biopsies before and after the treatment were analyzed. Hepatic progenitor cell activation, macrophage pool and GPR120 expression were evaluated and correlated with clinical and histo-pathological parameters. Results GPR120 was expressed by hepatocytes, liver macrophages, and hepatic progenitor cells. After DHA treatment, the following modifications were present: i) the improvement of histo-pathological parameters such as NAFLD activity score, ballooning, and steatosis; ii) the reduction of hepatic progenitor cell activation in correlation with histo-pathological parameters; iii) the reduction of the number of inflammatory macrophages; iv) the increase of GPR120 expression in hepatocytes; v) the reduction of serine-311-phosphorylated nuclear factor kappa B (NF-κB) nuclear translocation in hepatocytes and macrophages in correlation with serum inflammatory cytokines. Conclusions DHA could modulate hepatic progenitor cell activation, hepatocyte survival and macrophage polarization through the interaction with GPR120 and NF-κB repression. In this scenario, the modulation of GPR120 exploits a novel crucial role in the regulation of the cell-to-cell cross-talk that drives inflammatory response, hepatic progenitor cell activation and hepatocyte survival. PMID

  20. Serum Phospholipid Docosahexaenoic Acid Is Inversely Associated with Arterial Stiffness in Metabolically Healthy Men

    PubMed Central

    Lee, Mi-Hyang; Kwon, Nayeon; Yoon, So Ra

    2016-01-01

    We hypothesized that lower proportion of serum phospholipid docosahexaenoic acid (DHA) is inversely associated with increased cardiovascular risk and vascular function in metabolically healthy men. To elucidate it, we first compared serum phospholipid free fatty acid (FA) compositions and cardiovascular risk parameters between healthy men (n = 499) and male patients with coronary artery disease (CAD, n = 111) (30-69 years) without metabolic syndrome, and then further-analyzed the association of serum phospholipid DHA composition with arterial stiffness expressed by brachial-ankle pulse wave velocity (ba-PWV) in metabolically healthy men. Basic parameters, lipid profiles, fasting glycemic status, adiponectin, high sensitivity C-reactive protein (hs-CRP) and LDL particle size, and serum phospholipid FA compositions were significantly different between the two subject groups. Serum phospholipid DHA was highly correlated with most of long-chain FAs. Metabolically healthy men were subdivided into tertile groups according to serum phospholipid DHA proportion: lower (< 2.061%), middle (2.061%-3.235%) and higher (> 3.235%). Fasting glucose, insulin resistance, hs-CRP and ba-PWVs were significantly higher and adiponectin and LDL particle size were significantly lower in the lower-DHA group than the higher-DHA group after adjusted for confounding factors. In metabolically healthy men, multiple stepwise regression analysis revealed that serum phospholipid DHA mainly contributed to arterial stiffness (β′-coefficients = -0.127, p = 0.006) together with age, systolic blood pressure, triglyceride (r = 0.548, p = 0.023). Lower proportion of serum phospholipid DHA was associated with increased cardiovascular risk and arterial stiffness in metabolically healthy men. It suggests that maintaining higher proportion of serum phospholipid DHA may be beneficial for reducing cardiovascular risk including arterial stiffness in metabolically healthy men. PMID:27482523

  1. Response surface optimization of culture medium for enhanced docosahexaenoic acid production by a Malaysian thraustochytrid

    PubMed Central

    Manikan, Vidyah; Kalil, Mohd Sahaid; Hamid, Aidil Abdul

    2015-01-01

    Docosahexaenoic acid (DHA, C22:6n-3) plays a vital role in the enhancement of human health, particularly for cognitive, neurological, and visual functions. Marine microalgae, such as members of the genus Aurantiochytrium, are rich in DHA and represent a promising source of omega-3 fatty acids. In this study, levels of glucose, yeast extract, sodium glutamate and sea salt were optimized for enhanced lipid and DHA production by a Malaysian isolate of thraustochytrid, Aurantiochytrium sp. SW1, using response surface methodology (RSM). The optimized medium contained 60 g/L glucose, 2 g/L yeast extract, 24 g/L sodium glutamate and 6 g/L sea salt. This combination produced 17.8 g/L biomass containing 53.9% lipid (9.6 g/L) which contained 44.07% DHA (4.23 g/L). The optimized medium was used in a scale-up run, where a 5 L bench-top bioreactor was employed to verify the applicability of the medium at larger scale. This produced 24.46 g/L biomass containing 38.43% lipid (9.4 g/L), of which 47.87% was DHA (4.5 g/L). The total amount of DHA produced was 25% higher than that produced in the original medium prior to optimization. This result suggests that Aurantiochytrium sp. SW1 could be developed for industrial application as a commercial DHA-producing microorganism. PMID:25721623

  2. Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure.

    PubMed

    Wellmann, Kristen A; George, Finney; Brnouti, Fares; Mooney, Sandra M

    2015-06-01

    Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long-Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10g/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol's damaging effects. PMID:25746516

  3. Docosahexaenoic acid pretreatment confers protection and functional improvements after acute spinal cord injury in adult rats.

    PubMed

    Figueroa, Johnny D; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I; Walker, Robert L; Miranda, Jorge D; Leon, Marino De

    2012-02-10

    Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  4. Effects of PI3K inhibition and low docosahexaenoic acid on cognition and behavior.

    PubMed

    Bandaru, Sathyajit S; Lin, Kristen; Roming, Stephanie L; Vellipuram, Ramana; Harney, Jacob P

    2010-06-01

    Alterations in two components of the brain's insulin signaling pathway, docosahexaenoic acid (DHA) content and phosphoinositide 3-kinase (PI3K) activity, have been implicated in the insulin resistance that is central to type II diabetes mellitus (DM). A 2- to 3-fold increased risk of developing Alzheimer's disease (AD) in patients with type II DM suggests a potential link between cognition and insulin action. The current study was designed to examine the impact of DHA dietary content and PI3K activity on learning, memory, depression, and anxiety in rodents. Mice were divided into the following groups: (1) control diet and vehicle injection (control PI3K), (2) control diet and wortmannin injection (PI3K inhibition), (3) low DHA diet and vehicle, and (4) low DHA diet and wortmannin. Each group was assessed for effects on activity, cognition, depression, and anxiety. Concentrations of glucose and insulin in plasma were quantified to confirm insulin resistance. Results showed significant increases in depression, anxiety, plasma insulin and glucose, and significant decreases in activity in wortmannin-treated mice regardless of diet. The control diet/wortmannin-treated group showed a significant decrease in memory compared to all other groups. The low DHA diet/wortmannin-treated group had slightly improved memory and lower levels of depression compared to the control diet/wortmannin-treated group. Results of the present study suggest that inhibition of PI3K decreases activity and memory while increasing insulin resistance, depression, and anxiety. In addition, these results suggest a possible compensatory role of low DHA in decreasing the effects of dysfunctional PI3K in AD associated cognitive decline and depression. PMID:19914265

  5. Prenatal Docosahexaenoic Acid Supplementation and Offspring Development at 18 Months: Randomized Controlled Trial

    PubMed Central

    Ramakrishnan, Usha; Stinger, Amanda; DiGirolamo, Ann M.; Martorell, Reynaldo; Neufeld, Lynnette M.; Rivera, Juan A.; Schnaas, Lourdes; Stein, Aryeh D.; Wang, Meng

    2015-01-01

    Objective We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age. Design Randomized placebo double-blind controlled trial. Settings Cuernavaca, Mexico. Participants and Methods We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment. Interventions or Main Exposures 400 mg/day of algal DHA. Outcome Measures Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores. Results Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation. Conclusions Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments. Trial Registration Clinicaltrials.gov NCT00646360 PMID:26262896

  6. Docosahexaenoic Acid Pretreatment Confers Protection and Functional Improvements after Acute Spinal Cord Injury in Adult Rats

    PubMed Central

    Figueroa, Johnny D.; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I.; Walker, Robert L.; Miranda, Jorge D.

    2012-01-01

    Abstract Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  7. Human apolipoprotein E allele and docosahexaenoic acid intake modulate peripheral cholesterol homeostasis in mice.

    PubMed

    Pinçon, Anthony; Coulombe, Jean-Denis; Chouinard-Watkins, Raphaël; Plourde, Mélanie

    2016-08-01

    Carrying at least one apolipoprotein E ε4 allele (E4+) is the main genetic risk factor for Alzheimer's disease (AD). Epidemiological studies support that consuming fatty fish rich in docosahexaenoic acid (DHA; 22:6ω3) is protective against development of AD. However, this protective effect seems not to hold in E4+. The involvement of APOE genotype on the relationship between DHA intake and cognitive decline could be mediated through cholesterol. Many studies show a link between cholesterol metabolism and AD progression. In this study, we investigated whether cholesterol metabolism is improved in E3+ and E4+ mice consuming a diet rich in DHA. Plasma cholesterol was 36% lower in E4+ mice compared to E3+ mice fed the control diet (P=.02), and in the liver, there was a significant genotype effect where cholesterol levels were 18% lower in E4+ mice than E3+ mice. The low-density lipoprotein receptor was overexpressed in the liver of E4+ mice. Plasma cholesterol levels were 33% lower after the DHA diet (P=.02) in E3+ mice only, and there was a significant diet effect where cholesterol level was 67% lower in the liver of mice fed DHA. Mice fed the DHA diet also had 62% less lipolysis stimulated lipoprotein receptor expression in the liver compared to mice fed the control diet (P<.0001), but there was no genotype effect. These findings suggest that plasma and liver cholesterol homeostasis and the receptors regulating uptake of cholesterol in the liver are modulated differently and independently by APOE allele and DHA intake. PMID:27239755

  8. Omega-3 fatty acids, EPA and DHA induce apoptosis and enhance drug sensitivity in multiple myeloma cells but not in normal peripheral mononuclear cells.

    PubMed

    Abdi, J; Garssen, J; Faber, J; Redegeld, F A

    2014-12-01

    The n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to enhance the effect of chemotherapeutic drugs in clinical studies in cancer patients and to induce apoptotic tumor cell death in vitro. Until now, EPA and DHA have never been investigated in multiple myeloma (MM). Human myeloma cells (L363, OPM-1, OPM-2 and U266) and normal peripheral blood mononuclear cells were exposed to EPA and DHA, and effects on mitochondrial function and apoptosis, caspase-3 activation, gene expression and drug toxicity were measured. Exposure to EPA and DHA induced apoptosis and increased sensitivity to bortezomib in MM cells. Importantly, they did not affect viability of normal human peripheral mononuclear cells. Messenger RNA expression arrays showed that EPA and DHA modulated genes involved in multiple signaling pathways including nuclear factor (NF) κB, Notch, Hedgehog, oxidative stress and Wnt. EPA and DHA inhibited NFκB activity and induced apoptosis through mitochondrial perturbation and caspase-3 activation. Our study suggests that EPA and DHA induce selective cytotoxic effects in MM and increase sensitivity to bortezomib and calls for further exploration into a potential application of these n-3 polyunsaturated fatty acids in the therapy of MM. PMID:25277647

  9. Simulated moving bed chromatography for the separation of ethyl esters of eicosapentaenoic acid and docosahexaenoic acid under nonlinear conditions.

    PubMed

    Li, Min; Bao, Zongbi; Xing, Huabin; Yang, Qiwei; Yang, Yiwen; Ren, Qilong

    2015-12-18

    In this study, ethyl esters of eicosapentaenoic acid and docosahexaenoic acid were separated with simulated moving bed (SMB) chromatography, where the stationary phase was C18 silica gel with particle size of 10μm packed in eight columns, and the mobile phase was pure methanol. The Henry constants, transport parameters and total porosity were measured from pulse response chromatographic experiments using a single column. The Henry constants were obtained from the first moment analysis. The transport parameters including axial dispersion coefficients and effective mass transfer coefficients were obtained from the second moment analysis. Nonlinear adsorption equilibrium isotherms for the pure components and their mixture were determined from adsorption-desorption method. The Langmuir model was used to fit the experimental data, and the corresponding parameters were further used to predict the competitive adsorption equilibria of the mixture. The validity of mathematical model parameters was checked by a frontal chromatography experiment. The simulated results of the SMB process using these parameters agreed well with the experimental results. At the feed concentration of 100g/L, the SMB separation was able to produce both solutes with relative purity above 99%, productivity of 13.11g/L adsorbent/h, and solvent consumption of 0.46L/g. PMID:26620595

  10. Docosahexaenoic acid-containing phospholipid molecular species in brains of vertebrates

    PubMed Central

    Farkas, Tibor; Kitajka, Klara; Fodor, Elfrieda; Csengeri, István; Lahdes, Eila; Yeo, Young K.; Krasznai, Zoltán; Halver, John E.

    2000-01-01

    The fatty acid composition of phospholipids and the contents of docosahexaenoic acid (DHA)-containing diacyl phosphatidylcholine and diacyl phosphatidylethanolamine molecular species were determined from brains of five fresh-water fish species from a boreal region adapted to 5°C, five fresh-water fish species from a temperate region acclimated to 5°C, five fresh-water fish species from a temperate region acclimated to 20°C, and three fresh water fish species from a subtropic region adapted to 25–26°C, as well as six mammalian species and seven bird species. There was little difference in DHA levels of fish brains from the different thermal environments; mammalian and bird brain phospholipids contained a few percentage points less DHA than those of the fish investigated. Molecular species of 22:6/22:6, 22:6/20:5, 22:6/20:4, 16:0/22:6, 18:0/22:6, and 18:1/22:6 were identified from all brain probes, and 16:0/22:6, 18:0/22:6, and 18:1/22:6 were the dominating species. Cold-water fish brains were rich in 18:1/22:6 diacyl phosphatidylethanolamine (and, to a lesser degree, in diacyl phosphatidylcholine), and its level decreased with increasing environmental/body temperature. The ratio of 18:0/22:6 to 16:0/22:6 phosphatidylcholine and phosphatidylethanolamine was inversely related to body temperature. Phospholipid vesicles from brains of cold-acclimated fish were more fluid, as assessed by using a 1,6-diphenyl-1,3,5-hexatriene fluorescent probe, than those from bird brains, but the fluidities were almost equal at the respective body temperatures. It is concluded that the relative amounts of these molecular species and their ratios to each other are the major factors contributing to the maintenance of proper fluidity relationships throughout the evolutionary chain as well as helping to maintain important brain functions such as signal transduction and membrane permeability. PMID:10823917

  11. Silica-Triggered Autoimmunity in Lupus-Prone Mice Blocked by Docosahexaenoic Acid Consumption

    PubMed Central

    Bates, Melissa A.; Brandenberger, Christina; Langohr, Ingeborg I.; Kumagai, Kazuyoshi; Lock, Adam L.; Harkema, Jack R.; Holian, Andrij; Pestka, James J.

    2016-01-01

    Occupational exposure to respirable crystalline silica (cSiO2, quartz) is etiologically linked to systemic lupus erythematosus (lupus) and other human autoimmune diseases (ADs). In the female NZBWF1 mouse, a widely used animal model that is genetically prone to lupus, short-term repeated intranasal exposure to cSiO2 triggers premature initiation of autoimmune responses in the lungs and kidneys. In contrast to cSiO2’s triggering action, consumption of the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) prevents spontaneous onset of autoimmunity in this mouse strain. The aim of this study was to test the hypothesis that consumption of DHA will prevent cSiO2-triggered autoimmunity in the female NZBWF1 mouse. Mice (6 wk old) were fed isocaloric AIN-93G diets containing 0.0, 0.4, 1.2 or 2.4% DHA. Two wk after initiating feeding, mice were intranasally instilled with 1 mg cSiO2 once per wk for 4 wk and maintained on experimental diets for an additional 12 wk. Mice were then sacrificed and the lung, blood and kidney assessed for markers of inflammation and autoimmunity. DHA was incorporated into lung, red blood cells and kidney from diet in a concentration-dependent fashion. Dietary DHA dose-dependently suppressed cSiO2-triggered perivascular leukocyte infiltration and ectopic lymphoid tissue neogenesis in the lung. DHA consumption concurrently inhibited cSiO2–driven elevation of proinflammatory cytokines, B-cell proliferation factors, IgG and anti-dsDNA Ig in both bronchoalveolar lavage fluid and plasma. DHA’s prophylactic effects were further mirrored in reduced proteinuria and glomerulonephritis in cSiO2-treated mice. Taken together, these results reveal that DHA consumption suppresses cSiO2 triggering of autoimmunity in female NZBWF1 mice as manifested in the lung, blood and kidney. Our findings provide novel insight into how dietary modulation of the lipidome might be used to prevent or delay triggering of AD by cSiO2. Such knowledge opens the

  12. Silica-Triggered Autoimmunity in Lupus-Prone Mice Blocked by Docosahexaenoic Acid Consumption.

    PubMed

    Bates, Melissa A; Brandenberger, Christina; Langohr, Ingeborg I; Kumagai, Kazuyoshi; Lock, Adam L; Harkema, Jack R; Holian, Andrij; Pestka, James J

    2016-01-01

    Occupational exposure to respirable crystalline silica (cSiO2, quartz) is etiologically linked to systemic lupus erythematosus (lupus) and other human autoimmune diseases (ADs). In the female NZBWF1 mouse, a widely used animal model that is genetically prone to lupus, short-term repeated intranasal exposure to cSiO2 triggers premature initiation of autoimmune responses in the lungs and kidneys. In contrast to cSiO2's triggering action, consumption of the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) prevents spontaneous onset of autoimmunity in this mouse strain. The aim of this study was to test the hypothesis that consumption of DHA will prevent cSiO2-triggered autoimmunity in the female NZBWF1 mouse. Mice (6 wk old) were fed isocaloric AIN-93G diets containing 0.0, 0.4, 1.2 or 2.4% DHA. Two wk after initiating feeding, mice were intranasally instilled with 1 mg cSiO2 once per wk for 4 wk and maintained on experimental diets for an additional 12 wk. Mice were then sacrificed and the lung, blood and kidney assessed for markers of inflammation and autoimmunity. DHA was incorporated into lung, red blood cells and kidney from diet in a concentration-dependent fashion. Dietary DHA dose-dependently suppressed cSiO2-triggered perivascular leukocyte infiltration and ectopic lymphoid tissue neogenesis in the lung. DHA consumption concurrently inhibited cSiO2-driven elevation of proinflammatory cytokines, B-cell proliferation factors, IgG and anti-dsDNA Ig in both bronchoalveolar lavage fluid and plasma. DHA's prophylactic effects were further mirrored in reduced proteinuria and glomerulonephritis in cSiO2-treated mice. Taken together, these results reveal that DHA consumption suppresses cSiO2 triggering of autoimmunity in female NZBWF1 mice as manifested in the lung, blood and kidney. Our findings provide novel insight into how dietary modulation of the lipidome might be used to prevent or delay triggering of AD by cSiO2. Such knowledge opens the possibility

  13. Novel 14,21-dihydroxy-docosahexaenoic acids: structures, formation pathways, and enhancement of wound healing

    PubMed Central

    Lu, Yan; Tian, Haibin; Hong, Song

    2010-01-01

    Chronic wounds remain a medical challenge, where well-coordinated cellular and molecular processes required by optimal healing are impaired by diabetes, aging, or other diseases. In determining mechanisms that regulate wound healing, we found that wounding induced formation of novel endogenous 14S,21S-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acids (14S,21S-diHDHA);14R,21R-diHDHA; 14S,21R-diHDHA; and/or 14R,21S-diHDHA. 12-lipoxygenase and cytochrome P450 catalysis in tandem converted docosahexaenoic acid to 14S,21R-diHDHA and 14S,21S-diHDHA through the intermediacy of 14S-HDHA; P450 also converted 14R-HDHA to novel 14R,21R-diHDHA and 14R,21S-diHDHA. Macrophages function as the combination of 12-lipoxgenase and P450 to generate these 14,21-diHDHA stereoisomers, as well as their intermediates 14S-HDHA, 14R-HDHA, and 21-HDHA. The structure and formation pathways of 14,21-diHDHA stereoisomers were further confirmed by macrophage biosynthesis of 14,21-diHDHA-21,22,22,22-d4 stereoisomers, 14S-HDHA-d5, 14R-HDHA-d5, and 21-HDHA-d4 from DHA-21,21,22,22,22-d5. We found that 14S,21-diHDHA and 14R,21-diHDHA enhanced wound closure, reepithelialization, granulation tissue growth, and capillary vasculature formation of murine wounds. 14S,21-diHDHA and 14R,21-diHDHA produced by macrophages may partially represent the molecular mechanisms for macrophage pro-healing function. Taken together, 14,21-dihydroxy-DHA stereoisomers and their formation pathways may represent a novel mechanism in the orchestration of wound healing processes, which may provide new insight for developing novel therapeutic modalities that counteract impairments to wound healing. PMID:19965612

  14. Novel 14,21-dihydroxy-docosahexaenoic acids: structures, formation pathways, and enhancement of wound healing.

    PubMed

    Lu, Yan; Tian, Haibin; Hong, Song

    2010-05-01

    Chronic wounds remain a medical challenge, where well-coordinated cellular and molecular processes required by optimal healing are impaired by diabetes, aging, or other diseases. In determining mechanisms that regulate wound healing, we found that wounding induced formation of novel endogenous 14S,21S-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acids (14S,21S-diHDHA);14R,21R-diHDHA; 14S,21R-diHDHA; and/or 14R,21S-diHDHA. 12-lipoxygenase and cytochrome P450 catalysis in tandem converted docosahexaenoic acid to 14S,21R-diHDHA and 14S,21S-diHDHA through the intermediacy of 14S-HDHA; P450 also converted 14R-HDHA to novel 14R,21R-diHDHA and 14R,21S-diHDHA. Macrophages function as the combination of 12-lipoxgenase and P450 to generate these 14,21-diHDHA stereoisomers, as well as their intermediates 14S-HDHA, 14R-HDHA, and 21-HDHA. The structure and formation pathways of 14,21-diHDHA stereoisomers were further confirmed by macrophage biosynthesis of 14,21-diHDHA-21,22,22,22-d(4) stereoisomers, 14S-HDHA-d(5), 14R-HDHA-d(5), and 21-HDHA-d(4) from DHA-21,21,22,22,22-d(5). We found that 14S,21-diHDHA and 14R,21-diHDHA enhanced wound closure, reepithelialization, granulation tissue growth, and capillary vasculature formation of murine wounds. 14S,21-diHDHA and 14R,21-diHDHA produced by macrophages may partially represent the molecular mechanisms for macrophage pro-healing function. Taken together, 14,21-dihydroxy-DHA stereoisomers and their formation pathways may represent a novel mechanism in the orchestration of wound healing processes, which may provide new insight for developing novel therapeutic modalities that counteract impairments to wound healing. PMID:19965612

  15. The fatty acid desaturase 2 (FADS2) gene product catalyzes Δ4 desaturation to yield n-3 docosahexaenoic acid and n-6 docosapentaenoic acid in human cells

    PubMed Central

    Park, Hui Gyu; Park, Woo Jung; Kothapalli, Kumar S. D.; Brenna, J. Thomas

    2015-01-01

    Docosahexaenoic acid (DHA) is a Δ4-desaturated C22 fatty acid and the limiting highly unsaturated fatty acid (HUFA) in neural tissue. The biosynthesis of Δ4-desaturated docosanoid fatty acids 22:6n-3 and 22:5n-6 are believed to proceed via a circuitous biochemical pathway requiring repeated use of a fatty acid desaturase 2 (FADS2) protein to perform Δ6 desaturation on C24 fatty acids in the endoplasmic reticulum followed by 1 round of β-oxidation in the peroxisomes. We demonstrate here that the FADS2 gene product can directly Δ4-desaturate 22:5n-3→22:6n-3 (DHA) and 22:4n-6→22:5n-6. Human MCF-7 cells lacking functional FADS2-mediated Δ6-desaturase were stably transformed with FADS2, FADS1, or empty vector. When incubated with 22:5n-3 or 22:4n-6, FADS2 stable cells produce 22:6n-3 or 22:5n-6, respectively. Similarly, FADS2 stable cells when incubated with d5-18:3n-3 show synthesis of d5-22:6n-3 with no labeling of 24:5n-3 or 24:6n-3 at 24 h. Further, both C24 fatty acids are shown to be products of the respective C22 fatty acids via elongation. Our results demonstrate that the FADS2 classical transcript mediates direct Δ4 desaturation to yield 22:6n-3 and 22:5n-6 in human cells, as has been widely shown previously for desaturation by fish and many other organisms.—Park, H. G., Park, W. J., Kothapalli, K. S. D., Brenna, J. T. The fatty acid desaturase 2 (FADS2) gene product catalyzes Δ4 desaturation to yield n-3 docosahexaenoic acid and n-6 docosapentaenoic acid in human cells. PMID:26065859

  16. 17β-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

    PubMed

    Mason, Julie K; Kharotia, Shikhil; Wiggins, Ashleigh K A; Kitson, Alex P; Chen, Jianmin; Bazinet, Richard P; Thompson, Lilian U

    2014-08-01

    Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status. PMID:24913495

  17. Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid

    PubMed Central

    Tajuddin, Nuzhath; Moon, Kwan-Hoon; Marshall, S. Alex; Nixon, Kimberly; Neafsey, Edward J.; Kim, Hee-Yong; Collins, Michael A.

    2014-01-01

    Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼9 g/kg/d, achieving blood ethanol levels ∼375 mg/dl; “Majchrowicz” model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA (p-cPLA2), secretory PLA2 GIIA (sPLA2) and PARP-1 in regions incurring extensive neurodegeneration in this model—hippocampus, entorhinal cortex, and olfactory bulb—but not in two regions typically lacking neurodamage, frontal cortex and cerebellum. Also, ethanol reduced hippocampal Ca+2-independent PLA2 GVIA (iPLA2) levels and increased brain “oxidative stress footprints” (4-hydroxynonenal-adducted proteins). For in vitro studies, organotypic cultures of rat hippocampal-entorhinocortical slices of adult age (∼60 d) were ethanol-binged (100 mM or ∼450 mg/dl) for 4 d, which augments AQP4 and causes neurodegeneration (Collins et al. 2013). Reproducing the in vivo results, cPLA2, p-cPLA2, sPLA2 and PARP-1 were significantly elevated while iPLA2 was decreased. Furthermore, supplementation with docosahexaenoic acid (DHA; 22:6n-3), known to quell AQP4 and neurodegeneration in ethanol-treated slices, blocked PARP-1 and PLA2 changes while counteracting endogenous DHA reduction and increases in oxidative stress footprints (3-nitrotyrosinated proteins). Notably, the PARP-1 inhibitor PJ-34 suppressed binge ethanol-dependent neurodegeneration, indicating PARP upstream involvement. The results with corresponding models

  18. Delivery of Polyunsaturated Fatty Acids from a Glycerol Polyester Matrix with Anti-oxidant Properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Awareness of the health benefits associated with the polyunsaturated acids such as alpha linolenic (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), has generated interest in formulating foods and dietary supplements with these compounds. However, the highly unsaturated structure o...

  19. Enhanced absorption of n-3 fatty acids from emulsified compared with encapsulated fish oil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have important nutrition and disease management properties. Presently fish oil (FO) supplementation relies on capsular triglyceride. Flavored emulsified lipid preparations may provide an improved approach to FO del...

  20. Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder.

    PubMed

    McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Stanford, Kevin E; Hahn, Chang-Gyu; Richtand, Neil M

    2008-09-30

    Previous antemortem and postmortem tissue fatty acid composition studies have observed significant deficits in the omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3) in red blood cell (RBC) and postmortem cortical membranes of patients with unipolar depression. In the present study, we determined the fatty acid composition of postmortem orbitofrontal cortex (OFC, Brodmann area 10) of patients with bipolar disorder (n=18) and age-matched normal controls (n=19) by gas chromatography. After correction for multiple comparisons, DHA (-24%), arachidonic acid (-14%), and stearic acid (C18:0) (-4.5%) compositions were significantly lower, and cis-vaccenic acid (18:1n-7) (+12.5%) composition significantly higher, in the OFC of bipolar patients relative to normal controls. Based on metabolite:precursor ratios, significant elevations in arachidonic acid, stearic acid, and palmitic acid conversion/metabolism were observed in the OFC of bipolar patients, and were inversely correlated with DHA composition. Deficits in OFC DHA and arachidonic acid composition, and elevations in arachidonic acid metabolism, were numerically (but not significantly) greater in drug-free bipolar patients relative to patients treated with mood-stabilizer or antipsychotic medications. OFC DHA and arachidonic acid deficits were greater in patients plus normal controls with high vs. low alcohol abuse severity. These results add to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the OFC in the pathoaetiology of bipolar disorder. PMID:18715653

  1. Effect of unsaturations on the physical properties of a model membrane with the highly polyunsaturated docosahexaenoic fatty acid

    NASA Astrophysics Data System (ADS)

    Saiz, Leonor; Klein, Michael L.

    2001-03-01

    Polyunsaturated fatty acids are an essential component of biomembranes. The docosahexaenoic fatty acid (DHA), in particular, is found in high concentrations in retinal and neuronal tissue and in the olfactory bulb. Furthermore, it is well known the ability of DHA rich membranes to modulate membrane protein function, in some situations, by modifying the membrane physical properties. A particularly well studied situation is the DHA effect onthe activity of the visual receptor (protein) rhodopsin. Here, we study at a microscopic level this type of complex systems under physiological conditions. In this way, we can probe the molecular origin of the peculiarities that the system confers to membranes. To this purpose, the structure of a fully hydrated mixed (saturated/polyunsaturated) chain lipid bilayer in the biologically relevant liquid crystalline phase has been examined by performing molecular dynamics simulations. The model membrane, a 1-stearoyl- 2-docosahexaenoic- sn-glycero- 3-phosphatidylcholine (18:0/22:6 PC) lipid bilayer, was investigated at room temperature and ambient pressure and the results obtained in the nanosecond time scale were in good agreement with the available experimental data. Among the effects of the multiple unsaturations on the physical properties of these membranes, we focus on the enhanced permeability to water and small organic solvents, the decreased area compressibility modulus, and the domain formation and chain segregation.

  2. The Pattern of Fatty Acids Displaced by EPA and DHA Following 12 Months Supplementation Varies between Blood Cell and Plasma Fractions

    PubMed Central

    Walker, Celia G.; West, Annette L.; Browning, Lucy M.; Madden, Jackie; Gambell, Joanna M.; Jebb, Susan A.; Calder, Philip C.

    2015-01-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0–4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%–64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology. PMID:26247960

  3. The Pattern of Fatty Acids Displaced by EPA and DHA Following 12 Months Supplementation Varies between Blood Cell and Plasma Fractions.

    PubMed

    Walker, Celia G; West, Annette L; Browning, Lucy M; Madden, Jackie; Gambell, Joanna M; Jebb, Susan A; Calder, Philip C

    2015-08-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0-4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%-64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology. PMID:26247960

  4. Dietary supplementation with cholesterol and docosahexaenoic acid affects concentrations of amino acids in tissues of young pigs

    PubMed Central

    Li, Peng; Kim, Sung Woo; Li, Xilong; Datta, Sujay; Pond, Wilson G.

    2013-01-01

    Cholesterol and docosahexaenoic acid (DHA) are important nutrients for neural development of infants. However, little is known about the effect of cholesterol or DHA on concentrations of amino acids (AA) in neonatal tissues. This study was conducted with the piglet (an established model for studying human infant nutrition) to test the hypothesis that dietary supplementation with the lipids may modulate AA availability in tissues. Sixteen newborn pigs were nursed by sows for 24 h and then assigned to one of four treatment groups, representing supplementation with 0.0% (control), 0.2% cholesterol, 0.2% DHA, or cholesterol plus DHA to the basal milk-formula. All piglets were euthanized at 49 days of age. In brain, cholesterol supplementation reduced (P < 0.05) concentrations of glutamate, serine, glutamine, threonine, β-alanine, alanine, methionine, isoleucine, leucine, and γ-aminobutyrate but increased (P < 0.05) concentrations of glycine and lysine, whereas DHA supplementation similarly affected (P < 0.05) concentrations of the same AA (except for isoleucine and lysine) and taurine. In addition, concentrations of most AA in liver, muscle and plasma were substantially altered by dietary supplementation of cholesterol and DHA in a tissue-dependent manner. Further, DHA reduced concentrations of carnosine in skeletal muscle, as well as ammonia in both plasma and brain. The results reveal that cholesterol and DHA can regulate AA metabolism and availability in various tissues of piglets. These novel findings have important implications for designing the next generation of infant formula to optimize neonatal growth and development. PMID:18972185

  5. Hybrid striped bass feeds based on fish oil, beef tallow, and eicosapentaenoic acid/docosahexaenoic acid supplements: Insight regarding fish oil sparing and demand for -3 long-chain polyunsaturated fatty acids.

    PubMed

    Bowzer, J; Jackson, C; Trushenski, J

    2016-03-01

    Previous research suggests that saturated (SFA) and monounsaturated fatty acid (MUFA) rich lipids, including beef tallow, can make utilization or diet-to-tissue transfer of long-chain polyunsaturated fatty acids (LC-PUFA) more efficient. We hypothesized that using beef tallow as an alternative to fish oil may effectively reduce the LC-PUFA demand of hybrid striped bass × and allow for greater fish oil sparing. Accordingly, we evaluated growth performance and tissue fatty acid profiles of juvenile fish (23.7 ± 0.3 g) fed diets containing menhaden fish oil (considered an ideal source of LC-PUFA for this taxon), beef tallow (BEEF ONLY), or beef tallow amended with purified sources of eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) to achieve levels corresponding to 50 or 100% of those observed in the FISH ONLY feed. Diets were randomly assigned to quadruplicate tanks of fish ( = 4; 10 fish/tank), and fish were fed assigned diets to apparent satiation once daily for 10 wk. Survival (98-100%) was equivalent among treatments, but weight gain (117-180%), specific growth rate (1.1-1.5% BW/d), feed intake (1.4-1.8% BW/d), thermal growth coefficient (0.50-0.70), and feed conversion ratio (FCR; 1.1-1.4, DM basis) varied. Except for FCR, no differences were observed between the FISH ONLY and BEEF ONLY treatments, but performance was generally numerically superior among fish fed the diets containing beef tallow supplemented with DHA at the 100% or both EPA and DHA at the 50% or 100% level. Tissue fatty acid composition was significantly distorted in favor among fish fed the beef tallow-based feeds; however, profile distortion was most overt in peripheral tissues. Results suggest that beef tallow may be used as a primary lipid source in practical diets for hybrid striped bass, but performance may be improved by supplementation with LC-PUFA, particularly DHA. Furthermore, our results suggest that -3 LC-PUFA requirements reported for hybrid striped bass may not be

  6. [Determination of docosahexaenoic acid in milk powder by gas chromatography using acid hydrolysis].

    PubMed

    Shao, Shiping; Xiang, Dapeng; Li, Shuang; Xi, Xinglin; Chen, Wenrui

    2015-11-01

    A method to determine docosahexenoic acid (DHA) in milk powder by gas chromatography was established. The milk powder samples were hydrolyzed with hydrochloric acid, extracted to get total fatty acids by Soxhlet extractor, then esterified with potassium hydroxide methanol solution to form methyl esters, and treated with sodium hydrogen sulfate. The optimal experiment conditions were obtained from orthogonal experiment L9(3(3)) which performed with three factors and three levels, and it requires the reaction performed with 1 mol/L potassium hydroxide solution at 25 degrees C for 5 min. The derivative treated with sodium hydrogen sulfate was separated on a column of SP-2560 (100 m x 0.25 mm x 0.20 μm), and determined in 55 min by temperature programming-gas chromatography. Good linearity was obtained in the range 5.0-300 mg/L with the correlation coefficient of 0.999 9. The relative standard deviations (RSDs) were 3.4%, 1.2% and 1.1% for the seven repeated experiments of 10, 50 and 100 mg/L of DHA, respectively. The limit of detection was 2 mg/kg, and the recoveries of DHA were in the range of 90.4%-93.5%. The results are satisfactory through the tests of practical samples. PMID:26939370

  7. Selective incorporation of docosahexaenoic acid into lysobisphosphatidic acid in cultured THP-1 macrophages.

    PubMed

    Besson, Nelly; Hullin-Matsuda, Francoise; Makino, Asami; Murate, Motohide; Lagarde, Michel; Pageaux, Jean-Francois; Kobayashi, Toshihide; Delton-Vandenbroucke, Isabelle

    2006-02-01

    Lysobisphosphatidic acid (LBPA) is highly accumulated in specific domains of the late endosome and is involved in the biogenesis and function of this organelle. Little is known about the biosynthesis and metabolism of this lipid. We examined its FA composition and the incorporation of exogenous FA into LBPA in the human monocytic leukemia cell line THP-1. The LBPA FA composition in THP-1 cells exhibits an elevated amount of oleic acid (18:1n-9) and enrichment of PUFA, especially DHA (22:6n-3). DHA supplemented to the medium was efficiently incorporated into LBPA. In contrast, arachidonic acid (20:4n-6) was hardly esterified to LBPA under the same experimental conditions. The turnover of DHA in LBPA was similar to that in other phospholipids. Specific incorporation of DHA into LBPA was also observed in baby hamster kidney fibroblasts, although LBPA in these cells contains very low endogenous levels of DHA in normal growth conditions. Our resuIts, together with published observations, suggest that the specific incorporation of DHA into LBPA is a common phenomenon in mammalian cells. The physiological significance of DHA-enriched LBPA is discussed. PMID:17707985

  8. Utilization of High-Fructose Corn Syrup for Biomass Production Containing High Levels of Docosahexaenoic Acid by a Newly Isolated Aurantiochytrium sp. YLH70.

    PubMed

    Yu, Xin-Jun; Yu, Zhi-Qiang; Liu, Ying-Liang; Sun, Jie; Zheng, Jian-Yong; Wang, Zhao

    2015-11-01

    High-fructose corn syrup (HFCS) is an agro-source product and has been the most commonly used substitute for sugar as sweetener in food industry due to its low price and high solution property. In this study, the F55 HFCS, rich in fructose and glucose, was first tested for biomass and docosahexaenoic acid productions as a mixed carbon source by a newly isolated Aurantiochytrium sp.YLH70. After the compositions of the HFCS media were optimized, the results showed that the HFCS with additions of metal ion and vitamin at low concentrations was suitable for biomass and docosahexaenoic acid productions and the metal ion and sea salt had the most significant effects on biomass production. During the 5-l fed-batch fermentation, total HFCS containing 180 g l(-1) reducing sugar was consumed and yields of biomass, lipid, and DHA could reach 78.5, 51, and 20.1 g l(-1), respectively, at 114 h. Meanwhile, the daily productivity and the reducing sugar conversion yield for docosahexaenoic acid were up to 4.23 g l(-1)day(-1) and 0.11 g g(-1). The fatty acid profile of Aurantiochytrium sp.YLH70 showed that 46.4% of total fatty acid was docosahexaenoic acid, suggesting that Aurantiochytrium sp.YLH70 was a promising DHA producer. PMID:26299378

  9. Rapid incorporation of docosahexaenoic acid from dietary sources into brain microsomal, synaptosomal and mitochondrial membranes in adult mice.

    PubMed

    Suzuki, H; Manabe, S; Wada, O; Crawford, M A

    1997-01-01

    This study examined the incorporation of docosahexaenoic acid (DHA) from several dietary sources into the brain tissue and intracellular organelles in mice which had been fed a 5% palm oil (low n-3 fatty acid level) diet for 8 or 11 weeks. The percentages of DHA in the tissues of mice fed 5% representative oils for 30 days or 5% purified n-3 fatty acid diets for 6 days were analyzed using gas chromatography. The percentage of DHA in the brain was ranked in the following order: the salmon oil diet group > the sardine oil diet group > > the perilla oil diet group > > the lard and palm oil diet groups for the 30 day feeding trial; and the DHA diet group > > the eicosapentaenoic acid and alpha-linolenic acid diet groups for the 6 day feeding trial. The percentage of arachidonic acid showed a more dramatic decrease than that of docosapentaenoic acid. These results reflected the plasma fatty acid concentrations, but were not as pronounced as the changes observed in the plasma. The majority of the DHA incorporated into the brain was recovered in microsomal, synaptosomal, and mitochondrial fractions separated by density gradient centrifugation. These membrane fractions took up DHA within several days. These results suggest that the intake of DHA itself increases the DHA level of brain membranes more rapidly than intake of the precursors in animals fed a low n-3 fatty acid level diet. PMID:9285258

  10. Docosahexaenoic Acid, Inflammation, and Bacterial Dysbiosis in Relation to Periodontal Disease, Inflammatory Bowel Disease, and the Metabolic Syndrome

    PubMed Central

    Tabbaa, Maria; Golubic, Mladen; Roizen, Michael F.; Bernstein, Adam M.

    2013-01-01

    Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid, has been used to treat a range of different conditions, including periodontal disease (PD) and inflammatory bowel disease (IBD). That DHA helps with these oral and gastrointestinal diseases in which inflammation and bacterial dysbiosis play key roles, raises the question of whether DHA may assist in the prevention or treatment of other inflammatory conditions, such as the metabolic syndrome, which have also been linked with inflammation and alterations in normal host microbial populations. Here we review established and investigated associations between DHA, PD, and IBD. We conclude that by beneficially altering cytokine production and macrophage recruitment, the composition of intestinal microbiota and intestinal integrity, lipopolysaccharide- and adipose-induced inflammation, and insulin signaling, DHA may be a key tool in the prevention of metabolic syndrome. PMID:23966110

  11. Feeding nitrate and docosahexaenoic acid affects enteric methane production and milk fatty acid composition in lactating dairy cows.

    PubMed

    Klop, G; Hatew, B; Bannink, A; Dijkstra, J

    2016-02-01

    An experiment was conducted to study potential interaction between the effects of feeding nitrate and docosahexaenoic acid (DHA; C22:6 n-3) on enteric CH4 production and performance of lactating dairy cows. Twenty-eight lactating Holstein dairy cows were grouped into 7 blocks of 4 cows. Within blocks, cows were randomly assigned to 1 of 4 treatments: control (CON; urea as alternative nonprotein N source to nitrate), NO3 [21 g of nitrate/kg of dry matter (DM)], DHA (3 g of DHA/kg of DM and urea as alternative nonprotein N source to nitrate), or NO3 + DHA (21 g of nitrate/kg of DM and 3 g of DHA/kg of DM, respectively). Cows were fed a total mixed ration consisting of 21% grass silage, 49% corn silage, and 30% concentrates on a DM basis. Feed additives were included in the concentrates. Cows assigned to a treatment including nitrate were gradually adapted to the treatment dose of nitrate over a period of 21 d during which no DHA was fed. The experimental period lasted 17 d, and CH4 production was measured during the last 5d in climate respiration chambers. Cows produced on average 363, 263, 369, and 298 g of CH4/d on CON, NO3, DHA, and NO3 + DHA treatments, respectively, and a tendency for a nitrate × DHA interaction effect was found where the CH4-mitigating effect of nitrate decreased when combined with DHA. This tendency was not obtained for CH4 production relative to dry matter intake (DMI) or to fat- and protein corrected milk (FPCM). The NO3 treatment decreased CH4 production irrespective of the unit in which it was expressed, whereas DHA did not affect CH4 production per kilogram of DMI, but resulted in a higher CH4 production per kilogram of fat- and protein-corrected milk (FPCM) production. The FPCM production (27.9, 24.7, 24.2, and 23. 8 kg/d for CON, NO3, DHA, and NO3 + DHA, respectively) was lower for DHA-fed cows because of decreased milk fat concentration. The proportion of saturated fatty acids in milk fat was decreased by DHA, and the proportion of

  12. Docosahexaenoic acid supplementation decreases remnant-like particle-cholesterol and increases omega-3 index in hypertriglyceridemic men1-3.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Plasma remnant-like particle-cholesterol (RLP-C) and RBC omega-3 index are novel risk factors for cardiovascular disease. Effects of docosahexaenoic acid (DHA) supplementation on these risk factors in hypertriglyceridemic men have not been studied. Objective: We determined effects of DHA...

  13. Effect of early maternal docosahexaenoic acid intake on neuropsychological status and visual acuity at five years of age of breast-fed infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously reported better psychomotor development at 30 months of age in infants whose mothers received a docosahexaenoic acid (DHA) supplement for the first 4 months of lactation. We now assess neuropsychological and visual function of the same children at 5 years of age. Breastfeeding women w...

  14. Producing Docosahexaenoic Acid (DHA)-Rich Algae from Biodiesel-Derived Crude Glycerol: Effects of Impurities on DHA Production and Algal Biomass Composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crude glycerol is the primary byproduct of the biodiesel industry. Producing docosahexaenoic acid (DHA, 22:6 n-3) through fermentation of the alga Schizochytrium limacinum on crude glycerol provides a unique opportunity to utilize a large quantity of this byproduct. The objective of this work is to...

  15. Maternal Docosahexaenoic Acid Intake Levels during Pregnancy and Infant Performance on a Novel Object Search Task at 22 Months

    ERIC Educational Resources Information Center

    Rees, Alison; Sirois, Sylvain; Wearden, Alison

    2014-01-01

    This study investigated maternal prenatal docosahexaenoic acid (DHA) intake and infant cognitive development at 22 months. Estimates for second- and third-trimester maternal DHA intake levels were obtained using a comprehensive Food Frequency Questionnaire. Infants (n = 67) were assessed at 22 months on a novel object search task. Mothers'…

  16. alpha-Linolenic acid- and docosahexaenoic acid-enriched eggs from hens fed flaxseed: influence on blood lipids and platelet phospholipid fatty acids in humans.

    PubMed

    Ferrier, L K; Caston, L J; Leeson, S; Squires, J; Weaver, B J; Holub, B J

    1995-07-01

    This study was undertaken to examine the effects that consumption of eggs from hens fed diets containing flaxseed would have on plasma and platelet lipids of male volunteers. Feeding diets containing 0%, 10%, and 20% ground flaxseed to Leghorn pullets provided a marked progressive increase in n-3 fatty acid content as alpha-linolenic acid (alpha-LNA) (28, 261, and 527 mg/egg) and docosahexaenoic acid (DHA) (51, 81, and 87 mg/egg) but no alteration in the cholesterol concentration of the egg yolk. Twenty-eight male volunteers, divided into three groups, were fed four eggs per day for 2 wk according to a cyclic Latin-square design. No statistically significant changes were observed in total cholesterol, high-density-lipoprotein cholesterol, or plasma triglyceride concentrations. Significant increases in total n-3 fatty acids and in DHA content (which rose from 1.5 to 2.0% by wt or 33% overall), and a significant decrease in ratio of n-6 to n-3 fatty acids were found in platelet phospholipids of subjects consuming eggs from flaxseed-fed hens. Health and Welfare Canada in 1990 set recommended intakes for dietary n-3 fatty acids and for the ratio of n-6 to n-3 fatty acids, which are not being met currently by the overall population. Eggs modified by the inclusion of flaxseed in the laying hens' diet could provide an important nutritional source of n-3 fatty acid. PMID:7598070

  17. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  18. Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures.

    PubMed

    Tao, Guorong; Luo, Yan; Xue, Qingsheng; Li, Guohui; Tan, Yongchang; Xiao, Jinglei; Yu, Buwei

    2016-01-01

    Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures. PMID:27597963

  19. Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures

    PubMed Central

    Tao, Guorong; Luo, Yan; Xue, Qingsheng; Li, Guohui; Tan, Yongchang

    2016-01-01

    Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures. PMID:27597963

  20. Neuron-astrocyte interactions in spinal cord dorsal horn in neuropathic pain development and docosahexaenoic acid therapy.

    PubMed

    Manzhulo, Igor V; Ogurtsova, Olga S; Kipryushina, Yuliya O; Latyshev, Nikolay A; Kasyanov, Sergey P; Dyuizen, Inessa V; Tyrtyshnaia, Anna A

    2016-09-15

    The analgesic activity of docosahexaenoic acid (DHA, 22:6 n-3) was studied using a chronic constriction injury (CCI) rat model. Animals were subcutaneously injected with DHA emulsion at a dose of 4.5mg/kg (125mМ/kg) daily during 2weeks after surgery. We characterized the dynamics of GFAP-positive astrocyte, substance P (SP) and nNOS-positive neurons activity in the spinal cord dorsal horn (SCDH) superficial lamina. We found that DHA treatment decrease the intensity and duration of neurogenic pain syndrome, results in earlier stabilization of weight distribution, prevents the cold allodynia and dystrophic changings in denervated limb tissue. DHA treatment reduced the reactive astrocyte number, decrease SP-immunopositive fibers and nNOS-positive neurons number in the SCDH in neuropathic pain. PMID:27609281

  1. Plasma phospholipid pentadecanoic acid, EPA, and DHA, and the frequency of dairy and fish product intake in young children

    PubMed Central

    Lund-Blix, Nicolai A.; Rønningen, Kjersti S.; Bøås, Håkon; Tapia, German; Andersen, Lene F.

    2016-01-01

    Background There is a lack of studies comparing dietary assessment methods with the biomarkers of fatty acids in children. Objective The objective was to evaluate the suitability of a food frequency questionnaire (FFQ) to rank young children according to their intake of dairy and fish products by comparing food frequency estimates to the plasma phospholipid fatty acids pentadecanoic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Design Cross-sectional data for the present study were derived from the prospective cohort ‘Environmental Triggers of Type 1 Diabetes Study’. Infants were recruited from the Norwegian general population during 2001–2007. One hundred and ten (age 3–10 years) children had sufficient volumes of plasma and FFQ filled in within 2 months from blood sampling and were included in this evaluation study. The quantitative determination of plasma phospholipid fatty acids was done by fatty acid methyl ester analysis. The association between the frequency of dairy and fish product intake and the plasma phospholipid fatty acids was assessed by a Spearman correlation analysis and by investigating whether participants were classified into the same quartiles of distribution. Results Significant correlations were found between pentadecanoic acid and the intake frequency of total dairy products (r=0.29), total fat dairy products (r=0.39), and cheese products (r=0.36). EPA and DHA were significantly correlated with the intake frequency of oily fish (r=0.26 and 0.37, respectively) and cod liver/fish oil supplements (r=0.47 for EPA and r=0.50 DHA). To a large extent, the FFQ was able to classify individuals into the same quartile as the relevant fatty acid biomarker. Conclusions The present study suggests that, when using the plasma phospholipid fatty acids pentadecanoic acid, EPA, and DHA as biomarkers, the FFQ used in young children showed a moderate capability to rank the intake frequency of dairy products with a high-fat content

  2. CYP epoxygenase metabolites of docosahexaenoic acid protect HL-1 cardiac cells against LPS-induced cytotoxicity through SIRT1

    PubMed Central

    Samokhvalov, V; Jamieson, K L; Vriend, J; Quan, S; Seubert, J M

    2015-01-01

    Bacterial LPS is an environmental toxin capable of promoting various cardiac complications. Current evidence suggests that LPS-induced myocardial dysfunction emerges as a consequence of compromised quality of cardiac mitochondria. Docosahexaenoic acid (DHA, 22:6n3) is an n-3 polyunsaturated fatty acid (PUFA), which produces a broad spectrum of intrinsic physiological effects including regulation of cell survival and death mechanisms. Although, numerous studies revealed fundamentally beneficial effects of DHA on cardiovascular system, it remains unknown whether these effects were produced by DHA or one of its possibly more potent metabolites. Emerging evidence indicates that cytochrome P450 (CYP) epoxygenase metabolites of DHA, epoxydocosapentaenoic acids (EDPs), produce more potent biological activity compared to its precursor DHA. In this study, we investigated whether DHA and its metabolite 19,20-EDP could protect HL-1 cardiac cells against LPS-induced cytotoxicity. We provide evidence that exogenously added or DHA-derived EDPs promote mitochondrial biogenesis and function in HL-1 cardiac cells. Our results illustrate the CYP epoxygenase metabolite of DHA, 19,20-EDP, confers extensive protection to HL-1 cardiac cells against LPS-induced cytotoxicity via activation of SIRT1. PMID:27182450

  3. Improved docosahexaenoic acid production in Aurantiochytrium by glucose limited pH-auxostat fed-batch cultivation.

    PubMed

    Janthanomsuk, Panyawut; Verduyn, Cornelis; Chauvatcharin, Somchai

    2015-11-01

    Fed-batch, pH auxostat cultivation of the docosahexaenoic acid (DHA)-producing microorganism Aurantiochytrium B072 was performed to obtain high cell density and record high productivity of both total fatty acid (TFA) and DHA. Using glucose feeding by carbon excess (C-excess) and by C-limitation at various feeding rates (70%, 50% or 20% of C-excess), high biomass density was obtained and DHA/TFA content (w/w) was improved from 30% to 37% with a 50% glucose feed rate when compared with C-excess. To understand the biochemistry behind these improvements, lipogenic enzyme assays and in silico metabolic flux calculations were used and revealed that enzyme activity and C-fluxes to TFA were reduced with C-limited feeding but that the carbon flux to the polyketide synthase pathway increased relative to the fatty acid synthase pathway. As a result, a new strategy to improve the DHA to TFA content while maintaining relatively high DHA productivity is proposed. PMID:26298403

  4. The Role of Docosahexaenoic Acid (DHA) in the Control of Obesity and Metabolic Derangements in Breast Cancer

    PubMed Central

    Molfino, Alessio; Amabile, Maria Ida; Monti, Massimo; Arcieri, Stefano; Rossi Fanelli, Filippo; Muscaritoli, Maurizio

    2016-01-01

    Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies. PMID:27058527

  5. The Role of Docosahexaenoic Acid (DHA) in the Control of Obesity and Metabolic Derangements in Breast Cancer.

    PubMed

    Molfino, Alessio; Amabile, Maria Ida; Monti, Massimo; Arcieri, Stefano; Rossi Fanelli, Filippo; Muscaritoli, Maurizio

    2016-01-01

    Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies. PMID:27058527

  6. Effects of docosahexaenoic acid and sardine oil diets on the ultrastructure of jejunal absorptive cells in adult mice.

    PubMed

    Tamura, M; Suzuki, H

    1996-01-01

    The influence of docosahexaenoic acid (DHA) and sardine oil diets on the ultrastructure of jejunal absorptive cells was studied. Adult male Crj:CD-1 (ICR) mice were fed a fat-free semisynthetic diet supplemented with 5% (by weight) purified DHA ethyl ester, refined sardine oil, or palm oil. The mice received the DHA or palm oil diets for 7 days (groups 1 and 2) and the refined sardine oil or palm oil diets for 30 days (groups 3 and 4). There were significant ultrastructural changes in the jejunal absorptive cells between the mice fed on the palm oil diet and those receiving the DHA and sardine oil diets. The endoplasmic reticulum and Golgi apparatus of some jejunal absorptive cells in the mice fed on the palm oil diet for 7 and 30 days developed vacuolation on the upper site of the nucleus. In contrast, many granules, which appeared to be lipid droplets, were observed in the endoplasmic reticulum and Golgi apparatus of the jejunal absorptive cells in the DHA and sardine oil diet groups. These results suggest that ultrastructural differences in the jejunal absorptive cells between mice in the omega-3 fatty acid and palm oil diet groups may be associated with the changes in lipid metabolism. PMID:9001686

  7. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis.

    PubMed

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik; Jeong, Soyeon; Shin, Soyeon; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-01-30

    Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson's disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson's disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis. PMID:25545062

  8. Moderate oral supplementation with docosahexaenoic acid improves platelet function and oxidative stress in type 2 diabetic patients.

    PubMed

    Véricel, E; Colas, R; Calzada, C; Lê, Q H; Feugier, N; Cugnet, C; Vidal, H; Laville, M; Moulin, P; Lagarde, M

    2015-08-01

    Platelets from patients with type 2 diabetes are characterised by hyperactivation and high level of oxidative stress. Docosahexaenoic acid (DHA) may have beneficial effects on platelet reactivity and redox status. We investigated whether moderate DHA supplementation, given as a triglyceride form, may correct platelet dysfunction and redox imbalance in patients with type 2 diabetes. We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (n=11 post-menopausal women with type 2 diabetes) to test the effects of 400 mg/day of DHA intake for two weeks on platelet aggregation, markers of arachidonic acid metabolism, lipid peroxidation status, and lipid composition. Each two week-period was separated from the other by a six-week washout. Daily moderate dose DHA supplementation resulted in reduced platelet aggregation induced by collagen (-46.5 %, p< 0.001), and decreased platelet thromboxane B2 (-35 %, p< 0.001), urinary 11-dehydro-thromboxane B2 (-13.2 %, p< 0.001) and F2-isoprostane levels (-19.6 %, p< 0.001) associated with a significant increase of plasma and platelet vitamin E concentrations (+20 % and +11.8 %, respectively, p< 0.001). The proportions of DHA increased both in plasma lipids and in platelet phospholipids. After placebo treatment, there was no effect on any parameters tested. Our findings support a significant beneficial effect of low intake of DHA on platelet function and a favourable role in reducing oxidative stress associated with diabetes. PMID:25832443

  9. Oxidized derivative of docosahexaenoic acid preferentially inhibit cell proliferation in triple negative over luminal breast cancer cells

    PubMed Central

    El-Bayoumy, Karam; Amin, Shantu; Gowda, Krishne; de Cicco, Ricardo López; Barton, Maria; Su, Yanrong; Russo, Irma H.; Himmelberger, Julie A.; Slifker, Michael; Manni, Andrea; Russo, Jose

    2016-01-01

    Omega-3 polyunsaturated fatty acids (PUFAs) exert an anticancer effect by affecting multiple cellular mechanisms leading to inhibition of proliferation and induction of apoptosis. It is well known that breast cancer comprises distinct molecular subtypes which differ in their responsiveness to therapeutic and preventive agents. We tested the hypothesis that n-3FA may preferentially affect triple-negative breast cancer cells for which no targeted intervention is presently available. The in vitro antiproliferative effects of n-3 PUFA docosahexaenoic acid (DHA) and its metabolite, 4-OH-DHA as well as its putative metabolite 4-OXO-DHA, were tested in five triple-negative human basal breast cell lines at different stages of transformation (MCF-10F, trMCF, bsMCF, MDA-MB-231, and BT-549) and three luminal breast cancer cell lines (MCF-7, T-47D, and SK-BR-3). Cell proliferation was measured with the tetrazolium MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay. DHA and its oxidized derivatives significantly inhibited cell proliferation (20–90% reduction) of both basal and luminal breast cancer cell lines. The inhibitory effect was more pronounced on triple-negative basal breast cancer cell lines as compared to luminal breast cancer cell lines after 4-OXO-DHA treatment. Our data provide novel information regarding the preferential antitumor effect of oxidized derivatives of DHA on basal type breast cancer. PMID:25413005

  10. Docosahexaenoic acid inhibits the invasion of MDA-MB-231 breast cancer cells through upregulation of cytokeratin-1.

    PubMed

    Blanckaert, Vincent; Kerviel, Vincent; Lépinay, Alexandra; Joubert-Durigneux, Vanessa; Hondermarck, Hubert; Chénais, Benoît

    2015-01-01

    Docosahexaenoic acid (DHA), the main member of the omega-3 essential fatty acid family, has been shown to reduce the invasion of the triple-negative breast cancer cell line MDA-MB-231, but the mechanism involved remains unclear. In the present study, a proteomic approach was used to define changes in protein expression induced by DHA. Proteins from crude membrane preparations of MDA-MB-231 cells treated with 100 µM DHA were separated by two-dimensional electrophoresis (2-DE) and differentially expressed proteins were identified using MALDI-TOF mass spectrometry. The main changes observed were the upregulation of Keratin, type Ⅱ cytoskeletal 1 (KRT1), catalase and lamin-A/C. Immunocytochemistry analyses confirmed the increase in KRT1 induced by DHA. Furthermore, in vitro invasion assays showed that siRNA against KRT1 was able to reverse the DHA-induced inhibition of breast cancer cell invasion. In conclusion, KRT1 is involved in the anti-invasive activity of DHA in breast cancer cells. PMID:25825023

  11. Docosahexaenoic acid intake ameliorates ketamine-induced impairment of spatial cognition and learning ability in ICR mice.

    PubMed

    Huang, Shucai; Dai, Yuanyuan; Zhang, Zhiwen; Hao, Wei; Chen, Hongxian

    2014-09-19

    Several studies have reported the ketamine-induced cognitive impairment. Docosahexaenoic acid (DHA) supplementation improves cognitive function in human infants and protects against learning impairment in patients with Alzheimer's disease (AD). In this study, we investigated the effect of DHA on ketamine-induced impairment of spatial cognition and learning ability in Institute of Cancer Research (ICR) mice. Morris water maze (MWM) was used to assess spatial learning and memory. Gamma-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex were measured using high-performance liquid chromatography (HPLC). The results showed that intraperitoneal injection of ketamine (30mg/kg, twice per day) for 4 weeks led to the decline of spatial cognitive ability in mice, and 420mg/(kgd) DHA supplementation for 6 weeks improved ketamine-induced spatial cognitive impairment to a certain extent. The up-regulation of GABA levels in the hippocampus and prefrontal cortex was related to the improvement in spatial learning. Our results suggested that DHA supplementation would be a promising intervention to improve ketamine-induced spatial memory and cognitive dysfunction, and this effect of DHA might be correlated with the up-regulation of GABA levels. PMID:25123439

  12. Docosahexaenoic Acid Conjugation Enhances Distribution and Safety of siRNA upon Local Administration in Mouse Brain.

    PubMed

    Nikan, Mehran; Osborn, Maire F; Coles, Andrew H; Godinho, Bruno Mdc; Hall, Lauren M; Haraszti, Reka A; Hassler, Matthew R; Echeverria, Dimas; Aronin, Neil; Khvorova, Anastasia

    2016-01-01

    The use of siRNA-based therapies for the treatment of neurodegenerative disease requires efficient, nontoxic distribution to the affected brain parenchyma, notably the striatum and cortex. Here, we describe the synthesis and activity of a fully chemically modified siRNA that is directly conjugated to docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in the mammalian brain. DHA conjugation enables enhanced siRNA retention throughout both the ipsilateral striatum and cortex following a single, intrastriatal injection (ranging from 6-60 μg). Within these tissues, DHA conjugation promotes internalization by both neurons and astrocytes. We demonstrate efficient and specific silencing of Huntingtin mRNA expression in both the ipsilateral striatum (up to 73%) and cortex (up to 51%) after 1 week. Moreover, following a bilateral intrastriatal injection (60 μg), we achieve up to 80% silencing of a secondary target, Cyclophilin B, at both the mRNA and protein level. Importantly, DHA-hsiRNAs do not induce neural cell death or measurable innate immune activation following administration of concentrations over 20 times above the efficacious dose. Thus, DHA conjugation is a novel strategy for improving siRNA activity in mouse brain, with potential to act as a new therapeutic platform for the treatment of neurodegenerative disorders. PMID:27504598

  13. Docosahexaenoic acid attenuates in endocannabinoid synthesis in RAW 264.7 macrophages activated with benzo(a)pyrene and lipopolysaccharide.

    PubMed

    Gdula-Argasińska, Joanna; Bystrowska, Beata

    2016-09-01

    Endocannabinoids are synthetized as a results of demand from membrane phospholipids. The formation and actions of these lipid mediators depend to a great extent on the prevalence of precursor fatty acid (FA), and can be influenced by diet or supplementation. The purpose of this study was to evaluate the interactive effects of lipopolysaccharide (LPS) and benzo(a)pyrene (BaP) in RAW 264.7 cells supplemented with docosahexaenoic acid (DHA). After LPS and/or BaP treatment in macrophages pre-incubated with DHA, a significant decrease in the amount of fatty acid was observed. The highest content of monounsaturated fatty acids was detected in RAW 264.7 cells co-treated with LPS and BaP. Significant interactions between LPS and BaP co-treatment in terms of endocannabinoid levels were observed in RAW 264.7 cells after DHA supplementation. The highest amount of endocannabinoids was detected in macrophages supplemented with DHA and co-treated with BaP and LPS: arachidonoyl ethanolamine AEA (5.9μg/mL), docosahexaenoyl ethanolamide DHEA (10.6μg/mL) and nervonoyl ethanolamide NEA (16.5μg/mL). The highest expression of cyclooxygenase (COX-2) and cannabinoid receptor 2 (CB2) was noted in macrophages supplemented with DHA and activated with LPS and BaP. Our data suggested a novel, CB2 receptor-dependent, environmental stress reaction in macrophages co-treated with LPS and BaP after supplementation with DHA. Despite the synergistic LPS and BaP action DHA potentiates the anti-inflammatory response in RAW 264.7 cells. PMID:27329536

  14. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA

    PubMed Central

    Dyall, Simon C.

    2015-01-01

    Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for a variety of neurodegenerative and neurological disorders. However, traditionally there has been a lack of discrimination between the different omega-3 PUFAs and effects have been broadly accredited to the series as a whole. Evidence for unique effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood disorders have more consistently been reported in clinical trials using EPA; whereas, with neurodegenerative conditions such as Alzheimer’s disease, the focus has been on DHA. DHA is quantitatively the most important omega-3 PUFA in the brain, and consequently the most studied, whereas the availability of high purity DPA preparations has been extremely limited until recently, limiting research into its effects. However, there is now a growing body of evidence indicating both independent and shared effects of EPA, DPA and DHA. The purpose of this review is to highlight how a detailed understanding of these effects is essential to improving understanding of their therapeutic potential. The review begins with an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on the central nervous system (CNS), where DHA has unique and indispensable roles in neuronal membranes with levels preserved by multiple mechanisms. This is followed by a review of the different enzyme-derived anti-inflammatory mediators produced from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and DHA in normal brain aging and the most common neurodegenerative disorders are discussed. With a greater understanding of the individual roles of EPA, DPA and DHA in brain health and repair it is hoped that appropriate dietary recommendations can be established and therapeutic interventions can be more targeted and refined. PMID:25954194

  15. Docosahexaenoic acid differentially affects TNFα and IL-6 expression in LPS-stimulated RAW 264.7 murine macrophages.

    PubMed

    Honda, Kaori L; Lamon-Fava, Stefania; Matthan, Nirupa R; Wu, Dayong; Lichtenstein, Alice H

    2015-06-01

    Docosahexaenoic acid (DHA) is generally reported to have anti-inflammatory properties, however, prior work has documented differential effects on individual pro-inflammatory cytokines: reduced IL-6, but not TNFα, mRNA expression in macrophages. To elucidate the mechanism, the roles of prostaglandin E2 (PGE2), cyclic AMP response element-binding protein (CREB), and NFκB were examined in RAW 264.7 macrophages. DHA did not influence CREB activity, but significantly reduced PGE2 production by 41% and NFκB activity by 32%. Exogenous PGE2 inhibited TNFα mRNA expression dose dependently. Unexpectedly, inhibiting PGE2 production with NS-398 also decreased TNFα mRNA expression, suggesting a concentration-dependent dual role of PGE2 in regulating TNFα expression. IL-6 expression was unaffected by endogenous or exogenous PGE2. Partial block of NFκB activation (SN50; 46%, or, BAY-11-7082; 41%) lowered IL-6 to a greater extent than TNFα mRNA expression. The differential effect of DHA on TNFα and IL-6 mRNA expression may be mediated via reduction in NFκB activity. PMID:25921297

  16. Docosahexaenoic acid differentially affects TNFα and IL-6 expression in LPS-stimulated RAW 264.7 murine macrophages

    PubMed Central

    Honda, Kaori L.; Lamon-Fava, Stefania; Matthan, Nirupa R.; Wu, Dayong; Lichtenstein, Alice H.

    2015-01-01

    Docosahexaenoic acid (DHA) is generally reported to have anti-inflammatory properties, however, prior work has documented differential effects on individual pro-inflammatory cytokines: reduced IL-6, but not TNFα, mRNA expression in macrophages. To elucidate the mechanism, the roles of prostaglandin E2 (PGE2), cyclic AMP response element-binding protein (CREB), and NFκB were examined in RAW 264.7 macrophages. DHA did not influence CREB activity, but significantly reduced PGE2 production by 41% and NFκB activity by 32%. Exogenous PGE2 inhibited TNFα mRNA expression dose dependently. Unexpectedly, inhibiting PGE2 production with NS-398 also decreased TNFα mRNA expression, suggesting a concentration-dependent dual role of PGE2 in regulating TNFα expression. IL-6 expression was unaffected by endogenous or exogenous PGE2. Partial block of NFκB activation (SN50; 46%, or, BAY-11-7082; 41%) lowered IL-6 to a greater extent than TNFα mRNA expression. The differential effect of DHA on TNFα and IL-6 mRNA expression may be mediated via reduction in NFκB activity. PMID:25921297

  17. Feeding a Diet Enriched in Docosahexaenoic Acid to Lactating Dams Improves the Tolerance Response to Egg Protein in Suckled Pups

    PubMed Central

    Richard, Caroline; Lewis, Erin D.; Goruk, Susan; Field, Catherine J.

    2016-01-01

    The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) during the suckling period on the development of the immune system and oral tolerance (OT) in offspring. Dams were randomized to consume one of two nutritionally adequate diets throughout the suckling period: control (N = 12, 0% DHA) or DHA (N = 8, 0.9% DHA) diet. At 11 days, pups from each dam were randomly assigned to a mucosal OT challenge: the placebo or the ovalbumin (OVA) treatment. At three weeks, plasma immunoglobulins and splenocyte cytokine production ex vivo were measured. OVA-tolerized pups had a lower Th2 (IL-13) response to OVA despite the presence of more activated T cells and memory cells (CD27+, all p < 0.05). Feeding a high DHA diet improved the ability of splenocytes to respond to mitogens toward a skewed Th1 response and led to a higher IL-10 and a lower TGF-β production after stimulation with OVA (all p < 0.05). Untolerized DHA-fed pups had lower plasma concentrations of OVA-specific immunoglobulin E (p for interaction < 0.05). Overall, feeding a high DHA maternal diet improves the tolerance response in untolerized suckled pups in a direction that is thought to be beneficial for the establishment of OT. PMID:26907333

  18. Safety of docosahexaenoic acid (DHA) administered as DHA ethyl ester in a 9-month toxicity study in dogs.

    PubMed

    Dahms, Irina; Beilstein, Paul; Bonnette, Kimberly; Salem, Norman

    2016-06-01

    DHA Ethyl Ester (DHA-EE) is a 90% concentrated ethyl ester of docosahexaenoic acid manufactured from the microalgal oil. The objective of the 9-month study was to evaluate safety of DHA-EE administered to beagle dogs at dose levels 150, 1000 and 2000 mg/kg bw/day by oral gavage and to determine reversibility of any findings after a 2-month recovery period. DHA-EE was well tolerated at all doses. There were observations of dry flaky skin with occasional reddened areas at doses ≥1000 mg/kg bw/day. These findings lacked any microscopic correlate and were no longer present after the recovery period. There were no toxicologically relevant findings in body weights, body weight gains, food consumption, ophthalmological examinations, and ECG measurements. Test article-related changes in hematology parameters were limited to decreases in reticulocyte count in the high-dose males and considered non-adverse. In clinical chemistry parameters, dose-related decreases in cholesterol and triglycerides levels were observed at all doses in males and females and attributed to the known lipid-lowering effects of DHA. There were no effects on other clinical chemistry, urinalysis or coagulation parameters. There were no abnormal histopathology findings attributed to test article. The No-Observable-Adverse-Effect Level of DHA-EE was established at 2000 mg/kg bw/day for both genders. PMID:27036332

  19. Production of high docosahexaenoic acid by Schizochytrium sp. using low-cost raw materials from food industry.

    PubMed

    Song, Xiaojin; Zang, Xiaonan; Zhang, Xuecheng

    2015-01-01

    The low-cost substrates from food industry, including maize starch hydrolysate and soybean meal hydrolysate, were used to produce docosahexaenoic acid (DHA) by Schizochytrium limacinum OUC88. Glucose derived from maize starch hydrolysate was used as the carbon source and soybean meal hydrolysate as the nitrogen sources. In 10L bioreactor fermentation, by using the soybean meal hydrolysate as the main nitrogen source, the biomass of Schizochytrium limacinum OUC88 reached 85.27 g L(-1), and the yields of DHA was 20.7g L(-1). As a comparison, when yeast extract was used as the main nitrogen source, the yields of biomass and DHA were 68.93 g L(-1) and 13.3 g L(-1), respectively. From the results of this study, these hydrolysates can provide all the nutrients required for high-density cultivation of S. limacinum OUC88 and DHA production, that will improve the economical and competitive efficiency of commercial DHA production. PMID:25748379

  20. Neuroprotective effect of docosahexaenoic acid nanoemulsion on erectile function in a rat model of bilateral cavernous nerve injury.

    PubMed

    Liao, Chun-Hou; Wu, Yi-No; Chen, Bin-Huei; Lin, Ying-Hung; Ho, Hsiu-O; Chiang, Han-Sun

    2016-01-01

    There is an unmet need for treatment of erectile dysfunction resulting from radical prostatectomy and cavernous nerve (CN) injury. Given the neuroprotective properties of docosahexaenoic acid (DHA), we investigated its effect on penile functional and structural recovery in a rat model of bilateral cavernous nerve injury. Rats were subject to CN injury and received intraperitoneal administration of either vehicle or a DHA nanoemulsion (nano-DHA) at 10, 50, or 250 μg/kg. Functional testing and histological analyses were performed at 28 days post-injury. The maximum intracavernosal pressure (ICP) and other measures of erectile function were significantly higher in the nano-DHA groups than in the vehicle group (p < 0.05). The ratio of area of expression of neuronal nitric oxide synthase (nNOS)/β-III tubulin, numbers of axon and smooth muscle cell content were significantly higher in the 50 μg/kg nano-DHA group than in the vehicle group (p < 0.05). A qualitative increase in the smooth muscle cells/collagen ratio and decrease in apoptosis was observed in the nano-DHA groups relative to the vehicle group: however, these differences were not statistically significant. Our data demonstrate that nano-DHA, particularly the 50 μg/kg regimen, improves erectile function after bilateral CN injury in rats by neuroprotection and other anti-fibrotic and anti-apoptotic mechanisms. PMID:27625175

  1. Docosahexaenoic Acid-Phosphatidylcholine Improves Cognitive Deficits in an Aβ23-35-Induced Alzheimer's Disease Rat Model.

    PubMed

    Qu, Mei-Hua; Yang, Xiaoyun; Wang, Yuming; Tang, Qingjuan; Han, Hailin; Wang, Jia; Wang, Guo-Du; Xue, Changhu; Gao, Zhiqin

    2016-01-01

    Both Docosahexaenoic acid (DHA) and Phosphatidylcholine (PC) have been shown to halt the pathogenesis of Alzheimer disease (AD) and vascular dementia. This study aimed to investigate the role of DHA-containing PC (DHA-PC) in the improvement of Aβ25-35-induced cognitive deficits in rats. Aβ25-35-induced AD rats were treated for 30 days with DHA-PC, which was extracted from Sthenoteuthis oualaniensis spawns. Cognitive improvement of the AD rats was detected using the Morris water maze (MWM). The results demonstrated that DHA-PC could improve the learning and memory abilities of AD rats in a dose-dependent pattern. Further analyses showed that expression of phosphorylated tau decreased, and the neuronal morphology recovered in brains of DHA-PC-treated AD rats, as compared with mock-treated AD rats. In addition, DHAPC treatment increased the activity of GSH-Px and SOD in the cortex and hippocampus of AD rats. Taken together, these data suggest that DHA-PC is able to improve the cognitive deficits in AD rats, probably through decreasing the phosphorylation of tau in the cortex and hippocampus CA1 area, and increasing the GSH-Px and SOD activities in the brain of AD rats. PMID:26268328

  2. Docosahexaenoic acid enhances iron uptake by modulating iron transporters and accelerates apoptotic death in PC12 cells.

    PubMed

    Schonfeld, Eldi; Yasharel, Ilanit; Yavin, Ephraim; Brand, Annette

    2007-10-01

    The effect of docosahexaenoic acid (DHA; 22:6 n-3) on Fe(2+)-mediated and/or H(2)O(2)-mediated oxidative stress (OS) was investigated in a PC12 pheochromocytoma cell line in the presence or absence of 50 ng/ml nerve growth factor (NGF). DHA-supplemented cells showed enhanced Fe(2+)-induced cell damage as evident by increased lipid peroxides formation (10-fold) and reduced neutral red (NR) dye uptake in a NGF-independent fashion. DHA caused a nearly 10-fold increase in free iron uptake in NGF-treated cells and doubled iron uptake in nondifferentiated cells. DHA-enrichment induced an elevation in the transferrin receptor protein in the nondifferentiated cells whereas NGF-treatment led to a substantial increase in the ubiquitous divalent metal ion transporter 1 (DMT-1) as detected by mRNA levels using qRT-PCR. The mechanism of action of DHA to accelerate cell death may be associated with the externalization of amino-phosphoglycerides (PG) species of which, increased ethanolamine plasmalogen levels, may be essential for cell rescue as noted in NGF-treated PC12 cells. PMID:17551831

  3. Effects of Docosahexaenoic Acid Supplementation on Blood Pressure, Heart Rate, and Serum Lipids in Scottish Men with Hypertension and Hypercholesterolemia

    PubMed Central

    Sagara, Miki; Njelekela, Marina; Teramoto, Takanori; Taguchi, Takashi; Mori, Mari; Armitage, Lesley; Birt, Nina; Birt, Christopher; Yamori, Yukio

    2011-01-01

    To investigate the effects of daily supplementation with docosahexaenoic acid (DHA) on coronary heart disease risks in 38 middle-aged men with hypertension and/or hypercholesterolemia in Scotland, a five-week double-blind placebo-controlled dietary supplementation with either 2 g of DHA or active placebo (1 g of olive oil) was conducted. Percent composition of DHA in plasma phospholipids increased significantly in DHA group. Systolic and diastolic blood pressure and heart rate decreased significantly in DHA group, but not in placebo group. High-density lipoprotein cholesterol (HDL-C) increased significantly, and total cholesterol (TC)/HDL-C and non-HDL-C/HDL-C ratios decreased significantly in both groups. There was no change in TC and non-HDL-C. We conclude that 2 g/day of DHA supplementation reduced coronary heart disease risk factor level improving blood pressure, heart rate, and lipid profiles in hypertensive, hypercholesterolemic Scottish men who do not eat fish on a regular basis. PMID:21423683

  4. Mechanisms for the activation of Toll-like receptor 2/4 by saturated fatty acids and inhibition by docosahexaenoic acid.

    PubMed

    Hwang, Daniel H; Kim, Jeong-A; Lee, Joo Young

    2016-08-15

    Saturated fatty acids can activate Toll-like receptor 2 (TLR2) and TLR4 but polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA) inhibit the activation. Lipopolysaccharides (LPS) and lipopetides, ligands for TLR4 and TLR2, respectively, are acylated by saturated fatty acids. Removal of these fatty acids results in loss of their ligand activity suggesting that the saturated fatty acyl moieties are required for the receptor activation. X-ray crystallographic studies revealed that these saturated fatty acyl groups of the ligands directly occupy hydrophobic lipid binding domains of the receptors (or co-receptor) and induce the dimerization which is prerequisite for the receptor activation. Saturated fatty acids also induce the dimerization and translocation of TLR4 and TLR2 into lipid rafts in plasma membrane and this process is inhibited by DHA. Whether saturated fatty acids induce the dimerization of the receptors by interacting with these lipid binding domains is not known. Many experimental results suggest that saturated fatty acids promote the formation of lipid rafts and recruitment of TLRs into lipid rafts leading to ligand independent dimerization of the receptors. Such a mode of ligand independent receptor activation defies the conventional concept of ligand induced receptor activation; however, this may enable diverse non-microbial molecules with endogenous and dietary origins to modulate TLR-mediated immune responses. Emerging experimental evidence reveals that TLRs play a key role in bridging diet-induced endocrine and metabolic changes to immune responses. PMID:27085899

  5. Switching from EPA + DHA (Omega-3-acid Ethyl Esters) to High-Purity EPA (Icosapent Ethyl) in a Statin-Treated Patient with Persistent Dyslipidemia and High Cardiovascular Risk: A Case Study.

    PubMed

    Crandell, James R

    2016-01-01

    Cardiovascular (CV) risk may remain despite statin treatment, and there is a need to address this risk with add-on therapy. The lipid effects of two different prescription omega-3 fatty acid therapies are described in a 55-year-old statin- and niacin-treated female with severe dyslipidemia and high CV risk. The patient was initially treated with omega-3-acid ethyl esters (eicosapentaenoic acid [EPA] and docosahexaenoic acid) 4 g/day. Due to persistently elevated low-density lipoprotein cholesterol (LDL-C), she was switched to icosapent ethyl (high-purity EPA ethyl ester) 4 g/day. Approximately 28 months after switching to icosapent ethyl, her LDL-C decreased by 69% to 52 mg/dL, triglycerides decreased by 35% to 119 mg/dL, non-high-density lipoprotein cholesterol (non-HDL-C) decreased by 63% to 76 mg/dL, total cholesterol decreased by 44% to 137 mg/dL, and HDL-C increased by 45% to 61 mg/dL. Total and small dense LDL particle concentrations decreased by 60 and 59%, respectively. Treatment was well tolerated, with improvements maintained over two years. PMID:27478390

  6. Switching from EPA + DHA (Omega-3-acid Ethyl Esters) to High-Purity EPA (Icosapent Ethyl) in a Statin-Treated Patient with Persistent Dyslipidemia and High Cardiovascular Risk: A Case Study

    PubMed Central

    Crandell, James R.

    2016-01-01

    Cardiovascular (CV) risk may remain despite statin treatment, and there is a need to address this risk with add-on therapy. The lipid effects of two different prescription omega-3 fatty acid therapies are described in a 55-year-old statin- and niacin-treated female with severe dyslipidemia and high CV risk. The patient was initially treated with omega-3-acid ethyl esters (eicosapentaenoic acid [EPA] and docosahexaenoic acid) 4 g/day. Due to persistently elevated low-density lipoprotein cholesterol (LDL-C), she was switched to icosapent ethyl (high-purity EPA ethyl ester) 4 g/day. Approximately 28 months after switching to icosapent ethyl, her LDL-C decreased by 69% to 52 mg/dL, triglycerides decreased by 35% to 119 mg/dL, non-high-density lipoprotein cholesterol (non-HDL-C) decreased by 63% to 76 mg/dL, total cholesterol decreased by 44% to 137 mg/dL, and HDL-C increased by 45% to 61 mg/dL. Total and small dense LDL particle concentrations decreased by 60 and 59%, respectively. Treatment was well tolerated, with improvements maintained over two years. PMID:27478390

  7. Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways.

    PubMed

    Dyall, S C; Mandhair, H K; Fincham, R E A; Kerr, D M; Roche, M; Molina-Holgado, F

    2016-08-01

    Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects. EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists. Furthermore, in NSCs derived from IL-1β deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1β signalling in the effects observed. Although DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant increase in proliferation or p-p38 MAPK activity. In addition, in NSCs from IL-1β deficient mice, DHA significantly increased proliferation without effects on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling pathways. These results provide crucial new insights into the divergent effects of EPA and DHA in regulating NSC proliferation and the pathways involved, and highlight the therapeutic potential of their interplay with endocannabinoid signalling in brain repair. PMID:27044662

  8. Antimicrobial potential of bioconverted products of omega-3 fatty acids by Pseudomonas aeruginosa PR3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bioconverted omega-3 fatty acids, eicosapentaenoic acid (bEPA) and docosahexanoic acid (bDHA), obtained from the microbial conversion of non-bioconverted eicosapentaenoic and docosahexaenoic acids by Pseudomonas aeruginosa PR3 were evaluated for their antimicrobial potential. bEPA and bDHA at 5 µl/...

  9. Continuous culture of the microalgae Schizochytrium limacinum on biodiesel-derived crude glycerol for producing docosahexaenoic acid.

    PubMed

    Ethier, Shannon; Woisard, Kevin; Vaughan, David; Wen, Zhiyou

    2011-01-01

    Crude glycerol is a major byproduct of the biodiesel industry; previous research has proved the feasibility of producing docosahexaenoic acid (DHA, 22:6 n-3) through fermentation of the algae Schizochytrium limacinum on crude glycerol. The objective of this work is to investigate the cell growth kinetics, substrate utilization efficiency, and DHA production of the algae through a continuous culture. Steady-state biomass yield, biomass productivity, growth yield on glycerol, specific glycerol consumption rate, and fatty acid composition were investigated within the range of dilution rate (D) from 0.2 to 0.6 day(-1), and the range of feed crude glycerol concentration (S(0)) from 15 to 120 g/L. The maximum specific growth rate was determined as 0.692 day(-1). The cells had a true growth yield of 0.283 g/g but with a relatively high maintenance coefficient (0.2216 day(-1)). The highest biomass productivity of 3.88 g/L-day was obtained at D=0.3 day(-1) and S(0)=60 g/L, while the highest DHA productivity (0.52 g/L-day) was obtained at D=0.3 day(-1) and S(0)=90 g/L due to the higher DHA content at S(0)=90 g/L. The biomass and DHA productivity of the continuous culture was comparable to those of batch culture, while lower than the fed-batch culture, mainly because of the lower DHA content obtained by the continuous culture. Overall, the results show that continuous culture is a powerful tool to investigate the cell growth kinetics and physiological behaviors of the algae growing on biodiesel-derived crude glycerol. PMID:20570140

  10. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    SciTech Connect

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik; Jeong, Soyeon; Shin, Soyeon; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-01-30

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

  11. Effect of Dietary Docosahexaenoic Acid Supplementation on the Participation of Vasodilator Factors in Aorta from Orchidectomized Rats.

    PubMed

    Villalpando, Diva M; Navarro, Rocío; Del Campo, Lara; Largo, Carlota; Muñoz, David; Tabernero, María; Baeza, Ramiro; Otero, Cristina; García, Hugo S; Ferrer, Mercedes

    2015-01-01

    Benefits of n-3 polyunsaturated fatty acids (PUFAs) against cardiovascular diseases have been reported. Vascular tone regulation is largely mediated by endothelial factors whose release is modulated by sex hormones. Since the incidence of cardiovascular pathologies has been correlated with decreased levels of sex hormones, the aim of this study was to analyze whether a diet supplemented with the specific PUFA docosahexaenoic acid (DHA) could prevent vascular changes induced by an impaired gonadal function. For this purpose, control and orchidectomized rats were fed with a standard diet supplemented with 5% (w/w) sunflower oil or with 3% (w/w) sunflower oil plus 2% (w/w) DHA. The lipid profile, the blood pressure, the production of prostanoids and nitric oxide (NO), and the redox status of biological samples from control and orchidectomized rats, fed control or DHA-supplemented diet, were analyzed. The vasodilator response and the contribution of NO, prostanoids and hyperpolarizing mechanisms were also studied. The results showed that orchidectomy negatively affected the lipid profile, increased the production of prostanoids and reactive oxygen species (ROS), and decreased NO production and the antioxidant capacity, as well as the participation of hyperpolarizing mechanisms in the vasodilator responses. The DHA-supplemented diet of the orchidectomized rats decreased the release of prostanoids and ROS, while increasing NO production and the antioxidant capacity, and it also improved the lipid profile. Additionally, it restored the participation of hyperpolarizing mechanisms by activating potassium. Since the modifications induced by the DHA-supplemented diet were observed in the orchidectomized, but not in the healthy group, DHA seems to exert cardioprotective effects in physiopathological situations in which vascular dysfunction exists. PMID:26540339

  12. A 9-wk docosahexaenoic acid-enriched supplementation improves endurance exercise capacity and skeletal muscle mitochondrial function in adult rats.

    PubMed

    Le Guen, Marie; Chaté, Valérie; Hininger-Favier, Isabelle; Laillet, Brigitte; Morio, Béatrice; Pieroni, Gérard; Schlattner, Uwe; Pison, Christophe; Dubouchaud, Hervé

    2016-02-01

    Decline in skeletal muscle mass and function starts during adulthood. Among the causes, modifications of the mitochondrial function could be of major importance. Polyunsaturated fatty (ω-3) acids have been shown to play a role in intracellular functions. We hypothesize that docosahexaenoic acid (DHA) supplementation could improve muscle mitochondrial function that could contribute to limit the early consequences of aging on adult muscle. Twelve-month-old male Wistar rats were fed a low-polyunsaturated fat diet and were given DHA (DHA group) or placebo (control group) for 9 wk. Rats from the DHA group showed a higher endurance capacity (+56%, P < 0.05) compared with control animals. Permeabilized myofibers from soleus muscle showed higher O2 consumptions (P < 0.05) in the DHA group compared with the control group, with glutamate-malate as substrates, both in basal conditions (i.e., state 2) and under maximal conditions (i.e., state 3, using ADP), along with a higher apparent Km for ADP (P < 0.05). Calcium retention capacity of isolated mitochondria was lower in DHA group compared with the control group (P < 0.05). Phospho-AMPK/AMPK ratio and PPARδ mRNA content were higher in the DHA group compared with the control group (P < 0.05). Results showed that DHA enhanced endurance capacity in adult animals, a beneficial effect potentially resulting from improvement in mitochondrial function, as suggested by our results on permeabilized fibers. DHA supplementation could be of potential interest for the muscle function in adults and for fighting the decline in exercise tolerance with age that could imply energy-sensing pathway, as suggested by changes in phospho-AMPK/AMPK ratio. PMID:26646102

  13. Docosahexaenoic acid in Arctic charr (Salvelinus alpinus): the importance of dietary supply and physiological response during the entire growth period.

    PubMed

    Murray, David S; Hager, Hannes; Tocher, Douglas R; Kainz, Martin J

    2015-03-01

    The aim of this 14-month feeding study was to investigate the effects of dietary docosahexaenoic acid (DHA) on tissue fatty acid composition, DHA retention, and DHA content per biomass accrual in muscle tissues of Arctic charr (Salvelinus alpinus). A control feed, formulated with a relatively high DHA inclusion level (F1), was compared with feeds containing gradually reduced amounts of DHA (Feeds F2, F3, and F4). Arctic charr were randomly distributed among 12 tanks and fed one of the feeds in triplicate. The DHA content within muscle tissues of fish fed diets F1 and F2 was generally higher compared to fish fed diets F3 and F4. However, there was an interaction between dietary DHA treatment and season, which resulted in fish muscle tissues having similar DHA contents irrespective of dietary supply during specific sampling periods. Although diets F3 and F4 contained ~4-fold less DHA compared to diets F1 and F2, the retention of DHA in dorsal and ventral muscle tissue was up to 5-fold higher relative to the diet content in fish fed diets F3 and F4. However, the difference among treatments was dependent on the month sampled. In addition, younger fish retained DHA more efficiently compared to older fish. DHA (μg DHA/g/day) accrual in muscle tissue was independent of somatic growth, and there was no difference among treatments. The results suggested that dietary DHA may be essential throughout the life cycle of Arctic charr and that the DHA content of muscle tissues was influenced by diet and metabolic/physiological factors, such as specific DHA retention during the entire growth cycle . Finally, this long-term feeding study in Arctic charr indicated a non-linear function in DHA retention in dorsal and ventral muscle tissues throughout the life cycle, which varied in its relationship to dietary DHA. PMID:25461677

  14. Dietary docosahexaenoic acid-enriched glycerophospholipids exert cardioprotective effects in ouabain-treated rats via physiological and metabolic changes.

    PubMed

    Bernard, Monique; Maixent, Jean-Michel; Gerbi, Alain; Lan, Carole; Cozzone, Patrick Jean; Pieroni, Gérard; Armand, Martine; Coste, Thierry Charles

    2016-02-01

    Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 × 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analysed by gas chromatography. DHA accretion in the heart was dose-dependent (+8%, +30% and +45% for DHA10, DHA35 and DHA60, respectively). The cardiac phosphocreatine content significantly increased at the baseline in DHA35 (+45%) and DHA60 groups (+85%), and at the different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups versus control (+150%, +122.5% and +135% for DHA10, DHA35 and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional food, and possibly as a co-treatment with digitalis drugs in humans. PMID:26662260

  15. Effect of Dietary Docosahexaenoic Acid Supplementation on the Participation of Vasodilator Factors in Aorta from Orchidectomized Rats

    PubMed Central

    Largo, Carlota; Muñoz, David; Tabernero, María; Baeza, Ramiro; Otero, Cristina; García, Hugo S.; Ferrer, Mercedes

    2015-01-01

    Benefits of n-3 polyunsaturated fatty acids (PUFAs) against cardiovascular diseases have been reported. Vascular tone regulation is largely mediated by endothelial factors whose release is modulated by sex hormones. Since the incidence of cardiovascular pathologies has been correlated with decreased levels of sex hormones, the aim of this study was to analyze whether a diet supplemented with the specific PUFA docosahexaenoic acid (DHA) could prevent vascular changes induced by an impaired gonadal function. For this purpose, control and orchidectomized rats were fed with a standard diet supplemented with 5% (w/w) sunflower oil or with 3% (w/w) sunflower oil plus 2% (w/w) DHA. The lipid profile, the blood pressure, the production of prostanoids and nitric oxide (NO), and the redox status of biological samples from control and orchidectomized rats, fed control or DHA-supplemented diet, were analyzed. The vasodilator response and the contribution of NO, prostanoids and hyperpolarizing mechanisms were also studied. The results showed that orchidectomy negatively affected the lipid profile, increased the production of prostanoids and reactive oxygen species (ROS), and decreased NO production and the antioxidant capacity, as well as the participation of hyperpolarizing mechanisms in the vasodilator responses. The DHA-supplemented diet of the orchidectomized rats decreased the release of prostanoids and ROS, while increasing NO production and the antioxidant capacity, and it also improved the lipid profile. Additionally, it restored the participation of hyperpolarizing mechanisms by activating potassium. Since the modifications induced by the DHA-supplemented diet were observed in the orchidectomized, but not in the healthy group, DHA seems to exert cardioprotective effects in physiopathological situations in which vascular dysfunction exists. PMID:26540339

  16. Effects of docosahexaenoic acid on learning and memory impairment induced by repeated propofol anesthesia in young rats

    PubMed Central

    TIAN, MING; LI, ZHI; WANG, GAO; PAN, WEIZHONG; LI, KEZHONG

    2016-01-01

    The aim of the present study was to investigate the effects of docosahexaenoic acid (DHA) on the learning and memory ability of young rats exposed to propofol, and its underlying mechanisms. Sprague Dawley rats (n=60) were randomly divided into six groups: Control group (group A); solvent control group (group B); propofol group (group C); low-dose DHA + propofol group (group D); medium dose DHA + propofol group (group E); and high-dose DHA + propofol group (group F). The Morris water maze (MWM) test was performed to evaluate the rats' learning and memory ability, and tissue samples from the hippocampi of the rats were obtained for biochemical analysis. The results of the MWM test revealed that DHA supplementation administered to young rats led to an evident decrease in the latency to find the maze platform, and a significant increase in the number of platform crossings in groups E and F compared with group C (P<0.05). High-performance liquid chromatography indicated that glutamate concentration levels were significantly lower and γ-aminobutyric acid concentration levels were significantly higher in the hippocampi of group E and F rats treated with DHA compared with group C rats (P<0.05). Furthermore, DHA treatment alleviated the decrease in brain-derived neurotrophic factor levels (P<0.05), and superoxide dismutase (P<0.05) and glutathione peroxidase (P<0.05) activities induced by the administration of propofol. Additionally, DHA treatment decreased malondialdehyde levels in the hippocampi of rats (P<0.05). The aforementioned findings demonstrate that DHA was able to effectively improve learning and memory dysfunction induced by repeated propofol-induced anesthesia in young rats. This data suggests that DHA may be a potential candidate for further preclinical studies aimed at treating postoperative cognitive dysfunction. PMID:27073471

  17. Docosahexaenoic acid inhibited the Wnt/β-catenin pathway and suppressed breast cancer cells in vitro and in vivo.

    PubMed

    Xue, Meilan; Wang, Qing; Zhao, Jinglan; Dong, Liyan; Ge, Yinlin; Hou, Lin; Liu, Yongchao; Zheng, Zheng

    2014-02-01

    N-3 fatty acids (FAs) are essential FAs necessary for human health and are known to possess anticancer properties. However, the relationship between n-3 FAs and β-catenin, one of the key components of the Wnt signaling pathway, in mouse breast cancer remains poorly characterized. In this study, 4T1 mouse breast cancer cells were exposed to a representative n-3 FA, docosahexaenoic acid (DHA), to investigate the relationship between n-3 FAs and the Wnt/β-catenin signaling pathway in vivo and in vitro. In vitro studies showed that DHA strongly inhibited cell growth, and induced G1 cell cycle arrest both in 4T1 mouse breast cells and MCF-7 human breast cells. DHA reduced β-catenin expression and T cell factor/lymphoid-enhancing factor reporter activity in 4T1 mouse breast cells. In addition, DHA down-regulated the expression of downstream target genes such as c-myc and cyclinD1. In vivo, therapy experiments were conducted on Babl/c mice bearing breast cancer. We found that feeding mouse the 5% fish oil-supplemented diet for 30 days significantly reduced the growth of 4T1 mouse breast cancer in vivo through inhibition of cancer cell proliferation as well as induction of apoptosis. Feeding animals a 5% fish oil diet significantly induced down-regulation of β-catenin in tumor tissues with a notable increase in apoptosis. In addition, fish oil-supplemented diet decreased lung metastases of breast cancer. These observations suggested that DHA exerted its anticancer activity through down-regulation of Wnt/β-catenin signaling. Thus, our data call for further studies to assess the effectiveness of fish oil as a dietary supplement in the prevention and treatment of breast cancer. PMID:24290517

  18. Docosahexaenoic acid-enriched fish oil consumption modulates immunoglobulin responses to and clearance of enteric reovirus infection in mice.

    PubMed

    Beli, Eleni; Li, Maoxiang; Cuff, Christopher; Pestka, James J

    2008-04-01

    We hypothesized that consumption of the (n-3) PUFA, docosahexaenoic acid (DHA), modulates the mucosal immune response to enteric infection with respiratory enteric orphan virus (reovirus), a model intestinal pathogen. Mice were fed either AIN-93G control diet, containing 10 g/kg corn oil and 60 g/kg high oleic acid safflower oil, or AIN-93G, containing 10 g/kg corn oil and 60 g/kg DHA-enriched fish oil, for 4 wk and then orally gavaged with reovirus strain Type 1 Lang, (T1/L). Reovirus-specific IgA antibody was first detectable in the feces of mice fed a control diet at 6 d postinfection (PI) and was further elevated at 8 and 10 d PI. IgA responses in DHA-fed mice were similar at 6 and 8 d PI but greater at 10 d PI (P < 0.05). Both reovirus-specific serum IgA and IgG(2a) were comparably induced in mice fed control or DHA diets. Reovirus-specific IgA and IgG(2a) secretion by ex vivo Peyer's patch, lamina propria, and spleen cultures derived from control and DHA groups were comparable. Although both groups carried similar numbers of reovirus plaque forming units per intestine, DHA-fed mice shed nearly 10 times more viral RNA in feces than control mice at 2, 4, and 6 d PI (P < 0.05). However, viral RNA was not detectable in either group at 8 and 10 d. Taken together, these data suggest that DHA consumption did not markedly alter mucosal or systemic Ig responses to reovirus but delayed clearance of the virus from the intestinal tract. PMID:18356340

  19. Ability of rainbow trout (Oncorhynchus mykiss) to convert and store EPA and DHA when reared on plant oil replacement feeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine the potential for improving the conversion and deposition of the important omega-3 fatty acids docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) in fish, forty-three families of rainbow trout were fed a diet low in these components and then evaluated for their...

  20. Docosahexaenoic acid attenuates Western diet-induced hepatic fibrosis in Ldlr-/- mice by targeting the TGFβ-Smad3 pathway.

    PubMed

    Lytle, Kelli A; Depner, Christopher M; Wong, Carmen P; Jump, Donald B

    2015-10-01

    DHA (22:6,ω3), but not EPA (20:5,ω3), attenuates Western diet (WD)-induced hepatic fibrosis in a Ldlr(-/-) mouse model of nonalcoholic steatohepatitis. We examined the molecular basis for the differential effect of dietary EPA and DHA on WD-induced hepatic fibrosis. DHA was more effective than EPA at preventing WD-induced effects on hepatic transcripts linked to fibrosis, including collagen 1A1 (Col1A1), transforming growth factor-β (TGFβ) signaling and proteins involved in remodeling the extracellular matrix, including metalloproteases, tissue inhibitors of metalloproteases, and lysyl oxidase subtypes. Examination of the TGFβ pathway showed that mice fed the WD supplemented with either olive oil or EPA had a significant (≥2.5-fold) increase in hepatic nuclear abundance of phospho-mothers against decapentaplegic homolog (Smad)3 when compared with mice fed the reference diet (RD); Smad3 is a key regulator of Col1A1 expression in stellate cells. In contrast, mice fed the WD supplemented with DHA had no increase in phospho-Smad3 when compared with mice fed the RD. Changes in hepatic phospho-Smad3 nuclear content correlated with proCol1A1 mRNA and protein abundance. Pretreatment of human LX2 stellate cells with DHA, but not other unsaturated fatty acids, blocked TGFβ1-mediated induction of Col1A1. In conclusion, DHA attenuates WD-induced fibrosis by targeting the TGFβ-Smad3-Col1A1 pathway in stellate cells. PMID:26315048

  1. Docosahexaenoic acid supplementation improved lipocentric but not glucocentric markers of insulin sensitivity in hypertriglyceridemic men

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Obesity and metabolic syndrome are associated with increases in insulin resistance (IR) and type 2 diabetes mellitus. Results from animal intervention studies and human epidemiological studies suggest that n-3 polyunsaturated fatty acids can prevent and reverse IR, but results from huma...

  2. Extra virgin olive oil modulates brain docosahexaenoic acid level and oxidative damage caused by 2,4-Dichlorophenoxyacetic acid in rats.

    PubMed

    Amel, Nakbi; Wafa, Tayeb; Samia, Dabbou; Yousra, Belaid; Issam, Chargui; Cheraif, Imed; Attia, Nebil; Mohamed, Hammami

    2016-03-01

    Oxidative stress is an important pathomechanism of neurological disorders such as Alzheimer disease and Parkinson disease, cardiovascular disorders and many others. This study sought to verify whether extra-virgin olive oil (EVOO), lipophilic fraction (OOLF) and hydrophilic fraction (OOHF) exerted a brain protective effect against the oxidative stress caused by 2,4-dichlorophenoxyacetic acid (2,4-D) pesticide at a dose of 5 mg/kg body weight. 2,4-D, EVOO and its fractions were administered to rats by gavages for four consecutive weeks. Oxidative stress was assessed by measuring brain lipid peroxide level, acetylcholinesterase (AChE), antioxidant enzyme activities and fatty acid composition. 2,4-D induced a decrease in both plasma and brain acetylcholinesterase activity and a rise in Brain TBARS (Thiobarbituric acid reactive substances) level and antioxidant enzyme activities compared with the control group. These changes were partly reversed by either EVOO or its fractions oral administration to 2,4-D treated rats. EVOO enhanced a neuroprotective effect evaluated by the restoration of brain fatty acid composition especially the level of docosahexaenoic acid (DHA). Our results indicate that EVOO exerts a neuroprotective activity against oxidative damage in brain induced by 2,4-D, which could be attributed to its antioxidative property. PMID:27570270

  3. The role of EPA`s Acid Rain Division in the Ozone Transport Commission`s NOx budget program

    SciTech Connect

    Schary, C.; Culligan, K.

    1997-12-31

    The Ozone Transport Commission`s (OTC) Nitrogen Oxides (NO{sub x}) Budget Program will implement the emissions reduction goal of the 1994 Memorandum of Understanding between its twelve member states and the District of Columbia. The program will achieve its significant NO{sub x} reductions from electric utilities and industrial boilers using a {open_quotes}cap-and-trade{close_quotes} approach modeled after the US Environmental Protection Agency`s sulfur dioxide emissions trading under the Acid Rain Program. The similarity of the two programs has led to the development of an important partnership between the OTC states and EPA`s Acid Rain Division, Over the past two years, Acid Rain Program staff have shared their technical expertise and assisted extensively in the development of the program`s rules. Leveraging the investment EPA made in the systems used to run the Acid Rain Program, the OTC states have asked the Acid Rain Division to administer the data systems for them, and together are working to expand its existing Emissions Tracking System and to modify a clone of the sulfur dioxide Allowance Tracking System, to fulfill the unique requirements of the NO{sub x} Budget Program. This partnership is an important example of the new type of cooperation and sharing of expertise and resources that should develop between EPA and states as they launch multi-state programs to address regional pollution problems that defy a single-state solution.

  4. Docosahexaenoic acid consumption inhibits deoxynivalenol-induced CREB/ATF1 activation and IL-6 gene transcription in mouse macrophages.

    PubMed

    Jia, Qunshan; Zhou, Hui-Ren; Shi, Yuhui; Pestka, James J

    2006-02-01

    The mycotoxin deoxynivalenol (DON) induces IgA nephropathy in mice by upregulating IL-6 expression, which is suppressed by (n-3) PUFA consumption. The purpose of this study was to test the hypothesis that consumption of the (n-3) PUFA docosahexaenoic acid (DHA) interferes with DON-induced transcriptional and post-transcriptional upregulation of IL-6 mRNA in murine macrophages. DON evoked expression of IL-6 mRNA and IL-6 heterogenous nuclear RNA (hnRNA), an indicator of ongoing IL-6 transcription, in macrophages elicited from mice fed control AIN-93G diet for 4 wk, whereas expression of both RNA species was suppressed in macrophages from mice fed AIN-93G modified to contain 30 g DHA/kg diet for the same time period. DON enhanced IL-6 mRNA stability similarly in macrophages from control and DHA-fed mice suggesting that (n-3) PUFA effects were not post-transcriptional. DON upregulated binding activity of cAMP response element binding protein (CREB) and activator protein (AP-1) to their respective consensus sequences in nuclear extracts from control-fed mice, whereas both activities were suppressed in nuclear extracts from DHA-fed mice. DON induced phosphorylation of CREB at Ser-133 and ATF1 at Ser-63 as well as intranuclear binding of phospho-CREB/ATF1 to the cis element of the IL-6 promoter in control macrophages, whereas both activities were inhibited in macrophages from DHA-fed mice. DHA consumption blocked DON-induced phosphorylation of the CREB kinase AKT. Inhibition of AKT suppressed both CREB/ATF1 phosphorylation and IL-6 transcription. These data suggest that DHA consumption suppresses DON-induced IL-6 transcription in macrophages in part by interfering with AKT-dependent phosphorylation and subsequent binding of CREB/ATF1 to the IL-6 promoter. PMID:16424113

  5. Effect of Docosahexaenoic Acid (DHA) Supplementation on Inflammatory Cytokine Levels in Infants at High Genetic Risk for Type 1 Diabetes

    PubMed Central

    Chase, H. Peter; Boulware, David; Rodriguez, Henry; Donaldson, David; Chritton, Sonia; Rafkin-Mervis, Lisa; Krischer, Jeffrey; Skyler, Jay S.; Clare-Salzler, Michael

    2014-01-01

    OBJECTIVE Type 1 diabetes (T1D) results from the inflammatory destruction of pancreatic β-cells. In the present study, we investigated the effect of docosahexaenoic acid (DHA) supplementation on stimulated inflammatory cytokine production in white blood cells (WBC) from infants with a high genetic risk for T1D. RESEARCH DESIGN AND METHODS This was a multicenter, two-arm, randomized, double blind pilot trial of DHA supplementation, beginning either in the last trimester of pregnancy (41 infants) or in the first five months after birth (57 infants). Levels of DHA in infant and maternal red blood cell (RBC) membranes and in breast milk were analyzed by gas chromatography/mass spectrometry. Inflammatory cytokines were assayed from whole blood culture supernatants using the Luminex Multiplex assay after stimulation with high dose lipopolysaccharide (LPS), 1μg/mL. RESULTS The levels of RBC DHA were increased by 61–100% in treated compared to control infants at ages 6 to 36 months. There were no statistically significant reductions in production of the inflammatory cytokines, IL-1β, TNFα or IL-12p40 at any of the 6 time points measured. The inflammatory marker, hsCRP, was significantly lower in breast-fed DHA-treated infants compared to all formula-fed infants at age 12 months. Three infants (two received DHA) were removed from the study as a result of developing ≥ two persistently positive biochemical islet autoantibodies. CONCLUSIONS This pilot trial showed that supplementation of infant diets with DHA is safe and fulfilled the pre-study goal of increasing infant RBC DHA levels by at least 20%. Inflammatory cytokine production was not consistently reduced. PMID:25039804

  6. Imaging decreased brain docosahexaenoic acid metabolism and signaling in iPLA(2)β (VIA)-deficient mice.

    PubMed

    Basselin, Mireille; Rosa, Angelo O; Ramadan, Epolia; Cheon, Yewon; Chang, Lisa; Chen, Mei; Greenstein, Deanna; Wohltmann, Mary; Turk, John; Rapoport, Stanley I

    2010-11-01

    Ca(2+)-independent phospholipase A(2)β (iPLA(2)β) selectively hydrolyzes docosahexaenoic acid (DHA, 22:6n-3) in vitro from phospholipid. Mutations in the PLA2G6 gene encoding this enzyme occur in patients with idiopathic neurodegeneration plus brain iron accumulation and dystonia-parkinsonism without iron accumulation, whereas mice lacking PLA2G6 show neurological dysfunction and neuropathology after 13 months. We hypothesized that brain DHA metabolism and signaling would be reduced in 4-month-old iPLA(2)β-deficient mice without overt neuropathology. Saline or the cholinergic muscarinic M(1,3,5) receptor agonist arecoline (30 mg/kg) was administered to unanesthetized iPLA(2)β(-/-), iPLA(2)β(+/-), and iPLA(2)β(+/+) mice, and [1-(14)C]DHA was infused intravenously. DHA incorporation coefficients k* and rates J(in), representing DHA metabolism, were determined using quantitative autoradiography in 81 brain regions. iPLA(2)β(-/-) or iPLA(2)β(+/-) compared with iPLA(2)β(+/+) mice showed widespread and significant baseline reductions in k* and J(in) for DHA. Arecoline increased both parameters in brain regions of iPLA(2)β(+/+) mice but quantitatively less so in iPLA(2)β(-/-) and iPLA(2)β(+/-) mice. Consistent with iPLA(2)β's reported ability to selectively hydrolyze DHA from phospholipid in vitro, iPLA(2)β deficiency reduces brain DHA metabolism and signaling in vivo at baseline and following M(1,3,5) receptor activation. Positron emission tomography might be used to image disturbed brain DHA metabolism in patients with PLA2G6 mutations. PMID:20686114

  7. Docosahexaenoic acid reduces ER stress and abnormal protein accumulation and improves neuronal function following traumatic brain injury.

    PubMed

    Begum, Gulnaz; Yan, Hong Q; Li, Liaoliao; Singh, Amneet; Dixon, C Edward; Sun, Dandan

    2014-03-01

    In this study, we investigated the development of endoplasmic reticulum (ER) stress after traumatic brain injury (TBI) and the efficacy of post-TBI administration of docosahexaenoic acid (DHA) in reducing ER stress. TBI was induced by cortical contusion injury in Sprague-Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered intraperitoneally at 5 min after TBI, followed by a daily dose for 3-21 d. TBI triggered sustained expression of the ER stress marker proteins including phosphorylated eukaryotic initiation factor-2α, activating transcription factor 4, inositol requiring kinase 1, and C/EBP homologous protein in the ipsilateral cortex at 3-21 d after TBI. The prolonged ER stress was accompanied with an accumulation of abnormal ubiquitin aggregates and increased expression of amyloid precursor protein (APP) and phosphorylated tau (p-Tau) in the frontal cortex after TBI. The ER stress marker proteins were colocalized with APP accumulation in the soma. Interestingly, administration of DHA attenuated all ER stress marker proteins and reduced the accumulation of both ubiquitinated proteins and APP/p-Tau proteins. In addition, the DHA-treated animals exhibited early recovery of their sensorimotor function after TBI. In summary, our study demonstrated that TBI induces a prolonged ER stress, which is positively correlated with abnormal APP accumulation. The sustained ER stress may play a role in chronic neuronal damage after TBI. Our findings illustrate that post-TBI administration of DHA has therapeutic potentials in reducing ER stress, abnormal protein accumulation, and neurological deficits. PMID:24599472

  8. Fortification of pork loins with docosahexaenoic acid (DHA) and its effect on flavour

    PubMed Central

    2013-01-01

    Pork is traditionally low in docosahexanoic acid (DHA, C22:6n-3) and deficient in omega-3 fats for a balanced human diet. DHA as triglycerides was commercially prepared from the microalgae Schizochytrium and injected into fresh pork loins. Treatments of a mixed brine control (CON), 3.1% sunflower oil in mixed brine (SF) and a 3.1% DHA oil in mixed brine (DHA) were injected into pork loins at 10 mL/100 g and grilled at 205°C. After cooking, the CON and SF pork loins contained 0.03 to 0.05 mg DHA/g of pork and the DHA injected loins contained approximately 1.46 mg DHA/g. This also changed the fatty acid profile of omega-6: omega-3 from, 5 to 1 in the CON pork, to a ratio of 1.7 to 1 in DHA pork. The appearance, odor, oxidation rates and sensory taste, as judged by a trained panel, determined the DHA injected meat to be, 'slightly desirable’ and gave lower 'off flavour’ scores, relative to the CON and SF injected pork. Pork can be fortified with DHA oil to 146 mg/100 g serving, which would meet half the recommended daily omega 3 fatty acid requirements for adult humans and would be desirable in taste. PMID:24257205

  9. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

    PubMed Central

    Berger, Alvin; Roberts, Matthew A; Hoff, Bruce

    2006-01-01

    Introduction Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA) on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6), FISH (rich in 20:5n3, 22:5n3, and 22:6n3) and COMB, the combination of the two. Results Using a variance-stabilized F-statistic, 371 probe sets (out of 13 K probe sets in the Affymetrix Mu11K chip set) were changed by dietary treatment (P < 0.001). Relative to other groups, COMB had unique affects on murine hepatic transcripts involved in cytoskeletal and carbohydrate metabolism; whereas FUNG affected amino acid metabolism via CTNB1 signaling. All three diets affected transcripts linked to apoptosis and cell proliferation, with evidence FISH may have increased apoptosis and decreased cell proliferation via various transcription factors, kinases, and phosphatases. The three diets affected lipid transport, lipoprotein metabolism, and bile acid metabolism through diverse pathways. Relative to other groups, FISH activated cyps that form hydroxylated fatty acids known to affect vascular tone and ion channel activity. FA synthesis and delta 9 desaturation were down regulated by COMB relative to other groups, implying that a FA mixture of 20:4n6, 20:5n3, and 22:6n3 is most effective at down regulating synthesis, via INS1, SREBP, PPAR alpha, and TNF signaling. Heme synthesis and the utilization of heme for hemoglobin production were likely affected by FUNG and FISH. Finally, relative to other groups, FISH increased numerous transcripts linked to combating oxidative such as peroxidases, an aldehyde dehydrogenase, and heat shock proteins, consistent with the major LC-PUFA in FISH (20:5n3, 22:5n3, 22:6n3) being more oxidizable than the major fatty acids in FUNG (20:4n6). Conclusion Distinct

  10. Inverse Association of Serum Docosahexaenoic Acid With Newly Diagnosed Hypertension: A Community-based Case-control Study.

    PubMed

    Yang, Bo; Ding, Fang; Wang, Feng-Lei; Yu, Wei; Li, Duo

    2016-02-01

    Observational studies on circulating fatty acid (FA) and primary prevention of hypertension have yielded inconsistent results, and the association among the Chinese population is not fully clear. The aim of the study was to discern important FAs that can discriminate hypertensive patients from normotensive persons, and investigate associations between the important FAs and risk of hypertension.We conducted a case-control study nested within a community-based cohort of 2447 Chinese participants aged 35 to 79 years who completed a baseline assessment between October 2012 and April 2013. In all, 480 patients with newly diagnosed hypertension were identified at baseline and 480 normotensive individuals were randomly selected as matched normotensive controls. Controls were individually matched to cases by age (±2 y), sex, and recruitment center, with a 1:1 case-to-control ratio. Serum FA profile was compared between cases and controls by orthogonal partial least squares-discriminant analyses. Odds ratio (OR) with 95% confidence interval (CI) for newly diagnosed hypertension was estimated by a conditional logistical analysis.After adjustment for body mass index, education, profession, family history of hypertension, salt intake, heart rate, blood lipids, and fasting glucose levels, serum FA profile in hypertensive patients was typically characterized by higher 16:0 and 16:1n-7, and lower 18:2n-6 and 22:6n-3, compared with normotensive controls. Docosahexaenoic acid (22:6n-3) and palmitoleic acid (16:1n-7) were identified as the important FA contributing most to the intergroup separations. When comparing the highest and lowest quartile of FA composition, newly diagnosed hypertension was negatively associated with 22:6n-3 (OR 0.65; 95% CI, 0.45-0.93; P for trend = 0.02), but positively associated with 16:1n-7 (OR 2.14; 95% CI, 1.46-3.12; P for trend < 0.001). The associations remained pronounced after multiple adjustments and in further stratified analyses

  11. Temperature-Dependent Electron Paramagnetic Resonance Studies of Docosahexaenoic Acid and Gamma Linolenic Acid Effects on Phospholipid Membranes With and Without Cholesterol

    NASA Astrophysics Data System (ADS)

    Yonar, D.; Horasanb, N.; Sünnetçioğlu, M. Maral

    2016-07-01

    Free docosahexaenoic acid (DHAn-3) and gamma linolenic acid (GLAn-6) effects on dimyristoyl phosphatidylcholine (DMPC) membranes were studied as a function of temperature by electron paramagnetic resonance (EPR) spectroscopy. 5- and 16-doxyl stearic acid (5-, 16-DS) spin labels were utilized to obtain information from the interfacial and alkyl chain region, respectively. In the studied temperature range, the presence of DHAn-3 or GLAn-6 caused decreases in maximum hyperfi ne splitting values and correlation times of DMPC membranes. Both in the interfacial region and depths of membrane, changes were more pronounced for DHAn-3 in pure DMPC. In the presence of cholesterol (CH), DHAn-3 and GLAn-6 effects were similar and more pronounced in the depths of the membrane. The changes in the structure and dynamics of samples were obtained from simulations of spectra, which indicated some changes in the number of spectral components by incorporation of DHAn-3 and GLAn-6. In the interfacial region and below the main phase transition temperature of DMPC, there was an increase in heterogeneity. For temperatures above the phase transition, a more homogeneous environment for spin label was obtained in the presence of fatty acids.

  12. Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats

    PubMed Central

    Elsherbiny, Marwa E.; Goruk, Susan; Monckton, Elizabeth A.; Richard, Caroline; Brun, Miranda; Emara, Marwan; Field, Catherine J.; Godbout, Roseline

    2015-01-01

    Arachidonic (AA) and docosahexaenoic acid (DHA) brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lactation. Finally, our data indicate that brain fatty acid binding protein (FABP7), a marker of neural stem cells, is down-regulated in the brains of six-week pups with a high DHA:AA ratio. We propose that elevated levels of DHA in developing brain accelerate brain maturation relative to DHA-deficient brains. PMID:26506385

  13. Accumulation of docosahexaenoic acid-rich lipid in thraustochytrid Aurantiochytrium sp. strain T66: effects of N and P starvation and O2 limitation.

    PubMed

    Jakobsen, Anita N; Aasen, Inga M; Josefsen, Kjell D; Strøm, Arne R

    2008-08-01

    Aurantiochytrium sp. strain T66 was grown in batch bioreactor cultures in a defined glutamate- and glycerol-containing growth medium. Exponentially growing cells had a lipid content of 13% (w/w) of dry weight. A fattening of cells fed excess glycerol occurred in the post-exponential growth phase, after the medium was depleted of N or P. Lipid accumulation was also initiated by O2 limitation (below 1% of saturation). N starvation per se, or in combination with O2 limitation, gave the highest lipid content, i.e., 54% to 63% (w/w) of dry weight. The corresponding maximum culture density was 90 to 100 g/l dry biomass. The content of docosahexaenoic acid (22:6n-3) in N starved, well-oxygenated cells reached 29% (w/w) of total fatty acids but increased to 36% to 52% in O2-limited cells, depending on the time span of the limitation. O2-limited cells did not accumulate the monounsaturated fatty acids that were normally present. We inferred that the biological explanation is that O2 limitation hindered the O2-dependent desaturase(s) and favored the O2-independent polyunsaturated fatty acid synthase. The highest overall volumetric productivity of docosahexaenoic acid observed was 93 mg/l/h. Additionally, we present a protocol for quantitative lipid extraction, involving heat and protease treatment of freeze-dried thraustochytrids. PMID:18560831

  14. [Neurological, neuropsychological, and ophthalmological evolution after one year of docosahexaenoic acid supplementation in phenylketonuric patients].

    PubMed

    Gutiérrez-Mata, Alfonso P; Vilaseca, M Antonia; Capdevila-Cirera, Antoni; Vidal-Oller, Mariona; Alonso-Colmenero, Itziar; Colomé, Roser; López-Sala, Anna; Lambruschini-Ferri, Nilo; Gutiérrez, Alejandra; Gassió, Rosa; Artuch, Rafael; Campistol, Jaume

    2012-08-16

    INTRODUCTION. Phenylketonuria (PKU) is an autosomal recessive metabolic disease caused by a deficiency of phenylalanine hydroxylase. The dietary therapy for the effective management of PKU, in particular the restriction of high-protein foods of animal-origin, compromises patients' intake of fat and distorts the n-3:n-6 ratio of essential fatty acids in the diet. This deficiency can contribute to neurological and visual impairment. AIM. To evaluate changes in white matter alterations, visual evoked potential (VEP) latencies and performance in executive and motor functions in a group of early and continuously treated PKU patients after supplementation with docosahexaneoic acid (DHA). PATIENTS AND METHODS. We selected 21 PKU patients with early diagnosis (age range: 9-25 years), on a Phe-restricted diet and supplemented with PKU formula. Inclusion criteria were: low erythrocyte DHA values, prolonged P100 wave latencies in VEP and/or presence of white matter hyperintensities on brain magnetic resonance imaging (MRI), and intellectual quotient > 80. All patients were treated with DHA (10 mg/kg/day) for 12 months. Assessment was conducted at baseline and after 12 months of treatment, and included biochemical parameters, brain MRI, VEP, ophthalmologic evaluation and neuropsychological tests. RESULTS AND CONCLUSION. All the patients normalized the DHA levels after supplementation. Improvement in the P100 wave latencies, and fine motor skills was significant. No significant improvement in the other explorations was evident after supplementation. Further investigations seem advisable to establish a cause-effect relationship between DHA treatment and the slight improvement observed in some neurological functions. PMID:22829083

  15. Expanding the docosahexaenoic acid food web for sustainable production: engineering lower plant pathways into higher plants

    PubMed Central

    Petrie, James R.; Singh, Surinder P.

    2011-01-01

    Background Algae are becoming an increasingly important component of land plant metabolic engineering projects. Land plants and algae have similar enough genetics to allow relatively straightforward gene transfer and they also share enough metabolic similarities that algal enzymes often function in a plant cell environment. Understanding metabolic systems in algae can provide insights into homologous systems in land plants. As examples, algal models are currently being used by several groups to better understand starch and lipid metabolism and catabolism, fields which have relevance in land plants. Importantly, land plants and algae also have enough metabolic divergence that algal genes can often provide new metabolic traits to plants. Furthermore, many algal genomes have now been sequenced, with many more in progress, and this easy access to genome-wide information has revealed that algal genomes are often relatively simple when compared with plants. Scope One example of the importance of algal, and in particular microalgal, resources to land plant research is the metabolic engineering of long-chain polyunsaturated fatty acids into oilseed crops which typically uses microalgal genes to extend existing natural plant biosynthetic pathways. This review describes both recent progress and remaining challenges in this field. PMID:22476481

  16. Transcriptome-based identification of new anti-anti-inflammatory and vasodilating properties of the n-3 fatty acid docosahexaenoic acid in vascular endothelial cell under proinflammatory conditions

    PubMed Central

    Gatta, Valentina; Scoditti, Egeria; Pellegrino, Mariangela; Carluccio, Maria Annunziata; Calabriso, Nadia; Buonomo, Tonia; Stuppia, Liborio; Storelli, Carlo; De Caterina, Raffaele

    2015-01-01

    Scope High intakes of n-3 fatty acids exert anti-inflammatory effects and cardiovascular protection, but the underlying molecular basis is incompletely defined. By genome-wide analysis we searched for novel effects of docosahexaenoic acid (DHA) on gene expression and pathways in human vascular endothelium under pro-inflammatory conditions. Methods and Results Human umbilical vein endothelial cells were treated with DHA and then stimulated with interleukin(IL)-1β. Total RNA was extracted, and gene expression examined by DNA microarray. DHA alone altered the expression of 188 genes, decreasing 92 and increasing 96. IL-1β changed the expression of 2031 genes, decreasing 997 and increasing 1034. Treatment with DHA before stimulation significantly affected the expression of 116 IL-1β-deregulated genes, counter-regulating the expression of 55 genes among those decreased and of 61 among those increased. Functional and network analyses identified immunological, inflammatory and metabolic pathways as the most affected. Newly identified DHA-regulated genes are involved in stemness, cellular growth, cardiovascular system function and cancer, and included cytochrome p450 4F2(CYP4F2), transforming growth factor(TGF)-β2, Cluster of Differentiation (CD)47, caspase recruitment domain(CARD)11 and phosphodiesterase(PDE)5α. Conclusions Endothelial exposure to DHA regulates novel genes and related pathways. Such unbiased identification should increase our understanding of mechanisms by which n-3 fatty acids affect human diseases. PMID:26114549

  17. Oligomerization of Cu,Zn-Superoxide Dismutase (SOD1) by Docosahexaenoic Acid and Its Hydroperoxides In Vitro: Aggregation Dependence on Fatty Acid Unsaturation and Thiols

    PubMed Central

    Appolinário, Patricia Postilione; Medinas, Danilo Bilches; Chaves-Filho, Adriano B.; Genaro-Mattos, Thiago C.; Cussiol, José Renato Rosa; Netto, Luis Eduardo Soares; Augusto, Ohara; Miyamoto, Sayuri

    2015-01-01

    Docosahexaenoic acid (C22:6, n-3, DHA) is a polyunsaturated fatty acid highly enriched in the brain. This fatty acid can be easily oxidized yielding hydroperoxides as primary products. Cu, Zn-Superoxide dismutase (SOD1) aggregation is a common hallmark of Amyotrophic Lateral Sclerosis (ALS) and the molecular mechanisms behind their formation are not completely understood. Here we investigated the effect of DHA and its hydroperoxides (DHAOOH) on human SOD1 oligomerization in vitro. DHA induced the formation of high-molecular-weight (HMW) SOD1 species (>700 kDa). Aggregation was dependent on free thiols and occurred primarily with the protein in its apo-form. SOD1 incubation with DHA was accompanied by changes in protein structure leading to exposure of protein hydrophobic patches and formation of non-amyloid aggregates. Site-directed mutagenesis studies demonstrated that Cys 6 and Cys 111 in wild-type and Cys 6 in ALS-linked G93A mutant are required for aggregation. In contrast, DHAOOH did not induce HMW species formation but promoted abnormal covalent dimerization of apo-SOD1 that was resistant to SDS and thiol reductants. Overall, our data demonstrate that DHA and DHAOOH induce distinct types of apo-SOD1 oligomerization leading to the formation of HMW and low-molecular-weight species, respectively. PMID:25928076

  18. Low serum docosahexaenoic acid is associated with progression of coronary atherosclerosis in statin-treated patients with diabetes mellitus: results of the treatment with statin on atheroma regression evaluated by intravascular ultrasound with virtual histology (TRUTH) study

    PubMed Central

    2014-01-01

    Background Diabetes mellitus (DM) accelerates plaque progression despite the use of statin therapy. The purpose of the present study was to evaluate the determinants of atheroma progression in statin-treated patients with DM. Methods Coronary atherosclerosis in nonculprit lesions in a vessel undergoing percutaneous coronary intervention (PCI) was evaluated using virtual histology intravascular ultrasound. The study included 50 patients with DM who had been taking statin therapy for 8 months at the time of PCI. Results Twenty-six patients (52%) showed atheroma progression (progressors) and the remaining 24 patients (48%) showed atheroma regression (regressors) after 8 months of follow-up. Fewer progressors than regressors received intensive lipid-lowering therapy with pitavastatin (31% vs. 50%, p = 0.17) and the frequency of insulin use was higher in progressors (31% vs. 13%, p = 0.18). However, neither of these differences reached statistical significance. Risk factor control at baseline and at the 8-month follow-up did not differ between the 2 groups except for serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Univariate regression analysis showed that serum EPA (r = -0.317, p = 0.03) and DHA (r = -0.353, p = 0.02) negatively correlated with atheroma progression. Multivariate stepwise regression analysis showed that low serum DHA and pravastatin use were significant independent predictors for atheroma progression during statin therapy (DHA: β = -0.414, type of statin: β = -0.287, p = 0.001). Conclusions Low serum DHA is associated with progression of coronary atherosclerosis in statin-treated patients with DM. Trial registration UMIN Clinical Trials Registry, UMIN ID: C000000311. PMID:24410834

  19. Docosahexaenoic acid at the sn-2 position of structured triacylglycerols improved n-3 polyunsaturated fatty acid assimilation in tissues of hamsters.

    PubMed

    Bandarra, Narcisa M; Lopes, Paula A; Martins, Susana V; Ferreira, Júlia; Alfaia, Cristina M; Rolo, Eva A; Correia, Jorge J; Pinto, Rui M A; Ramos-Bueno, Rebeca P; Batista, Irineu; Prates, José A M; Guil-Guerrero, José L

    2016-05-01

    In this study, we hypothesized that the incorporation of docosahexaenoic acid (DHA) in tissues will be higher when it is ingested as triacylglycerols (TAG) structured at the sn-2 position, which enhances efficacy and health benefits of dietary DHA n-3 supplementation. Ten-week-old Golden Syrian male hamsters were randomly allocated into 4 dietary groups with 10 animals in each: linseed oil (LSO; control group), fish oil (FO), fish oil ethyl esters (FO-EE), and structured DHA at the sn-2 position of TAG (DHA-SL). After 12 weeks, there were no variations in the hamsters' body composition parameters across dietary groups. The DHA-SL diet had the lowest values of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total lipids, and aspartate aminotransferase activity, whereas the inverse was observed for the FO diet. Glucose was increased in the LSO diet without affecting insulin and insulin resistance markers. Whereas n-3 polyunsaturated fatty acid was increased in the brain of hamsters fed the DHA-SL diet, higher levels of n-6 polyunsaturated fatty acid were observed in the liver and erythrocytes of the LSO. The highest omega-3 index was obtained with the DHA-SL diet. The principal component analyses discriminated DHA from other metabolites and set apart 4 clusters matching the 4 diets. Similarly, liver, erythrocytes, and brain were separated from each other, pointing toward an individual signature on fatty acid deposition. The structured sn-2 position DHA-containing TAG ameliorated blood lipids and fatty acid incorporation, in particular eicosapentaenoic acid and DHA in liver, erythrocytes, and brain, relative to commercially FOs, thus improving the health benefits of DHA due to its higher bioavailability. PMID:27101763

  20. Intakes of dietary docosahexaenoic acid ethyl ester and egg phosphatidylcholine improve maze-learning ability in young and old mice.

    PubMed

    Lim, S Y; Suzuki, H

    2000-06-01

    The effect of dietary docosahexaenoic acid (DHA) [22:6 (n-3)] ethyl ester (EE) and egg-phosphatidylcholine (PC) on maze-learning ability in young and old mice was studied. Male Crj:CD-1 mice aged either 3 wk or 14 mo were fed a diet containing 2 g DHA-EE/100 g diet plus 3 g palm oil/100 g diet (DHA-EE Group), 5 g egg-PC/100 g diet (egg-PC Group), 1 g DHA-EE/100 g diet plus 2.5 g egg-PC/100 g diet plus 1.5 g palm oil/100 g diet (DHA-EE + egg-PC Group) or 5 g palm oil/100 g diet (Control Group) for 5 mo. Maze-learning ability was assessed 4 mo after the start of the experiment. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured in three trials every 4 d. In trial 2 of young mice, performed on d 4 after the first trial, the DHA-EE group required less (P < 0.05) time to reach the maze exit and DHA-EE and egg-PC groups strayed (P < 0.05) into blind alleys fewer times than the control group. In trial 2 of old mice, the DHA-EE, egg-PC and DHA-EE + egg-PC groups needed less (P < 0.05) time to find the exit and spent a fewer (P < 0.05) number of times in blind alleys than did the control group. The DHA-EE, DHA-EE + egg-PC and egg-PC groups strayed into blind alleys fewer times than the control group in trial 3 of old mice (P < 0.05). Our results suggest that the intake of DHA-EE and the egg-PC diet effectively enhances maze-learning ability and brain functions in old mice. PMID:10827221

  1. Lipid content in hepatic and gonadal adipose tissue parallel aortic cholesterol accumulation in mice fed diets with different omega-6 PUFA to EPA plus DHA ratios

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diets with low omega (u)-6 polyunsaturated fatty acids (PUFA) to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) ratios have been shown to decrease aortic cholesterol accumulation and have been suggested to promote weight loss. The involvement of the liver and gonadal adipose tissue (GAT...

  2. Dietary α-linolenic acid from flaxseed oil improved folliculogenesis and IVF performance in dairy cows, similar to eicosapentaenoic and docosahexaenoic acids from fish oil.

    PubMed

    Moallem, U; Shafran, A; Zachut, M; Dekel, I; Portnick, Y; Arieli, A

    2013-12-01

    The objectives of this study were to determine the differential incorporation of various omega-3 (n-3) fatty acids (FAs) supplemented to dairy cows into ovarian compartments and assess the effects on IVF. Forty-two 256-day pregnant cows were supplemented with encapsulated fats, in treatments designated as i) SFA - saturated fat at 240 and 560 g/day per cow, prepartum and post partum (PP) respectively; ii) FLX - flaxseed oil at 300 and 700 g/day per cow prepartum and PP respectively; and iii) FO - fish oil at 300 and 700 g/day per cow prepartum and PP respectively. Commencing at 60 days in lactation, ovum pickup (OPU) was performed twice weekly (20 sessions; five cows per group) and in vitro maturation and IVF were conducted. The proportion of α-linolenic acid (ALA) was greater in follicular fluid (FF), granulosa cells, and cumulus-oocyte complexes (COCs) of FLX cows than in other groups (P<0.001). The proportion of docosahexaenoic acid (DHA) was 6.7 times as great in FF of FO as in other groups (P<0.001); docosapentaenoic acid n-3 and DHA were detected in COCs of FO but not in others. The follicle number during OPU was higher in FLX and FO than in SFA (P<0.05), and the oocyte cleavage rate was higher in FLX and FO than in SFA (P<0.01). Also, the percentage of oocytes that developed to blastocysts tended to be higher in both n-3 groups than in SFA (P<0.1). In conclusion, both dietary n-3 FAs similarly improved folliculogenesis and IVF performance; therefore, ALA-rich botanical n-3 seems to be a satisfactory approach to improve oocyte quality. PMID:24062566

  3. Benefits of Docosahexaenoic Acid, Folic Acid, Vitamin D and Iodine on Foetal and Infant Brain Development and Function Following Maternal Supplementation during Pregnancy and Lactation

    PubMed Central

    Morse, Nancy L.

    2012-01-01

    Scientific literature is increasingly reporting on dietary deficiencies in many populations of some nutrients critical for foetal and infant brain development and function. Purpose: To highlight the potential benefits of maternal supplementation with docosahexaenoic acid (DHA) and other important complimentary nutrients, including vitamin D, folic acid and iodine during pregnancy and/or breast feeding for foetal and/or infant brain development and/or function. Methods: English language systematic reviews, meta-analyses, randomised controlled trials, cohort studies, cross-sectional and case-control studies were obtained through searches on MEDLINE and the Cochrane Register of Controlled Trials from January 2000 through to February 2012 and reference lists of retrieved articles. Reports were selected if they included benefits and harms of maternal supplementation of DHA, vitamin D, folic acid or iodine supplementation during pregnancy and/or lactation. Results: Maternal DHA intake during pregnancy and/or lactation can prolong high risk pregnancies, increase birth weight, head circumference and birth length, and can enhance visual acuity, hand and eye co-ordination, attention, problem solving and information processing. Vitamin D helps maintain pregnancy and promotes normal skeletal and brain development. Folic acid is necessary for normal foetal spine, brain and skull development. Iodine is essential for thyroid hormone production necessary for normal brain and nervous system development during gestation that impacts childhood function. Conclusion: Maternal supplementation within recommended safe intakes in populations with dietary deficiencies may prevent many brain and central nervous system malfunctions and even enhance brain development and function in their offspring. PMID:22852064

  4. PROCEEDINGS: EPA'S INDUSTRY BRIEFING ON THE ADIPIC ACID ENHANCED LIMESTONE FGD PROCESS (JULY 1981)

    EPA Science Inventory

    The proceedings document presentations made during an EPA-sponsored industry briefing, July 15, 1981, in Springfield, MO. The briefing dealt with the status of EPA's research activities on the adipic-acid-enhanced limestone flue gas desulfurization (FGD) process. Subjects covered...

  5. Long-Chain Omega-3 fatty acids associated with better cognitive function and less depressive symptoms in a population of Puerto Rican adults in Boston, MA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) found in fatty fish are increasingly recommended for promoting brain health with aging. Studies have reported protective associations between dietary DHA/EPA or fatty fish and incident dementia, but few have reported ...

  6. Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development.

    PubMed

    Wong, Bernice H; Chan, Jia Pei; Cazenave-Gassiot, Amaury; Poh, Rebecca W; Foo, Juat Chin; Galam, Dwight L A; Ghosh, Sujoy; Nguyen, Long N; Barathi, Veluchamy A; Yeo, Sia W; Luu, Chi D; Wenk, Markus R; Silver, David L

    2016-05-13

    Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the ω-3 fatty acid docosahexaenoic acid (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at the blood-brain barrier that transports LPCs containing DHA and other long-chain fatty acids. LPC transport via Mfsd2a has been shown to be necessary for human brain growth. Here we demonstrate that Mfsd2a is highly expressed in retinal pigment epithelium in embryonic eye, before the development of photoreceptors, and is the primary site of Mfsd2a expression in the eye. Eyes from whole body Mfsd2a-deficient (KO) mice, but not endothelium-specific Mfsd2a-deficient mice, were DHA-deficient and had significantly reduced LPC/DHA transport in vivo Fluorescein angiography indicated normal blood-retinal barrier function. Histological and electron microscopic analysis indicated that Mfsd2a KO mice exhibited a specific reduction in outer rod segment length, disorganized outer rod segment discs, and mislocalization of and reduction in rhodopsin early in postnatal development without loss of photoreceptors. Minor photoreceptor cell loss occurred in adult Mfsd2a KO mice, but electroretinography indicated visual function was normal. The developing eyes of Mfsd2a KO mice had activated microglia and up-regulation of lipogenic and cholesterogenic genes, likely adaptations to loss of LPC transport. These findings identify LPC transport via Mfsd2a as an important pathway for DHA uptake in eye and for development of photoreceptor membrane discs. PMID:27008858

  7. Evaluation of single-cell sources of docosahexaenoic acid and arachidonic acid: 3-month rat oral safety study with an in utero phase.

    PubMed

    Burns, R A; Wibert, G J; Diersen-Schade, D A; Kelly, C M

    1999-01-01

    Owing to the presence of the polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA) and arachidonic acid (ARA) in human milk and their important biological function, several authorities recommend that they be added to infant formulas. This study assessed the safety of an algal oil rich in DHA and a fungal oil rich in ARA, blended to provide a DHA to ARA ratio similar to human milk. The oil blend was incorporated into diets and fed to rats such that they received 3, 11 and 22 times the anticipated infant exposure to DHA and ARA. Low-fat and high-fat control groups received canola oil. Rats received experimental diets over a premating interval and throughout mating, gestation and lactation. Pups born during this period (F1) consumed treatment diets from weaning for 3 months. Physical observations, ophthalmoscopic examinations, body weight, food intake, clinical chemistry, neurobehavioural evaluations and postmortem histopathology of selected tissues were performed. No statistically significant, dose-dependent adverse effects were seen in reproductive performance or fertility, nor in the neonates from birth to weaning. Mid- and high-dose treated F1 animals exhibited increased white cell count, neutrophil count and blood urea nitrogen; increased liver and spleen weights (absolute and relative to body weight) also were observed. There were no corresponding microscopic findings. The clinical pathology and organ weight differences at these treatment levels represent physiological or metabolic responses to the test substance rather than adverse responses. These single-cell oils produced no adverse effects in rats when administered in utero and for 90 days at dietary levels resulting in exposures up to 22 or 66 times higher than those expected in infant formulas when extrapolated on the basis of diet composition (g/100 Cal) or intake (g/kg body weight), respectively. PMID:10069479

  8. Long-chain polyunsaturated fatty acids in chronic childhood disorders: panacea, promising, or placebo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-chain polyunsaturated fatty acids (LCPUFA, or LCP) include the essential fatty acids alpha-linolenic acid (ALA, 18:3 n-3) and linoleic acid (LA, 18:2 n-6) as well as a number of metabolites of both, including eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachid...

  9. Growth of the oleaginous microalga Aurantiochytrium sp. KRS101 on cellulosic biomass and the production of lipids containing high levels of docosahexaenoic acid.

    PubMed

    Hong, Won-Kyung; Kim, Chul Ho; Rairakhwada, Dina; Kim, Seonghun; Hur, Byung-Ki; Kondo, Akihiko; Seo, Jeong-Woo

    2012-01-01

    We examined the growth of a novel oleaginous microalga, Aurantiochytrium sp. KRS101, using cellulosic materials as nutrients, and the resultant production of lipids containing high levels of docosahexaenoic acid (DHA). The microalgal strain could grow using either carboxymethylcellulose or cellobiose as a carbon source, and produced lipids containing high levels of DHA (49-58% of total fatty acids). In line with this growth behavior, carboxymethylcellulase and cellobiohydrolase activities were evident in both cell-free lysates and culture broths. Additionally, an industrial cellulosic biomass, palm oil empty fruit bunches (POEFB), a by-product of the palm oil industry, were utilized by the microalgal strain for cell growth and lipid production. PMID:21959581

  10. Use of organic waste from the brewery industry for high-density cultivation of the docosahexaenoic acid-rich microalga, Aurantiochytrium sp. KRS101.

    PubMed

    Ryu, Byung-Gon; Kim, Kyochan; Kim, Jungmin; Han, Jong-In; Yang, Ji-Won

    2013-02-01

    In the present study, spent yeast from a brewery was used as the growth substrate for the docosahexaenoic acid (DHA)-rich microalga, Aurantiochytrium sp. KRS101. A significant biomass yield (6.69 g/l/d) was obtained using only spent yeast as the growth substrate, with simple stirring as pretreatment. Maximization of nutrient utilization through the use of stepwise cultivation increased the yield to 31.8 g/l of biomass. DHA constituted 38.2% (w/w) of the total fatty acids, and the highest DHA productivity was observed when the C/N ratio was 20:1 (w/w). Spent yeast thus served as a good growth substrate for the production of DHA. Economic assessment revealed that stepwise cultivation using spent yeast as either the sole growth substrate or as a nutrient source could substantially reduce the production cost of microalgal DHA. PMID:23262011

  11. EPA`s overview of the Acid Rain Program`s emissions tracking system (ETS) quarterly report process

    SciTech Connect

    Wockenfuss, M.E.

    1997-12-31

    The Acid Rain Program`s Emission Tracking System (ETS) was developed to collect, quality assure and publish the monitored and sampled emissions data collected and reported by the electric utility industry. Data are collected from fossil-fuel burning electrical generating stations that are affected by the Acid Rain Program. Since its operational start in 1993 the ETS and the data collection that surrounds it, the quarterly report process, has evolved to handle the Environmental Protection Agency`s (EPA) increased expectations of quarterly report data quality. The quarterly report process that supports the ETS provides utilities with multiple data submission options. It also provides software tools so that utilities can perform their own data assessment. This paper highlights the quarterly report process and the systems that are at the center of that process. It also analyzes utility performance relating to their 1995 and 1996 quarterly data reports and previews how the EPA`s quarterly report process will evolve over the next year.

  12. Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention.

    PubMed

    Ma, Qiu-Lan; Teter, Bruce; Ubeda, Oliver J; Morihara, Takashi; Dhoot, Dilsher; Nyby, Michael D; Tuck, Michael L; Frautschy, Sally A; Cole, Greg M

    2007-12-26

    Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate beta-amyloid (Abeta). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential omega-3 fatty acid related to reduced AD risk and reduced Abeta accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Abeta production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD. PMID:18160637

  13. The ability of walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Walnuts contain polyunsaturated fatty acids (PUFAs), specifically the omega-6 fatty acid linoleic acid (LA) as well as the omega-3 fatty acid, alpha-linolenic acid (ALA), which can be metabolized to generate eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Previous research from our lab h...

  14. Dietary docosahexaenoic acid and eicosapentaenoic acid influence liver triacylglycerol and insulin resistance in rats fed a high-fructose diet.

    PubMed

    de Castro, Gabriela Salim; Deminice, Rafael; Simões-Ambrosio, Livia Maria Cordeiro; Calder, Philip C; Jordão, Alceu A; Vannucchi, Helio

    2015-04-01

    This study aimed to examine the benefits of different amounts of omega-3 (n-3) polyunsaturated fatty acids from fish oil (FO) on lipid metabolism, insulin resistance and gene expression in rats fed a high-fructose diet. Male Wistar rats were separated into two groups: Control (C, n = 6) and Fructose (Fr, n = 32), the latter receiving a diet containing 63% by weight fructose for 60 days. After this period, 24 animals from Fr group were allocated to three groups: FrFO2 (n = 8) receiving 63% fructose and 2% FO plus 5% soybean oil; FrFO5 (n = 8) receiving 63% fructose and 5% FO plus 2% soybean oil; and FrFO7 (n = 8) receiving 63% fructose and 7% FO. Animals were fed these diets for 30 days. Fructose led to an increase in liver weight, hepatic and serum triacylglycerol, serum alanine aminotransferase and HOMA1-IR index. These alterations were reversed by 5% and 7% FO. FO had a dose-dependent effect on expression of genes related to hepatic β-oxidation (increased) and hepatic lipogenesis (decreased). The group receiving the highest FO amount had increased markers of oxidative stress. It is concluded that n-3 fatty acids may be able to reverse the adverse metabolic effects induced by a high fructose diet. PMID:25837985

  15. Dietary reference intakes for DHA and EPA.

    PubMed

    Kris-Etherton, Penny M; Grieger, Jessica A; Etherton, Terry D

    2009-01-01

    Various organizations worldwide have made dietary recommendations for eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and fish intake that are primarily for coronary disease risk reduction and triglyceride (TG) lowering. Recommendations also have been made for DHA intake for pregnant women, infants, and vegetarians/vegans. A Dietary Reference Intake (DRI), specifically, an Adequate Intake (AI), has been set for alpha-linolenic acid (ALA) by the Institute of Medicine (IOM) of The National Academies. This amount is based on an intake that supports normal growth and neural development and results in no nutrient deficiency. Although there is no DRI for EPA and DHA, the National Academies have recommended that approximately 10% of the Acceptable Macronutrient Distribution Range (AMDR) for ALA can be consumed as EPA and/or DHA. This recommendation represents current mean intake for EPA and DHA in the United States ( approximately 100mg/day), which is much lower than what many groups worldwide are currently recommending. Global recommendations for long-chain omega-3 fatty acids underscore the pressing need to establish DRIs for DHA and EPA because DRIs are recognized as the "official" standard by which federal agencies issue dietary guidance or policy directives for the health and well-being of individuals in the United States and Canada. Because of the many health benefits of DHA and EPA, it is important and timely that the National Academies establish DRIs for the individual long-chain (20 carbons or greater) omega-3 fatty acids. PMID:19525100

  16. A Novel Halophilic Lipase, LipBL, Showing High Efficiency in the Production of Eicosapentaenoic Acid (EPA)

    PubMed Central

    Pérez, Dolores; Martín, Sara; Fernández-Lorente, Gloria; Filice, Marco; Guisán, José Manuel; Ventosa, Antonio; García, María Teresa; Mellado, Encarnación

    2011-01-01

    Background Among extremophiles, halophiles are defined as microorganisms adapted to live and thrive in diverse extreme saline environments. These extremophilic microorganisms constitute the source of a number of hydrolases with great biotechnological applications. The interest to use extremozymes from halophiles in industrial applications is their resistance to organic solvents and extreme temperatures. Marinobacter lipolyticus SM19 is a moderately halophilic bacterium, isolated previously from a saline habitat in South Spain, showing lipolytic activity. Methods and Findings A lipolytic enzyme from the halophilic bacterium Marinobacter lipolyticus SM19 was isolated. This enzyme, designated LipBL, was expressed in Escherichia coli. LipBL is a protein of 404 amino acids with a molecular mass of 45.3 kDa and high identity to class C β-lactamases. LipBL was purified and biochemically characterized. The temperature for its maximal activity was 80°C and the pH optimum determined at 25°C was 7.0, showing optimal activity without sodium chloride, while maintaining 20% activity in a wide range of NaCl concentrations. This enzyme exhibited high activity against short-medium length acyl chain substrates, although it also hydrolyzes olive oil and fish oil. The fish oil hydrolysis using LipBL results in an enrichment of free eicosapentaenoic acid (EPA), but not docosahexaenoic acid (DHA), relative to its levels present in fish oil. For improving the stability and to be used in industrial processes LipBL was immobilized in different supports. The immobilized derivatives CNBr-activated Sepharose were highly selective towards the release of EPA versus DHA. The enzyme is also active towards different chiral and prochiral esters. Exposure of LipBL to buffer-solvent mixtures showed that the enzyme had remarkable activity and stability in all organic solvents tested. Conclusions In this study we isolated, purified, biochemically characterized and immobilized a lipolytic enzyme from

  17. Novel liquid chromatography–mass spectrometry method shows that vitamin E deficiency depletes arachidonic and docosahexaenoic acids in zebrafish (Danio rerio) embryos☆

    PubMed Central

    Lebold, Katie M.; Kirkwood, Jay S.; Taylor, Alan W.; Choi, Jaewoo; Barton, Carrie L.; Miller, Galen W.; Du, Jane La; Jump, Donald B.; Stevens, Jan Frederik; Tanguay, Robert L.; Traber, Maret G.

    2013-01-01

    To test the hypothesis that embryogenesis depends upon α-tocopherol (E) to protect embryo polyunsaturated fatty acids (PUFAs) from lipid peroxidation, new methodologies were applied to measure α-tocopherol and fatty acids in extracts from saponified zebrafish embryos. A solid phase extraction method was developed to separate the analyte classes, using a mixed mode cartridge (reverse phase, π–π bonding, strong anion exchange), then α-tocopherol and cholesterol were measured using standard techniques, while the fatty acids were quantitated using a novel, reverse phase liquid chromatography–mass spectrometry (LC–MS) approach. We also determined if α-tocopherol status alters embryonic lipid peroxidation products by analyzing 24 different oxidized products of arachidonic or docosahexaenoic (DHA) acids in embryos using LC with hybrid quadrupole-time of flight MS. Adult zebrafish were fed E− or E+ diets for 4 months, and then were spawned to obtain E− and E+ embryos. Between 24 and 72 hours post-fertilization (hpf), arachidonic acid decreased 3-times faster in E− (21 pg/h) compared with E+ embryos (7 pg/h, P<0.0001), while both α-tocopherol and DHA concentrations decreased only in E− embryos. At 36 hpf, E− embryos contained double the 5-hydroxy-eicosatetraenoic acids and 7-hydroxy-DHA concentrations, while other hydroxy-lipids remained unchanged. Vitamin E deficiency during embryogenesis depleted DHA and arachidonic acid, and increased hydroxy-fatty acids derived from these PUFA, suggesting that α-tocopherol is necessary to protect these critical fatty acids. PMID:24416717

  18. U.S. EPA WORKSHOP TO DEVELOP A SIMPLE MODEL FOR ACID DEPOSITION

    EPA Science Inventory

    The Acid Deposition Planning Staff in the Office of Acid Deposition/EPA requested that the Atmospheric Sciences Research Laboratory undertake the development of a low-computational-demanding model suitable for educational use in understanding the linear or non-linear nature of th...

  19. CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study

    PubMed Central

    Merle, Bénédicte M. J.; Richard, Florence; Benlian, Pascale; Puche, Nathalie; Delcourt, Cécile; Souied, Eric H.

    2015-01-01

    Purpose Genetic susceptibility could be modified by environmental factors and may also influence differential responses to treatments for age-related macular degeneration (AMD). We investigated whether genotype could influence response to docosahexaenoic acid (DHA)-supplementation in the occurrence of choroidal new vessels (CNV). Methods The Nutritional AMD Treatment 2 (NAT2) study was a randomized, placebo-controlled, double-blind, parallel, comparative study, including 250 patients aged 55 to 85 years with early lesions of age-related maculopathy, visual acuity better than 0.4 Logarithm of Minimum Angle of Resolution units in the study eye and neovascular AMD in the fellow eye. Patients were randomized at baseline to receive either 3 daily fish-oil capsules, each containing 280 mg DHA, 90 mg EPA and 2 mg Vitamin E, or placebo. Results Patients carrying the risk allele (C) for CFH Y402H had no statistically significant increased risk for developing CNV in the study eye (Hazard Ratio (HR)=0.97; 95% Confidence Interval (CI): 0.54-1.76 for heterozygous and HR=1.29; 95%CI: 0.69-2.40 for homozygous). Patients carrying the risk allele (T) for ARMS2 A69S had no statistically significant increased risk for developing CNV in the study eye (HR=1.68; 95%CI: 0.91-3.12) for heterozygous and HR=1.78; 95%CI: 0.90-3.52 for homozygous). A significant interaction was observed between CFH Y402H and DHA-supplementation (p=0.01). We showed a protective effect of DHA-supplementation among homozygous non-risk patients. Among these patients, occurrence of CNV was 38.2% in placebo group versus 16.7% in DHA group (p=0.008). Conclusions These results suggest that a genetic predisposition to AMD conferred by the CFH Y402H variant limits the benefit provided by DHA supplementation. Trial Registration ISRCTN registry 98246501 PMID:26132079

  20. The Quality Assurance Manual and EPA`s acid rain data quality

    SciTech Connect

    Bloomer, B.J.; Winkler, J.P.

    1995-12-31

    November 15, 1990 saw the passage of the Clean Air Act Amendments of 1990. Within this law was the requirements for all electric utility units greater than 25 megawatts of generated electrical capacity to monitor SO{sub 2}, NO{sub x}, CO{sub 2}, opacity, and volumetric flow of the stack gases. This paper summarizes the Acid Rain Program`s approach to Continuous Emissions Monitoring Systems (CEMS) Quality Control and Quality Assurance requirements and their use in the market based pollution control program of Title IV of the Clean Air Act Amendments of 1990. This paper attempts to present the perspective of the authors as to what is important for excellent monitoring system availability and ensuring accurate data acquisition. Emphasis is placed upon the Quality Assurance Manual required by the Acid Rain Regulations for affected unit`s to maintain and follow.

  1. Comparison of natural antioxidants and their effects on omega-3 fatty acid oxidation in fish oil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyunsaturated fatty acids (PUFA), such as the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been found to offer a variety of health benefits including cardiovascular protection, anti-inflammatory effect and human development. It is known that fish and algae o...

  2. A 3-week dietary bioequivalence study in preweaning farm piglets of two sources of docosahexaenoic acid produced from two different organisms.

    PubMed

    Fedorova-Dahms, Irina; Thorsrud, Bjorn A; Bailey, Eileen; Salem, Norman

    2014-03-01

    Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are components of human breast milk and commonly added to infant formula. The first DHA-containing algal oil for infant formulas was DHASCO® produced from the microalgae Crypthecodinium cohnii. Recently, new DHA-rich oil was obtained from the microalgae Schizochytrium sp., herein named DHASCO-B. The objectives of this study were to evaluate the bioequivalence of DHASCO-B to DHASCO when administered in a blend with ARA oil and the potential effects after 3weeks' administration in milk replacer formula to preweaning farm piglets. DHASCO-B and DHASCO were added to formula at concentrations 0.32% and 0.96% DHA (% of total fatty acids). There were no test article-related effects of any diet on piglet growth and development (clinical observations, body weight, food consumption), or clinical pathology parameters (hematology, clinical chemistry, coagulation and urinalysis). In addition, there were no adverse effects at terminal necropsy (macro- and microscopic pathology evaluations). DHA content in plasma, RBC, heart, liver and brain showed dose-related accumulation and confirmed no differences between corresponding DHASCO-B and DHASCO groups. Therefore, dietary exposure to DHASCO-B and DHASCO was well tolerated by the preweaning piglets during the 3-week dosing period right after birth and DHASCO-B and DHASCO were bioequivalent. PMID:24333867

  3. EPA releases study describing potential acid rain damage

    SciTech Connect

    Not Available

    1989-11-01

    The U.S. Environmental Protection Agency's acid rain researchers on August 24 offered evidence that if sulfur emissions are not reduced in the future, aquatic systems in the South will suffer damage from acid rain. Evidence also indicates that reductions in sulfur emissions could improve the health of damaged lakes in the Northeast. The study Future Effects of Long-Term Sulfur Deposition on Surface Water Chemistry: The Direct/Delayed Response Project, developed 50-year projections of watershed quality under three plausible acidic deposition, or acid rain, scenarios. Three areas were studied - the Northeast, comprising all of New England and parts of New York and Pennsylvania; the Mid-Appalachian Region, covering much of Pennsylvania, Maryland, Virginia, and West Virginia; and the Southern Blue Ridge Province, an area covering parts of North Carolina, Tennessee, South Carolina and Georgia. The study is a key element in the closing months of the 10-year National Acid Precipitation Assessment Program.

  4. Evidence for the essentiality of arachidonic and docosahexaenoic acid in the postnatal maternal and infant diet for the development of the infant's immune system early in life.

    PubMed

    Richard, Caroline; Lewis, Erin D; Field, Catherine J

    2016-05-01

    Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life. PMID:27138971

  5. Improvement of Omega-3 Docosahexaenoic Acid Production by Marine Dinoflagellate Crypthecodinium cohnii Using Rapeseed Meal Hydrolysate and Waste Molasses as Feedstock

    PubMed Central

    Gong, Yangmin; Liu, Jiao; Jiang, Mulan; Liang, Zhuo; Jin, Hu; Hu, Xiaojia; Wan, Xia; Hu, Chuanjiong

    2015-01-01

    Rapeseed meal and waste molasses are two important agro-industrial by-products which are produced in large quantities. In this study, solid state fermentation and fungal autolysis were performed to produce rapeseed meal hydrolysate (RMH) using fungal strains of Aspergillus oryzae, Penicillium oxalicum and Neurospora crassa. The hydrolysate was used as fermentation feedstock for heterotrophic growth of microalga Crypthecodinium cohnii that produce docosahexaenoic acid (DHA). The addition of waste molasses as a supplementary carbon source greatly increased the biomass and DHA yield. In the batch fermentations using media composed of diluted RMH (7%) and 1-9% waste molasses, the highest biomass concentration and DHA yield reached 3.43 g/L and 8.72 mg/L, respectively. The algal biomass produced from RMH and molasses medium also had a high percentage of DHA (22-34%) in total fatty acids similar to that of commercial algal biomass. RMH was shown to be rich in nitrogen supply comparable to the commercial nitrogen feedstock like yeast extract. Using RMH as sole nitrogen source, waste molasses excelled other carbon sources and produced the highest concentration of biomass. This study suggests that DHA production of the marine dinoflagellate C. cohnii could be greatly improved by concomitantly using the cheap by-products rapeseed meal hydrolysate and molasses as alternative feedstock. PMID:25942565

  6. Improvement of Omega-3 Docosahexaenoic Acid Production by Marine Dinoflagellate Crypthecodinium cohnii Using Rapeseed Meal Hydrolysate and Waste Molasses as Feedstock.

    PubMed

    Gong, Yangmin; Liu, Jiao; Jiang, Mulan; Liang, Zhuo; Jin, Hu; Hu, Xiaojia; Wan, Xia; Hu, Chuanjiong

    2015-01-01

    Rapeseed meal and waste molasses are two important agro-industrial by-products which are produced in large quantities. In this study, solid state fermentation and fungal autolysis were performed to produce rapeseed meal hydrolysate (RMH) using fungal strains of Aspergillus oryzae, Penicillium oxalicum and Neurospora crassa. The hydrolysate was used as fermentation feedstock for heterotrophic growth of microalga Crypthecodinium cohnii that produce docosahexaenoic acid (DHA). The addition of waste molasses as a supplementary carbon source greatly increased the biomass and DHA yield. In the batch fermentations using media composed of diluted RMH (7%) and 1-9% waste molasses, the highest biomass concentration and DHA yield reached 3.43 g/L and 8.72 mg/L, respectively. The algal biomass produced from RMH and molasses medium also had a high percentage of DHA (22-34%) in total fatty acids similar to that of commercial algal biomass. RMH was shown to be rich in nitrogen supply comparable to the commercial nitrogen feedstock like yeast extract. Using RMH as sole nitrogen source, waste molasses excelled other carbon sources and produced the highest concentration of biomass. This study suggests that DHA production of the marine dinoflagellate C. cohnii could be greatly improved by concomitantly using the cheap by-products rapeseed meal hydrolysate and molasses as alternative feedstock. PMID:25942565

  7. Docosahexaenoic acid inhibits proteolytic processing of sterol regulatory element-binding protein-1c (SREBP-1c) via activation of AMP-activated kinase.

    PubMed

    Deng, Xiong; Dong, Qingming; Bridges, Dave; Raghow, Rajendra; Park, Edwards A; Elam, Marshall B

    2015-12-01

    In hyperinsulinemic states including obesity and T2DM, overproduction of fatty acid and triglyceride contributes to steatosis of the liver, hyperlipidemia and hepatic insulin resistance. This effect is mediated in part by the transcriptional regulator sterol responsive element binding protein-1c (SREBP-1c), which stimulates the expression of genes involved in hepatic fatty acid and triglyceride synthesis. SREBP-1c is up regulated by insulin both via increased transcription of nascent full-length SREBP-1c and by enhanced proteolytic processing of the endoplasmic reticulum (ER)-bound precursor to yield the transcriptionally active n-terminal form, nSREBP-1c. Polyunsaturated fatty acids of marine origin (n-3 PUFA) prevent induction of SREBP-1c by insulin thereby reducing plasma and hepatic triglycerides. Despite widespread use of n-3 PUFA supplements to reduce triglycerides in clinical practice, the exact mechanisms underlying their hypotriglyceridemic effect remain elusive. Here we demonstrate that the n-3 PUFA docosahexaenoic acid (DHA; 22:5 n-3) reduces nSREBP-1c by inhibiting regulated intramembrane proteolysis (RIP) of the nascent SREBP-1c. We further show that this effect of DHA is mediated both via activation of AMP-activated protein kinase (AMPK) and by inhibition of mechanistic target of rapamycin complex 1 (mTORC1). The inhibitory effect of AMPK on SREBP-1c processing is linked to phosphorylation of serine 365 of SREBP-1c in the rat. We have defined a novel regulatory mechanism by which n-3 PUFA inhibit induction of SREBP-1c by insulin. These findings identify AMPK as an important negative regulator of hepatic lipid synthesis and as a potential therapeutic target for hyperlipidemia in obesity and T2DM. PMID:26327595

  8. Evaluation of a high-EPA oil from transgenic Camelina sativa in feeds for Atlantic salmon (Salmo salar L.): Effects on tissue fatty acid composition, histology and gene expression

    PubMed Central

    Betancor, M.B.; Sprague, M.; Sayanova, O.; Usher, S.; Campbell, P.J.; Napier, J.A.; Caballero, M.J.; Tocher, D.R.

    2015-01-01

    Currently, one alternative for dietary fish oil (FO) in aquafeeds is vegetable oils (VO) that are devoid of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs). Entirely new sources of n-3 LC-PUFA such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids through de novo production are a potential solution to fill the gap between supply and demand of these important nutrients. Camelina sativa was metabolically engineered to produce a seed oil (ECO) with > 20% EPA and its potential to substitute for FO in Atlantic salmon feeds was tested. Fish were fed with one of the three experimental diets containing FO, wild-type camelina oil (WCO) or ECO as the sole lipid sources for 7 weeks. Inclusion of ECO did not affect any of the performance parameters studied and enhanced apparent digestibility of individual n-6 and n-3 PUFA compared to dietary WCO. High levels of EPA were maintained in brain, liver and intestine (pyloric caeca), and levels of DPA and DHA were increased in liver and intestine of fish fed ECO compared to fish fed WCO likely due to increased LC-PUFA biosynthesis based on up-regulation of the genes. Fish fed ECO showed slight lipid accumulation within hepatocytes similar to that with WCO, although not significantly different to fish fed FO. The regulation of a small number of genes could be attributed to the specific effect of ECO (311 features) with metabolism being the most affected category. The EPA oil from transgenic Camelina (ECO) could be used as a substitute for FO, however it is a hybrid oil containing both FO (EPA) and VO (18:2n-6) fatty acid signatures that resulted in similarly mixed metabolic and physiological responses. PMID:26146421

  9. Hydrothermal-acid treatment for effectual extraction of eicosapentaenoic acid (EPA)-abundant lipids from Nannochloropsis salina.

    PubMed

    Lee, Ilgyu; Han, Jong-In

    2015-09-01

    Hydrothermal acid treatment, was adopted to extract eicosapentaenoic acid (EPA) from wet biomass of Nannochloropsis salina. It was found that sulfuric acid-based treatment increased EPA yield from 11.8 to 58.1 mg/g cell in a way that was nearly proportional to its concentration. Nitric acid exhibited the same pattern at low concentrations, but unlike sulfuric acid its effectiveness unexpectedly dropped from 0.5% to 2.0%. The optimal and minimal conditions for hydrothermal acid pretreatment were determined using a statistical approach; its maximum EPA yield (predicted: 43.69 mg/g cell; experimental: 43.93 mg/g cell) was established at a condition of 1.27% of sulfuric acid, 113.34 °C of temperature, and 36.71 min of reaction time. Our work demonstrated that the acid-catalyzed cell disruption, accompanied by heat, can be one potentially promising option for ω-3 fatty acids extraction. PMID:25966023

  10. Learning about Acid Rain: A Teacher's Guide for Grades 6 through 8. EPA 430-F-08-002

    ERIC Educational Resources Information Center

    US Environmental Protection Agency, 2008

    2008-01-01

    Acid rain is a complex environmental problem which affects the United States and many other countries around the world. The United States Environmental Protection Agency (EPA) was established in 1970 to address environmental issues, such as acid rain. Through its programs, EPA works to protect human health and the environment in the United States…

  11. Endogenous Ligand for GPR120, Docosahexaenoic Acid, Exerts Benign Metabolic Effects on the Skeletal Muscles via AMP-activated Protein Kinase Pathway*

    PubMed Central

    Kim, Nami; Lee, Jung Ok; Lee, Hye Jeong; Kim, Hyung Ip; Kim, Joong Kwan; Lee, Yong Woo; Lee, Soo Kyung; Kim, Su Jin; Park, Sun Hwa; Kim, Hyeon Soo

    2015-01-01

    Docosahexaenoic acid (DHA) is an endogenous ligand of G protein-coupled receptor 120 (GPR120). However, the mechanisms underlying DHA action are poorly understood. In this study, DHA stimulated glucose uptake in the skeletal muscles in an AMP-activated protein kinase (AMPK)-dependent manner. GPR120-mediated increase in intracellular Ca2+ was critical for DHA-mediated AMPK phosphorylation and glucose uptake. In addition, DHA stimulated GLUT4 translocation AMPK-dependently. Inhibition of AMPK and Ca2+/calmodulin-dependent protein kinase kinase blocked DHA-induced glucose uptake. DHA and GW9508, a GPR120 agonist, increased GPR120 expression. DHA-mediated glucose uptake was not observed in GPR120 knockdown conditions. DHA increased AMPK phosphorylation, glucose uptake, and intracellular Ca2+ concentration in primary cultured myoblasts. Taken together, these results indicated that the beneficial metabolic role of DHA was attributed to its ability to regulate glucose via the GPR120-mediated AMPK pathway in the skeletal muscles. PMID:26134561

  12. Regulation of Membrane Proteins by Dietary Lipids: Effects of Cholesterol and Docosahexaenoic Acid Acyl Chain-Containing Phospholipids on Rhodopsin Stability and Function

    PubMed Central

    Bennett, Michael P.; Mitchell, Drake C.

    2008-01-01

    Purified bovine rhodopsin was reconstituted into vesicles consisting of 1-stearoyl-2-oleoyl phosphatidylcholine or 1-stearoyl-2-docosahexaenoyl phosphatidylcholine with and without 30 mol % cholesterol. Rhodopsin stability was examined using differential scanning calorimetry (DSC). The thermal unfolding transition temperature (Tm) of rhodopsin was scan rate-dependent, demonstrating the presence of a rate-limited component of denaturation. The activation energy of this kinetically controlled process (Ea) was determined from DSC thermograms by four separate methods. Both Tm and Ea varied with bilayer composition. Cholesterol increased the Tm both the presence and absence of docosahexaenoic acid acyl chains (DHA). In contrast, cholesterol lowered Ea in the absence of DHA, but raised Ea in the presence of 20 mol % DHA-containing phospholipid. The relative acyl chain packing order was determined from measurements of diphenylhexatriene fluorescence anisotropy decay. The Tm for thermal unfolding was inversely related to acyl chain packing order. Rhodopsin kinetic stability (Ea) was reduced in highly ordered or disordered membranes. Maximal kinetic stability was found within the range of acyl chain order found in native bovine rod outer segment disk membranes. The results demonstrate that membrane composition has distinct effects on the thermal versus kinetic stabilities of membrane proteins, and suggests that a balance between membrane constituents with opposite effects on acyl chain packing, such as DHA and cholesterol, may be required for maximum protein stability. PMID:18424497

  13. Impact of carbon and nitrogen feeding strategy on high production of biomass and docosahexaenoic acid (DHA) by Schizochytrium sp. LU310.

    PubMed

    Ling, Xueping; Guo, Jing; Liu, Xiaoting; Zhang, Xia; Wang, Nan; Lu, Yinghua; Ng, I-Son

    2015-05-01

    A new isolated Schizochytrium sp. LU310 from the mangrove forest of Wenzhou, China, was found as a high producing microalga of docosahexaenoic acid (DHA). In this study, the significant improvements for DHA fermentation by the batch mode in the baffled flasks (i.e. higher oxygen supply) were achieved. By applied the nitrogen-feeding strategy in 1000 mL baffled flasks, the biomass, DHA concentration and DHA productivity were increased by 110.4%, 117.9% and 110.4%, respectively. Moreover, DHA concentration of 21.06 g/L was obtained by feeding 15 g/L of glucose intermittently, which was an increase of 41.25% over that of the batch mode. Finally, an innovative strategy was carried out by intermittent feeding carbon and simultaneously feeding nitrogen. The maximum DHA concentration and DHA productivity in the fed-batch cultivation reached to 24.74 g/L and 241.5 mg/L/h, respectively. PMID:25451778

  14. Producing docosahexaenoic acid (DHA)-rich algae from biodiesel-derived crude glycerol: effects of impurities on DHA production and algal biomass composition.

    PubMed

    Pyle, Denver J; Garcia, Rafael A; Wen, Zhiyou

    2008-06-11

    Crude glycerol is the primary byproduct of the biodiesel industry. Producing docosahexaenoic acid (DHA, 22:6 n-3) through fermentation of the alga Schizochytrium limacinum on crude glycerol provides a unique opportunity to utilize a large quantity of this byproduct. The objective of this work is to investigate the effects of impurities contained in the crude glycerol on DHA production and algal biomass composition. Crude glycerol streams were obtained from different biodiesel refineries. All of the glycerol samples contained methanol, soaps, and various elements including calcium, phosphorus, potassium, silicon, sodium, and zinc. Both methanol and soap were found to negatively influence algal DHA production; these two impurities can be removed from culture medium by evaporation through autoclaving (for methanol) and by precipitation through pH adjustment (for soap). The glycerol-derived algal biomass contained 45-50% lipid, 14-20% protein, and 25% carbohydrate, with 8-13% ash content. Palmitic acid (C16:0) and DHA were the two major fatty acids in the algal lipid. The algal biomass was rich in lysine and cysteine, relative to many common feedstuffs. Elemental analysis by inductively coupled plasma showed that boron, calcium, copper, iron, magnesium, phosphorus, potassium, silicon, sodium, and sulfur were present in the biomass, whereas no heavy metals (such as mercury) were detected in the algal biomass. Overall, the results show that crude glycerol was a suitable carbon source for algal fermentation. The crude glycerol-derived algal biomass had a high level of DHA and a nutritional profile similar to that of commercial algal biomass, suggesting a great potential for using crude glycerol-derived algae in omega-3-fortified food or feed. PMID:18465872

  15. Chemoprevention of DMBA-induced mammary carcinogenesis in rats by low-dose EPA and DHA.

    PubMed Central

    Noguchi, M.; Minami, M.; Yagasaki, R.; Kinoshita, K.; Earashi, M.; Kitagawa, H.; Taniya, T.; Miyazaki, I.

    1997-01-01

    We investigated the effects of low-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the incidence and growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in rats fed a high-fat (HF) diet. We also examined the effects of these treatments on the fatty acid composition of tumour and serum. Tumour incidence was significantly decreased by the administration of low-dose EPA and DHA, whereas their inhibitory effects on tumour growth did not reach significance. Serum arachidonic acid (AA) level was decreased by the administration of low-dose EPA and tended to be decreased by the administration of low-dose DHA, whereas tumour AA levels were not changed. The administration of low-dose EPA and DHA may be useful for inhibiting the incidence of breast cancer. PMID:9020478

  16. Docosahexaenoic Acid Modulates a HER2-Associated Lipogenic Phenotype, Induces Apoptosis, and Increases Trastuzumab Action in HER2-Overexpressing Breast Carcinoma Cells

    PubMed Central

    Ravacci, Graziela Rosa; Brentani, Maria Mitzi; Tortelli, Tharcisio Citrângulo; Torrinhas, Raquel Suzana M. M.; Santos, Jéssica Reis; Logullo, Angela Flávia; Waitzberg, Dan Linetzky

    2015-01-01

    In breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expression of lipogenic genes involved in uptake (CD36), transport (FABP4), and storage (DGAT) of exogenous fatty acids (FA), as well as increased activation of “de novo” FA synthesis (FASN). We further investigate whether this lipogenesis reprogramming might be regulated by mTOR/PPARγ pathway. Inhibition of the mTORC1 pathway markers, p70S6 K1, SREBP1, and LIPIN1, as well as an increase in DEPTOR expression (the main inhibitor of the mTOR) was detected in HB4aC5.2. Based on these results, a PPARγ selective antagonist, GW9662, was used to treat both cells lines, and the lipogenic genes remained overexpressed in the HB4aC5.2 but not HB4a cells. DHA treatment inhibited all lipogenic genes (except for FABP4) in both cell lines yet only induced death in the HB4aC5.2 cells, mainly when associated with trastuzumab. Neither trastuzumab nor GW9662 alone was able to induce cell death. In conclusion, oncogenic transformation of breast cells by HER2 overexpression may require a reprogramming of lipogenic genetic that is independent of mTORC1 pathway and PPARγ activity. This reprogramming was inhibited by DHA. PMID:26640797

  17. Nucleotide excision repair deficiency increases levels of acrolein-derived cyclic DNA adduct and sensitizes cells to apoptosis induced by docosahexaenoic acid and acrolein.

    PubMed

    Pan, Jishen; Sinclair, Elizabeth; Xuan, Zhuoli; Dyba, Marcin; Fu, Ying; Sen, Supti; Berry, Deborah; Creswell, Karen; Hu, Jiaxi; Roy, Rabindra; Chung, Fung-Lung

    2016-07-01

    The acrolein derived cyclic 1,N(2)-propanodeoxyguanosine adduct (Acr-dG), formed primarily from ω-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) under oxidative conditions, while proven to be mutagenic, is potentially involved in DHA-induced apoptosis. The latter may contribute to the chemopreventive effects of DHA. Previous studies have shown that the levels of Acr-dG are correlated with apoptosis induction in HT29 cells treated with DHA. Because Acr-dG is shown to be repaired by the nucleotide excision repair (NER) pathway, to further investigate the role of Acr-dG in apoptosis, in this study, NER-deficient XPA and its isogenic NER-proficient XAN1 cells were treated with DHA. The Acr-dG levels and apoptosis were sharply increased in XPA cells, but not in XAN1 cells when treated with 125μM of DHA. Because DHA can induce formation of various DNA damage, to specifically investigate the role of Acr-dG in apoptosis induction, we treated XPA knockdown HCT116+ch3 cells with acrolein. The levels of both Acr-dG and apoptosis induction increased significantly in the XPA knockdown cells. These results clearly demonstrate that NER deficiency induces higher levels of Acr-dG in cells treated with DHA or acrolein and sensitizes cells to undergo apoptosis in a correlative manner. Collectively, these results support that Acr-dG, a ubiquitously formed mutagenic oxidative DNA adduct, plays a role in DHA-induced apoptosis and suggest that it could serve as a biomarker for the cancer preventive effects of DHA. PMID:27036235

  18. Twice-weekly consumption of farmed Atlantic salmon increases plasma content of phospholipid n-3 fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated intake of the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is related to risk reduction of cardiovascular and other diseases. Increased consumption of seafood such as farmed Atlantic salmon is an effective way to consume n-3 but there is a paucity of data as ...

  19. Baking reduces prostaglandin, resolvin, and hydroxy-fatty acid content of farm-raised Atlantic salmon (Salmo salar)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consumption of seafood enriched in n-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of cardiovascular disease. Several n-3 oxidation products from eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) have known protective effects in the vasculature t...

  20. Effects of alpha-linolenic acid vs. docosahexaenoic acid supply on the distribution of fatty acids among the rat cardiac subcellular membranes after a short- or long-term dietary exposure

    PubMed Central

    Brochot, Amandine; Guinot, Marine; Auchere, Daniel; Macaire, Jean-Paul; Weill, Pierre; Grynberg, Alain; Rousseau-Ralliard, Delphine

    2009-01-01

    Background Previous work showed that the functional cardiac effect of dietary alpha-linolenic acid (ALA) in rats requires a long feeding period (6 months), although a docosahexaenoic (DHA) acid-supply affects cardiac adrenergic response after 2 months. However, the total cardiac membrane n-3 polyunsaturated fatty acid (PUFA) composition remained unchanged after 2 months. This delay could be due to a specific reorganization of the different subcellular membrane PUFA profiles. This study was designed to investigate the evolution between 2 and 6 months of diet duration of the fatty acid profile in sarcolemmal (SL), mitochondrial (MI), nuclear (NU) and sarcoplasmic reticulum (SR) membrane fractions. Methods Male Wistar rats were randomly assigned to 3 dietary groups (n = 10/diet/period), either n-3 PUFA-free diet (CTL), or ALA or DHA-rich diets. After 2 or 6 months, the subcellular cardiac membrane fractions were separated by differential centrifugations and sucrose gradients. Each membrane profile was analysed by gas chromatography (GC) after lipid extraction. Results As expected the n-3 PUFA-rich diets incorporated n-3 PUFA instead of n-6 PUFA in all the subcellular fractions, which also exhibited individual specificities. The diet duration increased SFA and decreased PUFA in SL, whereas NU remained constant. The SR and MI enriched in n-3 PUFA exhibited a decreased DHA level with ageing in the DHA and CTL groups. Conversely, the n-3 PUFA level remained unchanged in the ALA group, due to a significant increase in docosapentaenoic acid (DPA). N-3 PUFA rich diets lead to a better PUFA profile in all the fractions and significantly prevent the profile modifications induced by ageing. Conclusion With the ALA diet the n-3 PUFA content, particularly in SR and SL kept increasing between 2 and 6 months, which may partly account for the delay to achieve the modification of adrenergic response. PMID:19320987

  1. Docosahexaenoic acid-rich fish oil improves heart rate variability and heart rate responses to exercise in overweight adults.

    PubMed

    Ninio, Daniel M; Hill, Alison M; Howe, Peter R; Buckley, Jonathan D; Saint, David A

    2008-11-01

    Dietary fish oil supplementation and regular physical activity can improve outcomes in patients with established CVD. Exercise has been shown to improve heart rate variability (HRV), a predictor of cardiac death, but whether fish oil benefits HRV is controversial. Obese adults at risk of future coronary disease have impaired HRV and may benefit from these interventions. We evaluated the effect of DHA-rich tuna fish oil supplementation with and without regular exercise on HRV in sedentary, overweight adults with risk factors for coronary disease. In a randomised, double-blind, parallel comparison, sixty-five volunteers consumed 6 g fish oil/d (DHA 1.56 g/d, EPA 0.36 g/d) or sunflower-seed oil (placebo) for 12 weeks. Half of each oil group also undertook regular moderate physical activity (3 d/week for 45 min, at 75 % of age-predicted maximal heart rate (HR)). Resting HR and the HR response to submaximal exercise were measured at weeks 0, 6 and 12. In forty-six subjects, HRV was also assessed by power spectrum analysis of 20 min electrocardiogram recordings taken supine at baseline and 12 weeks. Fish oil supplementation improved HRV by increasing high-frequency power, representing parasympathetic activity, compared with placebo (P = 0.01; oil x time interaction). It also reduced HR at rest and during submaximal exercise (P = 0.008; oil x time interaction). There were no significant fish oil x exercise interactions. Dietary supplementation with DHA-rich fish oil reduced HR and modulated HRV in keeping with an improved parasympathetic-sympathetic balance in overweight adults with risk factors for future coronary disease. PMID:18339222

  2. Dietary Effects of Oxidized Eicosapentaenoic Acid (EPA) and Intact EPA on Hepatic Steatosis Induced by a High-sucrose Diet and Liver-X-receptor α Agonist in Mice.

    PubMed

    Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Hirata, Takashi; Sugawara, Tatsuya

    2016-01-01

    Numerous studies have shown that dietary omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA), improve lipid metabolism. The beneficial effects of PUFA-derived oxidation products have been increasingly reported. However, EPA is easily oxidized in food products and in the human body, generating various derivatives of oxidized EPA (oxEPA), such that these oxidation products may partially contribute to EPA's effect. We previously reported that oxEPA was more potent than intact EPA in reducing liver-X-receptor α (LXRα)-induced cellular triacylglycerol (TG) accumulation. However, the in vivo hypolipidemic effects of oxEPA remain unclear. In the present study, we evaluated the effect of oral administration of EPA and oxEPA on hepatic steatosis in mice induced by a high-sucrose diet and a synthetic LXRα agonist, TO-901317. Both EPA and oxEPA reduced TG accumulation in the liver and plasma biomarkers of liver injury. Furthermore, they suppressed the expression of lipogenic genes, but not β-oxidation genes, in a similar pattern as the biomarkers. Our results suggest that oxEPA and intact EPA suppress de novo lipogenesis to ameliorate hepatic steatosis. PMID:26876675

  3. Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury.

    PubMed

    Schober, Michelle E; Requena, Daniela F; Abdullah, Osama M; Casper, T Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R

    2016-02-15

    Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI. PMID:26247583

  4. Dietary supplementation with cholesterol and docosahexaenoic acid increases the activity of the arginine-nitric oxide pathway in tissues of young pigs

    PubMed Central

    Li, Peng; Woo Kim, Sung; Li, Xilong; Datta, Sujay; Pond, Wilson G.; Wu, Guoyao

    2008-01-01

    Nitric oxide (NO), synthesized from L-arginine by tetrahydrobiopterin (BH4)-dependent NO synthase (NOS), is critical for neurological and muscular development and function. This study was designed to test the hypothesis that cholesterol and docosahexaenoic acid (DHA) may modulate the arginine-NO pathway in tissues of the young pig. Sixteen newborn pigs were nursed by sows for 24 h and then assigned to one of 4 treatment groups, representing supplementation with 0.0%, 0.2% cholesterol, 0.2% DHA, or cholesterol plus DHA to the basal milk-formula. All piglets were euthanized at 49 days of age. Brain, liver and gastrocnemius muscle were analyzed for BH4, NADPH and arginine, GTP cyclohydrolase-I (GTP-CH) and NOS activities, and NOS protein isoforms. Hepatic NOS activity was below the detection limit in all pigs. DHA supplementation (P<0.01) increased GTP-CH activities, as well as BH4 and NADPH concentrations in brain, liver, and muscle by 24–46%, while enhancing (P<0.05) NOS activities by 45–48% in brain and muscle. Dietary cholesterol supplementation increased (P<0.05) NOS and GTP-CH activities by 17–26% in brain but had no effect in liver or muscle. The enhanced NOS activity in the brain or muscle of cholesterol- or DHA-supplemented piglets was attributable to the combined effects of increased eNOS and nNOS activation (changes in phosphorylation levels) and total iNOS protein. Additionally, DHA and cholesterol enhanced (P>0.05) arginine concentrations in brain (35–42%), but not in liver or muscle. These tissue-specific effects of cholesterol and DHA on NO synthesis may play an important role in postnatal growth and development. PMID:18555806

  5. Resolvin D1, Protectin D1, and Related Docosahexaenoic Acid-Derived Products: Analysis via Electrospray/Low Energy Tandem Mass Spectrometry based on Spectra and Fragmentation Mechanisms

    PubMed Central

    Hong, Song; Lu, Yan; Yang, Rong; Gotlinger, Katherine H.; Petasis, Nicos P.; Serhan, Charles N.

    2009-01-01

    Resolvin D1 (RvD1) and Protectin D1 (Neuroprotectin D1, PD1/NPD1) are newly identified anti-inflammatory lipid mediators biosynthesized from docosahexaenoic acid (DHA). In this report, the spectra-structure correlations and fragmentation mechanisms were studied using electrospray low-energy collision-induced dissociation tandem mass spectrometry (MS/MS) for biogenic RvD1 and PD1, as well as mono-hydroxy-DHA and related hydroperoxy-DHA. The loss of H2O and CO2 in the spectra indicates the number of functional group(s). Chain-cut ions are the signature of the positions and numbers of functional groups and double-bonds. The observed chain-cut ion is equivalent to a hypothetical homolytic-segment (cc, cm, mc, or mm) with addition or extraction of up to 2 protons (H). The α-cleavage ions are equivalent to: [cc + H], with H from the hydroxyl through a β-ene or γ-ene rearrangement; [cm - 2H], with 2H from hydroxyls of PD1 through a γ-ene rearrangement, or one H from the hydroxyl and the other H from the α-carbon of mono-HDHA through an α-H-β-ene rearrangement; [mc – H], with H from hydroxyl through a β-ene or γ-ene rearrangement, or from the α-carbon through an α-H-β-ene rearrangement; or [mm] through charge-direct fragmentations. The β-ene or γ-ene facilitates the H shift to γ position and α-cleavage. Deuterium labeling confirmed the assignment of MS/MS ions and the fragmentation mechanisms. Based on the MS/MS spectra and fragmentation mechanisms, we identified RvD1, PD1, and mono-hydroxy-DHA products in human neutrophils and blood, trout head-kidney, and stroke-injury murine brain-tissues. PMID:17055291

  6. The binding of Aβ1-42 to lipid rafts of RBC is enhanced by dietary docosahexaenoic acid in rats: Implicates to Alzheimer's disease.

    PubMed

    Hashimoto, Michio; Hossain, Shahdat; Katakura, Masanori; Al Mamun, Abdullah; Shido, Osamu

    2015-06-01

    Once amyloid β peptides (Aβs) of the Alzheimer's disease build up in blood circulation, they are capable of binding to red blood cell (RBC) and inducing hemolysis of RBC. The mechanisms of the interactions between RBC and Aβ are largely unknown; however, it is very important for the therapeutic target of Aβ-induced hemolysis. In the present study, we investigated whether Aβ1-42 interacts with caveolin-1-containing detergent-resistant membranes (DRMs) of RBC and whether the interaction could be modulated by dietary pre-administration of docosahexaenoic acid (DHA). DHA pre-administration to rats inhibited hemolysis by Aβ1-42. This activity was accompanied by increased DHA levels and membrane fluidity and decreased cholesterol level, lipid peroxidation, and reactive oxygen species in the RBCs of the DHA-pretreated rats, suggesting that the antioxidative property of DHA may rescue RBCs from oxidative damage by Aβ1-42. The level of caveolin-1 was augmented in the DRMs of DHA-pretreated rats. Binding between Aβ1-42 and DRMs of RBC significantly increased in DHA-rats. When fluorescently labeled Aβ1-42 (TAMRA-Aβ1-42) was directly infused into the bloodstream, it again occupied the caveolin-1-containing DRMs of the RBCs from the DHA-rats to a greater extent, indicating that circulating Aβs interact with the caveolin-1-rich lipid rafts of DRMs and the interaction is stronger in the DHA-enriched RBCs. The levels of TAMRA-Aβ1-42 also increased in liver DRMs, whereas it decreased in plasma of DHA-pretreated rats. DHA might help clearance of circulating Aβs by increased lipid raft-dependent degradation pathways and implicate to therapies in Alzheimer's disease. PMID:25782726

  7. Ameliorative effects of docosahexaenoic acid on the toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in cultured rat hepatocytes.

    PubMed

    Turkez, Hasan; Geyikoglu, Fatime; Yousef, Mokhtar I

    2016-06-01

    The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant toxicant that mediates carcinogenic effects associated with oxidative DNA damage. Docosahexaenoic acid (DHA) with antioxidant functions has many biochemical, cellular, and physiological functions for cells. The present study assessed, for the first time, the ameliorative effect of DHA in alleviating the toxicity of TCDD on primary cultured rat hepatocytes (HEPs). In vitro, isolated HEPs were incubated with TCDD (5 and 10 μM) in the presence and absence of DHA (5, 10, and 20 μM) for 48 h. The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release. DNA damage was analyzed by liver micronucleus assay and 8-oxo-2-deoxyguanosine (8-OH-dG) level. In addition, total antioxidant capacity (TAC) and total oxidative stress (TOS) were assessed to determine the oxidative injury in HEPs. The results of MTT and LDH assays showed that TCDD decreased cell viability but not DHA. On the basis of increasing treatment concentrations, the dioxin caused significant increases of micronucleated HEPs and 8-OH-dG as compared to control culture. TCDD also led to significant increases in TOS content. On the contrary, in cultures treated with DHA, the level of TAC was significantly increased during treatment in a concentration-dependent fashion. DHA showed therapeutic potential against TCDD-mediated cell viability and DNA damages. As conclusion, this study provides the first evidence that DHA has protective effects against TCDD toxicity on primary cultured rat hepatocytes. PMID:25187318

  8. Analysis of Phosphonic Acids: Validation of Semi-Volatile Analysis by HPLC-MS/MS by EPA Method MS999

    SciTech Connect

    Owens, J; Vu, A; Koester, C

    2008-10-31

    The Environmental Protection Agency's (EPA) Region 5 Chicago Regional Laboratory (CRL) developed a method titled Analysis of Diisopropyl Methylphosphonate, Ethyl Hydrogen Dimethylamidophosphate, Isopropyl Methylphosphonic Acid, Methylphosphonic Acid, and Pinacolyl Methylphosphonic Acid in Water by Multiple Reaction Monitoring Liquid Chromatography/Tandem Mass Spectrometry: EPA Version MS999. This draft standard operating procedure (SOP) was distributed to multiple EPA laboratories and to Lawrence Livermore National Laboratory, which was tasked to serve as a reference laboratory for EPA's Environmental Reference Laboratory Network (ERLN) and to develop and validate analytical procedures. The primary objective of this study was to validate and verify the analytical procedures described in EPA Method MS999 for analysis of the listed phosphonic acids and surrogates in aqueous samples. The gathered data from this validation study will be used to: (1) demonstrate analytical method performance; (2) generate quality control acceptance criteria; and (3) revise the SOP to provide a validated method that would be available for use during a homeland security event. The data contained in this report will be compiled, by EPA CRL, with data generated by other EPA Regional laboratories so that performance metrics of EPA Method MS999 can be determined.

  9. Effect of reduced dietary protein and supplementation with a docosahexaenoic acid product on broiler performance and meat quality.

    PubMed

    Ribeiro, T; Lordelo, M M; Costa, P; Alves, S P; Benevides, W S; Bessa, R J B; Lemos, J P C; Pinto, R M A; Ferreira, L M A; Fontes, C M G A; Prates, J A M

    2014-01-01

    1. Chicken breast meat is a lean meat due to its low content of intramuscular fat (IMF) resulting in an overall lower acceptability by consumers due to a decrease in juiciness, flavour and increased chewiness. Recently, studies performed in pigs suggested the possibility of increasing IMF by decreasing dietary crude protein (CP) content, an effect possibly mediated through an increased lipogenesis. 2. Dietary supplementation with lipids rich in omega 3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) may modulate an increase in the content of these fatty acids in meat from monogastric animals and, thus, promote the daily intake of n-3 LC-PUFA by humans. 3. LC-PUFA are very susceptible to oxidation, resulting in off-flavours that affect meat quality and consumers' acceptability. 4. This trial was conducted to assess the effect of reducing dietary CP, from 21% to 17%, on chicken's meat IMF content and, simultaneously, to evaluate if a complementary supplementation with a proprietary n-3 LC-PUFA source (DHA Gold™) could improve meat quality. These effects were assessed by measuring productive performance and meat quality, oxidative stability, sensory traits and fatty acid profile. 5. A reduction in CP content of broiler diets, from 21% to 17%, balanced for lysine, improved performance while it was not sufficient to increase IMF content in chicken meat. In contrast, DHA Gold™ supplementation had a positive impact both in broiler productive parameters and in meat fatty acid profile. 6. In addition, incorporation of 7.4% of DHA Gold™ in the diet promoted carcass yield but negatively affected chicken meat acceptability by consumers, due to a decrease of meat oxidative stability. 7. Overall the data suggest that neither a dietary supplementation with DHA Gold™ nor a reduction in CP have a direct positive effect in the levels of IMF present in broiler meat. PMID:25277689

  10. Omega-3 fatty acids for nutrition and medicine: considering microalgae oil as a vegetarian source of EPA and DHA.

    PubMed

    Doughman, Scott D; Krupanidhi, Srirama; Sanjeevi, Carani B

    2007-08-01

    Long-chain EPA/DHA omega-3 fatty acid supplementation can be co-preventative and co-therapeutic. Current research suggests increasing accumulated long chain omega-3s for health benefits and as natural medicine in several major diseases. But many believe plant omega-3 sources are nutritionally and therapeutically equivalent to the EPA/DHA omega-3 in fish oil. Although healthy, precursor ALA bio-conversion to EPA is inefficient and production of DHA is nearly absent, limiting the protective value of ALA supplementation from flax-oil, for example. Along with pollutants certain fish acquire high levels of EPA/DHA as predatory species. However, the origin of EPA/DHA in aquatic ecosystems is algae. Certain microalgae produce high levels of EPA or DHA. Now, organically produced DHA-rich microalgae oil is available. Clinical trials with DHA-rich oil indicate comparable efficacies to fish oil for protection from cardiovascular risk factors by lowering plasma triglycerides and oxidative stress. This review discusses 1) omega-3 fatty acids in nutrition and medicine; 2) omega-3s in physiology and gene regulation; 3) possible protective mechanisms of EPA/DHA in major diseases such as coronary heart disease, atherosclerosis, cancer and type 2 diabetes; 4) EPA and DHA requirements considering fish oil safety; and 5) microalgae EPA and DHA-rich oils and recent clinical results. PMID:18220672

  11. Effect of Dietary Levels of Menhaden Fish Oil and Feeding Duration on Growth Performance, and Proximate and Fatty Acid Composition of Channel Catfish, Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Omega-3 highly unsaturated fatty acids (HUFA n-3), which consist mainly of eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), plays vital roles in human nutrition, disease prevention and health promotion. As the general public becomes aware of the health benefits of cons...

  12. Dietary long-chain omega-3 fatty acids do not diminish eosinophilic pulmonary inflammation in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of fish oil supplements on diminishing airway inflammation in asthma have been studied in mouse models and human intervention trials with varying results. However, the independent effects of the main omega-3 PUFAs found in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (D...

  13. Docosahexaenoic Acid for Reading, Cognition and Behavior in Children Aged 7–9 Years: A Randomized, Controlled Trial (The DOLAB Study)

    PubMed Central

    Richardson, Alexandra J.; Burton, Jennifer R.; Sewell, Richard P.; Spreckelsen, Thees F.; Montgomery, Paul

    2012-01-01

    Background Omega-3 fatty acids are dietary essentials, and the current low intakes in most modern developed countries are believed to contribute to a wide variety of physical and mental health problems. Evidence from clinical trials indicates that dietary supplementation with long-chain omega-3 may improve child behavior and learning, although most previous trials have involved children with neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) or developmental coordination disorder (DCD). Here we investigated whether such benefits might extend to the general child population. Objectives To determine the effects of dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA) on the reading, working memory, and behavior of healthy schoolchildren. Design Parallel group, fixed-dose, randomized, double-blind, placebo-controlled trial (RCT). Setting Mainstream primary schools in Oxfordshire, UK (n = 74). Participants Healthy children aged 7–9 years initially underperforming in reading (≤33rd centile). 1376 invited, 362 met study criteria. Intervention 600 mg/day DHA (from algal oil), or taste/color matched corn/soybean oil placebo. Main Outcome Measures Age-standardized measures of reading, working memory, and parent- and teacher-rated behavior. Results ITT analyses showed no effect of DHA on reading in the full sample, but significant effects in the pre-planned subgroup of 224 children whose initial reading performance was ≤20th centile (the target population in our original study design). Parent-rated behavior problems (ADHD-type symptoms) were significantly reduced by active treatment, but little or no effects were seen for either teacher-rated behaviour or working memory. Conclusions DHA supplementation appears to offer a safe and effective way to improve reading and behavior in healthy but underperforming children from mainstream schools. Replication studies are clearly warranted, as such children are known

  14. Enhancement of Anti-Dermatitis Potential of Clobetasol Propionate by DHA [Docosahexaenoic Acid] Rich Algal Oil Nanoemulsion Gel

    PubMed Central

    Sarfaraz Alam, Mohammad; Ali, Mohammad Sajid; Zakir, Foziyah; Alam, Nawazish; Intakhab Alam, Mohammad; Ahmad, Faruque; Siddiqui, Masoom Raza; Ali, Mohammad Daud; Ansari, Mohammad Salahuddin; Ahmad, Sarfaraz; Ali, Maksood

    2016-01-01

    The aim of the present study was to investigate the potential of nanoemulsion formulation for topical delivery of Clobetasol propionate (CP) using algal oil (containing omega-3 fatty acids) as the oil phase. CP has anti-inflammatory, immunomodulatory and antiproliferative activities. However, its clinical use is restricted to some extent due to its poor permeability across the skin. Algal oil was used as the oil phase and was also exploited for its anti-inflammatory effect along with CP in the treatment of inflammation associated with dermatitis. Nanoemulsion formulations were prepared by aqueous phase titration method, using algal oil, tween 20, PEG 200 and water as the oil phase, surfactant, co-surfactant and aqueous phase respectively. Furthermore, different formulations were subjected to evaluate for ex-vivo permeation and in-vivo anti-inflammatory, irritation and contact dermatitis studies. The optimized nanoemulsion was converted into hydrogel-thickened nanoemulsion system (HTN) using carbopol 971 and had a viscosity of 97.57 ± 0.04 PaS. The optimized formulation had small average diameter (120 nm) with zeta potential of -37.01 mV which indicated good long-term stability. In-vivo anti-inflammatory activity indicated 84.55% and 41.04% inhibition of inflammation for drug loaded and placebo formulations respectively. The assessment of skin permeation was done by DSC and histopathology studies which indicated changes in the structure of epidermal membrane of skin. Contact dermatitis reveals that the higher NTPDase activity in the treatment with the CP-loaded nanoemulsion could be related to the higher anti-inflammatory effect in comparison with placebo nanoemulsion gel. PMID:27610146

  15. Enhancement of Anti-Dermatitis Potential of Clobetasol Propionate by DHA [Docosahexaenoic Acid] Rich Algal Oil Nanoemulsion Gel.

    PubMed

    Sarfaraz Alam, Mohammad; Ali, Mohammad Sajid; Zakir, Foziyah; Alam, Nawazish; Intakhab Alam, Mohammad; Ahmad, Faruque; Siddiqui, Masoom Raza; Ali, Mohammad Daud; Ansari, Mohammad Salahuddin; Ahmad, Sarfaraz; Ali, Maksood

    2016-01-01

    The aim of the present study was to investigate the potential of nanoemulsion formulation for topical delivery of Clobetasol propionate (CP) using algal oil (containing omega-3 fatty acids) as the oil phase. CP has anti-inflammatory, immunomodulatory and antiproliferative activities. However, its clinical use is restricted to some extent due to its poor permeability across the skin. Algal oil was used as the oil phase and was also exploited for its anti-inflammatory effect along with CP in the treatment of inflammation associated with dermatitis. Nanoemulsion formulations were prepared by aqueous phase titration method, using algal oil, tween 20, PEG 200 and water as the oil phase, surfactant, co-surfactant and aqueous phase respectively. Furthermore, different formulations were subjected to evaluate for ex-vivo permeation and in-vivo anti-inflammatory, irritation and contact dermatitis studies. The optimized nanoemulsion was converted into hydrogel-thickened nanoemulsion system (HTN) using carbopol 971 and had a viscosity of 97.57 ± 0.04 PaS. The optimized formulation had small average diameter (120 nm) with zeta potential of -37.01 mV which indicated good long-term stability. In-vivo anti-inflammatory activity indicated 84.55% and 41.04% inhibition of inflammation for drug loaded and placebo formulations respectively. The assessment of skin permeation was done by DSC and histopathology studies which indicated changes in the structure of epidermal membrane of skin. Contact dermatitis reveals that the higher NTPDase activity in the treatment with the CP-loaded nanoemulsion could be related to the higher anti-inflammatory effect in comparison with placebo nanoemulsion gel. PMID:27610146

  16. Beneficial effects of omega-3 fatty acids and vitamin B12 supplementation on brain docosahexaenoic acid, brain derived neurotrophic factor, and cognitive performance in the second-generation Wistar rats.

    PubMed

    Rathod, Richa S; Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

    2015-01-01

    In vegetarian population, vitamin B12 deficiency coexists with suboptimal levels of omega-3 fatty acids. Studies indicate a need for supplementation/fortification of vitamin B12 and omega-3 fatty acids to reduce the risk of brain disorders. We have described the effects of vitamin B12 and omega-3 fatty acid supplementation on brain development in F1 generation animals. The current study investigates the effects of vitamin B12 and omega-3 fatty acids supplementation on brain function and cognition. Pregnant Wistar rats were assigned the following groups: control, vitamin B12 deficient (BD), vitamin B12 deficient + omega-3 fatty acid (BDO), vitamin B12 supplemented (BS), vitamin B12 supplemented + omega-3 fatty acid (BSO). The same diets were continued for two generations. BDO group showed higher (P < 0.05) levels of BDNF (brain derived neurotrophic factor) and DHA (docosahexaenoic acid) in the cortex and hippocampus as compared with the BD group. The cognitive performance was also normalized in this group. BS showed comparable levels of DHA, BDNF (protein and mRNA), and CREB mRNA (cAMP response element-binding protein) to that of control group while Tropomyosin receptor kinase mRNA levels were higher. The combined vitamin B12 and omega-3 fatty acid supplementation further enhanced the levels of DHA (P < 0.05) and BDNF (P < 0.05) in the hippocampus and CREB mRNA (P < 0.01) in the cortex as compared with BS group. The cognitive performance of these animals was higher (P < 0.05) as compared with BS group. Our data indicates the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation across two generations on brain development and function. PMID:26249019

  17. Detection of omega-3 oxylipins in human plasma and response to treatment with omega-3 acid ethyl esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The long chain omega-3 fatty acids (n-3 FAs), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids have beneficial health effects, but the molecular mediators of these effects are not well-characterized. Oxygenated n-3 FAs (oxylipins) may be an important class of mediators. Members of this chemic...

  18. Synergistic anticancer properties of docosahexaenoic acid and 5-fluorouracil through interference with energy metabolism and cell cycle arrest in human gastric cancer cell line AGS cells

    PubMed Central

    Gao, Kun; Liang, Qi; Zhao, Zhi-Hao; Li, You-Fen; Wang, Shu-Feng

    2016-01-01

    AIM: To explore the synergistic effect of docosahexaenoic acid (DHA)/5-fluorouracil (5-FU) on the human gastric cancer cell line AGS and examine the underlying mechanism. METHODS: AGS cells were cultured and treated with a series of concentrations of DHA and 5-FU alone or in combination for 24 and 48 h. To investigate the synergistic effect of DHA and 5-FU on AGS cells, the inhibition of cell proliferation was determined by MTT assay and cell morphology. Flow cytometric analysis was also used to assess cell cycle distribution, and the expression of mitochondrial electron transfer chain complexes (METCs) I, II and V in AGS cells was further determined by Western blot analysis. RESULTS: DHA and 5-FU alone or in combination could markedly suppress the proliferation of AGS cells in a significant time and dose-dependent manner. DHA markedly strengthened the antiproliferative effect of 5-FU, decreasing the IC50 by 3.56-2.15-fold in an apparent synergy. The morphological changes of the cells were characterized by shrinkage, cell membrane blebbing and decreased adherence. Cell cycle analysis showed a shift of cells into the G0/G1 phase from the S phase following treatment with DHA or 5-FU (G0/G1 phase: 30.04% ± 1.54% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 56.76% ± 3.14% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). Combination treatment of DHA and 5-FU resulted in a significantly larger shift toward the G0/G1 phase and subsequent reduction in S phase (G0/G1 phase: 69.06% ± 2.63% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 19.80% ± 4.30% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). This synergy was also reflected in the significant downregulation of the expression of METCs in AGS cells. CONCLUSION: Synergistic anticancer properties of DHA and 5-FU may involve interference with energy production of AGS cells via downregulation of METCs and cell cycle arrest. PMID

  19. Production of omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia lipolytica.

    PubMed

    Xue, Zhixiong; Sharpe, Pamela L; Hong, Seung-Pyo; Yadav, Narendra S; Xie, Dongming; Short, David R; Damude, Howard G; Rupert, Ross A; Seip, John E; Wang, Jamie; Pollak, Dana W; Bostick, Michael W; Bosak, Melissa D; Macool, Daniel J; Hollerbach, Dieter H; Zhang, Hongxiang; Arcilla, Dennis M; Bledsoe, Sidney A; Croker, Kevin; McCord, Elizabeth F; Tyreus, Bjorn D; Jackson, Ethel N; Zhu, Quinn

    2013-08-01

    The availability of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is currently limited because they are produced mainly by marine fisheries that cannot keep pace with the demands of the growing market for these products. A sustainable non-animal source of EPA and DHA is needed. Metabolic engineering of the oleaginous yeast Yarrowia lipolytica resulted in a strain that produced EPA at 15% of dry cell weight. The engineered yeast lipid comprises EPA at 56.6% and saturated fatty acids at less than 5% by weight, which are the highest and the lowest percentages, respectively, among known EPA sources. Inactivation of the peroxisome biogenesis gene PEX10 was crucial in obtaining high EPA yields and may increase the yields of other commercially desirable lipid-related products. This technology platform enables the production of lipids with tailored fatty acid compositions and provides a sustainable source of EPA. PMID:23873085

  20. Preliminary Validation of a High Docosahexaenoic Acid (DHA) and -Linolenic Acid (ALA) Dietary Oil Blend: Tissue Fatty Acid Composition and Liver Proteome Response in Atlantic Salmon (Salmo salar) Smolts

    PubMed Central

    Nuez-Ortín, Waldo G.; Carter, Chris G.; Wilson, Richard; Cooke, Ira; Nichols, Peter D.

    2016-01-01

    Marine oils are important to human nutrition as the major source of docosahexaenoic acid (DHA), a key omega-3 long-chain (≥C20) polyunsaturated fatty acid (n-3 LC-PUFA) that is low or lacking in terrestrial plant or animal oils. The inclusion of fish oil as main source of n-3 LC-PUFA in aquafeeds is mostly limited by the increasing price and decreasing availability. Fish oil replacement with cheaper terrestrial plant and animal oils has considerably reduced the content of n-3 LC-PUFA in flesh of farmed Atlantic salmon. Novel DHA-enriched oils with high alpha-linolenic acid (ALA) content will be available from transgenic oilseeds plants in the near future as an alternative for dietary fish oil replacement in aquafeeds. As a preliminary validation, we formulated an oil blend (TOFX) with high DHA and ALA content using tuna oil (TO) high in DHA and the flaxseed oil (FX) high in ALA, and assessed its ability to achieve fish oil-like n-3 LC-PUFA tissue composition in Atlantic salmon smolts. We applied proteomics as an exploratory approach to understand the effects of nutritional changes on the fish liver. Comparisons were made between fish fed a fish oil-based diet (FO) and a commercial-like oil blend diet (fish oil + poultry oil, FOPO) over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish muscle concentration of n-3 LC-PUFA was significantly higher for TOFX than for FOPO fish, but not higher than for FO fish, while retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an oxidative stress response indicative of the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used oil blend. PMID:27556399

  1. Preliminary Validation of a High Docosahexaenoic Acid (DHA) and -Linolenic Acid (ALA) Dietary Oil Blend: Tissue Fatty Acid Composition and Liver Proteome Response in Atlantic Salmon (Salmo salar) Smolts.

    PubMed

    Nuez-Ortín, Waldo G; Carter, Chris G; Wilson, Richard; Cooke, Ira; Nichols, Peter D

    2016-01-01

    Marine oils are important to human nutrition as the major source of docosahexaenoic acid (DHA), a key omega-3 long-chain (≥C20) polyunsaturated fatty acid (n-3 LC-PUFA) that is low or lacking in terrestrial plant or animal oils. The inclusion of fish oil as main source of n-3 LC-PUFA in aquafeeds is mostly limited by the increasing price and decreasing availability. Fish oil replacement with cheaper terrestrial plant and animal oils has considerably reduced the content of n-3 LC-PUFA in flesh of farmed Atlantic salmon. Novel DHA-enriched oils with high alpha-linolenic acid (ALA) content will be available from transgenic oilseeds plants in the near future as an alternative for dietary fish oil replacement in aquafeeds. As a preliminary validation, we formulated an oil blend (TOFX) with high DHA and ALA content using tuna oil (TO) high in DHA and the flaxseed oil (FX) high in ALA, and assessed its ability to achieve fish oil-like n-3 LC-PUFA tissue composition in Atlantic salmon smolts. We applied proteomics as an exploratory approach to understand the effects of nutritional changes on the fish liver. Comparisons were made between fish fed a fish oil-based diet (FO) and a commercial-like oil blend diet (fish oil + poultry oil, FOPO) over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish muscle concentration of n-3 LC-PUFA was significantly higher for TOFX than for FOPO fish, but not higher than for FO fish, while retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an oxidative stress response indicative of the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used oil blend. PMID:27556399

  2. Engineering strategies for enhancing the production of eicosapentaenoic acid (EPA) from an isolated microalga Nannochloropsis oceanica CY2.

    PubMed

    Chen, Chun-Yen; Chen, Yu-Chun; Huang, Hsiao-Chen; Huang, Chieh-Chen; Lee, Wen-Lung; Chang, Jo-Shu

    2013-11-01

    Microalgae have emerged as promising resources for highly unsaturated fatty acids. In this study, an indigenous microalga identified as Nannochloropsis oceanica CY2 was grown photoautotrophically to produce eicosapentaenoic acid (EPA; 20:5, n-3). Specific engineering strategies were employed to stimulate EPA accumulation in the microalgal cells. The results show that BG-11 was the most effective medium to grow N. oceanica CY2, giving an EPA content and biomass concentration of 2.38% (per dry cell weight) and 1.53 g/l. The EPA content nearly doubled when using the optimal nitrogen source (NaNO3) at a concentration of 1.50 g/l. The illumination system also markedly affected the EPA content for the photoautotrophic microalga. When the microalgal culture was illuminated with a red LED, an impressively high EPA content of 5.5% was obtained. Finally, using semi-batch cultures operations with LED-blue illumination, the EPA content of N. oceanica CY2 was stably maintained at 5.0%. PMID:23994697

  3. Effects of eicosapentaenoic acid (EPA) treatment on insulin sensitivity in an animal model of diabetes: improvement of the inflammatory status.

    PubMed

    Figueras, Maite; Olivan, Mireia; Busquets, Sílvia; López-Soriano, Francisco J; Argilés, Josep M

    2011-02-01

    In addition to decreased insulin sensitivity, diabetes is a pathological condition associated with increased inflammation. The ω-3 fatty acids have been proposed as anti-inflammatory agents. Thus, the major goal of this study was to analyze the effects of fatty acid supplementation on both insulin sensitivity and inflammatory status in an animal model of type 2 diabetes. Diabetic rats (Goto-Kakizaki model) were treated with eicosapentaenoic acid (EPA) or linoleic acid at 0.5 g/kg body weigh (bw) dose. In vivo incorporation of (14)C-triolein into adipose tissue was improved by the ω-3 administration. In vitro incubations of adipose tissue slices from EPA-treated rats showed an increase in (14)C-palmitate incorporation into the lipid fraction. These observations were linked with a decreased rate of fatty acid oxidation. EPA treatment resulted in a decreased fatty acid oxidation in incubated strips from extensor digitorum longus (EDL) muscles. The changes in lipid utilization were associated with a decrease in insulin plasma concentration, suggesting an improvement in insulin sensitivity. These changes in lipid metabolism were associated with an activation of AMP-activated protein kinase (AMPK) in white adipose tissue. In addition, EPA treatment resulted in a decreased content of peroxisome proliferator-activated receptor-α (PPARα) and PPARδ and in increased GLUT4 expression in skeletal muscle. Moreover, EPA increased 2-deoxy-D-[(14)C]glucose (2-DOG) uptake in C2C12 myotubes, suggesting an improvement in glucose metabolism. Concerning the inflammatory status, EPA treatment resulted in a decreased gene expression for both tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) both in skeletal muscle and adipose tissue. The data suggest that EPA treatment to diabetic rats clearly improves lipid metabolism although the evidences on insulin sensitization are less clear. PMID:20885391

  4. (n-3) Fatty Acids and Cardiovascular Health: Are Effects of EPA and DHA Shared or Complementary?123

    PubMed Central

    Mozaffarian, Dariush; Wu, Jason H. Y.

    2012-01-01

    Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil. Whether individual long-chain (n-3) PUFA have shared or complementary effects is not well established. We reviewed evidence for dietary and endogenous sources and cardiovascular effects on biologic pathways, physiologic risk factors, and clinical endpoints of EPA [20:5(n-3)], docosapentaenoic acid [DPA, 22:5(n-3)], and DHA [22:6(n-3)]. DHA requires direct dietary consumption, with little synthesis from or retroconversion to DPA or EPA. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from EPA, and DPA can also undergo retroconversion back to EPA. In experimental and animal models, both EPA and DHA modulate several relevant biologic pathways, with evidence for some differential benefits. In humans, both fatty acids lower TG levels and, based on more limited studies, favorably affect cardiac diastolic filling, arterial compliance, and some metrics of inflammation and oxidative stress. All three (n-3) PUFA reduce ex vivo platelet aggregation and DHA also modestly increases LDL and HDL particle size; the clinical relevance of such findings is uncertain. Combined EPA+DHA or DPA+DHA levels are associated with lower risk of fatal cardiac events and DHA with lower risk of atrial fibrillation, suggesting direct or indirect benefits of DHA for cardiac arrhythmias (although not excluding similar benefits of EPA or DPA). Conversely, EPA and DPA, but not DHA, are associated with lower risk of nonfatal cardiovascular endpoints in some studies, and purified EPA reduced risk of nonfatal coronary syndromes in one large clinical trial. Overall, for many cardiovascular pathways and outcomes, identified studies of individual (n-3) PUFA were relatively limited, especially

  5. Use of biodiesel-derived crude glycerol for producing eicosapentaenoic acid (EPA) by the fungus Pythium irregulare.

    PubMed

    Athalye, Sneha K; Garcia, Rafael A; Wen, Zhiyou

    2009-04-01

    Crude glycerol is a major byproduct for the biodiesel industry. Producing value-added products through microbial fermentation on crude glycerol provides opportunities to utilize a large quantity of this byproduct. The objective of this study is to explore the potential of using crude glycerol for producing eicosapentaenoic acid (EPA, 20:5 n-3) by the fungus Pythium irregulare . When P. irregulare was grown in medium containing 30 g/L crude glycerol and 10 g/L yeast extract, EPA yield and productivity reached 90 mg/L and 14.9 mg/L x day, respectively. Adding pure vegetable oils (flaxseed oil and soybean oil) to the culture greatly enhanced the biomass and the EPA production. This enhancement was due to the oil absorption by the fungal cells and elongation of shorter chain fatty acids (e.g., linoleic acid and alpha-linolenic acid) into longer chain fatty acid (e.g., EPA). The major impurities contained in crude glycerol, soap and methanol, were inhibitory to fungal growth. Soap can be precipitated from the liquid medium through pH adjustment, whereas methanol can be evaporated from the medium during autoclaving. The glycerol-derived fungal biomass contained about 15% lipid, 36% protein, and 40% carbohydrate, with 9% ash. In addition to EPA, the fungal biomass was also rich in the essential amino acids lysine, arginine, and leucine, relative to many common feedstuffs. Elemental analysis by inductively coupled plasma showed that aluminum, calcium, copper, iron, magnesium, manganese, phosphorus, potassium, silicon, sodium, sulfur, and zinc were present in the biomass, whereas no heavy metals (such as mercury and lead) were detected. The results show that it is feasible to use crude glycerol for producing fungal biomass that can serve as EPA-fortified food or feed. PMID:19265450

  6. Effects of large doses of arachidonic acid added to docosahexaenoic acid on social impairment in individuals with autism spectrum disorders: a double-blind, placebo-controlled, randomized trial.

    PubMed

    Yui, Kunio; Koshiba, Mamiko; Nakamura, Shun; Kobayashi, Yuji

    2012-04-01

    Autism spectrum disorders are a neurodevelopmental disorders with reduced cortical functional connectivity relating to social cognition. Polyunsaturated fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) may have key role in brain network maturation. In particularly, ARA is important in signal transduction related to neuronal maturation. Supplementation with larger ARA doses added to DHA may therefore mitigate social impairment. In a 16-week, double-blind, randomized, placebo-controlled trial, we evaluated the efficacy of supplementation with large doses of ARA added to DHA (n = 7) or placebo (n = 6) in 13 participants (mean age, 14.6 [SD, 5.9] years). To examine underlying mechanisms underlying the effect of our supplementation regimen, we examined plasma levels of antioxidants transferrin and superoxide dismutase, which are useful markers of signal transduction. The outcome measures were the Social Responsiveness Scale and the Aberrant Behavior Checklist-Community. Repeated-measures analysis of variance revealed that our supplementation regimen significantly improved Aberrant Behavior Checklist-Community-measured social withdrawal and Social Responsiveness Scale-measured communication. Treatment effect sizes were more favorable for the treatment group compared with the placebo group (communication: treatment groups, 0.87 vs, placebo, 0.44; social withdrawal: treatment groups, 0.88, vs placebo, 0.54). There was a significant difference in the change in plasma transferrin levels and a trend toward a significant difference in the change in plasma superoxide dismutase levels between the 2 groups. This preliminary study suggests that supplementation with larger ARA doses added to DHA improves impaired social interaction in individuals with autism spectrum disorder by up-regulating signal transduction. PMID:22370992

  7. Fish oil supplementation of maternal rats on an n-3 fatty acid-deficient diet prevents depletion of maternal brain regional docosahexaenoic acid levels and has a postpartum anxiolytic effect.

    PubMed

    Chen, Hui-Feng; Su, Hui-Min

    2012-03-01

    Docosahexaenoic acid (DHA) and arachidonic acid (AA) are the major polyunsaturated fatty acids (PUFA) in the neuronal membrane. Most DHA and AA accumulation in the brain occurs during the perinatal period via placenta and milk. This study examined whether maternal brain levels of DHA and AA are depleted during pregnancy and lactation due to meeting the high demand of the developing nervous system in the offspring and evaluated the effects of the reproductive cycle on serotonin metabolism and of fish oil (FO) on postpartum anxiety. Pregnant rats were fed during pregnancy and lactation with a sunflower oil-based n-3 PUFA-deficient diet without or with FO supplementation, which provided 0.37% of the energy source as n-3 PUFA, and the age-matched virgin rats were fed the same diets for 41 days. In both sets of postpartum rats, decreased DHA levels compared to those in virgin females were seen in the hypothalamus, hippocampus, frontal cortex, cerebellum, olfactory bulb and retina, while AA depletion was seen only in the hypothalamus, hippocampus and frontal cortex. Serotonin levels were decreased and turnover increased in the brainstem and frontal cortex in postpartum rats compared to virgin rats. FO supplementation during pregnancy and lactation prevented the decrease in maternal brain regional DHA levels, inhibited monoamine oxidase-A activity in the brainstem and decreased anxiety-like behavior. We propose that the reproductive cycle depletes maternal brain DHA levels and modulates maternal brain serotonin metabolism to cause postpartum anxiety and suggest that FO supplementation may be beneficial for postpartum anxiety in women on an n-3 PUFA-deficient diet. PMID:21543216

  8. Effects of Dried Algae Schizochytrium Sp., A Rich Source of Docosahexaenoic Acid, on Growth, Fatty Acid Composition, and Sensory Quality of Channel Catfish Ictalurus Punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A laboratory study was conducted to investigate the effect of supplementation of dried algae Schizochytrium sp., a rich source of 22:6 n-3, on growth, fatty acid composition, and sensory quality of channel catfish Ictalurus punctatus. Five isonitrogenous (28% crude protein) and isocaloric (2.78 kcal...

  9. Use of dry-milling derived thin stillage for producing eicosapentaenoic acid (EPA) by the fungus Pythium irregulare.

    PubMed

    Liang, Yi; Zhao, Xuefei; Strait, Megan; Wen, Zhiyou

    2012-05-01

    This study was to explore the use of thin stillage, a major byproduct in dry milling corn-ethanol plants, for production of eicosapentaenoic acid (EPA) by the fungus Pythium irregulare. Thin stillage contains various compounds that were ideal for fungal growth. Thin stillage concentration and temperature played important roles in fungal growth and EPA production. When 50% thin stillage was used in a stepwise temperature shift culture process, the cell density reached 23 g/L at day 9 with EPA yield and productivity of 243 and 27 mg/L day, respectively. The fungal biomass contained 39% lipid, 28% protein, 30% carbohydrate, and 3% ash. The fungal culture also generated a nutrient-depleted liquid by removing organic compounds in the raw thin stillage. The results collectively showed a new use of thin stillage by feeding to the fungus P. irregulare for producing omega-3 fatty acids. PMID:22386467

  10. A new multiplex method for the diagnosis of peroxisomal disorders allowing simultaneous determination of plasma very-long-chain fatty acids, phytanic, pristanic, docosahexaenoic and bile acids by high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

    PubMed

    Semeraro, Michela; Rizzo, Cristiano; Boenzi, Sara; Cappa, Marco; Bertini, Enrico; Antonetti, Giacomo; Dionisi-Vici, Carlo

    2016-07-01

    Peroxisomal disorders (PDs) present with wide phenotypic variability. An appropriate diagnosis requires a complete analysis of peroxisomal metabolites. We developed a multiplex LC-MS/MS method, using atmospheric pressure chemical ionization allowing the simultaneous determination in plasma of very-long-chain fatty acids, phytanic, pristanic, docosahexaenoic acids and di- and tri-hydroxycolestanoic bile acids. Two hundred microliters of plasma extracted with acetonitrile and 200μl extracted with hexane after an acid hydrolysis were combined, evaporated, dissolved in 10μl of methanol and analyzed. The acquisition was in negative-ion mode using multiple reaction monitoring. The method was validated analytically and clinically. Linearity was 0.1-200μmol/l for docosanoic, cis-13-docosenoic, tetracosanoic, cis-15-tetracosenoic and phytanic acids; 0.01-10μmol/l for hexacosanoic acid; 0.02-20μmol/l for di-hydroxycolestanoic, tri-hydroxycolestanoic and pristanic acids; 0.3-300μmol/l for docosahexaenoic acid. Intra-day and inter-day CVs were below 3.88 and 3.98 respectively for all compounds. Samples from patients with known peroxisomal disorders were compared with controls and the method allowed to confirm the diagnosis in all subjects with a 100% sensitivity. The advantage of this multiplex method is to allow in a single chromatographic run the simultaneous determination of a large number of peroxisome biomarkers with a simple preparative phase without derivatization. PMID:27189059

  11. On the potential application of polar and temperate marine microalgae for EPA and DHA production

    PubMed Central

    2013-01-01

    Long chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered essential omega-3 fatty acids in human nutrition. In marine microalgae EPA and/or DHA are allegedly involved in the regulation of membrane fluidity and thylakoid membrane functioning. The cellular content of EPA and DHA may therefore be enhanced at low temperature and irradiance conditions. As a result, polar and cold temperate marine microalgal species might potentially be suitable candidates for commercial EPA and DHA production, given their adaptation to low temperature and irradiance habitats. In the present study we investigated inter- and intraspecific EPA and DHA variability in five polar and (cold) temperate microalgae. Intraspecific EPA and DHA content did not vary significantly in an Antarctic (Chaetoceros brevis) and a temperate (Thalassiosira weissflogii) centric diatom after acclimation to a range of irradiance levels at two temperatures. Interspecific variability was investigated for two Antarctic (Chaetoceros brevis and Pyramimonas sp. (Prasinophyceae)) and three cold-temperate species (Thalassiosira weissflogii, Emiliania huxleyi (Prymnesiophyceae) and Fibrocapsa japonica (Raphidophyceae)) during exponential growth. Interspecific variability was shown to be much more important than intraspecific variability. Highest relative and absolute levels of DHA were measured in the prymnesiophyte E. huxleyi and the prasinophyte Pyramimonas sp., while levels of EPA were high in the raphidophyte F. japonica and the diatoms C. brevis and T. weissflogii. Yet, no significant differences in LC-PUFA content were found between polar and cold-temperate species. Also, EPA and DHA production rates varied strongly between species. Highest EPA production rate (174 μg L-1 day-1) was found in the Antarctic diatom Chaetoceros brevis, while DHA production was highest in the cold-temperate prymnesiophyte Emiliania huxleyi (164 μg L-1 day-1). We

  12. Differential anti-cancer effects of purified EPA and DHA and possible mechanisms involved.

    PubMed

    Serini, S; Fasano, E; Piccioni, E; Cittadini, A R M; Calviello, G

    2011-01-01

    As the concepts of pharmaconutrition are receiving increasing attention, it seems essential to clearly assess the effects of specific dietary compounds in specific groups of patients or clinical conditions. We are herein interested in better defining the differential anti-neoplastic effects of the two major n-3 long chain polyunsaturated fatty acids present in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The efficiency of these fatty acids represents a subject of intense interest and debate, and whereas plenty of preclinical studies have strongly demonstrated their preventive and therapeutic effect in different kinds of cancers, the results of the epidemiologic studies are still controversial, and only a few trials have been performed. It has been reported that EPA and DHA may act either through the same or different mechanisms, thus suggesting that a differential efficacy could exist. At present, however, this point has not been clarified, although its better comprehension would allow a more proper and effective use of these fatty acids in the human interventional studies. In an attempt to elucidate this aspect we have herein analyzed the data obtained in the studies which have directly compared the antitumor effects of separate treatments with EPA or DHA. Most of the in vitro data indicate DHA as the more powerful antineoplastic agent. However, an equivalent efficiency of EPA and DHA is suggested by the few in vivo studies. Possible reasons for this discrepancy are discussed and pathways of cell growth that could be differentially influenced by EPA and DHA are described. PMID:21824086

  13. Amino acid amides of piperic acid (PA) and 4-ethylpiperic acid (EPA) as NorA efflux pump inhibitors of Staphylococcus aureus.

    PubMed

    Wani, Naiem Ahmad; Singh, Samsher; Farooq, Saleem; Shankar, Sudha; Koul, Surrinder; Khan, Inshad Ali; Rai, Rajkishor

    2016-09-01

    A total of eighteen piperic acid (PA) and 4-ethylpiperic acid (EPA) amides (C1-C18) with α-, β- and γ-amino acids were synthesized, characterized and evaluated for their efflux pump inhibitory activity against ciprofloxacin resistant Staphylococcus aureus. The amides were screened against NorA overexpressing S. aureus SA-1199B and wild type S. aureus SA-1199 using ethidium bromide as NorA efflux pump substrate. EPI C6 was found to be most potent and reduced the MIC of ciprofloxacin by 16 fold followed by C18 which showed 4 fold reduction of MIC. Ethidium bromide efflux inhibition and accumulation assay proved these compounds as NorA inhibitors. PMID:27503686

  14. PROCEEDINGS: EPA'S (ENVIRONMENTAL PROTECTION AGENCIES) INDUSTRY BRIEFING ON THE ORGANIC-ACID-ENHANCED LIMESTONE FGD (FLUE GAS DESULFURIZATION) PROCESS HELD AT SAN ANTONIO, TEXAS ON JULY 19, 1984

    EPA Science Inventory

    The proceedings document presentations made during an EPA-sponsored industry briefing, July 19, 1984, in San Antonio, TX. The briefing dealt with the status of EPA's research activities on the organic-acid-enhanced limestone flue gas desulfurization (FGD) process. Subjects covere...

  15. Syntaxin 3 and SNAP-25 pairing, regulated by omega-3 docosahexaenoic acid, controls the delivery of rhodopsin for the biogenesis of cilia-derived sensory organelles, the rod outer segments.

    PubMed

    Mazelova, Jana; Ransom, Nancy; Astuto-Gribble, Lisa; Wilson, Michael C; Deretic, Dusanka

    2009-06-15

    The biogenesis of cilia-derived sensory organelles, the photoreceptor rod outer segments (ROS), is mediated by rhodopsin transport carriers (RTCs). The small GTPase Rab8 regulates ciliary targeting of RTCs, but their specific fusion sites have not been characterized. Here, we report that the Sec6/8 complex, or exocyst, is a candidate effector for Rab8. We also show that the Qa-SNARE syntaxin 3 is present in the rod inner segment (RIS) plasma membrane at the base of the cilium and displays a microtubule-dependent concentration gradient, whereas the Qbc-SNARE SNAP-25 is uniformly distributed in the RIS plasma membrane and the synapse. Treatment with omega-3 docosahexaenoic acid [DHA, 22:6(n-3)] causes increased co-immunoprecipitation and colocalization of SNAP-25 and syntaxin 3 at the base of the cilium, which results in the increased delivery of membrane to the ROS. This is particularly evident in propranolol-treated retinas, in which the DHA-mediated increase in SNARE pairing overcomes the tethering block, including dissociation of Sec8 into the cytosol. Together, our data indicate that the Sec6/8 complex, syntaxin 3 and SNAP-25 regulate rhodopsin delivery, probably by mediating docking and fusion of RTCs. We show further that DHA, an essential polyunsaturated fatty acid of the ROS, increases pairing of syntaxin 3 and SNAP-25 to regulate expansion of the ciliary membrane and ROS biogenesis. PMID:19454479

  16. Total Synthesis of Four Stereoisomers of (4Z,7Z,10Z,12E,16Z,18E)-14,20-Dihydroxy-4,7,10,12,16,18-docosahexaenoic Acid and Their Anti-inflammatory Activities.

    PubMed

    Goto, Tomomi; Urabe, Daisuke; Masuda, Koji; Isobe, Yosuke; Arita, Makoto; Inoue, Masayuki

    2015-08-01

    A novel anti-inflammatory lipid mediator, (4Z,7Z,10Z,12E,14S,16Z,18E,20R)-14,20-dihydroxy-4,7,10,12,16,18-docosahexaenoic acid (1aa), and its three C14,C20 stereoisomers (1ab,ba,bb) were synthesized in a convergent fashion. The carbon backbone of the target compounds was assembled from seven simple fragments by employing two Sonogashira coupling and three SN2 alkynylation reactions. The thus constructed four internal alkynes were chemoselectively reduced to the corresponding (Z)-alkenes by applying a newly developed stepwise protocol: (i) hydrogenation of the three alkynes using Lindlar catalyst and (ii) formation of the dicobalt hexacarbonyl complex from the remaining alkyne and subsequent reductive decomplexation. The synthetic preparation of the stereochemically defined four isomers 1aa,ab,ba,bb permitted determination of the absolute structure of the isolated natural product to be 1aa. Biological testing of the four synthetic 14,20-dihydroxydocosahexaenoic acids disclosed similar anti-inflammatory activities of the non-natural isomers (1ab,ba,bb) and the natural form (1aa). PMID:26172872

  17. Placental docosahexaenoic and arachidonic acids correlate weakly with placental polychlorinated dibenzofurans (PCDF) and are uncorrelated with polychlorinated dibenzo-p-dioxins (PCDD) or polychlorinated biphenyls (PCB) at delivery: a pilot study.

    PubMed

    Huang, Meng-Chuan; Brenna, J Thomas; Sun, Pei-Yi; Chang, Wen-Tsan; Hung, Hsin-Chia; Chao, How-Ran; Wang, Shu-Li

    2011-08-01

    Long chain polyunsaturated fatty acids (LC-PUFA), ARA (arachidonic acid, 20:4n-6) and DHA (docosahexaenoic acid, 22:6n-3) have positive effects and environment pollutants, polychlorinated dibenzo-p-dioxins/dibenzofurans(PCDD/F) and polychlorinated biphenyls (PCB) have negative effects on neural development during early life. Placental dioxin/PCB serves as markers for cumulative exposure to fetus. Fatty acid composition of placenta depends on nutrient supply during pregnancy, serving as indicators for fetal ARA and DHA accretion. This study investigated correlation between placental PCDD/F and PCB toxic equivalent (TEQ) and LC-PUFA in 34 pregnant women from Taiwan. Placental PCDF TEQ were inversely correlated with placental ARA (p=0.020), C20:3n-6 (p=0.01), C22:4n-6 (p=0.04), C22:5n-6 (p<0.01) and with DHA (p=0.03), but ARA and DHA did not vary with PCDD, dioxin-like and indicator PCB. After adjustment for age and body mass index, a one-unit PCDF TEQ increase was associated with 1.021%w/w and 0.312%w/w decreases in ARA (β=-1.021, p=0.03) and DHA (β=-0.312, p=0.03). Since ARA and DHA were unrelated to three classes of toxins, and a weak negative association was found with PCDF, these data provide no basis for discouraging marine fish consumption during pregnancy for Taiwan women on the basis of these organics. Pregnant women should consume fish for its unique package of nutrients while avoiding few species with high organic pollutant or mercury contamination. PMID:21549173

  18. High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F2α concentrations relative to a control high–oleic acid meal: a randomized controlled trial1234

    PubMed Central

    Purcell, Robert; Latham, Sally H; Botham, Kathleen M; Hall, Wendy L; Wheeler-Jones, Caroline PD

    2014-01-01

    Background: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear. Objectives: The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high–oleic acid meals; the secondary objective was to characterize the effects of linoleic acid–enriched high-fat meals relative to the control meal. Design: We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high–oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high–linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35–70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.9 ± 0.5 mmol/L). Results: Elevations in triacylglycerol concentration relative to baseline were slightly reduced after FO and HLS compared with the HOS control (P < 0.05). The characteristic decrease from baseline in plasma nonesterified fatty acids after a mixed meal was inhibited after AO (Δ 0–3 h, P < 0.05). HLS increased the augmentation index compared with the other test meals (P < 0.05), although the digital volume pulse–reflection index was not significantly different. Plasma 8-isoprostane F2α analysis revealed opposing effects of FO (increased) and AO (reduced) compared with the control (P < 0.05). No differences in nitric oxide metabolites were observed. Conclusions: These data show differential postprandial 8-isoprostane F2α responses to high-fat meals containing EPA + DHA–rich fish oil compared with DHA-rich AO, but these differences were not associated with consistent effects on postprandial vascular function or lipemia. More detailed analyses of polyunsaturated fatty acid–derived lipid mediators are required to determine possible

  19. Effects of Iron Supplementation With and Without Docosahexaenoic Acid on the Cardiovascular Disease Risk Based on Paraoxonase-1, hs-CRP, and ApoB/ApoA-I Ratio in Women with Iron Deficiency Anemia.

    PubMed

    Shidfar, Farzad; Amani, Samira; Vafa, Mohammadreza; Shekarriz, Ramin; Hosseini, Sharieh; Shidfar, Shahrzad; Eshraghian, Mohammadreza; Mousavi, Seyedeh Neda

    2016-01-01

    Numerous studies have demonstrated that tissue deposition of iron following prolonged high dose of oral supplementation for treatment of iron deficiency anemia (IDA) leads to body iron overload and oxidative stress, which starts the process of atherosclerosis. This study aimed to determine the effect of iron supplementation in combination with docosahexaenoic acid (DHA) on the cardiovascular disease risk based on paraoxonase-1 (PON-1), high-sensitivity C-reactive protein (hs-CRP), and ApoB/ApoA-I ratio in women with IDA. In this randomized controlled trial, 76 women with IDA, aged 15-45 years, were included. The patients were randomly assigned to receive 500 mg of DHA supplement or placebo with an iron tablet, once daily for 12 weeks. The participants were assessed by measurement of the serum iron, ferritin, PON-1, hs-CRP levels, and the ApoB/ApoA-I ratio at the beginning and end of study. Serum hs-CRP decreased in the DHA-supplemented group (p = 0.036), and ApoA-I decreased in the placebo group (p = 0.013). No significant difference was detected for the serum PON-1 concentration and the ApoB/ApoA-I ratio in two groups. Iron supplementation combined with DHA may have favorable effects on serum hs-CRP in women with IDA. PMID:26077874

  20. A randomized, placebo-controlled, double-blind trial of supplemental docosahexaenoic acid on cognitive processing speed and executive function in females of reproductive age with phenylketonuria: A pilot study☆, ☆☆

    PubMed Central

    Yi, S.H.L.; Kable, J.A.; Evatt, M.L.; Singh, R.H.

    2014-01-01

    Low blood docosahexaenoic acid (DHA) is reported in patients with phenylketonuria (PKU); however, the functional implications in adolescents and adults are unknown. This pilot study investigated the effect of supplemental DHA on cognitive performance in 33 females with PKU ages 12–47 years. Participants were randomly assigned to receive DHA (10 mg/kg/day) or placebo for 4.5 months. Performance on cognitive processing speed and executive functioning tasks was evaluated at baseline and follow up. Intention-to-treat and per protocol analyses were performed. At follow up, biomarkers of DHA status were significantly higher in the DHA-supplemented group. Performance on the cognitive tasks and reported treatment-related adverse events did not differ. While no evidence of cognitive effect was seen, a larger sample size is needed to be conclusive, which may not be feasible in this population. Supplementation was a safe and effective way to increase biomarkers of DHA status (www.clinicaltrials.gov; Identifier: NCT00892554). PMID:22000478

  1. Continuous gradient temperature Raman spectroscopy of the long chain polyunsaturated fatty acids docosapentaenoic (DPA, 22:5n-6) and docosahexaenoic (DHA; 22:6n-3) from -100 to 20° C

    NASA Astrophysics Data System (ADS)

    Broadhurst, C. Leigh; Schmidt, Walter F.; Kim, Moon S.; Nguyen, Julie K.; Qin, Jianwei; Chao, Kuanglin; Bauchan, Gary L.; Shelton, Daniel R.

    2016-05-01

    The structural, cognitive and visual development of the human brain and retina strictly require long-chain polyunsaturated fatty acids (LC-PUFA). Excluding water, the mammalian brain is about 60% lipid. One of the great unanswered questions with respect to biological science in general is the absolute necessity of the LC-PUFA docosahexaenoic acid (DHA; 22:6n-3) in these fast signal processing tissues. A lipid of the same chain length with just one less diene group, docosapentaenoic acid (DPA; 22:5n-6) is fairly abundant in terrestrial food chains yet cannot substitute for DHA. Gradient Temperature Raman spectroscopy (GTRS) applies the temperature gradients utilized in differential scanning calorimetry to Raman spectroscopy, providing a straightforward technique to identify molecular rearrangements that occur near and at phase transitions. Herein we apply GTRS to DPA, and DHA from -100 to 20°C. 20 Mb three-dimensional data arrays with 1°C increments and first/second derivatives allows complete assignment of solid, liquid and transition state vibrational modes, including low intensity/frequency vibrations that cannot be readily analyzed with conventional Raman. DPA and DHA show significant spectral changes with premelting (-33 and -60°C, respectively) and melting (-27 and -44°C, respectively). The CH2-(HC=CH)-CH2 moieties are not identical in the second half of the DHA and DPA structures. The DHA molecule contains major CH2 twisting (1265 cm-1) with no noticeable CH2 bending, consistent with a flat helical structure with small pitch. Further modeling of neuronal membrane phospholipids must take into account this structure for DHA, which would be configured parallel to the hydrophilic head group line.

  2. Long-chain polyunsaturated fatty acid sources and evaluation of their nutritional and functional properties

    PubMed Central

    Abedi, Elahe; Sahari, Mohammad Ali

    2014-01-01

    Recent studies have clearly shown the importance of polyunsaturated fatty acids (as essential fatty acids) and their nutritional value for human health. In this review, various sources, nutritional properties, and metabolism routes of long-chain polyunsaturated fatty acids (LC-PUFA) are introduced. Since the conversion efficiency of linoleic acid (LA) to arachidonic acid (AA) and also α-linolenic acid (ALA) to docosahexaenoic acid (DHA) and eicosatetraenoic acid (EPA) is low in humans, looking for the numerous sources of AA, EPA and EPA fatty acids. The sources include aquatic (fish, crustaceans, and mollusks), animal sources (meat, egg, and milk), plant sources including 20 plants, most of which were weeds having a good amount of LC-PUFA, fruits, herbs, and seeds; cyanobacteria; and microorganisms (bacteria, fungi, microalgae, and diatoms). PMID:25473503

  3. Increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acid levels in human plasma after a single dose of long-chain omega-3 PUFA

    PubMed Central

    Schuchardt, Jan Philipp; Schneider, Inga; Willenberg, Ina; Yang, Jun; Hammock, Bruce D.; Hahn, Andreas; Schebb, Nils Helge

    2014-01-01

    Introduction Several supplementation studies with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) describe an increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acids in blood, while changes in levels of other LC n-3 and n-6 PUFA-derived oxylipins were minor. In order to investigate the kinetics of changes in oxylipin levels in response to LC n-3 PUFA ingestion, we conducted a single dose treatment study with healthy subjects. Subjects and methods In the present kinetic study, we compared patterns of hydroxy, epoxy and dihydroxy fatty acids in plasma of 6 healthy men before and after 6, 8, 24, and 48 h of fish oil (1008 mg EPA and 672 mg DHA) ingestion. Levels of EPA- as well as other LC PUFA-derived hydroxy, epoxy and dihydroxy fatty acids were analyzed in plasma by LC–MS. Additionally, levels of these oxylipins were compared with their parent PUFA levels in plasma phospholipids. Results All EPA-derived oxylipin levels were significantly increased 6 h after LC n-3 PUFA ingestion and gradually drop thereafter reaching the baseline levels about 48 h after treatment. The relative increase in EPA plasma phospholipid levels highly correlated with the increase of plasma EPA-derived oxylipin levels at different time points. In contrast, plasma levels of arachidonic acid- and DHA-derived oxylipins as well as parent PUFA levels in plasma phospholipids were hardly changed. Discussion and conclusions Our findings demonstrate that a single dose of LC n-3 PUFAs can rapidly induce a shift in the EPA oxylipin profile of healthy subjects within a few hours. Taking the high biological activity of the EPA-derived epoxy fatty acids into account, even short-term treatment with LC n-3 PUFAs may cause systemic effects, which warrant further investigation. PMID:24667634

  4. Eicosapentaenoic acid (EPA) induced apoptosis in HepG2 cells through ROS–Ca{sup 2+}–JNK mitochondrial pathways

    SciTech Connect

    Zhang, Yuanyuan; Han, Lirong; Qi, Wentao; Cheng, Dai; Ma, Xiaolei; Hou, Lihua; Cao, Xiaohong; Wang, Chunling

    2015-01-24

    Highlights: • EPA evoked ROS formation, [Ca{sup 2+}]{sub c} accumulation, the opening of MPTP and the phosphorylation of JNK. • EPA-induced [Ca{sup 2+}]{sub c} elevation was depended on production of ROS. • EPA-induced ROS generation, [Ca{sup 2+}]{sub c} increase, and JNK activated caused MPTP opening. • The apoptosis induced by EPA was related to release of cytochrome C through the MPTP. • EPA induced HepG2 cells apoptosis through ROS–Ca{sup 2+}–JNK mitochondrial pathways. - Abstract: Eicosapentaenoic acid (EPA), a well-known dietary n−3 PUFAS, has been considered to inhibit proliferation of tumor cells. However, the molecular mechanism related to EPA-induced liver cancer cells apoptosis has not been reported. In this study, we investigated the effect of EPA on HepG2 cells proliferation and apoptosis mechanism through mitochondrial pathways. EPA inhibited proliferation of HepG2 cells in a dose-dependent manner and had no significant effect on the cell viability of humor normal liver L-02 cells. It was found that EPA initially evoked ROS formation, leading to [Ca{sup 2+}]{sub c} accumulation and the mitochondrial permeability transition pore (MPTP) opening; EPA-induced HepG2 cells apoptosis was inhibited by N-acetylcysteine (NAC, an inhibitor of ROS), 1,2-bis (2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM, a chelator of calcium) and CsA (inhibitor of MPTP). The relationship between ROS production, the increase of cytoplasmic Ca and MPTP opening was detected. It seems that ROS may act as an upstream regulator of EPA-induced [Ca{sup 2+}]{sub c} generation, moreover, generation of ROS, overload of mitochondrial [Ca{sup 2+}]{sub c}, and JNK activated cause the opening of MPTP. Western blotting results showed that EPA elevated the phosphorylation status of JNK, processes associated with the ROS generation. Simultaneously, the apoptosis induced by EPA was related to release of cytochrome C from mitochondria to cytoplasm through the MPTP

  5. Impact of Genotype on EPA and DHA Status and Responsiveness to Increased Intakes.

    PubMed

    Minihane, Anne Marie

    2016-03-01

    At a population level, cardioprotective and cognitive actions of the fish oil (FO) derived long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been extensively demonstrated. In addition to dietary intake, which is limited for many individuals, EPA and DHA status is dependent on the efficiency of their biosynthesis from α-linolenic acid. Gender and common gene variants have been identified as influencing the rate-limiting desaturase and elongase enzymes. Response to a particular intake or status is also highly heterogeneous and likely influenced by genetic variants which impact on EPA and DHA metabolism and tissue partitioning, transcription factor activity, or physiological end-point regulation. Here, available literature relating genotype to tissue LC n-3 PUFA status and response to FO intervention is considered. It is concluded that the available evidence is relatively limited, with much of the variability unexplained, though APOE and FADS genotypes are emerging as being important. Although genotype × LC n-3 PUFA interactions have been described for a number of phenotypes, few have been confirmed in independent studies. A more comprehensive understanding of the genetic, physiological and behavioural modulators of EPA and DHA status and response to intervention is needed to allow refinement of current dietary LC n-3 PUFA recommendations and stratification of advice to "vulnerable" and responsive subgroups. PMID:26950146

  6. Impact of Genotype on EPA and DHA Status and Responsiveness to Increased Intakes

    PubMed Central

    Minihane, Anne Marie

    2016-01-01

    At a population level, cardioprotective and cognitive actions of the fish oil (FO) derived long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been extensively demonstrated. In addition to dietary intake, which is limited for many individuals, EPA and DHA status is dependent on the efficiency of their biosynthesis from α-linolenic acid. Gender and common gene variants have been identified as influencing the rate-limiting desaturase and elongase enzymes. Response to a particular intake or status is also highly heterogeneous and likely influenced by genetic variants which impact on EPA and DHA metabolism and tissue partitioning, transcription factor activity, or physiological end-point regulation. Here, available literature relating genotype to tissue LC n-3 PUFA status and response to FO intervention is considered. It is concluded that the available evidence is relatively limited, with much of the variability unexplained, though APOE and FADS genotypes are emerging as being important. Although genotype × LC n-3 PUFA interactions have been described for a number of phenotypes, few have been confirmed in independent studies. A more comprehensive understanding of the genetic, physiological and behavioural modulators of EPA and DHA status and response to intervention is needed to allow refinement of current dietary LC n-3 PUFA recommendations and stratification of advice to “vulnerable” and responsive subgroups. PMID:26950146

  7. Trans isomers of EPA and DHA in omega-3 products on the European market.

    PubMed

    Sciotto, Caterina; Mjøs, Svein A

    2012-07-01

    The levels of trans isomers of eicosapentaenoic (EPA) acid and docosahexaenoic acid (DHA) in 77 omega-3 products on the European market have been studied. Fatty acids were analyzed as fatty acid methyl esters by gas chromatography with a flame ionization detector, using a cyanopropyl coated stationary phase. The amount of mono-trans EPA isomers relative to the corresponding all-cis isomer ranged from 0.19 to 4.5 %. The corresponding values for mono-trans DHA relative to the all-cis isomer ranged from 0.25 to 5.9 %. There was a strong correlation between the degree of isomerization of EPA and DHA, showing that DHA was 1.26 times more isomerized than EPA. Division of the samples into different product groups showed that samples with a low degree of isomerization were found in all groups, except one. This shows that a high degree of isomerization is avoidable, and also points to deodorization of the oils as the main source of trans isomers. PMID:22566205

  8. Eicosapentaenoic Acid Inhibits Oxidation of ApoB-containing Lipoprotein Particles of Different Size In Vitro When Administered Alone or in Combination With Atorvastatin Active Metabolite Compared With Other Triglyceride-lowering Agents.

    PubMed

    Mason, R Preston; Sherratt, Samuel C R; Jacob, Robert F

    2016-07-01

    Eicosapentaenoic acid (EPA) is a triglyceride-lowering agent that reduces circulating levels of the apolipoprotein B (apoB)-containing lipoprotein particles small dense low-density lipoprotein (sdLDL), very-low-density lipoprotein (VLDL), and oxidized low-density lipoprotein (LDL). These benefits may result from the direct antioxidant effects of EPA. To investigate this potential mechanism, these particles were isolated from human plasma, preincubated with EPA in the absence or presence of atorvastatin (active) metabolite, and subjected to copper-initiated oxidation. Lipid oxidation was measured as a function of thiobarbituric acid reactive substances formation. EPA inhibited sdLDL (IC50 ∼2.0 μM) and LDL oxidation (IC50 ∼2.5 μM) in a dose-dependent manner. Greater antioxidant potency was observed for EPA in VLDL. EPA inhibition was enhanced when combined with atorvastatin metabolite at low equimolar concentrations. Other triglyceride-lowering agents (fenofibrate, niacin, and gemfibrozil) and vitamin E did not significantly affect sdLDL, LDL, or VLDL oxidation compared with vehicle-treated controls. Docosahexaenoic acid was also found to inhibit oxidation in these particles but over a shorter time period than EPA. These data support recent clinical findings and suggest that EPA has direct antioxidant benefits in various apoB-containing subfractions that are more pronounced than those of other triglyceride-lowering agents and docosahexaenoic acid. PMID:26945158

  9. Eicosapentaenoic Acid Inhibits Oxidation of ApoB-containing Lipoprotein Particles of Different Size In Vitro When Administered Alone or in Combination With Atorvastatin Active Metabolite Compared With Other Triglyceride-lowering Agents

    PubMed Central

    Sherratt, Samuel C.R.; Jacob, Robert F.

    2016-01-01

    Abstract: Eicosapentaenoic acid (EPA) is a triglyceride-lowering agent that reduces circulating levels of the apolipoprotein B (apoB)-containing lipoprotein particles small dense low-density lipoprotein (sdLDL), very–low-density lipoprotein (VLDL), and oxidized low-density lipoprotein (LDL). These benefits may result from the direct antioxidant effects of EPA. To investigate this potential mechanism, these particles were isolated from human plasma, preincubated with EPA in the absence or presence of atorvastatin (active) metabolite, and subjected to copper-initiated oxidation. Lipid oxidation was measured as a function of thiobarbituric acid reactive substances formation. EPA inhibited sdLDL (IC50 ∼2.0 μM) and LDL oxidation (IC50 ∼2.5 μM) in a dose-dependent manner. Greater antioxidant potency was observed for EPA in VLDL. EPA inhibition was enhanced when combined with atorvastatin metabolite at low equimolar concentrations. Other triglyceride-lowering agents (fenofibrate, niacin, and gemfibrozil) and vitamin E did not significantly affect sdLDL, LDL, or VLDL oxidation compared with vehicle-treated controls. Docosahexaenoic acid was also found to inhibit oxidation in these particles but over a shorter time period than EPA. These data support recent clinical findings and suggest that EPA has direct antioxidant benefits in various apoB-containing subfractions that are more pronounced than those of other triglyceride-lowering agents and docosahexaenoic acid. PMID:26945158

  10. Evaluation of suppressive and pro-resolving effects of EPA and DHA in human primary monocytes and T-helper cells[S

    PubMed Central

    Jaudszus, Anke; Gruen, Michael; Watzl, Bernhard; Ness, Christina; Roth, Alexander; Lochner, Alfred; Barz, Dagmar; Gabriel, Holger; Rothe, Michael; Jahreis, Gerhard

    2013-01-01

    Despite their beneficial anti-inflammatory properties, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may increase the infection risk at high doses, likely by generating an immune-depressed state. To assess the contribution of different immune cell populations to the immunomodulatory fatty acid effect, we comparatively investigated several aspects of inflammation in human T-helper (Th) cells and monocytes. Both fatty acids, but DHA to a lesser extent compared with EPA, selectively and dose-dependently reduced the percentage of cytokine-expressing Th cells in a peroxisome proliferator-activated receptor (PPAR)γ-dependent fashion, whereas the expression of the cell surface marker CD69 was unaltered on activated T cells. In monocytes, both EPA and DHA increased interleukin (IL)-10 without affecting tumor necrosis factor (TNF)-α and IL-6. Cellular incorporation of EPA and DHA occurred mainly at the expense of arachidonic acid. Concomitantly, thromboxane B (TXB)2 and leukotriene B (LTB)4 in supernatants decreased, while levels of TXB3 and LTB5 increased. This increase was independent of activation and in accordance with cyclooxygenase expression patterns in monocytes. Moreover, EPA and DHA gave rise to a variety of mono- and trihydroxy derivatives of highly anti-inflammatory potential, such as resolvins and their precursors. Our results suggest that EPA and DHA do not generally affect immune cell functions in an inhibitory manner but rather promote pro-resolving responses. PMID:23349208

  11. Neurodevelopmental outcomes at 7 years’ corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial

    PubMed Central

    Gibson, Robert A; Anderson, Peter J; McPhee, Andrew J; Sullivan, Thomas R; Gould, Jacqueline F; Ryan, Philip; Doyle, Lex W; Davis, Peter G; McMichael, Judy E; French, Noel P; Colditz, Paul B; Simmer, Karen; Morris, Scott A; Makrides, Maria

    2015-01-01

    Objective To determine if improvements in cognitive outcome detected at 18 months’ corrected age (CA) in infants born <33 weeks’ gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood. Design Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital. Setting Five Australian tertiary hospitals from 2008 to 2013. Participants 626 of the 657 participants randomised between 2001 and 2005 were eligible to participate. Interventions High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2–4 days until term CA. Primary outcome Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted. Results 604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital −0.3, 95% CI −2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet. Conclusions Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years’ CA. Trial registration number

  12. Short communication: Using diurnal patterns of (13)C enrichment of CO2 to evaluate the effects of nitrate and docosahexaenoic acid on fiber degradation in the rumen of lactating dairy cows.

    PubMed

    Klop, G; Bannink, A; Dieho, K; Gerrits, W J J; Dijkstra, J

    2016-09-01

    Nitrate decreases enteric CH4 production in ruminants, but may also negatively affect fiber degradation. In this experiment, 28 lactating Holstein dairy cows were grouped into 7 blocks. Within blocks, cows were randomly assigned to 1 of 4 isonitrogenous treatments in a 2×2 factorial arrangement: control (CON); NO3 [21g of nitrate/kg of dry matter (DM)]; DHA [3g of docosahexaenoic acid (DHA)/kg of DM]; or NO3+DHA (21g of nitrate/kg of DM and 3g of DHA/kg of DM). Cows were fed a total mixed ration consisting of 21% grass silage, 49% corn silage, and 30% concentrates on a DM basis. Based on the difference in natural (13)C enrichment and neutral detergent fiber and starch content between grass silage and corn silage, we investigated whether a negative effect on rumen fiber degradation could be detected by evaluating diurnal patterns of (13)C enrichment of exhaled carbon dioxide. A significant nitrate × DHA interaction was found for neutral detergent fiber digestibility, which was reduced on the NO3 treatment to an average of 55%, as compared with 61, 64, and 65% on treatments CON, DHA, and NO3+DHA, respectively. Feeding nitrate, but not DHA, resulted in a pronounced increase in (13)C enrichment of CO2 in the first 3 to 4 h after feeding only. Results support the hypothesis that effects of a feed additive on the rate of fiber degradation in the rumen can be detected by evaluating diurnal patterns of (13)C enrichment of CO2. To be able to detect this, the main ration components have to differ considerably in fiber and nonfiber carbohydrate content as well as in natural (13)C enrichment. PMID:27344384

  13. Can a standard dose of eicosapentaenoic acid (EPA) supplementation reduce the symptoms of delayed onset of muscle soreness?

    PubMed Central

    2012-01-01

    Background Unaccustomed exercise can result in delayed onset of muscle soreness (DOMS) which can affect athletic performance. Although DOMS is a useful tool to identify muscle damage and remodelling, prolonged symptoms of DOMS may be associated with the over-training syndrome. In order to reduce the symptoms of DOMS numerous management strategies have been attempted with no significant effect on DOMS-associated cytokines surge. The present study aimed to investigate the acute and chronic effects of a 2 × 180 mg per day dose of eicosapentaenoic acid (EPA) on interleukin-6 (IL-6) mediated inflammatory response and symptoms associated with DOMS. Methods Seventeen healthy non-smoking females (age 20.4 ± 2.1 years, height 161.2 ± 8.3 cm and mass 61.48 ± 7.4 kg) were randomly assigned to either placebo (N = 10) or EPA (N = 7). Serum IL-6, isometric and isokinetic (concentric and eccentric) strength, and rating of perceived exertion (RPE) were recorded on four occasions: i-prior to supplementation, ii-immediately after three weeks of supplementation (basal effects), iii-48 hours following a single bout of resistance exercise (acute training response effects), and iv-48 hours following the last of a series of three bouts of resistance exercise (chronic training response effects). Results There was only a group difference in the degree of change in circulating IL-6 levels. In fact, relative to the first baseline, by the third bout of eccentric workout, the EPA group had 103 ± 60% increment in IL-6 levels whereas the placebo group only had 80 ± 26% incremented IL-6 levels (P = 0.020). We also describe a stable multiple linear regression model which included measures of strength and not IL-6 as predictors of RPE scale. Conclusion The present study suggests that in doubling the standard recommended dose of EPA, whilst this may still not be beneficial at ameliorating the symptoms of DOMS, it counter intuitively appears to enhance the cytokine response to exercise. In a

  14. Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.

    PubMed

    Kidd, Parris M

    2007-09-01

    The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications. PMID:18072818

  15. Docosahexaenoic Acid Attenuates Cardiovascular Risk Factors via a Decline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Plasma Levels.

    PubMed

    Rodríguez-Pérez, Celia; Ramprasath, Vanu Ramkumar; Pu, Shuaihua; Sabra, Ali; Quirantes-Piné, Rosa; Segura-Carretero, Antonio; Jones, Peter J H

    2016-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that regulates cholesterol metabolism by promoting LDL receptor degradation in the liver and has recently been proposed as a therapeutic target in the management of hyperlipidaemia. We investigated the impact of dietary fat on the metabolism of sterols and on plasma PCSK9 concentrations to explore likely clinical usefulness. In a post hoc analysis of a double-blind randomised crossover controlled feeding trial, the Canola Oil Multicenter Intervention Trial (COMIT), volunteers (n = 54) with at least one condition related to metabolic syndrome consumed diets with one of the following treatment oils in beverages: (1) conventional canola oil (Canola); (2) canola oil rich in docosahexanoic acid (DHA) (CanolaDHA); and (3) high-oleic acid canola oil (CanolaOleic). The enrichment in oleic acid resulted in lower plasma cholesterol concentration compared with diets enriched in DHA. Contrarily, DHA-enriched oil significantly decreased plasma PCSK9 and triacylglycerols levels, but increased circulating levels of sterols. The variations in lathosterol, sitosterol, and campesterol indicate that plasma PCSK9 levels are sensitive to changes in cholesterol synthesis and/or absorption. There was a significant correlation between plasma PCSK9 levels and plasma triacylglicerol and apolipoprotein B levels, which was not affected by dietary fat. Therefore, our results suggest that the impact of dietary fats should not be discarded as complementary treatment in the management of patients with hyperlipidaemia. These findings should be considered in the analysis of ongoing studies and may represent a cautionary note in the treatment of patients with cardiovascular risk. PMID:26620373

  16. Chronic oral or intraarticular administration of docosahexaenoic acid reduces nociception and knee edema and improves functional outcomes in a mouse model of Complete Freund’s Adjuvant–induced knee arthritis

    PubMed Central

    2014-01-01

    Introduction Clinical and preclinical studies have shown that supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs) reduce joint destruction and inflammation present in rheumatoid arthritis (RA). However, the effects of individual ω-3 PUFAs on chronic arthritic pain have not been evaluated to date. Thus, our aim in this study was to examine whether purified docosahexaenoic acid (DHA, an ω-3 PUFA) reduces spontaneous pain-related behavior and knee edema and improves functional outcomes in a mouse model of knee arthritis. Methods Unilateral arthritis was induced by multiple injections of Complete Freund’s Adjuvant (CFA) into the right knee joints of male ICR adult mice. Mice that received CFA injections were then chronically treated from day 15 until day 25 post–initial CFA injection with oral DHA (10, 30 and 100 mg/kg daily) or intraarticular DHA (25 and 50 μg/joint twice weekly). Spontaneous flinching of the injected extremity (considered as spontaneous pain-related behavior), vertical rearing and horizontal exploratory activity (considered as functional outcomes) and knee edema were assessed. To determine whether an endogenous opioid mechanism was involved in the therapeutic effect of DHA, naloxone (NLX, an opioid receptor antagonist, 3 mg/kg subcutaneously) was administered in arthritic mice chronically treated with DHA (30 mg/kg by mouth) at day 25 post–CFA injection. Results The intraarticular CFA injections resulted in increasing spontaneous flinching and knee edema of the ipsilateral extremity as well as worsening functional outcomes as time progressed. Chronic administration of DHA, given either orally or intraarticularly, significantly improved horizontal exploratory activity and reduced flinching behavior and knee edema in a dose-dependent manner. Administration of NLX did not reverse the antinociceptive effect of DHA. Conclusions To the best of our knowledge, this report is the first to demonstrate DHA’s antinociceptive and

  17. Omega-3 polyunsaturated fatty acids and vegetarian diets.

    PubMed

    Saunders, Angela V; Davis, Brenda C; Garg, Manohar L

    2013-08-19

    While intakes of the omega-3 fatty acid α-linolenic acid (ALA) are similar in vegetarians and non-vegetarians, intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low in vegetarians and virtually absent in vegans. Plasma, blood and tissue levels of EPA and DHA are lower in vegetarians than in non-vegetarians, although the clinical significance of this is unknown. Vegetarians do not exhibit clinical signs of DHA deficiency, but further research is required to ascertain whether levels observed in vegetarians are sufficient to support optimal health. ALA is endogenously converted to EPA and DHA, but the process is slow and inefficient and is affected by genetics, sex, age and dietary composition. Vegetarians can take practical steps to optimise conversion of ALA to EPA and DHA, including reducing intake of linoleic acid. There are no official separate recommendations for intake of fatty acids by vegetarians. However, we suggest that vegetarians double the current adequate intake of ALA if no direct sources of EPA and DHA are consumed. Vegetarians with increased needs or reduced conversion ability may receive some advantage from DHA and EPA supplements derived from microalgae. A supplement of 200-300 mg/day of DHA and EPA is suggested for those with increased needs, such as pregnant and lactating women, and those with reduced conversion ability, such as older people or those who have chronic disease (eg, diabetes). PMID:25369925

  18. Supplementation of milled chia seeds increases plasma ALA and EPA in postmenopausal women.

    PubMed

    Jin, Fuxia; Nieman, David C; Sha, Wei; Xie, Guoxiang; Qiu, Yunping; Jia, Wei

    2012-06-01

    Ten postmenopausal women (age 55.6 ± 0.8 years, BMI 24.6 ± 1.1 kg/m²) ingested 25 g/day milled chia seed during a 7-week period, with six plasma samples collected for measurement of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Subjects operated as their own controls with overnight fasted blood samples taken at baseline (average of two samples), and then after 1, 2, 3, 5, and 7 weeks supplementation. Plasma ALA increased significantly after one week supplementation and was 138 % above baseline levels by the end of the study (overall time effect, P < 0.001). EPA increased 30 % above baseline (overall time effect, P = 0.019) and was correlated across time with ALA (r = 0.84, P = 0.02). No significant change in plasma DPA levels was measured (overall time effect, P = 0.067). Plasma DHA decreased slightly by the end of the study (overall time effect, P = 0.030) and was not correlated with change in ALA. In conclusion, ingestion of 25 g/day milled chia seeds for seven weeks by postmenopausal women resulted in significant increases in plasma ALA and EPA but not DPA and DHA. PMID:22538527

  19. Protective role of n6/n3 PUFA supplementation with varying DHA/EPA ratios against atherosclerosis in mice.

    PubMed

    Liu, Liang; Hu, Qinling; Wu, Huihui; Xue, Yihong; Cai, Liang; Fang, Min; Liu, Zhiguo; Yao, Ping; Wu, Yongning; Gong, Zhiyong

    2016-06-01

    The effects of n3 polyunsaturated fatty acids (PUFA) on cardiovascular disease are controversial. We currently explored the effects of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on high-fat-induced atherosclerosis. In model apoE(-/-) mice, high-fat diets (HFD) were partially replaced with fish and algal oils (DHA/EPA 2:1, 1:1 and 1:2) and/or plant oils enriched in linoleic and alpha-linolenic acids with an n6/n3 ratio of 4:1. PUFA supplementation significantly reduced the atherosclerotic plaque area, serum lipid profile, inflammatory response, aortic ROS production, proinflammatory factors and scavenger receptor expression as compared to those in the HFD group. However, plant oils did not have a significant effect on the following: serum HDL-C level; aortic ABCA1, ABCG1 and LAL mRNA expression; and CD36 and LOX-1 protein expression. Compared to the plant-oil-treated group, the DHA/EPA 1:1 group had a smaller atherosclerotic plaque area, higher serum HDL-C levels and lesser CD36 and MSR-1 mRNA expression; the DHA/EPA 2:1 group had lower serum TC, LDL-C and TNF-α levels and lower aortic ROS levels. Our study suggested that n3 PUFA from animals had more potent atheroprotective effects than that from plants. Supplementation involving higher DHA/EPA ratios and an n6/n3 ratio of 4:1 was beneficial for reducing serum "bad cholesterol" and a 1:1 DHA/EPA ratio with an n6/n3 ratio of 4:1 was beneficial for improving serum "good cholesterol" and inhibiting ox-LDL uptake. Our results suggest that achieving an n6/n3 ratio of 4:1 in the diet is also important in addition to having an optimal DHA/EPA ratio. PMID:27142749

  20. EPA (ENVIRONMENTAL PROTECTION AGENCY) METHOD STUDY 30, METHOD 625 - BASE/NEUTRALS, ACIDS AND PESTICIDES

    EPA Science Inventory

    The work which is described in this report was performed for the purpose of validating, through an interlaboratory study, Method 625 for the analysis of the base/neutral, acid, and pesticide priority pollutants. This method is based on the extraction and concentration of the vari...

  1. A Comparative Overview of Prescription Omega-3 Fatty Acid Products

    PubMed Central

    Ito, Matthew K.

    2015-01-01

    An estimated 25% of adults in the United States have elevated triglyceride (TG) levels. This is of particular concern given the evidence for a causal role of TG in the pathway of cardiovascular (CV) disease. Approved prescription omega-3 fatty acid products (RxOM3FAs) contain the long-chain fatty acids docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) and are effective options for the treatment of high TG levels. RxOM3FAs that contain both EPA and DHA include omega-3-acid ethyl esters (ethyl esters of EPA and DHA; brand and generic products) and omega-3-carboxylic acids (free fatty acids primarily composed of EPA and DHA), while the RxOM3FA icosapent ethyl (the ethyl ester of EPA) contains EPA only. All RxOM3FA products produce substantial TG reduction and other beneficial effects on atherogenic lipid and inflammation-related parameters, blood pressure, and heart rate variability, but products that contain DHA may raise low-density lipoprotein-cholesterol (LDL-C). This commentary provides an overview of hypertriglyceridemia while summarizing the pharmacology, efficacy, and safety of prescription RxOM3FAs. PMID:26681905

  2. Comparison of the effects of EPA and DHA alone or in combination in a murine model of myocardial infarction.

    PubMed

    Madingou, Ness; Gilbert, Kim; Tomaro, Leandro; Prud'homme Touchette, Charles; Trudeau, François; Fortin, Samuel; Rousseau, Guy

    2016-08-01

    The aim of this project was to investigate the impact of two dietary omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alone or in combination, on infarct size. Adult, male Sprague-Dawley rats were fed for 14 days with different omega-3 diets. The animals were subjected to ischemia for 40min followed by reperfusion. Infarct size, Akt (protein kinase B) activation level, caspase-3 activity and mitochondrial permeability transition pore (mPTP) opening were measured. The results indicate that EPA or DHA alone significantly reduced infarct size compared to the other diets. Akt activity was increased in the group fed EPA or DHA alone, whereas no significant activation was observed in the other groups compared to no omega-3 PUFA. DHA alone reduced caspase-3 activity and conferred resistance to mPTP opening. In conclusion, our results demonstrate that EPA and DHA are individually effective in diminishing infarct size in our experimental model while their combination is not. PMID:27499449

  3. Are all n-3 polyunsaturated fatty acids created equal?

    PubMed Central

    2009-01-01

    N-3 Polyunsaturated fatty acids have been shown to have potential beneficial effects for chronic diseases including cancer, insulin resistance and cardiovascular disease. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in particular have been studied extensively, whereas substantive evidence for a biological role for the precursor, alpha-linolenic acid (ALA), is lacking. It is not enough to assume that ALA exerts effects through conversion to EPA and DHA, as the process is highly inefficient in humans. Thus, clarification of ALA's involvement in health and disease is essential, as it is the principle n-3 polyunsaturated fatty acid consumed in the North American diet and intakes of EPA and DHA are typically very low. There is evidence suggesting that ALA, EPA and DHA have specific and potentially independent effects on chronic disease. Therefore, this review will assess our current understanding of the differential effects of ALA, EPA and DHA on cancer, insulin resistance, and cardiovascular disease. Potential mechanisms of action will also be reviewed. Overall, a better understanding of the individual role for ALA, EPA and DHA is needed in order to make appropriate dietary recommendations regarding n-3 polyunsaturated fatty acid consumption. PMID:19664246

  4. EPA/DHA and Vitamin A Supplementation Improves Spatial Memory and Alleviates the Age-related Decrease in Hippocampal RXRγ and Kinase Expression in Rats

    PubMed Central

    Létondor, Anne; Buaud, Benjamin; Vaysse, Carole; Richard, Emmanuel; Layé, Sophie; Pallet, Véronique; Alfos, Serge

    2016-01-01

    Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore, we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ, and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT, and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging. PMID:27242514

  5. EPA/DHA and Vitamin A Supplementation Improves Spatial Memory and Alleviates the Age-related Decrease in Hippocampal RXRγ and Kinase Expression in Rats.

    PubMed

    Létondor, Anne; Buaud, Benjamin; Vaysse, Carole; Richard, Emmanuel; Layé, Sophie; Pallet, Véronique; Alfos, Serge

    2016-01-01

    Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore, we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ, and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT, and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging. PMID:27242514

  6. Muscle fatigue resistance in the rat hindlimb in vivo from low dietary intakes of tuna fish oil that selectively increase phospholipid n-3 docosahexaenoic acid according to muscle fibre type.

    PubMed

    Henry, R; Peoples, G E; McLennan, P L

    2015-09-28

    Dietary fish oil (FO) modulates muscle O2 consumption and contractile function, predictive of effects on muscle fatigue. High doses unattainable through human diet and muscle stimulation parameters used engender uncertainty in their physiological relevance. We tested the hypothesis that nutritionally relevant FO doses can modulate membrane fatty acid composition and muscle fatigue. Male Sprague-Dawley rats were randomised to control (10% olive oil (OO) by weight) or low or moderate FO diet (LowFO and ModFO) (HiDHA tuna fish oil) for 15 weeks (LowFO: 0.3% FO, 9.7% OO, 0.25% energy as EPA+DHA; ModFO: 1.25% FO, 8.75% OO, 1.0% energy as EPA+DHA). Hindlimb muscle function was assessed under anaesthesia in vivo using repetitive 5 s burst sciatic nerve stimulation (0.05 ms, 7-12 V, 5 Hz, 10 s duty cycle, 300 s). There were no dietary differences in maximum developed muscle force. Repetitive peak developed force fell to 50% within 62 (SEM 10) s in controls and took longer to decline in FO-fed rats (LowFO 110 (SEM 15) s; ModFO 117 (sem 14) s) (P<0.05). Force within bursts was better sustained with FO and maximum rates of force development and relaxation declined more slowly. The FO-fed rats incorporated higher muscle phospholipid DHA-relative percentages than controls (P<0.001). Incorporation of DHA was greater in the fast-twitch gastrocnemius (Control 9.3 (SEM 0.8) %, LowFO 19.9 (SEM 0.4), ModFO 24.3 (SEM 1.0)) than in the slow-twitch soleus muscle (Control 5.1 (SEM 0.2), LowFO 14.3 (SEM 0.7), ModFO 18.0 (SEM 1.4)) (P<0.001), which was comparable with the myocardium, in line with muscle fibre characteristics. The LowFO and ModFO diets, emulating human dietary and therapeutic supplement intake, respectively, both elicited muscle membrane DHA enrichment and fatigue resistance, providing a foundation for translating these physiological effects to humans. PMID:26266774

  7. Odour characteristics of seafood flavour formulations produced with fish by-products incorporating EPA, DHA and fish oil.

    PubMed

    Peinado, I; Miles, W; Koutsidis, G

    2016-12-01

    Thermal degradation of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids was investigated. As a novelty, EPA, DHA or fish oil (FO) were incorporated as ω-fatty acid sources into model systems containing fish powder produced via Maillard reactions. Aroma composition of the resulting products was determined and complemented with sensory evaluation. Heating of the oils led to a fast decrease of both, EPA and DHA, and to the development of characteristic volatile compounds including hexanal, 2,4-heptadienal and 4-heptenal, the most abundant being (E,E)-2,4-heptadienal (132±44-329±122μmol/g). EPA and DHA addition to the model systems increased the concentration of these characteristic volatile compounds. However, it did not have a considerable impact on the development of characteristic Maillard reaction products, such as pyrazines and some aldehydes. Finally, the results of the sensory evaluation illustrated that panellists would chose samples fortified with FO as the ones with a more pleasant aroma. PMID:27374575

  8. Production of structured phosphatidylcholine with high content of DHA/EPA by immobilized phospholipase A₁-catalyzed transesterification.

    PubMed

    Li, Xiang; Chen, Jia-Feng; Yang, Bo; Li, Dao-Ming; Wang, Yong-Hua; Wang, Wei-Fei

    2014-01-01

    This paper presents the synthesis of structured phosphatidylcholine (PC) enriched with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) by transesterification of DHA/EPA-rich ethyl esters with PC using immobilized phospholipsase A1 (PLA1) in solvent-free medium. Firstly, liquid PLA1 was immobilized on resin D380, and it was found that a pH of 5 and a support/PLA1 ratio (w/v) of 1:3 were the best conditions for the adsorption. Secondly, the immobilized PLA1 was used to catalyze transesterification of PC and DHA/EPA-rich ethyl esters. The maximal incorporation of DHA and EPA achieved was 30.7% for 24 h of reaction at 55 °C using a substrate mass ratio (PC/ethyl esters) of 1:6, an immobilized PLA1 loading of 15% and water dosage of 1.25%. Then the reaction mixture was analyzed by 31P nuclear magnetic resonance (NMR). The composition of reaction product included 16.5% PC, 26.3% 2-diacyl-sn-glycero-3-lysophosphatidylcholine (1-LPC), 31.4% 1-diacyl-sn-glycero-3-lysophosphatidylcholine (2-LPC), and 25.8% sn-glycerol-3-phosphatidylcholine (GPC). PMID:25170810

  9. Recent trends in the advanced analysis of bioactive fatty acids.

    PubMed

    Ruiz-Rodriguez, Alejandro; Reglero, Guillermo; Ibañez, Elena

    2010-01-20

    The consumption of dietary fats have been long associated to chronic diseases such as obesity, diabetes, cancer, arthritis, asthma, and cardiovascular disease; although some controversy still exists in the role of dietary fats in human health, certain fats have demonstrated their positive effect in the modulation of abnormal fatty acid and eicosanoid metabolism, both of them associated to chronic diseases. Among the different fats, some fatty acids can be used as functional ingredients such as alpha-linolenic acid (ALA), arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), stearidonic acid (STA) and conjugated linoleic acid (CLA), among others. The present review is focused on recent developments in FAs analysis, covering sample preparation methods such as extraction, fractionation and derivatization as well as new advances in chromatographic methods such as GC and HPLC. Special attention is paid to trans fatty acids due its increasing interest for the food industry. PMID:19525080

  10. The effects of diets containing standard soybean oil, soybean oil enhanced with conjugated linoleic acids, menhaden fish oil, or an algal docosahexaenoic acid supplement on channel catfish performance, body composition,...

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fish consumption is a common method of obtaining beneficial n-3 highly unsaturated fatty acids (HUFAs), but increased use of vegetable oils in fish diets to reduce dependence on fish oil dilutes these HUFAs. Conjugated linoleic acids (CLA) are also considered beneficial for human health. Therefore,...

  11. Effects of n-3 fatty acids on growth and survival of J774 macrophages.

    PubMed

    Fyfe, D J; Abbey, M

    2000-03-01

    To further understand potential mechanisms underlying the protective effects of eicosapentanoic acid (EPA) against atherosclerosis, J774 macrophages were used to explore cellular responses to growth in the presence of PUFA in vitro. Clonogenic assays indicated that 15 microg/ml of EPA killed over 90% of J774 populations. Docosapentaenoic acid (DPA) was more cytotoxic than either EPA or docosahexaenoic acid (DHA). EPA was shown to be elongated to DPA. Cytotoxicity induced by EPA was not inhibited by the presence of alpha-tocopherol (a-toc) in the medium. Immunological screening for caspase enzymes and microscopic examination indicated that apoptosis was not the major cause of cell death. Proliferation assays demonstrated that total cell numbers of EPA-treated cells were not significantly different to control cells. Increasing does of EPA were correlated with increasing levels of intracellular malondialdehyde (MDA). These observations suggest that EPA may influence the growth parameters of macrophages whilst inducing moderately elevated levels of oxidative stress. PMID:10841044

  12. The effects of the oral administration of fish oil concentrate on the release and the metabolism of (/sup 14/C)arachidonic acid and (/sup 14/C)eicosapentaenoic acid by human platelets

    SciTech Connect

    Hirai, A.; Terano, T.; Hamazaki, T.; Sajiki, J.; Kondo, S.; Ozawa, A.; Fujita, T.; Miyamoto, T.; Tamura, Y.; Kumagai, A.

    1982-11-01

    It has been suggested by several investigators that eicosapentaenoic acid (C20:5 omega 3, EPA) might have anti-thrombotic effects. In this experiment, the effect of the oral administration of EPA rich fish oil concentrate on platelet aggregation and the release and the metabolism of (/sup 1 -14/C)arachidonic acid and ((U)-/sup 14/C)eicosapentaenoic acid by human platelets was studied. Eight healthy male subjects ingested 18 capsules of fish oil concentrate (EPA 1.4 g) per day for 4 weeks. Plasma and platelet concentrations of EPA markedly increased, while those of arachidonic acid (C20:4 omega 6, AA) and docosahexaenoic acid (C22:6 omega 3, DHA) did not change. Platelet aggregation induced by collagen and ADP was reduced. Collagen induced (/sup 14/C)thromboxane B2 (TXB2) formation from (/sup 14/C)AA prelabeled platelets decreased. There was no detectable formation of (/sup 14/C)TXB3 from (/sup 14/C)EPA prelabeled platelets, and the conversion of exogenous (/sup 14/C)EPA to (/sup 14/C)TXB3 was lower than that of (/sup 14/C)AA to (/sup 14/C)TXB2. The release of (/sup 14/C)AA from (/sup 14/C)AA prelabeled platelets by collagen was significantly decreased. These observations raise the possibility that the release of arachidonic acid from platelet lipids might be affected by the alteration of EPA content in platelets.

  13. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

    PubMed Central

    Leikin-Frenkel, Alicia I.

    2016-01-01

    The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring. PMID:27023621

  14. Achieving optimal essential fatty acid status in vegetarians: current knowledge and practical implications.

    PubMed

    Davis, Brenda C; Kris-Etherton, Penny M

    2003-09-01

    Although vegetarian diets are generally lower in total fat, saturated fat, and cholesterol than are nonvegetarian diets, they provide comparable levels of essential fatty acids. Vegetarian, especially vegan, diets are relatively low in alpha-linolenic acid (ALA) compared with linoleic acid (LA) and provide little, if any, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Clinical studies suggest that tissue levels of long-chain n-3 fatty acids are depressed in vegetarians, particularly in vegans. n-3 Fatty acids have numerous physiologic benefits, including potent cardioprotective effects. These effects have been demonstrated for ALA as well as EPA and DHA, although the response is generally less for ALA than for EPA and DHA. Conversion of ALA by the body to the more active longer-chain metabolites is inefficient: < 5-10% for EPA and 2-5% for DHA. Thus, total n-3 requirements may be higher for vegetarians than for nonvegetarians, as vegetarians must rely on conversion of ALA to EPA and DHA. Because of the beneficial effects of n-3 fatty acids, it is recommended that vegetarians make dietary changes to optimize n-3 fatty acid status. PMID:12936959

  15. EPA- and DHA-derived resolvins' actions in inflammatory bowel disease.

    PubMed

    Schwanke, Raquel Cristina; Marcon, Rodrigo; Bento, Allisson Freire; Calixto, João B

    2016-08-15

    Inflammatory bowel diseases are chronic diseases divided into two major forms, ulcerative colitis and Crohn's disease, which are both associated with a chronic inflammatory condition of the gastrointestinal tract. Recent studies have shown that the resolution of inflammatory conditions is a biosynthetically active process where new pro-resolution lipid mediators derived from omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), such as E- and D-series resolvins, protectins, and macrophage mediator in resolving inflammation (maresins), have potent anti-inflammatory activity and serve as specialised mediators that play an important role in the resolution of inflammation. Recent studies have also shown the role of resolvins in referred hyperalgesia associated with different inflammatory processes, such as the visceral pain caused by inflammatory bowel disease. There are many reports describing the principal effects of EPA- and DHA-derived mediators in experimental models of inflammatory bowel diseases. This review focuses on the recent studies on the important role played by pro-resolution lipid mediators in controlling the inflammatory process associated with inflammatory bowel diseases. PMID:26325092

  16. EPA GEOBOOK

    EPA Science Inventory

    The EPA GeoBook is a computer application that resembles a notebook with pages of information on the Southeastern Ecological Framework, a powerpoint presentation, a short video and a map viewer. It was developed to forge partnerships with local, state and federal partners to work...

  17. Effect of eicosapentaenoic acid on cholesterol gallstone formation in C57BL/6J mice.

    PubMed

    Cho, Soo-Min; Park, Jin-A; Kim, Na-Hyun; Kim, Dong-Soon; Zhang, Dan; Yi, Hee; Cho, Hee-Jung; Kim, Ja Kyung; Lee, Dong Ki; Kim, Jin-Suk; Shin, Ho-Chul

    2015-01-01

    The present study investigated the preventive effect of ω-3 fatty acids against cholesterol gallstone (CG) formation. CG formation was induced in C57BL/6J mice using a lithogenic diet (LD). The mice were divided into four treatment groups: i) LD, ii) LD plus eicosapentaenoic acid (EPA), iii) LD plus docosahexaenoic acid (DHA) and iv) LD plus EPA plus DHA. Subsequent to feeding the mice the LD for four weeks, EPA and/or DHA (70 mg/kg/day) were orally administered for eight weeks. The mice in the EPA treatment groups exhibited significantly less gallstone formation than those in the LD group. By contrast, DHA treatment only slightly suppressed gallstone formation. The expression of mucin 2, 5AC, 5B and 6 was significantly decreased in the gallbladders of mice in the EPA groups (70-90%) and the LD plus DHA group (30-50%), compared with that in the mice in the LD group. In addition, the mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase was significantly decreased in the livers of mice in the EPA treatment group compared with that in the livers of mice in the LD group. In conclusion, EPA was found to have a dominant anti-lithogenic effect in C57BL/6J mice. PMID:25333303

  18. Fish meal lecithin as alternative precursor of docosahexaenoate and choline.

    PubMed

    Dahlan, W; Chatnilbandhu, S; Na-Nagara, B; Carpentier, Y A

    1996-09-01

    Choline and docosahexaenoate (DHA) are essential nutrients for maintaining normal brain function. However, their existence in fish lecithin is ignored and excluded during the degumming step of conventional fish oil manufacturing process. The study aims to introduce fish lecithin as alternative precursor of choline and omega-3 fatty acids especially DHA for nutritional supplements. Four grades of Thai fish meals with protein contents ranging from 60-70% were used. Their lipid characteristics were examined. Fish meal's fats and lecithin were 9-15 and 2-3 g/100 g, respectively. Total fatty acids constitute 23-27% monoenes without erucic acid and 24-28% polyenes including 15-19% DHA. Lecithin with 50% purity was prepared from grade-1 fish meal by means of consecutive methanol/n-hexane/acetone extraction. The obtained lecithin contains choline upto 66-70 mole% with DHA reaches to 20-23%. Its peroxide value of 57 and acid value of 9 are accepted for food grade lecithin preparation, however, the further refinery process is still suggested. Since the world consumption of nutritional supplement foods is increasing steadily, the results of our study implies that fish lecithin is probably a promising source of choline and omega-3 fatty acids especially DHA for such an objective. PMID:8886341

  19. Sustainable source of omega-3 eicosapentaenoic acid from metabolically engineered Yarrowia lipolytica: from fundamental research to commercial production.

    PubMed

    Xie, Dongming; Jackson, Ethel N; Zhu, Quinn

    2015-02-01

    The omega-3 fatty acids, cis-5, 8, 11, 14, and 17-eicosapentaenoic acid (C20:5; EPA) and cis-4, 7, 10, 13, 16, and 19-docosahexaenoic acid (C22:6; DHA), have wide-ranging benefits in improving heart health, immune function, mental health, and infant cognitive development. Currently, the major source for EPA and DHA is from fish oil, and a minor source of DHA is from microalgae. With the increased demand for EPA and DHA, DuPont has developed a clean and sustainable source of the omega-3 fatty acid EPA through fermentation using metabolically engineered strains of Yarrowia lipolytica. In this mini-review, we will focus on DuPont's technology for EPA production. Specifically, EPA biosynthetic and supporting pathways have been introduced into the oleaginous yeast to synthesize and accumulate EPA under fermentation conditions. This Yarrowia platform can also produce tailored omega-3 (EPA, DHA) and/or omega-6 (ARA, GLA) fatty acid mixtures in the cellular lipid profiles. Fundamental research such as metabolic engineering for strain construction, high-throughput screening for strain selection, fermentation process development, and process scale-up were all needed to achieve the high levels of EPA titer, rate, and yield required for commercial application. Here, we summarize how we have combined the fundamental bioscience and the industrial engineering skills to achieve large-scale production of Yarrowia biomass containing high amounts of EPA, which led to two commercial products, New Harvest™ EPA oil and Verlasso® salmon. PMID:25567511

  20. Omega-3 fatty acids for breast cancer prevention and survivorship.

    PubMed

    Fabian, Carol J; Kimler, Bruce F; Hursting, Stephen D

    2015-01-01

    Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case-control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship. PMID:25936773

  1. Omega-3 Fatty Acid Formulations in Cardiovascular Disease: Dietary Supplements are Not Substitutes for Prescription Products.

    PubMed

    Fialkow, Jonathan

    2016-08-01

    Omega-3 fatty acid products are available as prescription formulations (icosapent ethyl, omega-3-acid ethyl esters, omega-3-acid ethyl esters A, omega-3-carboxylic acids) and dietary supplements (predominantly fish oils). Most dietary supplements and all but one prescription formulation contain mixtures of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Products containing both EPA and DHA may raise low-density lipoprotein cholesterol (LDL-C). In clinical trials, the EPA-only prescription product, icosapent ethyl, did not raise LDL-C compared with placebo. To correct a common misconception, it is important to note that omega-3 fatty acid dietary supplements are not US FDA-approved over-the-counter drugs and are not required to demonstrate safety and efficacy prior to marketing. Conversely, prescription products are supported by extensive clinical safety and efficacy investigations required for FDA approval and have active and ongoing safety monitoring programs. While omega-3 fatty acid dietary supplements may have a place in the supplementation of diet, they generally contain lower levels of EPA and DHA than prescription products and are not approved or intended to treat disease. Perhaps due to the lack of regulation of dietary supplements, EPA and DHA levels may vary widely within and between brands, and products may also contain unwanted cholesterol or fats or potentially harmful components, including toxins and oxidized fatty acids. Accordingly, omega-3 fatty acid dietary supplements should not be substituted for prescription products. Similarly, prescription products containing DHA and EPA should not be substituted for the EPA-only prescription product, as DHA may raise LDL-C and thereby complicate the management of patients with dyslipidemia. PMID:27138439

  2. Impact of sustainable feeds on omega-3 long-chain fatty acid levels in farmed Atlantic salmon, 2006-2015.

    PubMed

    Sprague, M; Dick, J R; Tocher, D R

    2016-01-01

    As the global population and its demand for seafood increases more of our fish will come from aquaculture. Farmed Atlantic salmon are a global commodity and, as an oily fish, contain a rich source of the health promoting long-chain omega-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Replacing the traditional finite marine ingredients, fishmeal and fish oil, in farmed salmon diets with sustainable alternatives of terrestrial origin, devoid of EPA and DHA, presents a significant challenge for the aquaculture industry. By comparing the fatty acid composition of over 3,000 Scottish Atlantic salmon farmed between 2006 and 2015, we find that terrestrial fatty acids have significantly increased alongside a decrease in EPA and DHA levels. Consequently, the nutritional value of the final product is compromised requiring double portion sizes, as compared to 2006, in order to satisfy recommended EPA + DHA intake levels endorsed by health advisory organisations. Nevertheless, farmed Scottish salmon still delivers more EPA + DHA than most other fish species and all terrestrial livestock. Our findings highlight the global shortfall of EPA and DHA and the implications this has for the human consumer and examines the potential of microalgae and genetically modified crops as future sources of these important fatty acids. PMID:26899924

  3. EPA GEOSPATIAL QUALITY COUNCIL

    EPA Science Inventory

    The EPA Geospatial Quality Council (previously known as the EPA GIS-QA Team - EPA/600/R-00/009 was created to fill the gap between the EPA Quality Assurance (QA) and Geospatial communities. All EPA Offices and Regions were invited to participate. Currently, the EPA Geospatial Q...

  4. PTH1 Receptor Is Involved in Mediating Cellular Response to Long-Chain Polyunsaturated Fatty Acids

    PubMed Central

    Chachisvilis, Mirianas

    2012-01-01

    The molecular pathways by which long chain polyunsaturated fatty acids (LCPUFA) influence skeletal health remain elusive. Both LCPUFA and parathyroid hormone type 1 receptor (PTH1R) are known to be involved in bone metabolism while any direct link between the two is yet to be established. Here we report that LCPUFA are capable of direct, PTH1R dependent activation of extracellular ligand-regulated kinases (ERK). From a wide range of fatty acids studied, varying in chain length, saturation, and position of double bonds, eicosapentaenoic (EPA) and docosahexaenoic fatty acids (DHA) caused the highest ERK phosphorylation. Moreover, EPA potentiated the effect of parathyroid hormone (PTH(1–34)) in a superagonistic manner. EPA or DHA dependent ERK phosphorylation was inhibited by the PTH1R antagonist and by knockdown of PTH1R. Inhibition of PTH1R downstream signaling molecules, protein kinases A (PKA) and C (PKC), reduced EPA and DHA dependent ERK phosphorylation indicating that fatty acids predominantly activate G-protein pathway and not the β-arrestin pathway. Using picosecond time-resolved fluorescence microscopy and a genetically engineered PTH1R sensor (PTH-CC), we detected conformational responses to EPA similar to those caused by PTH(1–34). PTH1R antagonist blocked the EPA induced conformational response of the PTH-CC. Competitive binding studies using fluorescence anisotropy technique showed that EPA and DHA competitively bind to and alter the affinity of PTH1 receptor to PTH(1–34) leading to a superagonistic response. Finally, we showed that EPA stimulates protein kinase B (Akt) phosphorylation in a PTH1R-dependent manner and affects the osteoblast survival pathway, by inhibiting glucocorticoid-induced cell death. Our findings demonstrate for the first time that LCPUFAs, EPA and DHA, can activate PTH1R receptor at nanomolar concentrations and consequently provide a putative molecular mechanism for the action of fatty acids in bone. PMID:23300710

  5. Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids

    PubMed Central

    Lotrich, Francis E.; Sears, Barry; McNamara, Robert K.

    2013-01-01

    Objective Anger worsens in some patients during interferon-alpha (IFN-α) therapy. Elevated anger has also been associated with lower long-chain omega-3 (LCn-3) fatty acid levels. We examined whether fatty acids could influence vulnerability to anger during IFN-α exposure. Methods Plasma arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were determined prior to IFN-α therapy by mass spectroscopy. Repeated-measure analyses examined the relationship between AA/EPA+DHA and the subsequent development of labile anger and irritability in 82 subjects who prospectively completed the Anger, Irritability, and Assault Questionnaire (AIAQ) during the first eight weeks of IFN-α therapy. Results Prior to IFN-α therapy, AA/EPA+DHA did not correlate with either labile anger or irritability. Pre-treatment AA/EPA+DHA did correlate with the subsequent maximal increase in labile anger during IFN-α therapy (r=0.33; p=0.005). Over time, labile anger increased more in subjects with above median AA/EPA+DHA ratios (p<0.05). Of the 17 subjects ultimately requiring psychiatric intervention for anger, 14/17 had above-median AA/EPA+DHA ratios (p=0.009). There was also an interaction with the tumor necrosis factor-alpha (TNF-α) promoter polymorphism (A-308G), such that only those with both elevated AA/EPA+DHA and the A allele had increased labile anger (p=0.001). In an additional 18 subjects, we conversely observed that selective serotonin reuptake inhibitor treatment was associated with increased irritability during IFN-α therapy. Conclusion LCn-3 fatty acid status may influence anger development during exposure to elevated inflammatory cytokines, and may interact with genetic risk for increased brain TNF-α. LCn-3 supplements may be one strategy for minimizing this adverse side effect of IFN-α. PMID:24182638

  6. Microalgal biofactories: a promising approach towards sustainable omega-3 fatty acid production

    PubMed Central

    2012-01-01

    Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provide significant health benefits and this has led to an increased consumption as dietary supplements. Omega-3 fatty acids EPA and DHA are found in animals, transgenic plants, fungi and many microorganisms but are typically extracted from fatty fish, putting additional pressures on global fish stocks. As primary producers, many marine microalgae are rich in EPA (C20:5) and DHA (C22:6) and present a promising source of omega-3 fatty acids. Several heterotrophic microalgae have been used as biofactories for omega-3 fatty acids commercially, but a strong interest in autotrophic microalgae has emerged in recent years as microalgae are being developed as biofuel crops. This paper provides an overview of microalgal biotechnology and production platforms for the development of omega-3 fatty acids EPA and DHA. It refers to implications in current biotechnological uses of microalgae as aquaculture feed and future biofuel crops and explores potential applications of metabolic engineering and selective breeding to accumulate large amounts of omega-3 fatty acids in autotrophic microalgae. PMID:22830315

  7. Increase of eicosapentaenoic acid in thraustochytrids through thraustochytrid ubiquitin promoter-driven expression of a fatty acid {delta}5 desaturase gene.

    PubMed

    Kobayashi, Takumi; Sakaguchi, Keishi; Matsuda, Takanori; Abe, Eriko; Hama, Yoichiro; Hayashi, Masahiro; Honda, Daiske; Okita, Yuji; Sugimoto, Shinichi; Okino, Nozomu; Ito, Makoto

    2011-06-01

    Thraustochytrids, marine protists known to accumulate polyunsaturated fatty acids (PUFAs) in lipid droplets, are considered an alternative to fish oils as a source of PUFAs. The major fatty acids produced in thraustochytrids are palmitic acid (C(16:0)), n - 6 docosapentaenoic acid (DPA) (C(22:5)(n) (- 6)), and docosahexaenoic acid (DHA) (C(22:6)(n) (- 3)), with eicosapentaenoic acid (EPA) (C(20:5)(n) (- 3)) and arachidonic acid (AA) (C(20:4)(n) (- 6)) as minor constituents. We attempted here to alter the fatty acid composition of thraustochytrids through the expression of a fatty acid Δ5 desaturase gene driven by the thraustochytrid ubiquitin promoter. The gene was functionally expressed in Aurantiochytrium limacinum mh0186, increasing the amount of EPA converted from eicosatetraenoic acid (ETA) (C(20:4)(n) (- 3)) by the Δ5 desaturase. The levels of EPA and AA were also increased by 4.6- and 13.2-fold in the transgenic thraustochytrids compared to levels in the mock transfectants when ETA and dihomo-γ-linolenic acid (DGLA) (C(20:3)(n) (- 6)) were added to the culture at 0.1 mM. Interestingly, the amount of EPA in the transgenic thraustochytrids increased in proportion to the amount of ETA added to the culture up to 0.4 mM. The rates of conversion and accumulation of EPA were much higher in the thraustochytrids than in baker's yeasts when the desaturase gene was expressed with the respective promoters. This report describes for the first time the finding that an increase of EPA could be accomplished by introducing the Δ5 desaturase gene into thraustochytrids and indicates that molecular breeding of thraustochytrids is a promising strategy for generating beneficial PUFAs. PMID:21478316

  8. Increase of Eicosapentaenoic Acid in Thraustochytrids through Thraustochytrid Ubiquitin Promoter-Driven Expression of a Fatty Acid Δ5 Desaturase Gene▿†

    PubMed Central

    Kobayashi, Takumi; Sakaguchi, Keishi; Matsuda, Takanori; Abe, Eriko; Hama, Yoichiro; Hayashi, Masahiro; Honda, Daiske; Okita, Yuji; Sugimoto, Shinichi; Okino, Nozomu; Ito, Makoto

    2011-01-01

    Thraustochytrids, marine protists known to accumulate polyunsaturated fatty acids (PUFAs) in lipid droplets, are considered an alternative to fish oils as a source of PUFAs. The major fatty acids produced in thraustochytrids are palmitic acid (C16:0), n − 6 docosapentaenoic acid (DPA) (C22:5n − 6), and docosahexaenoic acid (DHA) (C22:6n − 3), with eicosapentaenoic acid (EPA) (C20:5n − 3) and arachidonic acid (AA) (C20:4n − 6) as minor constituents. We attempted here to alter the fatty acid composition of thraustochytrids through the expression of a fatty acid Δ5 desaturase gene driven by the thraustochytrid ubiquitin promoter. The gene was functionally expressed in Aurantiochytrium limacinum mh0186, increasing the amount of EPA converted from eicosatetraenoic acid (ETA) (C20:4n − 3) by the Δ5 desaturase. The levels of EPA and AA were also increased by 4.6- and 13.2-fold in the transgenic thraustochytrids compared to levels in the mock transfectants when ETA and dihomo-γ-linolenic acid (DGLA) (C20:3n − 6) were added to the culture at 0.1 mM. Interestingly, the amount of EPA in the transgenic thraustochytrids increased in proportion to the amount of ETA added to the culture up to 0.4 mM. The rates of conversion and accumulation of EPA were much higher in the thraustochytrids than in baker's yeasts when the desaturase gene was expressed with the respective promoters. This report describes for the first time the finding that an increase of EPA could be accomplished by introducing the Δ5 desaturase gene into thraustochytrids and indicates that molecular breeding of thraustochytrids is a promising strategy for generating beneficial PUFAs. PMID:21478316

  9. Quantitative Determination of Fatty Acids in Marine Fish and Shellfish from Warm Water of Straits of Malacca for Nutraceutical Purposes

    PubMed Central

    Abd Aziz, Nurnadia; Azlan, Azrina; Ismail, Amin; Mohd Alinafiah, Suryati; Razman, Muhammad Rizal

    2013-01-01

    This study was conducted to quantitatively determine the fatty acid contents of 20 species of marine fish and four species of shellfish from Straits of Malacca. Most samples contained fairly high amounts of polyunsaturated fatty acids (PUFAs), especially alpha-linolenic acid (ALA, C18:3 n3), eicosapentaenoic acid (EPA, C20:5 n3), and docosahexaenoic acid (DHA, C22:6 n3). Longtail shad, yellowstripe scad, and moonfish contained significantly higher (P < 0.05) amounts of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), respectively. Meanwhile, fringescale sardinella, malabar red snapper, black pomfret, Japanese threadfin bream, giant seaperch, and sixbar grouper showed considerably high content (537.2–944.1 mg/100g wet sample) of desirable omega-3 fatty acids. The polyunsaturated-fatty-acids/saturated-fatty-acids (P/S) ratios for most samples were higher than that of Menhaden oil (P/S = 0.58), a recommended PUFA supplement which may help to lower blood pressure. Yellowstripe scad (highest DHA, ω − 3/ω − 6 = 6.4, P/S = 1.7), moonfish (highest ALA, ω − 3/ω − 6 = 1.9, P/S = 1.0), and longtail shad (highest EPA, ω − 3/ω − 6 = 0.8, P/S = 0.4) were the samples with an outstandingly desirable overall composition of fatty acids. Overall, the marine fish and shellfish from the area contained good composition of fatty acids which offer health benefits and may be used for nutraceutical purposes in the future. PMID:23509703

  10. Quantitative determination of fatty acids in marine fish and shellfish from warm water of Straits of Malacca for nutraceutical purposes.

    PubMed

    Abd Aziz, Nurnadia; Azlan, Azrina; Ismail, Amin; Mohd Alinafiah, Suryati; Razman, Muhammad Rizal

    2013-01-01

    This study was conducted to quantitatively determine the fatty acid contents of 20 species of marine fish and four species of shellfish from Straits of Malacca. Most samples contained fairly high amounts of polyunsaturated fatty acids (PUFAs), especially alpha-linolenic acid (ALA, C18:3 n3), eicosapentaenoic acid (EPA, C20:5 n3), and docosahexaenoic acid (DHA, C22:6 n3). Longtail shad, yellowstripe scad, and moonfish contained significantly higher (P < 0.05) amounts of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), respectively. Meanwhile, fringescale sardinella, malabar red snapper, black pomfret, Japanese threadfin bream, giant seaperch, and sixbar grouper showed considerably high content (537.2-944.1 mg/100 g wet sample) of desirable omega-3 fatty acids. The polyunsaturated-fatty-acids/saturated-fatty-acids (P/S) ratios for most samples were higher than that of Menhaden oil (P/S = 0.58), a recommended PUFA supplement which may help to lower blood pressure. Yellowstripe scad (highest DHA, ω - 3/ω - 6 = 6.4, P/S = 1.7), moonfish (highest ALA, ω - 3/ω - 6 = 1.9, P/S = 1.0), and longtail shad (highest EPA, ω - 3/ω - 6 = 0.8, P/S = 0.4) were the samples with an outstandingly desirable overall composition of fatty acids. Overall, the marine fish and shellfish from the area contained good composition of fatty acids which offer health benefits and may be used for nutraceutical purposes in the future. PMID:23509703

  11. Long-Chain Omega-3 Polyunsaturated Fatty Acids Have Developmental Effects on the Crop Pest, the Cabbage White Butterfly Pieris rapae

    PubMed Central

    Hixson, Stefanie M.; Shukla, Kruti; Campbell, Lesley G.; Hallett, Rebecca H.; Smith, Sandy M.; Packer, Laurence; Arts, Michael T.

    2016-01-01

    Nutritional enhancement of crops using genetic engineering can potentially affect herbivorous pests. Recently, oilseed crops have been genetically engineered to produce the long-chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at levels similar to that found in fish oil; to provide a more sustainable source of these compounds than is currently available from wild fish capture. We examined some of the growth and development impacts of adding EPA and DHA to an artificial diet of Pieris rapae, a common pest of Brassicaceae plants. We replaced 1% canola oil with EPA: DHA (11:7 ratio) in larval diets, and examined morphological traits and growth of larvae and ensuing adults across 5 dietary treatments. Diets containing increasing amounts of EPA and DHA did not affect developmental phenology, larval or pupal weight, food consumption, nor larval mortality. However, the addition of EPA and DHA in larval diets resulted in progressively heavier adults (F 4, 108 = 6.78; p = 0.011), with smaller wings (p < 0.05) and a higher frequency of wing deformities (R = 0.988; p = 0.001). We conclude that the presence of EPA and DHA in diets of larval P. rapae may alter adult mass and wing morphology; therefore, further research on the environmental impacts of EPA and DHA production on terrestrial biota is advisable. PMID:27011315

  12. Long-Chain Omega-3 Polyunsaturated Fatty Acids Have Developmental Effects on the Crop Pest, the Cabbage White Butterfly Pieris rapae.

    PubMed

    Hixson, Stefanie M; Shukla, Kruti; Campbell, Lesley G; Hallett, Rebecca H; Smith, Sandy M; Packer, Laurence; Arts, Michael T

    2016-01-01

    Nutritional enhancement of crops using genetic engineering can potentially affect herbivorous pests. Recently, oilseed crops have been genetically engineered to produce the long-chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at levels similar to that found in fish oil; to provide a more sustainable source of these compounds than is currently available from wild fish capture. We examined some of the growth and development impacts of adding EPA and DHA to an artificial diet of Pieris rapae, a common pest of Brassicaceae plants. We replaced 1% canola oil with EPA: DHA (11:7 ratio) in larval diets, and examined morphological traits and growth of larvae and ensuing adults across 5 dietary treatments. Diets containing increasing amounts of EPA and DHA did not affect developmental phenology, larval or pupal weight, food consumption, nor larval mortality. However, the addition of EPA and DHA in larval diets resulted in progressively heavier adults (F 4, 108 = 6.78; p = 0.011), with smaller wings (p < 0.05) and a higher frequency of wing deformities (R = 0.988; p = 0.001). We conclude that the presence of EPA and DHA in diets of larval P. rapae may alter adult mass and wing morphology; therefore, further research on the environmental impacts of EPA and DHA production on terrestrial biota is advisable. PMID:27011315

  13. Dietary omega-3 fatty acids for women.

    PubMed

    Bourre, Jean-Marie

    2007-01-01

    This review details the specific needs of women for omega-3 fatty acids, including alpha linoleic acid (ALA) and the very long chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid (dietary or in capsules) ensures that a woman's adipose tissue contains a reserve of these fatty acids for the developing fetus and the breast-fed newborn infant. This ensures the optimal cerebral and cognitive development of the infant. The presence of large quantities of EPA and DHA in the diet slightly lengthens pregnancy, and improves its quality. Human milk contains both ALA and DHA, unlike that of other mammals. Conditions such as diabetes can alter the fatty acid profile of mother's milk, while certain diets, like those of vegetarians, vegans, or even macrobiotic diets, can have the same effect, if they do not include seafood. ALA, DHA and EPA, are important for preventing ischemic cardiovascular disease in women of all ages. Omega-3 fatty acids can help to prevent the development of certain cancers, particularly those of the breast and colon, and possibly of the uterus and the skin, and are likely to reduce the risk of postpartum depression, manic-depressive psychosis, dementias (Alzheimer's disease and others), hypertension, toxemia, diabetes and, to a certain extend, age-related macular degeneration. Omega-3 fatty acids could play a positive role in the prevention of menstrual syndrome and postmenopausal hot flushes. The normal western diet contains little ALA (less than 50% of the RDA). The only adequate sources are rapeseed oil (canola), walnuts and so-called "omega-3" eggs (similar to wild-type or Cretan eggs). The amounts of EPA and DHA in the diet vary greatly from person to person. The only good sources are fish and seafood, together with "omega-3" eggs. PMID:17254747

  14. Whole-body DHA synthesis-secretion kinetics from plasma eicosapentaenoic acid and alpha-linolenic acid in the free-living rat.

    PubMed

    Metherel, Adam H; Domenichiello, Anthony F; Kitson, Alex P; Hopperton, Kathryn E; Bazinet, Richard P

    2016-09-01

    Whole body docosahexaenoic acid (DHA, 22:6n-3) synthesis from α-linolenic acid (ALA, 18:3n-3) is considered to be very low, however, the daily synthesis-secretion of DHA may be sufficient to supply the adult brain. The current study aims to assess whether whole body DHA synthesis-secretion kinetics are different when comparing plasma ALA versus eicosapentaenoic acid (EPA, 20:5n-3) as the precursor. Male Long Evans rats (n=6) were fed a 2% ALA in total fat diet for eight weeks, followed by surgery to implant a catheter into each of the jugular vein and carotid artery and 3h of steady-state infusion with a known amount of (2)H-ALA and (13)C-eicosapentaenoic acid (EPA, 20:5n3). Blood samples were collected at thirty-minute intervals and plasma enrichment of (2)H- and (13)C EPA, n-3 docosapentaenoic acid (DPAn-3, 22:5n-3) and DHA were determined for assessment of synthesis-secretion kinetic parameters. Results indicate a 13-fold higher synthesis-secretion coefficient for DHA from EPA as compared to ALA. However, after correcting for the 6.6 fold higher endogenous plasma ALA concentration, no significant differences in daily synthesis-secretion (nmol/day) of DHA (97.6±28.2 and 172±62), DPAn-3 (853±279 and 1139±484) or EPA (1587±592 and 1628±366) were observed from plasma unesterified ALA and EPA sources, respectively. These results suggest that typical diets which are significantly higher in ALA compared to EPA yield similar daily DHA synthesis-secretion despite a significantly higher synthesis-secretion coefficient from EPA. PMID:27263420

  15. Structural Basis of Fatty Acid Substrate Binding to Cyclooxygenase-2*

    PubMed Central

    Vecchio, Alex J.; Simmons, Danielle M.; Malkowski, Michael G.

    2010-01-01

    The cyclooxygenases (COX-1 and COX-2) are membrane-associated heme-containing homodimers that generate prostaglandin H2 from arachidonic acid (AA). Although AA is the preferred substrate, other fatty acids are oxygenated by these enzymes with varying efficiencies. We determined the crystal structures of AA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) bound to Co3+-protoporphyrin IX-reconstituted murine COX-2 to 2.1, 2.4, and 2.65 Å, respectively. AA, EPA, and docosahexaenoic acid bind in different conformations in each monomer constituting the homodimer in their respective structures such that one monomer exhibits nonproductive binding and the other productive binding of the substrate in the cyclooxygenase channel. The interactions identified between protein and substrate when bound to COX-1 are conserved in our COX-2 structures, with the only notable difference being the lack of interaction of the carboxylate of AA and EPA with the side chain of Arg-120. Leu-531 exhibits a different side chain conformation when the nonproductive and productive binding modes of AA are compared. Unlike COX-1, mutating this residue to Ala, Phe, Pro, or Thr did not result in a significant loss of activity or substrate binding affinity. Determination of the L531F:AA crystal structure resulted in AA binding in the same global conformation in each monomer. We speculate that the mobility of the Leu-531 side chain increases the volume available at the opening of the cyclooxygenase channel and contributes to the observed ability of COX-2 to oxygenate a broad spectrum of fatty acid and fatty ester substrates. PMID:20463020

  16. Update on marine omega-3 fatty acids: management of dyslipidemia and current omega-3 treatment options.

    PubMed

    Weintraub, Howard

    2013-10-01

    Low-density lipoprotein cholesterol (LDL-C) is currently the primary target in the management of dyslipidemia, and statins are first-line pharmacologic interventions. Adjunct therapy such as niacins, fibrates, bile acid sequestrants, or cholesterol absorption inhibitors may be considered to help reduce cardiovascular risk. This review discusses the need for alternative adjunct treatment options and the potential place for omega-3 fatty acids as such. The cardiovascular benefits of fish consumption are attributed to the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and a variety of omega-3 fatty acid products are available with varied amounts of EPA and DHA. The product types include prescription drugs, food supplements, and medical foods sourced from fish, krill, algal and plant oils or purified from these oils. Two prescription omega-3 fatty acids are currently available, omega-3 fatty acid ethyl esters (contains both EPA and DHA ethyl esters), and icosapent ethyl (IPE; contains high-purity EPA ethyl ester). A pharmaceutical containing free fatty acid forms of omega-3 is currently in development. Omega-3 fatty acid formulations containing EPA and DHA have been shown to increase LDL-C levels while IPE has been shown to lower triglyceride levels without raising LDL-C levels, alone or in combination with statin therapy. In addition, recent studies have not been able to demonstrate reduced cardiovascular risk following treatment with fibrates, niacins, cholesterol absorption inhibitors, or omega-3 fatty acid formulations containing both EPA and DHA in statin-treated patients; thus, there remains a need for further cardiovascular outcomes studies for adjunct therapy. PMID:24075771

  17. Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop.

    PubMed

    Ruiz-Lopez, Noemi; Haslam, Richard P; Napier, Johnathan A; Sayanova, Olga

    2014-01-01

    Omega-3 (also called n-3) long-chain polyunsaturated fatty acids (≥C20; LC-PUFAs) are of considerable interest, based on clear evidence of dietary health benefits and the concurrent decline of global sources (fish oils). Generating alternative transgenic plant sources of omega-3 LC-PUFAs, i.e. eicosapentaenoic acid (20:5 n-3, EPA) and docosahexaenoic acid (22:6 n-3, DHA) has previously proved problematic. Here we describe a set of heterologous genes capable of efficiently directing synthesis of these fatty acids in the seed oil of the crop Camelina sativa, while simultaneously avoiding accumulation of undesirable intermediate fatty acids. We describe two iterations: RRes_EPA in which seeds contain EPA levels of up to 31% (mean 24%), and RRes_DHA, in which seeds accumulate up to 12% EPA and 14% DHA (mean 11% EPA and 8% DHA). These omega-3 LC-PUFA levels are equivalent to those in fish oils, and represent a sustainable, terrestrial source of these fatty acids. We also describe the distribution of these non-native fatty acids within C. sativa seed lipids, and consider these data in the context of our current understanding of acyl exchange during seed oil synthesis. PMID:24308505

  18. Sex Differences in the Association between the Eicosapentaenoic Acid/Arachidonic Acid Ratio and the Visceral Fat Area among Patients with Type 2 Diabetes.

    PubMed

    Nakanishi, Shuhei; Nagano, Chihiro; Miyahara, Mitsue; Sawano, Fumio

    2016-01-01

    Objective To examine the serum levels of eicosapentaenoic acid (EPA) and the ratios of docosahexaenoic acid (DHA), and the EPA/arachidonic acid (AA) and DHA/AA and to clarify their association with the areas of subcutaneous and visceral fat separately by sex among patients with type 2 diabetes. Methods The study participants included 118 men and 96 women who were hospitalized to receive treatment for type 2 diabetes. We examined the serum levels of EPA and DHA and the ratios of EPA/AA and DHA/AA, and analyzed their association with the total fat area (TFA), subcutaneous fat area (SFA), and visceral fat area (VFA), as measured by computed tomography. Results The mean age of the study participants was 62.6±13.6 years. The mean HbA1c level was 9.37±2.27%. Among men, a multivariate regression analysis adjusted for age and BMI, revealed a significant negative association between VFA and the EPA/AA ratio. When the multivariate regression analysis was adjusted for age, BMI, and HbA1c level, VFA was still found to be significantly negatively associated with the EPA/AA ratio. Although a crude analysis revealed a significant negative association between SFA and the EPA/AA ratio in women, no association was observed in multivariate regression analyses. Conclusion These results suggest the possibility that EPA inhibits the accumulation of visceral fat in men. Furthermore, there appear to be marked differences in the relationships between EPA and DHA and visceral fat accumulation. PMID:27181531

  19. Neutrophil fatty acid composition: effect of a single session of exercise and glutamine supplementation.

    PubMed

    Lagranha, C J; Alba-Loureiro, T C; Martins, E F; Pithon-Curi, T C; Curi, R

    2008-06-01

    The fatty acid composition of immune cells appears to contribute to variations of cell function. The independent and combined effects of a single session of exercise (SSE) and glutamine supplementation (GS) on neutrophil fatty acid composition were investigated. Compared to control (no treatment given--i.e. neither SSE or GS), single session of exercise decreased myristic, palmitic and eicosapentaenoic (EPA) acids, and increased lauric, oleic, linoleic, arachidonic (AA) and docosahexaenoic (DHA) acids whereas glutamine supplementation combined with SSE (GS+SSE) increased oleic acid. Polyunsaturated/saturated fatty acid ratio and Unsaturation index were higher in neutrophils from the SSE and GS groups as compared with control. These findings support the proposition that SSE and GS may modulate neutrophil function through alterations in fatty acid composition. PMID:17721676

  20. EPA`s integrated nitrogen oxides strategy

    SciTech Connect

    Grano, D.H.

    1997-12-31

    Nitrogen oxides (NO{sub x}) are highly reactive and play a major role in the formation of various gases and particles in the atmosphere which lead to harmful effects on human health and welfare. This paper briefly describes the multiple impacts on human health and welfare that result from emissions of NO{sub x} and describes EPA`s strategy to integrate NO{sub x} reductions from various mobile and stationary sources in a balanced manner to achieve environmental benefits. Based on modeling information, it is clear that substantial reductions in NO{sub x} emissions over large geographic areas are needed if many densely populated areas of the nation are to attain the national ambient air quality standard for ozone. In addition to attainment of the health standard for ozone, the reduction of NO{sub x} emissions will also likely improve the nation`s environment by reducing adverse impacts of acid deposition, eutrophication of waterbodies, global warming, nitrogen dioxide, particulate matter, stratospheric ozone depletion, toxics, and visibility.

  1. Fish oil omega-3 fatty acids and cardio-metabolic health, alone or with statins.

    PubMed

    Minihane, Anne Marie

    2013-05-01

    The impact of the fish-derived omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease (CVD) and type 2 diabetes incidence and risk has been widely investigated. Although the balance of evidence suggests substantial benefits with respect to CVD mortality, there is little evidence for an impact of these fatty acids on insulin sensitivity and diabetes incidence, despite very promising data from animal models. The focus here will be the plasma lipid modulatory effects of EPA and DHA and will include an exploration of the potential and demonstrated complementarity between statins and EPA/DHA on overall CVD risk and the plasma cholesterol and triglyceride profile. Although there is some justification for greater general population and patient EPA+DHA intakes, an often overlooked major obstacle is that global fish stocks are limited and insufficient to meet demands. The potential of emerging 'non-fish foods' to provide affordable and sustainable sources of EPA+DHA will also be briefly discussed. PMID:23403872

  2. Eicosapentaenoic acid inhibits intestinal β-carotene absorption by downregulation of lipid transporter expression via PPAR-α dependent mechanism.

    PubMed

    Mashurabad, Purna Chandra; Kondaiah, Palsa; Palika, Ravindranadh; Ghosh, Sudip; Nair, Madhavan K; Raghu, Pullakhandam

    2016-01-15

    The involvement of lipid transporters, the scavenger receptor class B, type I (SR-BI) and Niemann-Pick type C1 Like 1 protein (NPC1L1) in carotenoid absorption is demonstrated in intestinal cells and animal models. Dietary ω-3 fatty acids are known to possess antilipidemic properties, which could be mediated by activation of PPAR family transcription factors. The present study was conducted to determine the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on intestinal β-carotene absorption. β-carotene uptake in Caco-2/TC7 cells was inhibited by EPA (p < 0.01) and PPARα agonist (P < 0.01), but not by DHA, PPARγ or PPARδ agonists. Despite unaltered β-carotene uptake, both DHA and PPARδ agonists inhibited the NPC1L1 expression. Further, EPA also induced the expression of carnitine palmitoyl transferase 1A (CPT1A) expression, a PPARα target gene. Interestingly, EPA induced inhibition of β-carotene uptake and SR B1 expression were abrogated by specific PPARα antagonist, but not by PPARδ antagonist. EPA and PPARα agonist also inhibited the basolateral secretion of β-carotene from Caco-2 cells grown on permeable supports. These results suggest that EPA inhibits intestinal β-carotene absorption by down regulation of SR B1 expression via PPARα dependent mechanism and provide an evidence for dietary modulation of intestinal β-carotene absorption. PMID:26577021

  3. Inhibition of tumour-induced lipolysis in vitro and cachexia and tumour growth in vivo by eicosapentaenoic acid.

    PubMed

    Tisdale, M J; Beck, S A

    1991-01-01

    Stimulation of lipolysis in murine adipocytes in response to a lipid-mobilizing factor produced by a cachexia-inducing murine adenocarcinoma was inhibited by eicosapentaenoic acid (EPA) with a Ki value of 104 microM. The inhibitory effect was strictly structurally specific, since other related fatty acids of both the (n-3) and (n-6) series were ineffective as inhibitors of the lipolytic process. Induction of lipolysis by both salbutamol and ACTH was also inhibited by EPA, suggesting that the effect is exerted on a step central to the process of lipolysis. Lipolysis induced with the tumour lipid-mobilizing factor was associated with a prolonged elevation of the intracellular level of cyclic AMP in adipocytes, in contrast with ACTH and salbutamol. The elevation of adipocyte cyclic AMP in response to the tumour lipid-mobilizing factor and lipolytic hormones was inhibited by EPA. In vivo, administration of pure EPA to weight losing mice bearing the MAC16 adenocarcinoma completely prevented weight loss and tumour growth rate. In contrast both the other (n-3) fatty acid present in fish oil, docosahexaenoic acid (DHA), and linoleic acid were ineffective in inhibiting weight loss or the growth of the MAC16 tumour. This suggests that inhibition of tumour lipolytic activity accounts for the anticachectic effect of EPA, and that a correlation may exist between the inhibition of cachexia and the inhibition of tumour growth. PMID:1846070

  4. Marine-derived omega-3 fatty acids: fishing for clues for cancer prevention.

    PubMed

    Fabian, Carol J; Kimler, Bruce F

    2013-01-01

    Omega-3 fatty acids (FA) are polyunsaturated essential FA with anti-inflammatory properties. The most potent are the marine-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which counteract the pro-inflammatory omega-6 FA. Americans take in an average of only 100 mg of EPA plus DHA per day resulting in a low omega-3:omega-6 intake ratio of 1:10 favoring inflammation. Cohort and/or case control studies suggest EPA and DHA are promising for breast, colon, and prostate cancer risk reduction. Mechanistic studies largely in preclinical models suggest EPA and DHA reduce synthesis of prostaglandin E2 and other inflammatory cytokines, decrease aromatase activity and proliferation, promote differentiation and apoptosis, and enhance insulin sensitivity. Animal models using 7% to 20% omega-3 added to chow are promising; however, this amount of omega-3 in a diet is unlikely to be acceptable to humans. The optimal EPA:DHA ratio or the lowest effective dose of EPA and DHA for cancer prevention is unclear, but it is likely to be more than 600 mg/day, which is six times the average American intake. Most phase II prevention trials use 1 to 3.3 g of EPA and DHA, which is safe and well tolerated. Two grams of EPA was associated with fewer polyps in individuals with familial adenomatous polyposis in a randomized, placebo-controlled trial. Identification of serum risk biomarkers modulated by EPA and DHA in healthy humans has remained elusive, but phase II prevention trials with tissue obtained for risk and response biomarkers are ongoing. PMID:23714467

  5. Deficit in Prepulse Inhibition in Mice Caused by Dietary n-3 Fatty Acid Deficiency

    PubMed Central

    Fedorova, Irina; Alvheim, Anita R.; Hussein, Nahed; Salem, Norman

    2010-01-01

    Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may be biosynthesized from a precursor α-linolenic acid (LNA) or obtained preformed in the diet. Dams were fed four diets with different levels of the various n-3 fatty acids during pregnancy and lactation, and their offspring were weaned to the same diets: “n-3 Deficient”, containing (as % total fatty acids) 0.07% of LNA; “Low LNA” (0.4%); “High LNA” (4.8%); and a “DHA+EPA” diet, containing 0.4% of LNA, 2% DHA and 2% EPA. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response in C57Bl6 mice. The n-3 Deficient and Low LNA diets caused a substantial deficit in PPI compared to the DHA+EPA diet, whereas the High LNA diet induced a less pronounced, but significant reduction of PPI. These are the first data that demonstrate a deficit in sensorimotor gating in rodents caused by an inadequate amount of the n-3 fatty acids in the diet. Our results differentiate the effects of a High LNA diet from one with added EPA and DHA even though the difference in brain DHA content is only 12% between these dietary groups. PMID:20001105

  6. ADIPIC ACID-ENHANCED LIME AND LIMESTONE TESTING AT THE EPA ALKALI SCRUBBING TEST FACILITY. VOLUME 1

    EPA Science Inventory

    The report gives results of an advanced test program on a prototype lime/limestone wet-scrubbing test facility for removing SO2 and particulates from coal-fired boiler flue gases. Major effort during the tests was concentrated on evaluating adipic acid as an additive for enhancin...

  7. ADIPIC ACID-ENHANCED LIME AND LIMESTONE TESTING AT THE EPA ALKALI SCRUBBING TEST FACILITY. VOLUME 2: APPENDICES

    EPA Science Inventory

    The report gives results of an advanced test program on a prototype lime/limestone wet-scrubbing test facility for removing SO2 and particulates from coal-fired boiler flue gases. Major effort during the tests was concentrated on evaluating adipic acid as an additive for enhancin...

  8. Analysis of fatty acid composition of sea cucumber Apostichopus japonicus using multivariate statistics

    NASA Astrophysics Data System (ADS)

    Xu, Qinzeng; Gao, Fei; Xu, Qiang; Yang, Hongsheng

    2014-11-01

    Fatty acids (FAs) provide energy and also can be used to trace trophic relationships among organisms. Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months. We examined fatty acid profiles in aestivated and non-aestivated A. japonicus using multivariate analyses (PERMANOVA, MDS, ANOSIM, and SIMPER). The results indicate that the fatty acid profiles of aestivated and non-aestivated sea cucumbers differed significantly. The FAs that were produced by bacteria and brown kelp contributed the most to the differences in the fatty acid composition of aestivated and nonaestivated sea cucumbers. Aestivated sea cucumbers may synthesize FAs from heterotrophic bacteria during early aestivation, and long chain FAs such as eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) that produced from intestinal degradation, are digested during deep aestivation. Specific changes in the fatty acid composition of A. japonicus during aestivation needs more detailed study in the future.

  9. Oxidative stability and ignition quality of algae derived methyl esters containing varying levels of methyl eicosapentaenoate and methyl docosahexaenoate

    NASA Astrophysics Data System (ADS)

    Bucy, Harrison

    Microalgae is currently receiving strong consideration as a potential biofuel feedstock to help meet the advanced biofuels mandate of the 2007 Energy Independence and Security Act because of its theoretically high yield (gallons/acre/year) in comparison to current terrestrial feedstocks. Additionally, microalgae also do not compete with food and can be cultivated with wastewater on non-arable land. Microalgae lipids can be converted into a variety of biofuels including fatty acid methyl esters (e.g. FAME biodiesel), renewable diesel, renewable gasoline, or jet fuel. For microalgae derived FAME, the fuel properties will be directly related to the fatty acid composition of the lipids produced by the given microalgae strain. Several microalgae species under consideration for wide scale cultivation, such as Nannochloropsis, produce lipids with fatty acid compositions containing substantially higher quantities of long chainpolyunsaturated fatty acids (LC-PUFA) in comparison to terrestrial feedstocks. It is expected that increased levels of LC-PUFA will be problematic in terms of meeting all of the current ASTM specifications for biodiesel. For example, it is known that oxidative stability and cetane number decrease with increasing levels of LC-PUFA. However, these same LC-PUFA fatty acids, such as eicosapentaenoic acid (EPA: C20:5) and docosahexaenoic acid (DHA: C22:6) are known to have high nutritional value thereby making separation of these compounds economically attractive. Given the uncertainty in the future value of these LC-PUFA compounds and the economic viability of the separation process, the goal of this study was to examine the oxidative stability and ignition quality of algae-based FAME with varying levels of EPA and DHA removal. Oxidative stability tests were conducted at a temperature of 110°C and airflow of 10 L/h using a Metrohm 743 Rancimat with automatic induction period determination following the EN 14112 Method from the ASTM D6751 and EN 14214

  10. Regulation of inflammatory and lipid metabolism genes by eicosapentaenoic acid-rich oil[S

    PubMed Central

    Gillies, Peter J.; Bhatia, Sujata K.; Belcher, Leigh A; Hannon, Daniel B.; Thompson, Jerry T.; Vanden Heuvel, John P.

    2012-01-01

    Omega-3-PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are associated with prevention of various aspects of metabolic syndrome. In the present studies, the effects of oil rich in EPA on gene expression and activation of nuclear receptors was examined and compared with other ω3-PUFAs. The EPA-rich oil (EO) altered the expression of FA metabolism genes in THP-1 cells, including stearoyl CoA desaturase (SCD) and FA desaturase-1 and -2 (FASDS1 and -2). Other ω3-PUFAs resulted in a similar gene expression response for a subset of genes involved in lipid metabolism and inflammation. In reporter assays, EO activated human peroxisome proliferator-activated receptor α (PPARα) and PPARβ/γ with minimal effects on PPARγ, liver X receptor, retinoid X receptor, farnesoid X receptor, and retinoid acid receptor γ (RARγ); these effects were similar to that observed for purified EPA. When serum from a 6 week clinical intervention with dietary supplements containing olive oil (control), DHA, or two levels of EPA were applied to THP-1 cells, the expression of SCD and FADS2 decreased in the cells treated with serum from the ω3-PUFA-supplemented individuals. Taken together, these studies indicate regulation of gene expression by EO that is consistent with treating aspects of dyslipidemia and inflammation. PMID:22556214

  11. The Effect of Marine Derived n-3 Fatty Acids on Adipose Tissue Metabolism and Function

    PubMed Central

    Todorčević, Marijana; Hodson, Leanne

    2015-01-01

    Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity. PMID:26729182

  12. Incorportation of Ethyl Esters of EPA and DHA in Soybean Lecithin Using Rhizomucor miehei Lipase: Effect of Additives and Solvent-Free Conditions.

    PubMed

    Marsaoui, Nabil; Naghmouchi, Karim; Baah, John; Raies, Aly; Laplante, Serge

    2015-06-01

    The transesterification of soybean lecithin with ethyl esters of polyunsaturated fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) using immobilized lipase from Rhizomucor miehei was tested in the presence or absence of organic solvent (hexane) and additives (urea with Ca(2+) or Mg(2+)). The reaction was carried out at a water concentration of 4 % and ethyl ester to phospholipid mass ratio of 3:1. After 24 h of reaction without solvent or additive, fatty acid incorporation reached 29.1 % and thereafter increased only slightly. After 48 h, incorporation was highest in the presence of Mg(2+), urea, and solvent. After 72 h, it was highest with Mg(2+) and urea in the presence or absence of solvent (56.8 and 45.7 %, respectively). Incorporation of EPA and DHA was thus initially fast without solvent and additive, but was increased after prolonged reaction in the presence of Mg(2+) and urea with or without solvent. These results are innovative and promising since they show that immobilized Rhizomucor miehei lipase has potential as a biocatalyst for interesterification reactions without solvent. PMID:25894950

  13. Vascular composition data supporting the role of N-3 polyunsaturated fatty acids in the prevention of cardiovascular disease events

    PubMed Central

    Ohwada, Takayuki; Yokokawa, Tetsuro; Kanno, Yuki; Hotsuki, Yu; Sakamoto, Takayuki; Watanabe, Kenichi; Nakazato, Kazuhiko; Takeishi, Yasuchika

    2016-01-01

    N-3 polyunsaturated fatty acids (PUFAs) are thought to have protective effects against cardiovascular disease. Here, we report the relationship between serum PUFA concentrations and plaque composition, as evaluated by virtual histology-intravascular ultrasound (VH-IVUS). Consecutive patients (n=61) who underwent percutaneous coronary intervention (PCI) were pre-operatively examined using VH-IVUS to assess the composition of culprit plaques. Gray-scale IVUS and VH-IVUS data of fibrous, fibro-fatty, necrotic core, and dense calcium regions of plaques were estimated at the minimal luminal area sites of culprit lesions. Serum levels of high-sensitivity C-reactive protein (hsCRP) and PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA), were compared between patients with (ACS, n=27) and without acute coronary syndrome (non-ACS, n=34) before PCI. Multiple logistic regression analysis of the data showed that EPA/AA under the median was more highly associated with ACS than hsCRP over the median. In addition, EPA/AA was negatively correlated with the percentage of fibrous plaque regions and EPA/AA and DHA/AA were positively correlated with the percentage of dense calcium regions in plaques. Furthermore, the correlation index of EPA/AA was the most highly (R=0.513) correlated with the percentage of dense calcium regions in plaques. PMID:27222841

  14. Vascular composition data supporting the role of N-3 polyunsaturated fatty acids in the prevention of cardiovascular disease events.

    PubMed

    Ohwada, Takayuki; Yokokawa, Tetsuro; Kanno, Yuki; Hotsuki, Yu; Sakamoto, Takayuki; Watanabe, Kenichi; Nakazato, Kazuhiko; Takeishi, Yasuchika

    2016-06-01

    N-3 polyunsaturated fatty acids (PUFAs) are thought to have protective effects against cardiovascular disease. Here, we report the relationship between serum PUFA concentrations and plaque composition, as evaluated by virtual histology-intravascular ultrasound (VH-IVUS). Consecutive patients (n=61) who underwent percutaneous coronary intervention (PCI) were pre-operatively examined using VH-IVUS to assess the composition of culprit plaques. Gray-scale IVUS and VH-IVUS data of fibrous, fibro-fatty, necrotic core, and dense calcium regions of plaques were estimated at the minimal luminal area sites of culprit lesions. Serum levels of high-sensitivity C-reactive protein (hsCRP) and PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA), were compared between patients with (ACS, n=27) and without acute coronary syndrome (non-ACS, n=34) before PCI. Multiple logistic regression analysis of the data showed that EPA/AA under the median was more highly associated with ACS than hsCRP over the median. In addition, EPA/AA was negatively correlated with the percentage of fibrous plaque regions and EPA/AA and DHA/AA were positively correlated with the percentage of dense calcium regions in plaques. Furthermore, the correlation index of EPA/AA was the most highly (R=0.513) correlated with the percentage of dense calcium regions in plaques. PMID:27222841

  15. A Transgenic Camelina sativa Seed Oil Effectively Replaces Fish Oil as a Dietary Source of Eicosapentaenoic Acid in Mice123

    PubMed Central

    Tejera, Noemi; Vauzour, David; Betancor, Monica B; Sayanova, Olga; Usher, Sarah; Cochard, Marianne; Rigby, Neil; Ruiz-Lopez, Noemi; Menoyo, David; Tocher, Douglas R; Napier, Johnathan A; Minihane, Anne Marie

    2016-01-01

    Background: Fish currently supplies only 40% of the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) required to allow all individuals globally to meet the minimum intake recommendation of 500 mg/d. Therefore, alternative sustainable sources are needed. Objective: The main objective was to investigate the ability of genetically engineered Camelina sativa (20% EPA) oil (CO) to enrich tissue EPA and DHA relative to an EPA-rich fish oil (FO) in mammals. Methods: Six-week-old male C57BL/6J mice were fed for 10 wk either a palm oil–containing control (C) diet or diets supplemented with EPA-CO or FO, with the C, low-EPA CO (COL), high-EPA CO (COH), low-EPA FO (FOL), and high-EPA FO (FOH) diets providing 0, 0.4, 3.4, 0.3, and 2.9 g EPA/kg diet, respectively. Liver, muscle, and brain were collected for fatty acid analysis, and blood glucose and serum lipids were quantified. The expression of selected hepatic genes involved in EPA and DHA biosynthesis and in modulating their cellular impact was determined. Results: The oils were well tolerated, with significantly greater weight gain in the COH and FOH groups relative to the C group (P < 0.001). Significantly lower (36–38%) blood glucose concentrations were evident in the FOH and COH mice relative to C mice (P < 0.01). Hepatic EPA concentrations were higher in all EPA groups relative to the C group (P < 0.001), with concentrations of 0.0, 0.4, 2.9, 0.2, and 3.6 g/100 g liver total lipids in the C, COL, COH, FOL, and FOH groups, respectively. Comparable dose-independent enrichments of liver DHA were observed in mice fed CO and FO diets (P < 0.001). Relative to the C group, lower fatty acid desaturase 1 (Fads1) expression (P < 0.005) was observed in the COH and FOH groups. Higher fatty acid desaturase 2 (Fads2), peroxisome proliferator–activated receptor α (Ppara), and peroxisome proliferator–activated receptor γ (Pparg) (P < 0.005) expressions were induced by CO. No impact of treatment on liver X receptor

  16. Effect of polyunsaturated fatty acids on drug-sensitive and resistant tumor cells in vitro

    PubMed Central

    2011-01-01

    Previous studies showed that γ-linolenic acid (GLA, 18: 3 ω-6), arachidonic acid (AA, 20:4 ω -6), eicosapentaenoic acid (EPA, 20: 5 ω -3) and docosahexaenoic acid (DHA, 22:6 ω -3) have selective tumoricidal action. In the present study, it was observed that dihomo-gamma-linolenic acid (DGLA) and AA, EPA and DHA have cytotoxic action on both vincristine-sensitive (KB-3-1) and resistant (KB-ChR-8-5) cancer cells in vitro that appeared to be a free-radical dependent process but not due to the formation of prostaglandins, leukotrienes and thromboxanes. Uptake of vincristine and fatty acids was higher while their efflux was lower in KB-3-1 cells compared with KB-ChR-8-5 cells, suggesting that drug resistant cells have an effective efflux pump. GLA, DGLA, AA, EPA and DHA enhanced the uptake and decreased efflux in both drug-sensitive and drug-resistant cells and augmented the susceptibility of tumor cells especially, of drug-resistant cells to the cytotoxic action of vincristine. These results suggest that certain polyunsaturated fatty acids have tumoricidal action and are capable of enhancing the cytotoxic action of anti-cancer drugs specifically, on drug-resistant cells by enhancing drug uptake and reducing its efflux. Thus, polyunsaturated fatty acids either by themselves or in combination with chemotherapeutic drugs have the potential as anti-cancer molecules. PMID:21917129

  17. Effects of n-3 Fatty Acids Supplementation on Plasma Phospholipids Fatty Acid Composition in Patients with Obstructive Jaundice- a Pilot Study

    PubMed Central

    Popovic, Tamara; Ranic, Marija; Bulajic, Predrag; Milicevic, Miroslav; Arsic, Aleksandra; Vucic, Vesna; Glibetic, Marija

    2009-01-01

    Nutritional and immunological status of patients with obstructive jaundice is usually severely altered, with high mortality rates. The n-3 polyunsaturate fatty acids (PUFA), particularly eicosapentaenoic acid (EPA, 20:5 n-3), posess potent immunomodulatory activities. Thus, our aim was to compare the plasma phospholipid fatty acid (FA) composition of these patients with healthy subjects, as well as before and after 7 days preoperative supplementation with high doses of EPA (0.9 g per day) and docosahexaenoic acid (DHA, 22:6 n-3, 0.6 g per day). We found impaired FA status in obstructive jaundice patients, especially EPA, DHA and PUFA, but significantly increased content of total n-3 FA, 22:5 n-3 FA and particularly EPA, which increased more than 3 fold, after 7 days supplementation. In addition, the n6/n3 ratio significantly decreased from 14.24 to 10.24, demonstrating severely improved plasma phospholipid profile in these patients after the intervention. PMID:19902030

  18. Serum level changes of long chain-polyunsaturated fatty acids in patients undergoing periodontal therapy combined with one year of omega-3 supplementation: a pilot randomized clinical trial

    PubMed Central

    2014-01-01

    Purpose We aimed to investigate the impact of nonsurgical periodontal treatment combined with one-year dietary supplementation with omega (ω)-3 on the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and arachidonic acid (AA). Methods Fifteen patients with chronic generalized periodontitis were treated with scaling and root planing. The test group consisted of seven patients (43.1±6.0 years) supplemented with ω-3, consisting of EPA plus DHA, three capsules, each of 300 mg of ω-3 (180-mg EPA/120-mg DHA), for 12 months. The control group was composed of eight patients (46.1±11.6 years) that took a placebo capsule for 12 months. The periodontal examination and the serum levels of DPA, EPA, DHA, and AA were performed at baseline (T0), and 4 (T1), and 12 (T2) months after therapy. Results In the test group, AA and DPA levels had been reduced significantly at T1 (P<0.05). AA and EPA levels had been increased significantly at T2 (P<0.05). The ΔEPA was significantly higher in the test compared to the placebo group at T2-T0 (P=0.02). The AA/EPA had decreased significantly at T1 and T2 relative to baseline (P<0.05). Conclusions Nonsurgical periodontal treatment combined with ω-3 supplementation significantly increased the EPA levels and decreased the AA/EPA ratio in serum after one year follow-up. However, no effect on the clinical outcome of periodontal therapy was observed. Graphical Abstract PMID:25177518

  19. EPA`s cooperative research opportunities

    SciTech Connect

    Gatchett, A.M.; Fradkin, L.; James, S.

    1994-12-31

    The US Environmental Protection Agency (EPA) and the private sector find an increasing need for new cost-effective environmental technologies to treat, control, and prevent pollution. Many cooperative research programs to address this concern are available through the EPA. The Office of Research and Development (ORD) currently operates two of the most visible innovative technology development programs: (1) Superfund Innovative Technology Evaluation (SITE) Program; (2) Federal Technology Transfer Act (FTTA) Program. These programs work very closely with the other EPA program offices. A brief overview of these activities and the new Environmental Technology Initiative within EPA are presented in this paper.

  20. Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells.

    PubMed

    Schley, Patricia D; Jijon, Humberto B; Robinson, Lindsay E; Field, Catherine J

    2005-07-01

    The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells in animal models and cell lines, but the mechanism by which this occurs is not well understood. In order to explore possible mechanisms for the modulation of breast cancer cell growth by omega-3 fatty acids, we examined the effects of EPA and DHA on the human breast cancer cell line MDA-MB-231. Omega-3 fatty acids (a combination of EPA and DHA) inhibited the growth of MDA-MB-231 cells by 30-40% (p<0.05) in both the presence and absence of linoleic acid, an essential omega-6 fatty acid. When provided individually, DHA was more potent than EPA in inhibiting the growth of MDA-MB-231 cells (p<0.05). EPA and DHA treatment decreased tumor cell proliferation (p<0.05), as estimated by decreased [methyl-(3)H]-thymidine uptake and expression of proliferation-associated proteins (proliferating cell nuclear antigen, PCNA, and proliferation-related kinase, PRK). In addition, EPA and DHA induced apoptosis, as indicated by a loss of mitochondrial membrane potential, increased caspase activity and increased DNA fragmentation (p<0.05). Cells incubated with omega-3 fatty acids demonstrated decreased Akt phosphorylation, as well as NFkappaB DNA binding activity (p<0.05). The results of this study indicate that omega-3 fatty acids decrease cell proliferation and induce apoptotic cell death in human breast cancer cells, possibly by decreasing signal transduction through the Akt/NFkappaB cell survival pathway. PMID:15986129

  1. Validating sample preservation techniques and holding times for the approved compliance monitoring methods for haloacetic acids under the US EPA's stage 1 D/DBP rule.

    PubMed

    Pepich, Barry V; Domino, Mark M; Dattilio, Teri A; Fair, Patricia S; Munch, David J

    2004-02-01

    Haloacetic acids (HAAs), which are formed during the disinfection of drinking waters with chlorine, are regulated by the US Environmental Protection Agency (EPA) under the Stage 1 Disinfectant/Disinfection Byproducts (D/DBP) Rule. Recently, three studies have been reported indicating that low concentrations of HAAs can also be formed during disinfection with chloramines. Methods currently approved for compliance monitoring under the Stage 1 Rule arrest the chlorine-mediated formation of HAAs by adding ammonium chloride, which forms chloramines. Studies were undertaken using an in-process water that favored the formation of HAAs with moderate total organic carbon concentration and high levels of chlorine to investigate the potential formation of HAAs under sample storage conditions. The ammonium chloride-quenched sample did form a small amount of HAAs, but total formation over a period equal to the 14-day sample storage time was less than 2 microg/l, whereas the unquenched samples increased 41 microg/l during the same period. Pour plate studies indicated that chlorinated drinking waters quenched with ammonium chloride are protected from microbial growth, which is an important additional advantage to this preservation scheme. The presence of a combined chlorine residual should prevent microbial degradation of HAAs in samples. These studies support the preservation protocols and the sample storage times promulgated for compliance monitoring under the Stage 1 D/DBP Rule. PMID:14769409

  2. Adipose tissue n-3 fatty acids and metabolic syndrome

    PubMed Central

    Cespedes, Elizabeth; Baylin, Ana; Campos, Hannia

    2014-01-01

    Background Evidence regarding the relationship of n-3 fatty acids (FA) to type 2 diabetes (T2D) and metabolic syndrome components (MetS) is inconsistent. Objective To examine associations of adipose tissue n-3 FA with MetS. Design We studied 1611 participants without prior history of diabetes or heart disease who were participants in a population-based case-control study of diet and heart disease (The Costa Rica Heart Study). We calculated prevalence ratios (PR) and 95% confidence intervals (CI) for MetS by quartile of n-3 FA in adipose tissue derived mainly from plants [α-Linolenic acid (ALA)], fish [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], or metabolism [docosapentaenoic acid (DPA), as well as the EPA:ALA ratio, a surrogate marker of delta-6 desaturase activity]. Results N-3 FA levels in adipose tissue were associated with MetS prevalence in opposite directions. The PR (95% CI) for the highest compared to the lowest quartile adjusted for age, sex, BMI, residence, lifestyle, diet and other fatty acids were 0.60 (0.44, 0.81) for ALA, 1.43 (1.12, 1.82) for EPA, 1.63 (1.22, 2.18) for DPA, and 1.47 (1.14, 1.88) for EPA:ALA, all p for trend <0.05. Although these associations were no longer significant (except DPA) after adjustment for BMI, ALA and DPA were associated with lower glucose and higher triglyceride levels, p<0.05 (respectively). Conclusions These results suggest that ALA could exert a modest protective benefit, while EPA and DHA are not implicated in MetS. The positive associations for DPA and MetS could reflect higher delta-6 desaturase activity caused by increased adiposity. PMID:25097001

  3. Impact of dietary fatty acids on muscle composition, liver lipids, milt composition and sperm performance in European eel.

    PubMed

    Butts, Ian Anthony Ernest; Baeza, Rosa; Støttrup, Josianne Gatt; Krüger-Johnsen, Maria; Jacobsen, Charlotte; Pérez, Luz; Asturiano, Juan F; Tomkiewicz, Jonna

    2015-05-01

    In order for European eel aquaculture to be sustainable, the life cycle should be completed in captivity. Development of broodstock diets may improve the species' reproductive success in captivity, through the production of high-quality gametes. Here, our aim was to evaluate the influence of dietary regime on muscle composition, and liver lipids prior to induced maturation, and the resulting sperm composition and performance. To accomplish this fish were reared on three "enhanced" diets and one commercial diet, each with different levels of fatty acids, arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Neutral lipids from the muscle and liver incorporated the majority of the fatty acid profile, while phospholipids incorporated only certain fatty acids. Diet had an effect on the majority of sperm fatty acids, on the total volume of extractable milt, and on the percentage of motile sperm. Here, our results suggest that the total volume of extractable milt is a DHA-dependent process, as we found the diets with the highest DHA levels induced the most milt while the diet with the lowest DHA level induced the least amount of milt. The diet with the highest level of ARA induced medium milt volumes but had the highest sperm motility. EPA also seems important for sperm quality parameters since diets with higher EPA percentages had a higher volume of milt and higher sperm motility. In conclusion, dietary fatty acids had an influence on fatty acids in the tissues of male eel and this impacted sperm performance. PMID:25638567

  4. Comparative Study of EPA-enriched Phosphatidylcholine and EPA-enriched Phosphatidylserine on Lipid Metabolism in Mice.

    PubMed

    Ding, Lin; Wang, Dan; Zhou, Miaomiao; Du, Lei; Xu, Jie; Xue, Changhu; Wang, Yuming

    2016-07-01

    Recent studies have shown that EPA enriched PLs have beneficial effects on lipid metabolism. Our previous study has demonstrated that the anti-obesity and hypolipidemic effects of EPA-PL were superior to DHA-PL. In the present study, we comparatively evaluated the effects of EPA-enriched phosphatidylcholine (EPA-PC) and EPA-enriched phosphatidylserine (EPA-PS) on lipid metabolism in mice. Both 2% dietary EPA-PC and EPA-PS significantly improved serum and hepatic lipid levels in mice. The HDL-c level in mice on EPA-PC diet was significantly higher than the other two groups. The level of DHA in hepatic TG and PL were significantly increased in both EPA-PC and EPA-PS fed groups (98.3 and 117.8%, respectively; p < 0.05). Notably, the proportion of DHA in EPA-PS group was significantly higher than the EPA-PC group. EPA-PC and EPA-PS suppressed hepatic SREBP-1c mediated lipogenesis and activated PPARα mediated fatty acid β-oxidation in the liver. These data are the first to indicate that EPA-PS has beneficial effects on lipid metabolism. PMID:27321119

  5. Past and Present Insights on Alpha-linolenic Acid and the Omega-3 Fatty Acid Family.

    PubMed

    Stark, Aliza H; Reifen, Ram; Crawford, Michael A

    2016-10-25

    Alpha-linolenic acid (ALA) is the parent essential fatty acid of the omega-3 family. This family includes docosahexaenoic acid (DHA), which has been conserved in neural signaling systems in the cephalopods, fish, amphibian, reptiles, birds, mammals, primates, and humans. This extreme conservation, in spite of wide genomic changes of over 500 million years, testifies to the uniqueness of this molecule in the brain and affirms the importance of omega-3 fatty acids. While DHA and its close precursor, eicosapentaenoic acids (EPA), have received much attention by the research community, ALA, as the precursor of both, has been considered of little interest. There are many papers on ALA requirements in experimental animals. Unlike humans, rats and mice can readily convert ALA to EPA and DHA, so it is unclear whether the effect is solely due to the conversion products or to ALA itself. The intrinsic role of ALA has yet to be defined. This paper will discuss both recent and historical findings related to this distinctive group of fatty acids, and will highlight the physiological significance of the omega-3 family. PMID:25774650

  6. Recombinant production of omega-3 fatty acids by probiotic Escherichia coli Nissle 1917.

    PubMed

    Amiri-Jami, Mitra; Abdelhamid, Ahmed Ghamry; Hazaa, Mahmoud; Kakuda, Yukio; Griffths, Mansel W

    2015-10-01

    Omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on human health. The probiotic bacterium Escherichia coli Nissle is unable to produce either EPA or DHA. Escherichia coli Nissle was transformed with the pfBS-PS plasmid carrying the EPA/DHA gene cluster, previously isolated from a marine bacterium. The transgenic E. coli Nissle produced EPA when grown at 10ºC (16.52 ± 1.4 mg g(-1) cell dry weight), 15ºC (31.36 ± 0.25 mg g(-1) cell dry weight), 20ºC (13.71 ± 2.8 mg g(-1) cell dry weight), 25ºC (11.33 ± 0.44 mg g(-1) cell dry weight) or 30ºC (0.668 ± 0.073 mg g(-1) cell dry weight). Although DHA was also produced at all these temperatures, it comprised less than 0.2% of total extracted fatty acids. Transcriptomic analysis using Reverse Transcription qPCR showed upregulation of the entire gene cluster in E. coli Nissle. Among EPA/DHA genes, pfaB, pfaC and pfaD were overexpressed (expression ratio of 181.9, 39.86 and 131.61, respectively) as compared to pfaA (expression ratio of 3.40) and pfaE (expression ratio of 4.05). The EPA/DHA-producing probiotic E. coli Nissle may be used as a safe, alternative and economic source for the industrial and pharmaceutical production of EPA and DHA. PMID:26371149

  7. Impact of sustainable feeds on omega-3 long-chain fatty acid levels in farmed Atlantic salmon, 2006–2015

    PubMed Central

    Sprague, M.; Dick, J.R.; Tocher, D.R.

    2016-01-01

    As the global population and its demand for seafood increases more of our fish will come from aquaculture. Farmed Atlantic salmon are a global commodity and, as an oily fish, contain a rich source of the health promoting long-chain omega-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Replacing the traditional finite marine ingredients, fishmeal and fish oil, in farmed salmon diets with sustainable alternatives of terrestrial origin, devoid of EPA and DHA, presents a significant challenge for the aquaculture industry. By comparing the fatty acid composition of over 3,000 Scottish Atlantic salmon farmed between 2006 and 2015, we find that terrestrial fatty acids have significantly increased alongside a decrease in EPA and DHA levels. Consequently, the nutritional value of the final product is compromised requiring double portion sizes, as compared to 2006, in order to satisfy recommended EPA + DHA intake levels endorsed by health advisory organisations. Nevertheless, farmed Scottish salmon still delivers more EPA + DHA than most other fish species and all terrestrial livestock. Our findings highlight the global shortfall of EPA and DHA and the implications this has for the human consumer and examines the potential of microalgae and genetically modified crops as future sources of these important fatty acids. PMID:26899924

  8. DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice

    PubMed Central

    Sosunov, Sergey A.; Williams, Jill J.; Zirpoli, Hylde; Vlasakov, Iliyan; Deckelbaum, Richard J.; Ten, Vadim S.

    2016-01-01

    Background and Purpose Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury. Methods 10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4–5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8–9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA. Results Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia. Conclusions Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA. PMID:27513579

  9. Dietary fatty acids modulate associations between genetic variants and circulating fatty acids in plasma and erythrocyte membranes: meta-analysis of 9 studies in the CHARGE consortium

    PubMed Central

    Smith, Caren E.; Follis, Jack L.; Nettleton, Jennifer A.; Foy, Millennia; Wu, Jason H.Y.; Ma, Yiyi; Tanaka, Toshiko; Manichakul, Ani W.; Wu, Hongyu; Chu, Audrey Y.; Steffen, Lyn M.; Fornage, Myriam; Mozaffarian, Dariush; Kabagambe, Edmond K.; Ferruci, Luigi; da Chen, Yii-Der I; Rich, Stephen S.; Djoussé, Luc; Ridker, Paul M.; Tang, Weihong; McKnight, Barbara; Tsai, Michael Y.; Bandinelli, Stefania; Rotter, Jerome I.; Hu, Frank B.; Chasman, Daniel I.; Psaty, Bruce M.; Arnett, Donna K.; King, Irena B.; Sun, Qi; Wang, Lu; Lumley, Thomas; Chiuve, Stephanie E.; Siscovick, David S; Ordovás, José M.; Lemaitre, Rozenn N.

    2015-01-01

    Scope Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. Objective We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). Methods and Results We conducted meta-analyses (N to 11,668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein) and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma vs. erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary ALA and linoleic acid for DHA and DPA. Conclusion Our findings reinforce earlier reports that genetically-based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene-diet relationships, and considering compartment may improve the detection of gene-fatty acids interactions for circulating fatty acid outcomes. PMID:25626431

  10. Fatty Acid Composition and Levels of Selected Polyunsaturated Fatty Acids in Four Commercial Important Freshwater Fish Species from Lake Victoria, Tanzania

    PubMed Central

    Robert, Agnes; Mfilinge, Prosper; Limbu, Samwel M.; Mwita, Chacha J.

    2014-01-01

    Fatty acids (FAs) particularly ω3 and ω6 polyunsaturated fatty acids (PUFAs) play important role in human health. This study aimed to investigate the composition and levels of selected ω3 PUFAs in four commercial fish species, Nile perch (Lates niloticus), Nile tilapia (Oreochromis niloticus), Tilapia zillii, and dagaa (Rastrineobola argentea) from Mwanza Gulf in Lake Victoria. The results indicated that 36 types of FAs with different saturation levels were detected. These FAs were dominated by docosahexaenoic (DHA), eicosapentaenoic (EPA), docosapentaenoic (DPA), and eicosatetraenoic acids. O. niloticus had the highest composition of FAs (34) compared to L. niloticus (27), T. zillii (26), and R. argentea (21). The levels of EPA differed significantly among the four commercial fish species (F = 6.19,  P = 0.001). The highest EPA levels were found in R. argentea followed by L. niloticus and O. niloticus and the lowest in T. zillii. The DPA levels showed no significant difference among the four fish species studied (F = 0.652,  P = 0.583). The study concluded that all four commercial species collected from Mwanza Gulf are good for human health, but R. argentea is the best for consumption because it contains higher levels of ω3 FAs, mainly EPA. PMID:25610654

  11. Comparative Analysis of Lipid Content and Fatty Acid Composition of Commercially Important Fish and Shellfish from Sri Lanka and Japan.

    PubMed

    Devadason, Chandravathany; Jayasinghe, Chamila; Sivakanesan, Ramiah; Senarath, Samanthika; Beppu, Fumiaki; Gotoh, Naohiro

    2016-01-01

    Sri Lanka is surrounded by the Indian Ocean, allowing plenty of fishes to be caught. Moreover, these fishes represent one of the undocumented fish resources in the world and their detailed lipid profiles have not been previously examined. In this study, the lipid content and fatty acid composition of 50 commercially important fishes from the Indian Ocean (Sri Lanka) and the Pacific Ocean (Japan) were compared. The total lipid content and fatty acid composition, including eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA), differed significantly among species. Fish from the Pacific Ocean had higher proportions of fatty acids, including EPA and DHA. Herrings and mackerels from both oceanic areas demonstrated high levels of EPA and DHA, and n-3/n-6 ratio. Brackish and freshwater fishes from both groups showed low levels of PUFAs. Fish from the Indian Ocean were high in n-6 fatty acids. Monounsaturated fatty acid levels were high in omnivorous fish from the Pacific Ocean, and saturated fatty acid levels were high in fish from the Indian Ocean. The results of this study will be of value in determining the dietary usefulness of fish caught in Sri Lanka. PMID:27373421

  12. Are the Adaptogenic Effects of Omega 3 Fatty Acids Mediated via Inhibition of Proinflammatory Cytokines?

    PubMed Central

    Bradbury, Joanne; Brooks, Lyndon; Myers, Stephen P.

    2012-01-01

    The study was undertaken to estimate the size of the impact of n-3 fatty acids in psychological stress and the extent to which it is mediated via proinflammatory cytokines. Structural equation modeling (SEM) was used to analyze data from 194 healthy Australians. Biomarkers used were erythrocyte polyunsaturated fatty acids (docosahexaenoic acid (DHA) and arachidonic acid (AA)), ex-vivo stimulated secretion of proinflammatory cytokines (interleukins (IL-1 and IL-6), and tumor necrosis factor (TNF)). Stress was measured with the perceived stress scale (PSS-10), found to comprise three factors: Coping (items 4, 7, 5), Overwhelm (2, 10, 6 and 8), and Emotional (1, 9 and 3). This modeling demonstrated that the effects of DHA on coping are largely direct effects (0.26, t = 2.05) and were not significantly mediated via the suppression of proinflammatory cytokines. Future modeling should explore whether adding EPA to the model would increase the significance of the mediation pathways. PMID:22007258

  13. EPA SCIENCE FORUM

    EPA Science Inventory

    Every year, the world's leading environmental scientists and policy makers meet at the EPA Science Forum to explore the latest discoveries in the world of environmental research.

    Background

    EPA's Research & Development's Office has been hosting the EPA Scien...

  14. Adult medication-free schizophrenic patients exhibit long-chain omega-3 Fatty Acid deficiency: implications for cardiovascular disease risk.

    PubMed

    McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Dwivedi, Yogesh; Pandey, Ghanshyam N

    2013-01-01

    Deficiency in long-chain omega-3 (LCn - 3) fatty acids, eicosapentaenoic acid (EPA, 20:5n - 3) and docosahexaenoic acid (DHA, 22:6n - 3), has been implicated in the pathoetiology of cardiovascular disease, a primary cause of excess premature mortality in patients with schizophrenia (SZ). In the present study, we determined erythrocyte EPA + DH