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Sample records for chain polyunsaturated fatty

  1. Significance of long chain polyunsaturated fatty acids in human health.

    PubMed

    Zárate, Rafael; El Jaber-Vazdekis, Nabil; Tejera, Noemi; Pérez, José A; Rodríguez, Covadonga

    2017-12-01

    In the last decades, the development of new technologies applied to lipidomics has revitalized the analysis of lipid profile alterations and the understanding of the underlying molecular mechanisms of lipid metabolism, together with their involvement in the occurrence of human disease. Of particular interest is the study of omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFAs), notably EPA (eicosapentaenoic acid, 20:5n-3), DHA (docosahexaenoic acid, 22:6n-3), and ARA (arachidonic acid, 20:4n-6), and their transformation into bioactive lipid mediators. In this sense, new families of PUFA-derived lipid mediators, including resolvins derived from EPA and DHA, and protectins and maresins derived from DHA, are being increasingly investigated because of their active role in the "return to homeostasis" process and resolution of inflammation. Recent findings reviewed in the present study highlight that the omega-6 fatty acid ARA appears increased, and omega-3 EPA and DHA decreased in most cancer tissues compared to normal ones, and that increments in omega-3 LC-PUFAs consumption and an omega-6/omega-3 ratio of 2-4:1, are associated with a reduced risk of breast, prostate, colon and renal cancers. Along with their lipid-lowering properties, omega-3 LC-PUFAs also exert cardioprotective functions, such as reducing platelet aggregation and inflammation, and controlling the presence of DHA in our body, especially in our liver and brain, which is crucial for optimal brain functionality. Considering that DHA is the principal omega-3 FA in cortical gray matter, the importance of DHA intake and its derived lipid mediators have been recently reported in patients with major depressive and bipolar disorders, Alzheimer disease, Parkinson's disease, and amyotrophic lateral sclerosis. The present study reviews the relationships between major diseases occurring today in the Western world and LC-PUFAs. More specifically this review focuses on the dietary omega-3 LC

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

    USDA-ARS?s Scientific Manuscript database

    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...

  3. Long-chain polyunsaturated fatty acid supplementation in preterm infants.

    PubMed

    Simmer, K; Schulzke, S M; Patole, S

    2008-01-23

    The n-3 and n-6 essential fatty acids alpha linolenic acid (ALA) and linoleic acid (LA) are the precursors of the n-3 and n-6 longchain polyunsaturated fatty acids (LCPUFA). Controversy exists over whether LCPUFA are essential nutrients for preterm infants, who may not be able to synthesise sufficient amounts of LCPUFA to satisfy the needs of the developing brain and retina. The aim of this review is to assess whether supplementation of formula with LCPUFA is safe and of benefit to preterm infants. Trials were identified by MEDLINE (February 2007), Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007) and by checking reference lists of relevant articles and conference proceedings. All randomised trials of formula supplemented with LCPUFA and with clinical endpoints were reviewed. Fifteen randomised trials assessing the clinical effects of feeding formula supplemented with LCPUFA were included in the review. Of the fifteen randomised trials included in the review, four of these were not classified as of high quality, due to low follow-up, uncertainty regarding concealment of patient allocation and randomisation, and problems with assessment methodology. VISUAL ACUITY: Visual acuity over the first year was measured by Teller or Lea acuity cards in eight studies, by VEP in six studies and by ERG in two studies. Most studies found no significant differences in any visual assessment between supplemented and control infants. Most of the trials have used Bayley Scales of Infant Development (BSID) at 12 to 24 months post-term with three out of seven studies reporting some benefit of LCPUFA in different populations of supplemented infants at different postnatal ages. Meta-analysis of BSID of four studies at 12 months (N = 364) and three studies at 18 months (N = 494) post-term showed no significant effect of supplementation on neurodevelopment. Carlson 1992 and Carlson 1996 demonstrated lower

  4. 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

  5. Endogenous Production of Long-Chain Polyunsaturated Fatty Acids and Metabolic Disease Risk

    PubMed Central

    Murff, Harvey J; Edwards, Todd L.

    2015-01-01

    Long chain polyunsaturated fatty acids (PUFAs) are important structural components of cellular membranes and are converted into eicosanoids which serve various biological roles. The most common dietary n-6 and n-3 PUFAs are linoleic acid and α-linoleic acid, respectively. These 18-carbon chain fatty acids undergo a series of desaturation and elongation steps to become the 20-carbon fatty acids arachidonic acid and eicosapentaenoic acid, respectively. Evidence from genome wide association studies has consistently demonstrated that plasma and tissue levels of the n-6 long-chain PUFA arachidonic acid and to a lesser extent the n-3 long-chain PUFA eicosapentaenoic acid, are strongly influenced by variation in fatty acid desaturase-1,-2, and elongation of very long chain fatty acid genes. Studies of functional variants in these genes, as well as studies in which desaturase activity has been indirectly estimated by fatty acid product-to -precursor ratios, have suggested that endogenous capacity to synthesize long-chain PUFAs may be associated with metabolic diseases such as diabetes mellitus. Interventional studies are starting to tease out the complicated relationship between dietary intakes of specific fatty acids, variation in desaturase and elongase genes and tissue levels of long chain PUFAs. Thus future studies of dietary PUFA interventions designed to reduce inflammatory and metabolic diseases will need to carefully consider how an individual's genetically-determined endogenous long-chain PUFA synthesis capacity might modify therapeutic response. PMID:26392837

  6. Stepwise engineering to produce high yields of very long-chain polyunsaturated fatty acids in plants.

    PubMed

    Wu, Guohai; Truksa, Martin; Datla, Nagamani; Vrinten, Patricia; Bauer, Joerg; Zank, Thorsten; Cirpus, Petra; Heinz, Ernst; Qiu, Xiao

    2005-08-01

    Very long chain polyunsaturated fatty acids (VLCPUFAs) such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are valuable commodities that provide important human health benefits. We report the transgenic production of significant amounts of AA and EPA in Brassica juncea seeds via a stepwise metabolic engineering strategy. Using a series of transformations with increasing numbers of transgenes, we demonstrate the incremental production of VLCPUFAs, achieving AA levels of up to 25% and EPA levels of up to 15% of total seed fatty acids. Both fatty acids were almost exclusively found in triacylglycerols, with AA located preferentially at sn-2 and sn-3 positions and EPA distributed almost equally at all three positions. Moreover, we reconstituted the DHA biosynthetic pathway in plant seeds, demonstrating the practical feasibility of large-scale production of this important omega-3 fatty acid in oilseed crops.

  7. Bacterial Long-Chain Polyunsaturated Fatty Acids: Their Biosynthetic Genes, Functions, and Practical Use

    PubMed Central

    Yoshida, Kiyohito; Hashimoto, Mikako; Hori, Ryuji; Adachi, Takumi; Okuyama, Hidetoshi; Orikasa, Yoshitake; Nagamine, Tadashi; Shimizu, Satoru; Ueno, Akio; Morita, Naoki

    2016-01-01

    The nutritional and pharmaceutical values of long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic, eicosapentaenoic and docosahexaenoic acids have been well recognized. These LC-PUFAs are physiologically important compounds in bacteria and eukaryotes. Although little is known about the biosynthetic mechanisms and functions of LC-PUFAs in bacteria compared to those in higher organisms, a combination of genetic, bioinformatic, and molecular biological approaches to LC-PUFA-producing bacteria and some eukaryotes have revealed the notably diverse organization of the pfa genes encoding a polyunsaturated fatty acid synthase complex (PUFA synthase), the LC-PUFA biosynthetic processes, and tertiary structures of the domains of this enzyme. In bacteria, LC-PUFAs appear to take part in specific functions facilitating individual membrane proteins rather than in the adjustment of the physical fluidity of the whole cell membrane. Very long chain polyunsaturated hydrocarbons (LC-HCs) such as hentriacontanonaene are considered to be closely related to LC-PUFAs in their biosynthesis and function. The possible role of LC-HCs in strictly anaerobic bacteria under aerobic and anaerobic environments and the evolutionary relationships of anaerobic and aerobic bacteria carrying pfa-like genes are also discussed. PMID:27187420

  8. The function of very long chain polyunsaturated fatty acids in the pineal gland.

    PubMed

    Catalá, Angel

    2010-02-01

    The mammalian pineal gland is a prominent secretory organ with a high metabolic activity. Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals counteracting lipid peroxidation in biological membranes. Approximately 25% of the total fatty acids present in the rat pineal lipids are represented by arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). These very long chain polyunsaturated fatty acids play important roles in the pineal gland. In addition to the production of melatonin, the mammalian pineal gland is able of convert these polyunsaturated fatty acids into bioactive lipid mediators. Lipoxygenation is the principal lipoxygenase (LOX) activity observed in the rat pineal gland. Lipoxygenation in the pineal gland is exceptional because no other brain regions express significant LOX activities under normal physiological conditions. The rat pineal gland expresses both 12- and 15-lipoxygenase (LOX) activities, producing 12- and 15-hydroperoxyeicosatetraenoic acid (12- and 15-HpETE) from arachidonic acid and 14- and 17-hydroxydocosahexaenoic acid (14- and 17-HdoHE) from docosahexaenoic acid, respectively. The rat pineal also produces hepoxilins via LOX pathways. The hepoxilins are bioactive epoxy-hydroxy products of the arachidonic acid metabolism via the 12S-lipoxygenase (12S-LOX) pathway. The two key pineal biochemical functions, lipoxygenation and melatonin synthesis, may be synergistically regulated by the status of n-3 essential fatty acids.

  9. Associations of birth weight with serum long chain polyunsaturated fatty acids in adolescents; the HELENA study.

    PubMed

    Labayen, Idoia; Moreno, Luis A; Ruiz, Jonatan R; Ortega, Francisco B; Sjostrom, Michael; Huybrechts, Inge; Gonzalez-Gross, Marcela; Spinneker, André; De Henauw, Stefaan; Manios, Yannis; Molnar, Dénés; Leclercq, Catherine; Gottrand, Frédéric

    2011-07-01

    Nutritional factors in early life may have long-term physiologic effects in humans. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play important roles in protecting against cardiovascular disease (CVD) risk. Our aim was to examine the association of birth weight (BW) with serum long chain polyunsaturated fatty acids (LCPUFA) profile in adolescents. A total of 772 European adolescents (56.3% females) aged 14.7 ± 1.2 years were included in this study. Information on BW and gestational age was obtained from parental records. DHA, EPA and arachidonic acid (AA) concentrations were measured in serum phospholipids. Alfa-linolenic (ALA), linoleic (LA), AA, EPA and DHA intakes assessed by a computer based 24h dietary recall. Gender, gestational age, pubertal status, body mass index, center and total energy and LCPUFA intakes were used as confounders in all the analyses. BW was significantly associated with serum DHA and EPA (both adjusted P<0.05) independently of potential confounders including their main dietetic source. We did not observe any significant relationship between BW and serum AA levels. Our findings suggest that early metabolic changes, as a result from prenatal environmental influences, could affect long chain polyunsaturated fatty acid metabolism later in life. These results may contribute to explain the relationship between early nutrition and growth and later metabolic disorders as CVD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. [Biology and biochemical aspects of long-chains polyunsaturated fatty acid during gestation].

    PubMed

    Bautista, Claudia Janet; Zambrano, Elena

    2010-01-01

    During pregnancy, the mother must provide the nutrients necessary for proper differentiation, maturation and growth of fetal organs and systems. During this period, the mother adapts her metabolism to address the continuing demand for substrates to be transferred to the fetus through the placenta. Essential fatty acids cannot be synthesized by humans, therefore, should be consumed as part of the diet. Its derivates, long-chain polyunsaturated fatty acids (LC-PUFAs) from biosynthesis in the maternal liver during pregnancy and lactation are compounds that will form part of the cell membranes of the brain, retina, and liver, fetal and newborn heart, thereby enabling the smooth, activation and regulation of cellular functions. Therefore, adequate nutritional status of the mother during pregnancy and lactation is necessary to ensure adequate product development. This article aims to review some aspects of the adaptive mechanisms of maternal lipid metabolism, mainly from LC-PUFAs compensating energy expenditure and allow the proper development of the product.

  11. Desaturase and elongase limiting endogenous long chain polyunsaturated fatty acid biosynthesis

    PubMed Central

    Zhang, Ji Yao; Kothapalli, Kumar S.D.; Brenna, J. Thomas

    2016-01-01

    Purpose of Review Endogenous synthesis of the long chain polyunsaturated fatty acids (LCPUFA) is mediated by the fatty acid desaturase (FADS) gene cluster (11q12-13.1) and elongation of very long chain fatty acids 2 (ELOVL2) (6p24.2) and ELOVL5 (6p12.1). Though older biochemical work identified the product of one gene, FADS2, rate limiting for LCPUFA synthesis, recent studies suggest that polymorphisms in any of these genes can limit accumulation of product LCPUFA. Recent findings Genome-wide association study (GWAS) of Greenland Inuit show strong adaptation signals within FADS gene cluster, attributed to high omega-3 fatty acid intake, while GWAS found ELOVL2 associated with sleep duration, age and DNA methylation. ELOVL5 coding mutations cause spinocerebellar ataxia 38, and epigenetic marks were associated with depression and suicide risk. Two sterol response element binding sites were found on ELOVL5, a SREBP-1c target gene. Minor allele carriers of a 3 single nucleotide polymorphism (SNP) haplotype in ELOVL2 have decreased 22:6n-3 levels. Unequivocal molecular evidence shows mammalian FADS2 catalyzes direct Δ4-desaturation to yield 22:6n-3 and 22:5n-6. A SNP near FADS1 influences the levels of 5-lipoxygenase products and epigenetic alteration. Summary Genetic polymorphisms within FADS and ELOVL can limit LCPUFA product accumulation at any step of the biosynthetic pathway. PMID:26828581

  12. Metabolic engineering of microorganisms to produce omega-3 very long-chain polyunsaturated fatty acids.

    PubMed

    Gong, Yangmin; Wan, Xia; Jiang, Mulan; Hu, Chuanjiong; Hu, Hanhua; Huang, Fenghong

    2014-10-01

    Omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) have received growing attention due to their significant roles in human health. Currently the main source of these nutritionally and medically important fatty acids is marine fish, which has not met ever-increasing global demand. Microorganisms are an important alternative source also being explored. Although many microorganisms accumulate omega-3 LC-PUFAs naturally, metabolic engineering might still be necessary for significantly improving their yields. Here, we review recent research involving the engineering of microorganisms for production of omega-3 LC-PUFAs, including eicospentaenoic acid and docosohexaenoic acid. Both reconstitution of omega-3 LC-PUFA biosynthetic pathways and modification of existing pathways in microorganisms have demonstrated the potential to produce high levels of omega-3 LC-PUFAs. However, the yields of omega-3 LC-PUFAs in host systems have been substantially limited by potential metabolic bottlenecks, which might be caused partly by inefficient flux of fatty acid intermediates between the acyl-CoA and different lipid class pools. Although fatty acid flux in both native and heterologous microbial hosts might be controlled by several acyltransferases, evidence has suggested that genetic manipulation of one acyltransferase alone could significantly increase the accumulation of LC-PUFAs. The number of oleaginous microorganisms that can be genetically transformed is increasing, which will advance engineering efforts to maximize LC-PUFA yields in microbial strains.

  13. Alternative Sources of n-3 Long-Chain Polyunsaturated Fatty Acids in Marine Microalgae

    PubMed Central

    Martins, Dulce Alves; Custódio, Luísa; Barreira, Luísa; Pereira, Hugo; Ben-Hamadou, Radhouan; Varela, João; Abu-Salah, Khalid M.

    2013-01-01

    The main source of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in human nutrition is currently seafood, especially oily fish. Nonetheless, due to cultural or individual preferences, convenience, geographic location, or awareness of risks associated to fatty fish consumption, the intake of fatty fish is far from supplying the recommended dietary levels. The end result observed in most western countries is not only a low supply of n-3 LC-PUFA, but also an unbalance towards the intake of n-6 fatty acids, resulting mostly from the consumption of vegetable oils. Awareness of the benefits of LC-PUFA in human health has led to the use of fish oils as food supplements. However, there is a need to explore alternatives sources of LC-PUFA, especially those of microbial origin. Microalgae species with potential to accumulate lipids in high amounts and to present elevated levels of n-3 LC-PUFA are known in marine phytoplankton. This review focuses on sources of n-3 LC-PUFA, namely eicosapentaenoic and docosahexaenoic acids, in marine microalgae, as alternatives to fish oils. Based on current literature, examples of marketed products and potentially new species for commercial exploitation are presented. PMID:23807546

  14. Short chain and polyunsaturated fatty acids in host gut health and foodborne bacterial pathogen inhibition.

    PubMed

    Peng, Mengfei; Biswas, Debabrata

    2017-12-12

    As a major source of microbes and their numerous beneficial effects, the gut microflora/microbiome is intimately linked to human health and disease. The exclusion of enteric pathogens by these commensal microbes partially depends upon the production of bioactive compounds such as short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs). These key intestinal microbial byproducts are crucial to the maintenance of a healthy gut microbial community. Moreover, SCFAs and PUFAs play multiple critical roles in host defense and immunity, including anti-cancer, anti-inflammation, and anti-oxidant activities, as well as out-competition of enteric bacterial pathogens. In this review article, we hereby aim to highlight the importance of SCFAs and PUFAs and the microbes involved in production of these beneficial intestinal components, and their biological functions, specifically as to their immunomodulation and interactions with enteric bacterial pathogens. Finally, we also advance potential applications of these fatty acids with regards to food safety and human gut health.

  15. Dietary long-chain polyunsaturated fatty acids from different sources affect fat and fatty acid excretions in rats.

    PubMed

    Amate, L; Gil, A; Ramírez, M

    2001-12-01

    Several sources of long-chain polyunsaturated fatty acids (LCP) have been evaluated for infant-formula supplementation. These sources differ in their chemical structure [triglyceride (TG) or phospholipid (PL)], arrangement of fatty acids on the TG or PL backbone, fatty acid composition and presence of other lipid components. All of these characteristics influence fat digestion, may affect fat and fatty acid absorption, and hence, LCP bioavailability and metabolism in infancy. The main objective of this work was to establish the influence of different dietary LCP sources on overall fat and LCP absorption in early life. We compared fat and fatty acid excretions at weaning in rats fed control diets or diets supplemented with LCP as TG or PL. Two separate experiments were conducted. In Experiment 1, weanling rats were fed for 3 wk a control diet (C1), a diet with TG from tuna and fungal oils (TF-TG) or a diet with PL from pig brain concentrate (PB-PL). In Experiment 2, weanling rats were fed for 3 wk a control diet (C2), a diet containing egg-TG (EG-TG) or a diet containing egg-PL (EG-PL). Fat, mineral and saturated fatty acid excretions in feces were higher in rats fed PB-PL compared with those fed TF-TG diet. In Experiment 2, groups did not differ in fat and mineral excretions. However, the EG-PL group had lower fecal excretions of saturated fatty acids than the C2 and EG-TG groups. The 16:1(n-7), 18:1(n-9), 18:2(n-6) and 22:6(n-3) levels in feces were higher in the EG-TG group than in the EG-PL group. In summary, total fat and LCP excretions differed among rats fed diets supplemented with LCP from different sources.

  16. Omega-3 long-chain polyunsaturated fatty acids support aerial insectivore performance more than food quantity

    PubMed Central

    Twining, Cornelia W.; Brenna, J. Thomas; Lawrence, Peter; Shipley, J. Ryan; Tollefson, Troy N.; Winkler, David W.

    2016-01-01

    Once-abundant aerial insectivores, such as the Tree Swallow (Tachycineta bicolor), have declined steadily in the past several decades, making it imperative to understand all aspects of their ecology. Aerial insectivores forage on a mixture of aquatic and terrestrial insects that differ in fatty acid composition, specifically long-chain omega-3 polyunsaturated fatty acid (LCPUFA) content. Aquatic insects contain high levels of both LCPUFA and their precursor omega-3 PUFA, alpha-linolenic acid (ALA), whereas terrestrial insects contain much lower levels of both. We manipulated both the quantity and quality of food for Tree Swallow chicks in a full factorial design. Diets were either high-LCPUFA or low in LCPUFA but high in ALA, allowing us to separate the effects of direct LCPUFA in diet from the ability of Tree Swallows to convert their precursor, ALA, into LCPUFA. We found that fatty acid composition was more important for Tree Swallow chick performance than food quantity. On high-LCPUFA diets, chicks grew faster, were in better condition, and had greater immunocompetence and lower basal metabolic rates compared with chicks on both low LCPUFA diets. Increasing the quantity of high-LCPUFA diets resulted in improvements to all metrics of performance while increasing the quantity of low-LCPUFA diets only resulted in greater immunocompetence and lower metabolic rates. Chicks preferentially retained LCPUFA in brain and muscle when both food quantity and LCPUFA were limited. Our work suggests that fatty acid composition is an important dimension of aerial insectivore nutritional ecology and reinforces the importance of high-quality aquatic habitat for these declining birds. PMID:27638210

  17. Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants.

    PubMed Central

    Faldella, G; Govoni, M; Alessandroni, R; Marchiani, E; Salvioli, G P; Biagi, P L; Spano, C

    1996-01-01

    The influence of dietary long chain polyunsaturated fatty acid (LCP) supply, and especially of docosahexaenoic acid (DHA), on evoked potential maturation, was studied in 58 healthy preterm infants using flash visual evoked potentials (VEPs), flash electroretinography (ERG), and brainstem acoustic evoked potentials (BAEPs) at 52 weeks of postconceptional age. At the same time, the fatty acid composition of red blood cell membranes was examined. The infants were fed on breast milk (n = 12), a preterm formula supplemented with LCP (PF-LCP) (n = 21), or a traditional preterm formula (PF) (n = 25). In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar; in the PF group the morphology was quite different and the wave latencies were significantly longer. This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower. Moreover, a higher level of erythrocyte LCP, especially DHA, was found in breast milk and PF-LCP groups compared with the PF group. ERG and BAEP recordings were the same in all three groups. These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available. PMID:8949693

  18. The effect of dietary sulfur on the metabolism of long chain polyunsaturated fatty acids

    SciTech Connect

    Chen, M.F.

    1988-01-01

    The effect of methionine-supplemented diet on the metabolism of polyunsaturated fatty acids was studied by comparing results of control and cysteine-supplemented diets in rats. Adult Sprague-Dawley rats were fed for a period of 17 days one of the following diets: control, cysteine-supplemented, and/or methionine-supplemented. On the last day of the feeding period, the rats were administered either (1-{sup 14}C) arachidonic acid (AA) or (1-{sup 14}C) eicosapentaenoic acid (EPA) by stomach tube five hours before sacrificing. The cyclooxygenase activity in liver microsomes, the apparent Km of the fatty acyl-CoA synthetase in liver and brain homogenates, and the incorporation of polyunsaturated fatty acids into the phosphatidylinositol fraction of brain, heat, lung, spleen, and kidney tissues were analyzed.

  19. Nutritional evaluation of microalgae oils rich in omega-3 long chain polyunsaturated fatty acids as an alternative for fish oil.

    PubMed

    Ryckebosch, Eline; Bruneel, Charlotte; Termote-Verhalle, Romina; Goiris, Koen; Muylaert, Koenraad; Foubert, Imogen

    2014-10-01

    The purpose of this work was to evaluate the nutritional value of the total lipid extract of different omega-3 long chain polyunsaturated fatty acids producing photoautotrophic microalgae in one study. It was shown that microalgae oils from Isochrysis, Nannochloropsis, Phaeodactylum, Pavlova and Thalassiosira contain sufficient omega-3 LC-PUFA to serve as an alternative for fish oil, which was used as the 'golden standard'. In the microalgae oils an important part of the omega-3 long chain polyunsaturated fatty acids are present in the polar lipid fraction, which may be favourable from a bioavailability and stability viewpoint. Consumption of microalgae oil ensures intake of sterols and carotenoids. The intake of sterols, including cholesterol and phytosterols, is probably not relevant. The intake of carotenoids is however definitely significant and could give the microalgae oils a nutritional added value compared to fish oil.

  20. Long-chain polyunsaturated fatty acid status in children, adolescents and adults with phenylketonuria.

    PubMed

    Gramer, Gwendolyn; Haege, Gisela; Langhans, Claus-Dieter; Schuhmann, Vera; Burgard, Peter; Hoffmann, Georg F

    2016-06-01

    Patients with phenylketonuria have been reported to be deficient in long-chain polyunsaturated fatty acids (LCPUFAs). It has been postulated that good compliance with the dietary regimen negatively influences LCPUFA status. In 36 patients with phenylketonuria and 18 age-matched healthy control subjects LCPUFA-levels in plasma phospholipids and cholesteryl esters, erythrocyte phosphatidylcholine and phosphatidylethanolamine were evaluated. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels did not differ significantly between patients and control subjects in plasma and erythrocyte fractions. There was a significant negative correlation between SDS (standard deviation) scores of DHA-levels in erythrocyte parameters from the respective age-matched control group and patients' concurrent and long-term phenylalanine levels for erythrocyte phosphatidylethanolamine and erythrocyte phosphatidylcholine. Patients with lower (higher) phenylalanine levels had positive (negative) DHA-SDS. In contrast to previous reports we did not find lower LCPUFA-levels in patients with phenylketonuria compared to age-matched healthy control subjects. Good dietary control was associated with better LCPUFA status. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Long-chain polyunsaturated fatty acids regulation of PPARs, signaling: Relationship to tissue development and aging.

    PubMed

    Echeverría, Francisca; Ortiz, Macarena; Valenzuela, Rodrigo; Videla, Luis A

    2016-11-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that function as ligand-dependent transcription factors that can be activated by different types of fatty acids (FAs). Three isoforms of PPARs have been identify, namely, PPARα, PPARβ/δ, and PPARγ, which are able to bind long-chain polyunsaturated FAs (LCPUFAs), n-3 LCPUFAs being bound with greater affinity to achieve activation. FA binding induces a conformational change of the nuclear receptors, triggering the transcription of specific genes including those encoding for various metabolic and cellular processes such as FA β-oxidation and adipogenesis, thus representing key mediators of lipid homeostasis. In addition, PPARs have important roles during placental, embryonal, and fetal development, and in the regulation of processes related to aging comprising oxidative stress, inflammation, and neuroprotection. The aim of this review was to assess the role of FAs as PPARs ligands, in terms of their main functions associated with FA metabolism and their relevance in the prevention and treatment of related pathologies during human life span.

  2. Role of dietary long-chain polyunsaturated fatty acids in infant allergies and respiratory diseases.

    PubMed

    Shek, Lynette P; Chong, Mary Foong-Fong; Lim, Jia Yi; Soh, Shu-E; Chong, Yap-Seng

    2012-01-01

    Maternal nutrition has critical effects on the developing structures and functions of the fetus. Malnutrition during pregnancy can result in low birth weight and small for gestational age babies, increase risk for infection, and impact the immune system. Long-chain polyunsaturated fatty acids (PUFAs) have been reported to have immunomodulatory effects. Decreased consumption of omega-6 PUFAs, in favor of more anti-inflammatory omega-3 PUFAs in modern diets, has demonstrated the potential protective role of omega-3 PUFAs in allergic and respiratory diseases. In this paper, we examine the role of PUFAs consumption during pregnancy and early childhood and its influence on allergy and respiratory diseases. PUFAs act via several mechanisms to modulate immune function. Omega-3 PUFAs may alter the T helper (Th) cell balance by inhibiting cytokine production which in turn inhibits immunoglobulin E synthesis and Th type 2 cell differentiation. PUFAs may further modify cellular membrane, induce eicosanoid metabolism, and alter gene expression. These studies indicate the benefits of omega-3 PUFAs supplementation. Nevertheless, further investigations are warranted to assess the long-term effects of omega-3 PUFAs in preventing other immune-mediated diseases, as well as its effects on the later immunodefense and health status during early growth and development.

  3. n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review.

    PubMed

    Nettleton, Joyce A; Katz, Robert

    2005-03-01

    Historically, epidemiologic studies have reported a lower prevalence of impaired glucose tolerance and type 2 diabetes in populations consuming large amounts of the n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) found mainly in fish. Controlled clinical studies have shown that consumption of n-3 LC-PUFAs has cardioprotective effects in persons with type 2 diabetes without adverse effects on glucose control and insulin activity. Benefits include lower risk of primary cardiac arrest; reduced cardiovascular mortality, particularly sudden cardiac death; reduced triglyceride levels; increased high-density lipoprotein levels; improved endothelial function; reduced platelet aggregability; and lower blood pressure. These favorable effects outweigh the modest increase in low-density lipoprotein levels that may result from increased n-3 LC-PUFA intake. Preliminary evidence suggests increased consumption of n-3 LC-PUFAs with reduced intake of saturated fat may reduce the risk of conversion from impaired glucose tolerance to type 2 diabetes in overweight persons. Reported improvements in hemostasis, slower progression of artery narrowing, albuminuria, subclinical inflammation, oxidative stress, and obesity require additional confirmation. Expected health benefits and public health implications of consuming 1 to 2 g/day n-3 LC-PUFA as part of lifestyle modification in insulin resistance and type 2 diabetes are discussed.

  4. Long chain N-3 polyunsaturated fatty acids in the prevention of allergic and cardiovascular disease.

    PubMed

    van den Elsen, Lieke; Garssen, Johan; Willemsen, Linette

    2012-01-01

    The diet is considered to have a major impact on human health. Dietary lipids including long chain polyunsaturated fatty acids (LCPUFA) possess potent immunomodulatory activities. Over the last decades the incidence of inflammatory disorders including allergic and cardiovascular diseases (CVD) has been rising. This phenomenon is associated with deficiencies in N-3 LCPUFA, found in fatty fish, and increased content of N-6 LCPUFA in the Western diet. LCPUFA act via different mechanisms including membrane fluidity, raft composition, lipid mediator formation, signaling pathways and transmembrane receptors. N-3 LCPUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce the development of allergic disease by affecting both the innate and adaptive immune system involved in the initiation and persistence of allergic disease. Fish oil has been shown to be effective in the primary prevention of allergic disease in infants at risk when supplemented during pregnancy and lactation. Subtle effects of N-3 LCPUFA on the outcome of the immune response may underlie these protective effects. This review describes the currently reported effects of LCPUFA on dendritic cells, T cells, B cells and mast cells. Also CVD are positively affected by N-3 LCPUFA. Populations consuming high amounts of oily fish are protected against CVD. Moreover N-3 LCPUFA are effective in the secondary prevention of cardiovascular events. Amongst other effects, EPA and DHA have been shown to suppress endothelial cell activation hereby reducing adhesion molecule expression and endothelial cell - leukocyte interactions. This review describes the mechanistic basis of the preventive role for N-3 LCPUFA in allergic disease and CVD.

  5. Dietary polychlorinated biphenyls, long-chain n-3 polyunsaturated fatty acids and incidence of malignant melanoma.

    PubMed

    Donat-Vargas, Carolina; Berglund, Marika; Glynn, Anders; Wolk, Alicja; Åkesson, Agneta

    2017-02-01

    For malignant melanoma, other risk factors aside from sun exposure have been hardly explored. Polychlorinated biphenyls (PCBs)-mainly from fatty fish- may affect melanogenesis and promote melanoma progression, while long-chain n-3 polyunsaturated fatty acids seem to exert antineoplastic actions in melanoma cells. We aimed to assess the association of validated estimates of dietary PCB exposure as well as the intake of eicosapentaenoic acid and docosahexaenoic acid (EPA-DHA), accounting for sun habits and skin type, with the risk of malignant melanoma in middle-aged and elderly women. We included 20,785 women at baseline in 2009 from the prospective population-based Swedish Mammography Cohort. Validated estimates of dietary PCB exposure and EPA-DHA intake were obtained via a food frequency questionnaire. Incident melanoma cases were ascertained through register-linkage. During 4.5 years of follow-up, we ascertained 67 incident cases of melanoma. After multivariable adjustments, exposure to dietary PCBs was associated with four-fold increased risk of malignant melanoma (hazard ratio [HR], 4.0 [95% confidence interval {CI}, 1.2-13; P for trend = 0.02]), while EPA-DHA intake was associated with 80% lower risk (HR, 0.2 [95% CI, 0.1-0.8; P for trend = 0.03]), comparing the highest exposure tertiles with the lowest. While we found a direct association between dietary PCB exposure and risk of melanoma, EPA-DHA intake showed to have a substantial protective association. Question of benefits and risk from fish consumption is very relevant and further prospective studies in the general population verifying these findings are warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Dietary n-3 long chain polyunsaturated fatty acids in allergy prevention and asthma treatment.

    PubMed

    Willemsen, Linette E M

    2016-08-15

    The rise in non-communicable diseases, such as allergies, in westernized countries links to changes in lifestyle and diet. N-3 long chain polyunsaturated fatty acids (LCPUFA) present in marine oils facilitate a favorable milieu for immune maturation and may contribute to allergy prevention. N-3 LCPUFA can suppress innate and adaptive immune activation and induce epigenetic changes. Murine studies convincingly show protective effects of fish oil, a source of n-3 LCPUFA, in food allergy and asthma models. Observational studies in human indicate that high dietary intake of n-3 LCPUFA and low intake of n-6 PUFA may protect against the development of allergic disease early in life. High n-6 PUFA intake is also associated with an increased asthma risk while n-3 LCPUFA may be protective and reduce symptoms. The quality of the marine oil used has impact on efficacy of allergy prevention and several observations link in particular n-3 LCPUFA DHA to allergy suppression. Randomized controlled trials indicate that optimal timing, duration and dosage of n-3 LC-PUFA is required to exert an allergy protective effect. Supplementation during early pregnancy and lactation has shown promising results regarding allergy prevention. However these findings should be confirmed in a larger cohort. Although clinical trials in asthma patients reveal no consistent clinical benefits of n-3 LCPUFA supplementation on lung function, it can suppress airway inflammation. Future food-pharma approaches may reveal whether adjunct therapy with dietary n-3 LCPUFA can improve allergy prevention or immunotherapy via support of allergen specific oral tolerance induction or contribute to the efficacy of drug therapy for asthma patients.

  7. Formula with long-chain polyunsaturated fatty acids reduces incidence of allergy in early childhood.

    PubMed

    Foiles, Amanda M; Kerling, Elizabeth H; Wick, Jo A; Scalabrin, Deolinda M F; Colombo, John; Carlson, Susan E

    2016-03-01

    Allergy has sharply increased in affluent Western countries in the last 30 years. N-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) may protect the immune system against development of allergy. We prospectively categorized illnesses by body system in a subset of 91 children from the Kansas City cohort of the DIAMOND (DHA Intake and Measurement of Neural Development) study who had yearly medical records through 4 years of age. As infants, they were fed either a control formula without LCPUFA (n = 19) or one of three formulas with LCPUFA from docosahexaenoic acid (DHA) and arachidonic acid (ARA) (n = 72). Allergic illnesses in the first year were lower in the combined LCPUFA group compared to the control. LCPUFAs significantly delayed time to first allergic illness (p = 0.04) and skin allergic illness (p = 0.03) and resulted in a trend to reduced wheeze/asthma (p = 0.1). If the mother had no allergies, LCPUFAs reduced the risk of any allergic diseases (HR = 0.24, 95% CI = 0.1, 0.56, p = 0.0.001) and skin allergic diseases (HR = 0.35, 95% CI = 0.13, 0.93, p = 0.04). In contrast, if the mother had allergies, LCPUFAs reduced wheezing/asthma (HR = 0.26, 95% CI = 0.07, 0.9, p = 0.02). LCPUFA supplementation during infancy reduced the risk of skin and respiratory allergic diseases in childhood with effects influenced by maternal allergies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Breastfeeding, long-chain polyunsaturated fatty acids in colostrum, and infant mental development.

    PubMed

    Guxens, Mònica; Mendez, Michelle A; Moltó-Puigmartí, Carolina; Julvez, Jordi; García-Esteban, Raquel; Forns, Joan; Ferrer, Muriel; Vrijheid, Martine; López-Sabater, M Carmen; Sunyer, Jordi

    2011-10-01

    Breastfeeding has been associated with improved neurodevelopment in children. However, it remains unknown to what extent nutritional advantages of breast milk may explain this relationship. We assessed the role of parental psychosocial factors and colostrum long-chain polyunsaturated fatty acid (LC-PUFA) levels in the relationship between breastfeeding and children's neurodevelopment. A population-based birth cohort was established in the city of Sabadell (Catalonia, Spain) as part of the INMA-INfancia y Medio Ambiente Project. A total of 657 women were recruited during the first trimester of pregnancy. Information about parental characteristics and breastfeeding was obtained by using a questionnaire, and trained psychologists assessed mental and psychomotor development by using the Bayley Scales of Infant Development in 504 children at 14 months of age. A high percentage of breastfeeds among all milk feeds accumulated during the first 14 months was positively related with child mental development (0.37 points per month of full breastfeeding [95% confidence interval: 0.06-0.67]). Maternal education, social class, and intelligence quotient only partly explained this association. Children with a longer duration of breastfeeding also exposed to higher ratios between n-3 and n-6 PUFAs in colostrum had significantly higher mental scores than children with low breastfeeding duration exposed to low levels. Greater levels of accumulated breastfeeding during the first year of life were related to higher mental development at 14 months, largely independently from a wide range of parental psychosocial factors. LC-PUFA levels seem to play a beneficial role in children's mental development when breastfeeding levels are high.

  9. Long-chain polyunsaturated fatty acid requirements during pregnancy and lactation.

    PubMed

    Makrides, M; Gibson, R A

    2000-01-01

    Much interest has been expressed about the long-chain polyunsaturated fatty acid (LCPUFA) requirements of both preterm and term infants, whereas relatively little attention has been given to the LCPUFA needs of mothers, who may provide the primary source of LCPUFAs for their fetuses and breast-fed infants. Although maternal requirements for LCPUFAs are difficult to estimate because of large body stores and the capacity to synthesize LCPUFAs from precursors, biochemical and clinical intervention studies have provided some clues. From a biochemical viewpoint, there appears to be no detectable reduction in plasma n-3 LCPUFA concentrations during pregnancy, whereas there is a clear decline during the early postpartum period. The postpartum decrease in maternal plasma docosahexaenoic acid (DHA) concentration is not instantaneous, may be long-term, is independent of lactation, and is reversible with dietary DHA supplementation (200-400 mg/d). From a functional standpoint, the results of randomized clinical studies suggest that n-3 LCPUFA supplementation during pregnancy does not affect the incidences of pregnancy-induced hypertension and preeclampsia without edema. However, n-3 LCPUFA supplementation may cause modest increases in the duration of gestation, birth weight, or both. To date, there is little evidence of harm as a result of n-3 LCPUFA supplementation during either pregnancy or lactation. However, researchers need to further elucidate any potential benefits of supplementation for mothers and infants. Careful attention should be paid to study design, measurement of appropriate health outcomes, and defining minimum and maximum plasma n-3 LCPUFA concentrations that are optimal for both mothers and infants.

  10. Long-chain omega-3 polyunsaturated fatty acid intake and risk of colorectal cancer

    PubMed Central

    Kantor, Elizabeth D; Lampe, Johanna W.; Peters, Ulrike; Vaughan, Thomas L.; White, Emily

    2013-01-01

    Research suggests that long-chain omega-3 polyunsaturated fatty acids (LC-PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-neoplastic properties, yet evidence for association between LC-PUFAs and colorectal cancer (CRC) remains inconsistent. Using the VITamins And Lifestyle (VITAL) cohort, we evaluated how EPA/DHA intake, and its primary sources, fish oil supplement use and dark fish consumption, relate to CRC risk. A total of 68,109 Washington residents aged 50-76 completed a questionnaire between 2000-2002 and were followed for CRC through 2008 (n=488). Persons using fish oil supplements on 4+days/week for 3+years experienced 49% lower CRC risk than non-users (HR:0.51; 95% CI:0.26-1.00; p-trend=0.06). The association between fish oil use and decreased CRC risk was primarily observed for men (p-interaction=0.02; p-trend men=0.02; p-trend women=0.88) and for colon cancer (p-difference=0.05; p-trend colon=0.03; p-trend rectum=0.87). While dark fish and total EPA+DHA intake were not associated with CRC risk overall, these associations varied by genetic risk (p-interaction=0.009 and 0.02, respectively), with inverse associations observed among low-moderate genetic risk groups and positive associations observed among high risk groups. Results suggest that associations between LC-PUFA intake and CRC may vary by gender, subsite, and genetic risk, providing additional insight into the potential role of LC-PUFAs in cancer prevention. PMID:24053119

  11. Formula with long chain polyunsaturated fatty acids reduces incidence of allergy in early childhood

    PubMed Central

    Foiles, Amanda M.; Kerling, Elizabeth H.; Wick, Jo A.; Scalabrin, Deolinda M.F.; Colombo, John; Carlson, Susan E.

    2016-01-01

    Background Allergy has sharply increased in affluent Western countries in the last 30 years. N-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) may protect the immune system against development of allergy. Methods We prospectively categorized illnesses by body system in a subset of 91 children from the Kansas City cohort of the DIAMOND (DHA Intake and Measurement of Neural Development) study who had yearly medical records through 4 years of age. As infants, they were fed either a control formula without LCPUFA (n=19) or one of three formulas with LCPUFA from docosahexaenoic acid (DHA) and arachidonic acid (ARA) (n=72). Results Allergic illnesses in the first year were lower in the combined LCPUFA group compared to the control. LCPUFAs significantly delayed time to first allergic illness (p=0.04) and skin allergic illness (p=0.03); and resulted in a trend to reduced wheeze/asthma (p=0.1). If the mother had no allergies, LCPUFAs reduced the risk of any allergic diseases (HR = 0.24, 95% CI = 0.1, 0.56, p=0.0.001) and skin allergic diseases (HR = 0.35, 95% CI = 0.13, 0.93, p=0.04). In contrast, if the mother had allergies, LCPUFAs reduced wheezing/asthma (HR = 0.26, 95% CI = 0.07, 0.9, p = 0.02). Conclusions LCPUFA supplementation during infancy reduced the risk of skin and respiratory allergic diseases in childhood with effects influenced by maternal allergies. PMID:26613373

  12. [Comparison of long-chain polyunsaturated fatty acids in plasma and erythrocyte phospholipids for biological monitoring].

    PubMed

    Kawabata, Terue; Nakai, Kunihiko; Hagiwara, Chie; Kurokawa, Naoyuki; Murata, Katsuyuki; Yaginuma, Kozue; Satoh, Hiroshi

    2011-01-01

    Previous data have indicated that the erythrocyte membrane may be the preferred sample type for assessing long-chain polyunsaturated fatty acid (LCPUFA) contents in cardiac and cerebral membranes. In this epidemiological study, we examined whether plasma phospholipids can be used for accurate biological monitoring of the LCPUFA state or whether analysis of erythrocyte membrane phospholipids is indispensable. (1) The analysis of LCPUFA contents in erythrocyte membrane phospholipids was conducted at baseline and after 1 and 3 days at 4°C, and 21 days at -40°C, after blood drawing, and the changes in LCPUFA content were examined. (2) The LCPUFA compositions of plasma and erythrocyte phospholipids in 133 young women (18-30 years old) were examined and the relationships between the sample type and the levels of LCPUFAs were determined. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and DHA/arachidonic acid (AA) and (EPA+DHA)/AA ratios in erythrocyte membrane phospholipids after 21 days of blood drawing significantly decreased compared with the corresponding baseline data. Regarding AA, EPA and DHA, a significant positive correlation was shown between levels of erythrocyte membrane phospholipids and plasma phospholipids (AA, r=0.364; EPA, r=0.709; DHA, r=0.653). The predictive value of plasma phospholipids for determining the highest concentration quartile in erythrocyte phospholipids was better in EPA (70%) than in DHA (55%) and AA (42%). The measurement of LCPUFA content in erythrocyte membrane phospholipids is necessary for accurate biological monitoring. We also found that LCPUFA in erythrocyte membrane phospholipids is stable in cold storage (4°C) for 3 days after blood drawing.

  13. ω-3 Long-Chain Polyunsaturated Fatty Acids and Fatty Acid Desaturase Activity Ratios as Eventual Endophenotypes for ADHD.

    PubMed

    Henríquez-Henríquez, Marcela; Solari, Sandra; Várgas, Gisela; Vásquez, Luis; Allende, Fidel; Castañón S, Carla; Tenorio, Marcela; Quiroga Gutiérrez, Teresa

    2015-11-01

    Epidemiological studies suggest that long-chain polyunsaturated fatty acids (LC-PUFAs) may be suitable as endophenotypes for ADHD. To be appropriated vulnerability traits, endophenotypes should be altered in unaffected relatives of index cases. Serum profiles of LC-PUFAs in unaffected relatives of ADHD patients remain understudied. The main objective of this study was to compare serum LC-PUFAs in ADHD patients, unaffected relatives of index cases, and general-population unaffected participants. LC-PUFA profiles of 72 participants (27 ADHD patients, 27 unaffected relatives, and 18 general-population participants) were obtained by gas chromatography-mass spectrometry (GC-MS). Groups were compared by parametrical statistics. Unaffected females from the general population presented lower Docosapentaenoic acid (DPA; p = .0012) and a-linolenic acid (ALA; p = .0091) levels compared with ADHD females and unaffected relatives. In addition, docosahexaenoic acid (DHA)/ALA and DHA/DPA ratios, addressing desaturase activity, were significantly lower in ADHD patients and unaffected relatives of ADHD patients in the female-subgroup (p = .022 and .04, respectively). DHA/ALA, DHA/DPA, serum DPA, and serum ALA may be suitable as endophenotypes for ADHD women. © The Author(s) 2012.

  14. Fish oil and mental health: the role of n-3 long-chain polyunsaturated fatty acids in cognitive development and neurological disorders.

    PubMed

    Assisi, Alessandro; Banzi, Rita; Buonocore, Carmela; Capasso, Filippo; Di Muzio, Valeria; Michelacci, Francesca; Renzo, Danila; Tafuri, Giovanni; Trotta, Francesco; Vitocolonna, Maria; Garattini, Silvio

    2006-11-01

    Epidemiological and experimental studies have indicated that consumption of more n-3 long-chain polyunsaturated fatty acids may reduce the risk for a variety of diseases, including cardiovascular, neurological and immunological disorders, diabetes and cancer. This article focuses on the role of marine n-3 long-chain polyunsaturated fatty acids in brain functions, including the development of the central nervous system and neurological disorders. An overview of the major animal studies and clinical trials is provided here, focusing on fatty acid supplementation during pregnancy and infancy, and prevention and management of Alzheimer's disease, schizophrenia, depression and attention deficit hyperactive disorder. Although an optimal balance in n-3/n-6 long-chain polyunsaturated fatty acid ratio is important for proper neurodevelopment and cognitive functions, results from randomized controlled trials are controversial and do not confirm any useful effect of supplementation on development of preterm and term infants. The relationship between fatty acid status and mental disorders is confirmed by reduced levels of n-3 long-chain polyunsaturated fatty acids in erythrocyte membranes of patients with central nervous system disorders. Nevertheless, there are very little data supporting the use of fish oil in those patients. The only way to verify whether n-3 long-chain polyunsaturated fatty acids are a potential therapeutic option in the management and prevention of mental disorders is to conduct a large definitive randomized controlled trials similar to those required for the licensing of any new pharmacological treatment.

  15. Long chain n-3 polyunsaturated fatty acids and vascular function in patients with chronic kidney disease and healthy subjects: a cross-sectional and comparative study.

    PubMed

    Borg, Morten; Svensson, My; Povlsen, Johan V; Schmidt, Erik B; Aalkjær, Christian; Christensen, Jeppe H; Ivarsen, Per

    2016-11-21

    Patients with chronic kidney disease have a markedly increased cardiovascular mortality compared with the general population. Long chain n-3 polyunsaturated fatty acids have been suggested to possess cardioprotective properties. This cross-sectional and comparative study evaluated correlations between hemodynamic measurements, resistance artery function and fish consumption to the content of long chain n-3 polyunsaturated fatty acids in adipose tissue, a long-term marker of seafood intake. Seventeen patients with chronic kidney disease stage 5 + 5d and 27 healthy kidney donors were evaluated with hemodynamic measurements before surgery; from these subjects, 11 patients and 11 healthy subjects had vasodilator properties of subcutaneous resistance arteries examined. The measurements were correlated to adipose tissue n-3 polyunsaturated fatty acids. Information on fish intake was obtained from a dietary questionnaire and compared with adipose tissue n-3 polyunsaturated fatty acids. Fish intake and the content of n-3 polyunsaturated fatty acids in adipose tissue did not differ between patients and controls. n-3 polyunsaturated fatty acid levels in adipose tissue were positively correlated to systemic vascular resistance index; (r = 0.44; p = 0.07 and r = 0.62; p < 0.05, chronic kidney disease and healthy subjects respectively) and negatively correlated to cardiac output index (r = -0.69; p < 0.01 and r = -0.50; p < 0.05, chronic kidney disease and healthy subjects respectively). No correlation was observed between n-3 polyunsaturated fatty acid levels in adipose tissue and vasodilator properties in resistance arteries. n-3 PUFA content in adipose tissue increased with increasing self-reported fish intake. The correlations found, suggest a role for n-3 polyunsaturated fatty acids in hemodynamic properties. However, this is apparently not due to changes in intrinsic properties of the resistance arteries as no correlation was found to n

  16. Flexibility of "polyunsaturated fatty acid chains" and peptide backbones: A comparative ab initio study.

    PubMed

    Law, Jacqueline M S; Setiadi, David H; Chass, Gregory A; Csizmadia, Imre G; Viskolcz, Béla

    2005-01-27

    The conformational properties of omega-3 type of polyunsaturated fatty acid (PUFA) chains and their fragments were studied using Hartree-Fock (RHF/3-21G) and DFT (B3LYP/6-31G(d)) methods. Comparisons between a unit (U) fragment of the PUFA chain and a mono N-Ac-glycine-NHMe residue show that both structures have the same sequence of sp2-sp3-sp2 atoms. The flexibility of PUFA originates in the internal rotation about the above pairs of sigma bonds. Therefore, potential energy surfaces (PESs) were generated by a scan around the terminal dihedral angles (phi t1 and phi t2) as well as the phi 1 and psi 1 dihedrals of both 1U congeners (Me-CHCH-CH2-CHCHMe and MeCONH-CH2-CONHMe) at the RHF/3-21G level of theory. An interesting similarity was found in the flexibility between the cis allylic structure and the trans peptide models. A flat landscape can be seen in the cis 1U (hepta-2,5-diene) surface, implying that several conformations are expected to be found in this (PES). An exhaustive search carried out on the 1U and 2U models revealed that straight chain structures such as trans and cis beta (phi 1 approximately psi 1 approximately 120 degrees; phi 2 approximately psi 2 approximately -120 degrees) or trans and cis extended (phi 1 approximately psi 1 approximately phi 2 approximately psi 2 approximately 120 degrees) can be formed at the lowest energy of both isomers. However, forming helical structures, such as trans helix (phi 1 approximately -120 degrees, psi 1 approximately 12 degrees; phi 2 approximately -120 degrees, psi 2 approximately 12 degrees) or cis helix (phi 1 approximately -130 degrees, psi 1 approximately 90 degrees; phi 2 approximately -145 degrees, psi 2 approximately 90 degrees) will require more energy. These six conformations, found in 2U, were selected to construct longer chains such as 3U, 4U, 5U, and 6U to obtain the thermochemistry of secondary structures. The variation in the extension or compression of the chain length turned out to be a factor

  17. Very low n-3 long-chain polyunsaturated fatty acid status in Austrian vegetarians and vegans.

    PubMed

    Kornsteiner, Margit; Singer, Ingrid; Elmadfa, Ibrahim

    2008-01-01

    The objective of the study was to collect data on dietary fat intake of omnivores, vegetarians, vegans and semi-omnivores as well as its impact on n-3 and n-6 fatty acids in long-term markers such as sphingolipids, phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) as well as the calculated sphingo- and phospholipids (SPL) of erythrocytes. The present observational study included 98 Austrian adult volunteers of both genders, of which 23 were omnivores, 25 vegetarians, 37 vegans, and 13 semi-omnivores. Information on anthropometry using measured body weight and height was obtained. The amount and composition of ingested fat were calculated from 24-hour recalls and the fatty acid pattern in the phospholipids was assessed using gas chromatography. The unbalanced n-6/n-3 ratio and the limited dietary sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in vegans and vegetarians led to reductions in C20:5n-3, C22:5n-3, C22:6n-3 and total n-3 fatty acids in SPL, PC, PS and PE compared with omnivores and semi-omnivores. The total content of polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids remained unchanged. The vegetarian diet, with an average n-6/n-3 ratio of 10/1, promotes biochemical n-3 tissue decline. To ensure physical, mental and neurological health vegetarians have to reduce the n-6/n-3 ratio with an additional intake of direct sources of EPA and DHA, regardless of age and gender. (c) 2008 S. Karger AG, Basel.

  18. Visual functions in phenylketonuria-evaluating the dopamine and long-chain polyunsaturated fatty acids depletion hypotheses.

    PubMed

    Gramer, Gwendolyn; Förl, Birgit; Springer, Christina; Weimer, Petra; Haege, Gisela; Mackensen, Friederike; Müller, Edith; Völcker, Hans Eberhard; Hoffmann, Georg Friedrich; Lindner, Martin; Krastel, Hermann; Burgard, Peter

    2013-01-01

    In phenylketonuria presymptomatic treatment following newborn screening prevents severe mental and physical impairment. The reasons for subtle impairments of cerebral functions despite early treatment remain unclear. We assessed a broad spectrum of visual functions in early-treated patients with phenylketonuria and evaluated two hypotheses-the dopamine and the long-chain polyunsaturated fatty acids (LCPUFAs) depletion hypotheses. Contrast sensitivity, colour vision, electroretinography, frequency doubling technology campimetry (FDT), and their relation with blood phenylalanine and docosahexaenoic acid levels were assessed in 36 patients with phenylketonuria and 18 age-matched healthy controls. Contrast sensitivity was significantly lower and total error scores in colour vision significantly higher in patients than controls. Electroretinography results differed significantly between patients and controls. We found a trend for the effect of phenylalanine-levels on contrast sensitivity and a significant effect on colour vision/FDT results. Docosahexaenoic acid levels in erythrocytes were not associated with visual functions. This is the first evaluation of visual functions in phenylketonuria using a comprehensive ophthalmological test battery. We found no evidence supporting the long-chain polyunsaturated fatty acids depletion hypothesis. However, the effect of phenylalanine-levels on visual functions suggests that imbalance between phenylalanine and tyrosine may affect retinal dopamine levels in phenylketonuria. This is supported by the similar patterns of visual functions in patients with phenylketonuria observed in our study and patients with Parkinson's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. High feeding intensity increases the severity of fatty liver in the American mink (Neovison vison) with potential ameliorating role for long-chain n-3 polyunsaturated fatty acids

    PubMed Central

    2014-01-01

    Background Rapid body fat mobilization, obesity, and an inadequate supply of n-3 polyunsaturated fatty acids (PUFA) have been suggested to play roles in the etiology of fatty liver in the American mink (Neovison vison). This study examined the effects of feeding intensity and dietary fat source on fatty liver induced by fasting. In a multi-factorial design, 3 different fat sources (herring oil, rich in n-3 PUFA, soya oil, rich in n-6 PUFA, and canola oil, rich in n-9 monounsaturated fatty acids) were fed to mink at a low and high feeding intensity for 10 weeks, followed by an overnight or a 5-day fasting treatment to induce fatty liver. Results Fasting led to the development of fatty liver with increased severity in the mink fed at the high feeding intensity. The herring oil diet, high in long-chain n-3 PUFA, was found to decrease the severity of fatty liver in the mink at the high feeding intensity. Conclusion Preventing excessive weight gain and increasing dietary intake of n-3 long-chain PUFA may help prevent excessive lipid accumulation during prolonged periods of fasting or inappetence by promoting hepatic fatty acid oxidation. PMID:24438337

  20. High feeding intensity increases the severity of fatty liver in the American mink (Neovison vison) with potential ameliorating role for long-chain n-3 polyunsaturated fatty acids.

    PubMed

    Dick, Morag F; Hurford, Jennifer; Lei, Sha; Mustonen, Anne-Mari; Nieminen, Petteri; Rouvinen-Watt, Kirsti

    2014-01-16

    Rapid body fat mobilization, obesity, and an inadequate supply of n-3 polyunsaturated fatty acids (PUFA) have been suggested to play roles in the etiology of fatty liver in the American mink (Neovison vison). This study examined the effects of feeding intensity and dietary fat source on fatty liver induced by fasting. In a multi-factorial design, 3 different fat sources (herring oil, rich in n-3 PUFA, soya oil, rich in n-6 PUFA, and canola oil, rich in n-9 monounsaturated fatty acids) were fed to mink at a low and high feeding intensity for 10 weeks, followed by an overnight or a 5-day fasting treatment to induce fatty liver. Fasting led to the development of fatty liver with increased severity in the mink fed at the high feeding intensity. The herring oil diet, high in long-chain n-3 PUFA, was found to decrease the severity of fatty liver in the mink at the high feeding intensity. Preventing excessive weight gain and increasing dietary intake of n-3 long-chain PUFA may help prevent excessive lipid accumulation during prolonged periods of fasting or inappetence by promoting hepatic fatty acid oxidation.

  1. Fads1 and 2 are promoted to meet instant need for long-chain polyunsaturated fatty acids in goose fatty liver.

    PubMed

    Osman, Rashid H; Liu, Long; Xia, Lili; Zhao, Xing; Wang, Qianqian; Sun, Xiaoxian; Zhang, Yihui; Yang, Biao; Zheng, Yun; Gong, Daoqing; Geng, Tuoyu

    2016-07-01

    Global prevalence of non-alcoholic fatty liver disease (NAFLD) constitutes a threat to human health. Goose is a unique model of NAFLD for discovering therapeutic targets as its liver can develop severe steatosis without overt injury. Fatty acid desaturase (Fads) is a potential therapeutic target as Fads expression and mutations are associated with liver fat. Here, we hypothesized that Fads was promoted to provide a protection for goose fatty liver. To test this, goose Fads1 and Fads2 were sequenced. Fads1/2/6 expression was determined in goose liver and primary hepatocytes by quantitative PCR. Liver fatty acid composition was also analyzed by gas chromatography. Data indicated that hepatic Fads1/2/6 expression was gradually increased with the time of overfeeding. In contrast, trans-C18:1n9 fatty acid (Fads inhibitor) was reduced. However, enhanced Fads capacity for long-chain polyunsaturated fatty acid (LC-PUFA) synthesis was not sufficient to compensate for the depleted LC-PUFAs in goose fatty liver. Moreover, cell studies showed that Fads1/2/6 expression was regulated by fatty liver-associated factors. Together, these findings suggest Fads1/2 as protective components are promoted to meet instant need for LC-PUFAs in goose fatty liver, and we propose this is required for severe hepatic steatosis without liver injury.

  2. Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids

    PubMed Central

    Song, Byoung-Joon; Moon, Kwan-Hoon; Olsson, Nils U.; Salem, Norman

    2008-01-01

    Background/Aims We reported that reduced dietary intake of polyunsaturated fatty acids (PUFA) such as arachidonic (AA,20:4n6, omega-6) and docosahexaenoic (DHA,22:6n3, omega-3) acids led to alcohol-induced fatty liver and fibrosis. This study was aimed at studying the mechanisms by which a DHA/AA-supplemented diet prevents alcohol-induced fatty liver. Methods Male Long-Evans rats were fed an ethanol or control liquid-diet with or without DHA/AA for 9 weeks. Plasma transaminase levels, liver histology, oxidative/nitrosative stress markers, and activities of oxidatively-modified mitochondrial proteins were evaluated. Results Chronic alcohol administration increased the degree of fatty liver but fatty liver decreased significantly in rats fed the alcohol-DHA/AA-supplemented diet. Alcohol exposure increased oxidative/nitrosative stress with elevated levels of ethanol-inducible CYP2E1, nitric oxide synthase, nitrite and mitochondrial hydrogen peroxide. However, these increments were normalized in rats fed the alcohol-DHA/AA-supplemented diet. The number of oxidatively-modified mitochondrial proteins was markedly increased following alcohol exposure but significantly reduced in rats fed the alcohol-DHA/AA-supplemented diet. The suppressed activities of mitochondrial aldehyde dehydrogenase, ATP synthase, and 3-ketoacyl-CoA thiolase in ethanol-exposed rats were also recovered in animals fed the ethanol-DHA/AA-supplemented diet. Conclusions Addition of DHA/AA prevents alcohol-induced fatty liver and mitochondrial dysfunction in an animal model by protecting various mitochondrial enzymes most likely through reducing oxidative/nitrosative stress. PMID:18571270

  3. Long-chain polyunsaturated fatty acid biosynthesis in chordates: Insights into the evolution of Fads and Elovl gene repertoire.

    PubMed

    Castro, L Filipe C; Tocher, Douglas R; Monroig, Oscar

    2016-04-01

    Long-chain polyunsaturated fatty acids (LC-PUFA) are major components of complex lipid molecules and are also involved in numerous critical biological processes. Studies conducted mainly in vertebrates have demonstrated that LC-PUFA can be biosynthesized through the concerted action of two sets of enzymes, namely fatty acyl desaturases (Fads) and elongation of very long-chain fatty acid (Elovl) proteins. While LC-PUFA research is a thriving field, mainly focused on human health, an integrated view regarding the evolution of LC-PUFA biosynthetic genetic machinery in chordates is yet to be produced. Particularly important is to understand whether lineage specific life history trajectories, as well as major biological transitions, or particular genomic processes such as genome duplications have impacted the evolution of LC-PUFA biosynthetic pathways. Here we review the gene repertoire of Fads and Elovl in chordate genomes and the diversity of substrate specificities acquired during evolution. We take advantage of the magnitude of genomic and functional data to show that combination duplication processes and functional plasticity have generated a wide diversity of physiological capacities in extant lineages. A clear evolutionary framework is provided, which will be instrumental for the full clarification of functional capacities between the various vertebrate groups.

  4. Omega-3 polyunsaturated fatty acids.

    PubMed

    Hull, Mark A

    2011-08-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are naturally occurring omega (ω)-3 long-chain polyunsaturated fatty acids (PUFAs), which are found in highest quantities in oily fish such as sardines and mackerel. Epidemiological studies of the association between fish intake, ω-3 PUFA intake or blood ω-3 PUFA levels and colorectal cancer (CRC) risk have not consistently suggested beneficial effects of ω-3 PUFAs on CRC (and other gastrointestinal cancer) risk. However, dietary administration of one or both of the main ω-3 PUFAs in rodent models of colorectal carcinogenesis has been demonstrated to reduce colorectal tumour size and multiplicity, compatible with CRC chemopreventative activity. EPA has now been demonstrated to reduce rectal polyp number and size in patients with familial adenomatous polyposis. A randomized polyp prevention trial of EPA is underway in order to test chemopreventative efficacy against 'sporadic' colorectal neoplasia. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Long chain polyunsaturated fatty acid supplementation in infants born at term.

    PubMed

    Jasani, Bonny; Simmer, Karen; Patole, Sanjay K; Rao, Shripada C

    2017-03-10

    The long chain polyunsaturated fatty acids (LCPUFA) docosahexaenoic acid (DHA) and arachidonic acid (AA) are considered essential for maturation of the developing brain, retina and other organs in newborn infants. Standard infant milk formulae are not supplemented with LCPUFA; they contain only alpha-linolenic acid and linoleic acid, from which formula-fed infants must synthesise their own DHA and AA, respectively. Over the past few years, some manufacturers have added LCPUFA to formula milk and have marketed these products as providing an advantage for the overall development of full-term infants. To assess whether supplementation of formula milk with LCPUFA is both safe and beneficial for full-term infants, while focusing on effects on visual function, neurodevelopment and physical growth. Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL; December 2016), MEDLINE (Ovid, 1966 to December 2016), Embase (Ovid, 1980 to December 2016), the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1980 to December 2016) and abstracts of the Pediatric Academic Societies (2000 to 2016). We applied no language restrictions. We reviewed all randomised controlled trials (RCTs) evaluating effects of LCPUFA supplemented versus non-supplemented formula milk on visual function, neurodevelopment and physical growth. We did not include trials reporting only biochemical outcomes. Two review authors extracted data independently. We assessed risk of bias of included studies using the guidelines of the Cochrane Neonatal Review Group. When appropriate, we conducted meta-analysis to determine a pooled estimate of effect. We identified 31 RCTs and included 15 of these in the review (N = 1889).Nine studies assessed visual acuity, six of which used visual evoked potentials (VEP), two Teller cards and one both. Four studies reported beneficial effects, and the remaining five did not. Meta-analysis of three RCTs showed significant

  6. Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men.

    PubMed

    Rosell, Magdalena S; Lloyd-Wright, Zouë; Appleby, Paul N; Sanders, Thomas A B; Allen, Naomi E; Key, Timothy J

    2005-08-01

    Plasma concentrations of long-chain n-3 polyunsaturated fatty acids are lower in vegetarians and in vegans than in omnivores. No data are available on whether these concentrations differ between long- and short-term vegetarians and vegans. We compared plasma fatty acid composition in meat-eaters, vegetarians, and vegans and examined whether the proportions of eicosapentaenoic acid (20:5n-3; EPA), docosapentaenoic acid (22:5n-3; DPA), and docosahexaenoic acid (22:6n-3; DHA) were related to the subjects' duration of adherence to their diets or to the proportions of plasma linoleic acid (18:2n-6; LA) and alpha-linolenic acid (18:3n-3; ALA). The present cross-sectional study included 196 meat-eating, 231 vegetarian, and 232 vegan men in the United Kingdom. Information on anthropometry, diet, and smoking habits was obtained through a questionnaire. Total fatty acid composition in plasma was measured. The proportions of plasma EPA and DHA were lower in the vegetarians and in the vegans than in the meat-eaters, whereas only small differences were seen for DPA. Plasma EPA, DPA, and DHA proportions were not significantly associated with the duration of time since the subjects became vegetarian or vegan, which ranged from <1 y to >20 y. In the vegetarians and the vegans, plasma DHA was inversely correlated with plasma LA. The proportions of plasma long-chain n-3 fatty acids were not significantly affected by the duration of adherence to a vegetarian or vegan diet. This finding suggests that when animal foods are wholly excluded from the diet, the endogenous production of EPA and DHA results in low but stable plasma concentrations of these fatty acids.

  7. The impact of dietary long-chain polyunsaturated fatty acids on respiratory illness in infants and children.

    PubMed

    Hageman, Jeske H J; Hooyenga, Pieter; Diersen-Schade, Deborah A; Scalabrin, Deolinda M Felin; Wichers, Harry J; Birch, Eileen E

    2012-12-01

    Increasing evidence suggests that intake of long-chain polyunsaturated fatty acids (LCPUFA), especially omega-3 LCPUFA, improves respiratory health early in life. This review summarizes publications from 2009 through July 2012 that evaluated effects of fish, fish oil or LCPUFA intake during pregnancy, lactation, and early postnatal years on allergic and infectious respiratory illnesses. Studies during pregnancy found inconsistent effects in offspring: two showed no effects and three showed protective effects of omega-3 LCPUFA on respiratory illnesses or atopic dermatitis. Two studies found that infants fed breast milk with higher omega-3 LCPUFA had reduced allergic manifestations. Earlier introduction of fish improved respiratory health or reduced allergy in four studies. Three randomized controlled trials showed that providing LCPUFA during infancy or childhood reduced allergy and/or respiratory illness while one found no effect. Potential explanations for the variability among studies and possible mechanisms of action for LCPUFA in allergy and respiratory disease are discussed.

  8. Reducing the burden of obesity-associated cancers with anti-inflammatory long-chain omega-3 polyunsaturated fatty acids

    PubMed Central

    Khatib, Subreen A.; Rossi, Emily L.; Bowers, Laura W.; Hursting, Stephen D.

    2016-01-01

    Today’s world population has an unprecedented risk of dying from the consequences of being overweight and obese. Chronic diseases such as cardiovascular disease, type 2 diabetes, and cancer are often accelerated because of excessive adiposity. Various biological mechanisms are implicated in the obesity-cancer link, particularly local and systemic inflammation as well as altered growth factor signaling pathways. In order to combat obesity-induced inflammation and the resulting increases in cancer risk and progression, the identification of safe and effective mechanism-based interventions is imperative. Notably, long chain omega-3 polyunsaturated fatty acids (PUFAs) modulate the secretion of pro-inflammatory cytokines, prostaglandins and other inflammatory mediators, restore insulin sensitivity, and can prevent or delay tumorigenesis. Delineating the precise mechanisms by which omega-3 PUFAs suppress obesity-induced inflammation will help identify promising key mechanistic targets and intervention strategies to break the obesity-cancer link. PMID:27448716

  9. Effects of Long-Chain Polyunsaturated Fatty Acid Supplementation of Infant Formula on Cognition and Behaviour at 9 Years of Age

    ERIC Educational Resources Information Center

    de Jong, Corina; Kikkert, Hedwig K.; Fidler, Vaclav; Hadders-Algra, Mijna

    2012-01-01

    Aim: Long-chain polyunsaturated fatty acid (LCPUFA) supplementation of infant formula may have a beneficial effect on cognitive development. This study aimed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years. Special attention was paid to the potentially modifying effect…

  10. Three Randomized Controlled Trials of Early Long-Chain Polyunsaturated Fatty Acid Supplementation on Means-End Problem Solving in 9-Month-Olds

    ERIC Educational Resources Information Center

    Drover, James; Hoffman, Dennis R.; Castaneda, Yolanda S.; Morale, Sarah E.; Birch, Eileen E.

    2009-01-01

    This study examines whether feeding infants formula supplemented with long-chain polyunsaturated fatty acids (LCPUFA) improves cognitive function of 9-month-olds. Participants included 229 infants from 3 randomized controlled trials. Children received either formula supplemented with docosahexaenoic acid and arachidonic acid, or a control formula…

  11. Effects of Long-Chain Polyunsaturated Fatty Acid Supplementation of Infant Formula on Cognition and Behaviour at 9 Years of Age

    ERIC Educational Resources Information Center

    de Jong, Corina; Kikkert, Hedwig K.; Fidler, Vaclav; Hadders-Algra, Mijna

    2012-01-01

    Aim: Long-chain polyunsaturated fatty acid (LCPUFA) supplementation of infant formula may have a beneficial effect on cognitive development. This study aimed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years. Special attention was paid to the potentially modifying effect…

  12. Three Randomized Controlled Trials of Early Long-Chain Polyunsaturated Fatty Acid Supplementation on Means-End Problem Solving in 9-Month-Olds

    ERIC Educational Resources Information Center

    Drover, James; Hoffman, Dennis R.; Castaneda, Yolanda S.; Morale, Sarah E.; Birch, Eileen E.

    2009-01-01

    This study examines whether feeding infants formula supplemented with long-chain polyunsaturated fatty acids (LCPUFA) improves cognitive function of 9-month-olds. Participants included 229 infants from 3 randomized controlled trials. Children received either formula supplemented with docosahexaenoic acid and arachidonic acid, or a control formula…

  13. Spray-dried structured lipid containing long-chain polyunsaturated fatty acids for use in infant formulas.

    PubMed

    Nagachinta, Supakana; Akoh, Casimir C

    2013-10-01

    Human milk fat (HMF) analogs are structured lipids (SLs) modified to have palmitic acid content at the sn-2 position of the triacylglycerol (TAG) and fatty acid composition comparable to HMF. Some of these SLs are also designed to incorporate long-chain polyunsaturated fatty acids (LCPUFAs) because of their important role in infant development. In this study, Maillard reaction products (MRPs), obtained from heated whey protein isolates and corn syrup solids (CSS) solution, were used as encapsulants for microencapsulation of 2 enzymatically synthesized SLs for infant formula applications. The encapsulated SL powders were obtained through spray-drying and evaluated in terms of their microencapsulation efficiency, chemical and physical properties, oxidative stability, and dispersibility. The microencapsulation efficiency of the SLs was 90%. Dispersibility test using particle size measurement demonstrated that these powders dispersed quickly into a homogeneous suspension. The encapsulated SL powders had low peroxide and thiobarbituric acid-reactive substances values. Lower oxidative stability was obtained in the powder containing SL with a higher degree of unsaturation and a lower concentration of tocopherols. The results demonstrated that the degree of fatty acid unsaturation and concentration of endogenous antioxidant in starting oils influenced the oxidative stability of the encapsulated SLs.

  14. Combinations of distinct long-chain polyunsaturated fatty acid species for improved dietary treatment against allergic bronchial asthma.

    PubMed

    Beermann, Christopher; Neumann, Sandy; Fußbroich, Daniela; Zielen, Stefan; Schubert, Ralf

    2016-01-01

    Allergic bronchial asthma is a chronic inflammatory disease of the airways with an increasing incidence in Western societies. Exposure to allergens provokes recurrent attacks of breathlessness, airway hyperreactivity, wheezing, and coughing. For the early phase and milder forms of allergic asthma, dietary supplementation with long-chain polyunsaturated fatty acids (LCPUFA), predominantly fish oil-associated eicosapentaenoic (C20:5 ω-3) and docosahexaenoic acid (C22:6 ω-3), and distinct crop oil-derived fatty acids might provide a sustainable treatment strategy, as discussed in several studies. In addition to immune-controlling prostaglandins, leukotrienes, and thromboxanes, specialized proresolving mediators, such as lipoxins, resolvins, protectins, and maresins, are metabolized from different LCPUFA, which actively resolve inflammation. The aim of this review was to discuss the possible synergistic effects of ω-3 and ω-6 LCPUFA combinations concerning rebuilding fatty acid homeostasis in cellular membranes, modifying eicosanoid metabolic pathways, controlling inflammatory processes by focusing on resolving inflammation in the bronchoalveolar system on the cellular level, and helping to control clinical symptoms in bronchial asthma.

  15. Biosynthetic mechanism of very long chain polyunsaturated fatty acids in Thraustochytrium sp. 26185[S

    PubMed Central

    Meesapyodsuk, Dauenpen; Qiu, Xiao

    2016-01-01

    Thraustochytrium, a unicellular marine protist, has been used as a commercial source of very long chain PUFAs (VLCPUFAs) such as DHA (22:6n-3). Our recent work indicates coexistence of a Δ4-desaturation-dependent pathway (aerobic) and a polyketide synthase-like PUFA synthase pathway (anaerobic) to synthesize the fatty acids in Thraustochytrium sp. 26185. Heterologous expression of the Thraustochytrium PUFA synthase along with a phosphopantetheinyl transferase in Escherichia coli showed the anaerobic pathway was highly active in the biosynthesis of VLCPUFAs. The amount of Δ4 desaturated VLCPUFAs produced reached about 18% of the total fatty acids in the transformant cells at day 6 in a time course of the induced expression. In Thraustochytrium, the expression level of the PUFA synthase gene was much higher than that of the Δ4 desaturase gene, and also highly correlated with the production of VLCPUFAs. On the other hand, Δ9 and Δ12 desaturations in the aerobic pathway were either ineffective or absent in the species, as evidenced by the genomic survey, heterologous expression of candidate genes, and in vivo feeding experiments. These results indicate that the anaerobic pathway is solely responsible for the biosynthesis for VLCPUFAs in Thraustochytrium. PMID:27527703

  16. Essential and long-chain polyunsaturated fatty acid status and fatty acid composition of breast milk of lactating adolescents.

    PubMed

    Meneses, Flávia; Torres, Alexandre G; Trugo, Nádia M F

    2008-11-01

    The aims of the present study were to evaluate essential fatty acids (EFA) and long-chain PUFA (LCPUFA) status in lactating adolescents and its association with breast milk composition. Healthy nursing adolescents from Rio de Janeiro, Brazil (n 30; 14-19 years; 30-120 d postpartum), exclusively or predominantly breast-feeding, participated in this study. Breast milk and blood samples were collected after overnight fasting. Fatty acid composition of breast milk, erythrocyte membrane (EM) and plasma NEFA were determined by GC. Indices of fatty acid status (mean melting point (MMP); EFA status index; DHA status indices, 22 : 5n-6:22 : 4n-6 and 22 : 6n-3:22 : 5n-6 ratios) were calculated from EM fatty acid composition. Dietary intake of n-3 fatty acids was low when compared with current recommendations for lactating women. MMP was associated with indices of DHA status, some individual fatty acids in EM and years post-menarche and weeks postpartum, suggesting the use of erythrocyte MMP as a possible comprehensive biochemical marker of LCPUFA status in this physiological condition. The DHA status of lactating adolescents and their milk DHA concentrations were similar to the values of Brazilian lactating adults, but lower compared with the values of lactating adults from other countries. Therefore, these lactating adolescents were apparently not disadvantaged, as compared with the Brazilian adults, when EM and breast milk fatty acid composition were considered. In general, PUFA in milk from adolescents presented few associations with their concentrations in plasma NEFA and with maternal status. However, milk DHA was associated with maternal LCPUFA and DHA states.

  17. Comparison of triglycerides and phospholipids as supplemental sources of dietary long-chain polyunsaturated fatty acids in piglets.

    PubMed

    Mathews, Susan A; Oliver, William T; Phillips, Oulayvanh T; Odle, Jack; Diersen-Schade, Deborah A; Harrell, Robert J

    2002-10-01

    Addition of arachidonic acid (AA) and docosahexaenoic acid (DHA) to infant formula promotes visual and neural development. This study was designed to determine whether the source of dietary long-chain polyunsaturated fatty acids (LCPUFA) affected overall animal health and safety. Piglets consumed ad libitum from 1 to 16 d of age a skim milk-based formula with different fat sources added to provide 50% of the metabolizable energy. Treatment groups were as follows: control (CNTL; no added LCPUFA), egg phospholipid (PL), algal/fungal triglyceride (TG) oils, TG plus PL (soy lecithin source) added to match phospholipid treatment (TG + PL) and essential fatty acid deficient (EFAD). Formulas with LCPUFA provided 0.6 and 0.3 g/100 g total fatty acids as AA and DHA, respectively. CNTL piglets had 40% longer ileal villi than PL piglets (P < 0.03), but the TG group was not different from the CNTL group. Gross liver histology did not differ among any of the formula-fed groups (P > 0.1). Apparent dry matter digestibility was 10% greater in CNTL, TG and TG + PL groups compared with PL piglets (P < 0.002). No differences in alanine aminotransferase were detected among treatments, but aspartate aminotransferase was elevated (P < 0.03) in PL piglets compared with TG + PL piglets. Total plasma AA concentration was greater in the TG group compared with CNTL piglets (P < 0.05). Total plasma DHA concentrations were greater in TG piglets compared with PL (P < 0.06) or CNTL (P < 0.02) piglets. These data demonstrate that the algal/fungal TG sources of DHA and AA may be a more appropriate supplement for infant formulas than the egg PL source based on piglet plasma fatty acid profiles and apparent dry matter digestibilities.

  18. Heterotrophic Production of Omega-3 Long-Chain Polyunsaturated Fatty Acids by Trophically Converted Marine Diatom Phaeodactylum tricornutum

    PubMed Central

    Hamilton, Mary L.; Powers, Stephen; Napier, Johnathan A.; Sayanova, Olga

    2016-01-01

    We have created via metabolic engineering a heterotrophic strain of Phaeodactylum tricornutum that accumulates enhanced levels of the high value omega-3 long chain polyunsaturated fatty acid (LC-PUFAs) docosahexaenoic acid (DHA). This was achieved by generation of transgenic strains in which the Δ5-elongase from Ostreococcus tauri was co-expressed with a glucose transporter from the moss Physcomitrella patens. This double transformant has the capacity to grow in the dark in liquid medium supplemented with glucose and accumulate substantial levels of omega-3 LC-PUFAs. The effects of glucose concentrations on growth and LC-PUFA production of wild type and transformed strains cultivated in the light and dark were studied. The highest omega-3 LC-PUFAs accumulation was observed in cultures grown under mixotrophic conditions in the presence of 1% glucose (up to 32.2% of total fatty acids, TFA). Both DHA and EPA are detected at high levels in the neutral lipids of transgenic cells grown under phototrophic conditions, averaging 36.5% and 23.6% of TFA, respectively. This study demonstrates the potential for P. tricornutum to be developed as a viable commercial strain for both EPA and DHA production under mixo- and heterotrophic conditions. PMID:27005636

  19. Meta-Analysis of Long-Chain Omega-3 Polyunsaturated Fatty Acids (LCω-3PUFA) and Prostate Cancer

    PubMed Central

    Alexander, Dominik D.; Bassett, Julie K.; Weed, Douglas L.; Barrett, Erin Cernkovich; Watson, Heather; Harris, William

    2015-01-01

    We conducted a systematic review and meta-analysis to estimate the potential association between LCω-3PUFAs and prostate cancer (PC). A comprehensive literature search was performed through 2013 to identify prospective studies that examined dietary intakes of long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) or blood biomarkers of LCω-3PUFA status and risk of PC. Random-effects meta-analyses were conducted to generate summary relative risk estimates (SRREs) for LCω-3PUFAs and total PC, and by stage and grade. Subgroup analyses were also conducted for specific fatty acids and other study characteristics. Twelve self-reported dietary intake and 9 biomarker studies from independent study populations were included in the analysis, with 446,243 and 14,897 total participants, respectively. No association between LCω-3PUFAs and total PC was observed (SRRE = 1.00, 95% CI: 0.93–1.09) for the dietary intake studies (high vs. low LCω-3PUFAs category comparison) or for the biomarker studies (SRRE of 1.07, 95% CI: 0.94–1.20). In general, most summary associations for the dietary intake studies were in the inverse direction, whereas the majority of summary associations for the biomarker studies were in the positive direction, but all were weak in magnitude. The results from this meta-analysis do not support an association between LCω-3PUFAs and PC. PMID:25826711

  20. Long-chain polyunsaturated fatty acid supplementation in infants born at term.

    PubMed

    Simmer, Karen; Patole, Sanjay K; Rao, Shripada C

    2011-12-07

    The n-3 and n-6 fatty acids linolenic acid and linoleic acid are precursors of the n-3 and n-6 long chain fatty acids (LCPUFA). Infant formula has historically only contained the precursor fatty acids. Over the last few years, some manufacturers have added LCPUFA to formulae and marketed them as providing an advantage for the development of term infants. To assess whether supplementation of formula with LCPUFA is safe and of benefit to term infants. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, April, 2011), MEDLINE (1966 to April 2011), EMBASE (1980 to April 2011), CINAHL (December 1982 to April 2011) and abstracts of the Society for Pediatric Research (1980 to 2010). No language restrictions were applied. Randomised and quasi randomised trials comparing LCPUFA supplemented vs. non-supplemented formula milk and with clinical endpoints were reviewed. Methodological quality of studies was assessed using the guidelines of Cochrane neonatal review group. Data were sought regarding effects on visual acuity, neurodevelopmental outcomes and physical growth. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. Twenty-five randomised studies were identified; fifteen were included (n = 1889) and ten excluded.Visual acuity was assessed by nine studies. Visual evoked potential was used in six studies, two used Teller cards and one used both. Four studies reported beneficial effects while the remaining five did not.Neurodevelopmental outcome was measured by eleven studies. Bayley scales of infant development (BSID) was used in nine studies; only two showed beneficial effects. Meta-analysis did not show significant benefits of supplementation. One study followed the infants up to nine years of age and did not find benefit of supplementation. One study reported better novelty preference measured by Fagan Infant test at nine months. Another study reported better problem solving at 10 months. One study used

  1. Reduced Maternal Erythrocyte Long Chain Polyunsaturated Fatty Acids Exist in Early Pregnancy in Preeclampsia.

    PubMed

    Wadhwani, Nisha S; Narang, Ankita S; Mehendale, Savita S; Wagh, Girija N; Gupte, Sanjay A; Joshi, Sadhana R

    2016-01-01

    The present prospective study examines proportions of maternal erythrocyte fatty acids across gestation and their association with cord erythrocyte fatty acids in normotensive control (NC) and preeclamptic pregnancies. We hypothesize that maternal fatty acid status in early pregnancy influences fetal fatty acid stores in preeclampsia. 137 NC women and 58 women with preeclampsia were included in this study. Maternal blood was collected at 3 time points during pregnancy (16-20th weeks, 26-30th weeks and at delivery). Cord blood was collected at delivery. Fatty acids were analyzed using gas chromatography. The proportions of maternal erythrocyte α-linolenic acid, docosahexaenoic acid, nervonic acid, and monounsaturated fatty acids (MUFA) (p < 0.05 for all) were lower while total n-6 fatty acids were higher (p < 0.05) at 16-20th weeks of gestation in preeclampsia as compared with NC. Cord 18:3n-3, 22:6n-3, 24:1n-9, MUFA, and total n-3 fatty acids (p < 0.05 for all) were also lower in preeclampsia as compared with NC. A positive association was observed between maternal erythrocyte 22:6n-3 and 24:1n-9 at 16-20th weeks with the same fatty acids in cord erythrocytes (p < 0.05 for both) in preeclampsia. Our study for the first time indicates alteration in maternal erythrocyte fatty acids at 16th weeks of gestation which is further reflected in cord erythrocytes at delivery in preeclampsia.

  2. Ceramides and sphingomyelins with high proportions of very long-chain polyunsaturated fatty acids in mammalian germ cells.

    PubMed

    Furland, Natalia E; Zanetti, Samanta R; Oresti, Gerardo M; Maldonado, Eduardo N; Aveldaño, Marta I

    2007-06-22

    Very long-chain polyunsaturated fatty acids (VLCPUFA) have previously been shown to be components of sphingomyelin (SM) of mammalian testis and spermatozoa. Here we examined the fatty acids of testicular ceramide (Cer) in comparison with those of SM in some mammals with a special focus on the rat testis. In bull, cat, dog, rabbit, mouse, and rat, VLCPUFA were found in both testicular lipids, Cer having a higher percentage of VLCPUFA than SM. Rat testis had the highest percentage of VLCPUFA in both lipids, the major ones being 28:4n-6 and 30:5n-6. VLCPUFA-containing SM and Cer occurred in cells located in the seminiferous tubules, where germ cells had a higher percentage of these species than Sertoli cells. Seminiferous tubule fractionation showed that SM and Cer of mitochondria and lysosomes had mostly saturates and negligible VLCPUFA, the latter being important in the SM and Cer of microsomes and other membrane fractions. VLCPUFA were absent from the SM and Cer of rat prepuberal testis, increased with the onset of spermatogenesis to account for nearly 15 and 40% of the total fatty acids of testicular SM and Cer, respectively, remained at those levels throughout the adult life of fertile rats and tended to decrease at advanced ages. Four conditions that lead to selective death of germ cells in vivo, namely experimental cryptorchidism, post-ischemic reperfusion, focalized x-ray irradiation and treatments with the antineoplasic drug doxorubicin, caused the VLCPUFA to disappear from the testicular SM and Cer of adult fertile rats, showing that these lipids are specific traits of spermatogenic cells.

  3. Long-chain polyunsaturated fatty acid supplementation in infants born at term.

    PubMed

    Simmer, K; Patole, S K; Rao, S C

    2008-01-23

    The n-3 and n-6 fatty acids linolenic acid and linoleic acid are precursors of the n-3 and n-6 long chain fatty acids (LCPUFA). Infant formula has historically only contained the precursor fatty acids. Controversy exists over whether LCPUFA are also essential nutrients in infancy. Over the last few years, some manufacturers have added LCPUFA to formulae and marketed them as providing an advantage for the development of term infants. To assess whether supplementation of formula with LCPUFA is safe and of benefit to term infants. Eligible studies were identified by searching MEDLINE (March 2007), EMBASE 1980 - 2007, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007) and CINAHL (December 1982 - March 2007). Abstracts of the Society for Pediatric Research were hand searched from 1980 to 2006 inclusive. Reference lists of published narrative and systematic reviews were also reviewed. No language restrictions were applied. All randomised and quasi randomised trials comparing LCPUFA supplemented formula milk vs. non-supplemented formula milk and with clinical endpoints were reviewed. Methodological quality of eligible studies was assessed according to allocation concealment, blinding of intervention, blinding of outcome assessment and completeness of follow up. Data were sought regarding effects on visual acuity, neurodevelopmental outcomes and physical growth. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. Continuous data were analysed using weighted mean difference (WMD). There were no categorical outcomes in this review. Twenty randomised studies were identified. Fourteen were included (n = 1719) and six excluded. Eleven included studies were of good quality. The main outcomes assessed were visual acuity, neurodevelopmental and physical growth. Visual acuity was measured at various stages throughout the first three years of life by nine studies. Visual evoked potential was used to assess

  4. Climate warming is predicted to reduce omega-3, long-chain, polyunsaturated fatty acid production in phytoplankton.

    PubMed

    Hixson, Stefanie M; Arts, Michael T

    2016-08-01

    Phytoplankton are the main source of energy and omega-3 (n-3) long-chain essential fatty acids (EFA) in aquatic ecosystems. Their growth and biochemical composition are affected by surrounding environmental conditions, including temperature, which continues to increase as a result of climate warming. Increasing water temperatures may negatively impact the production of EFA by phytoplankton through the process of homeoviscous adaptation. To investigate this, we conducted an exploratory data synthesis with 952 fatty acid (FA) profiles from six major groups of marine and freshwater phytoplankton. Temperature was strongly correlated with a decrease in the proportion of n-3 long-chain polyunsaturated FA (LC-PUFA) and an increase in omega-6 FA and saturated FA. Based on linear regression models, we predict that global n-3 LC-PUFA production will be reduced by 8.2% for eicosapentaenoic acid (EPA) and 27.8% for docosahexaenoic acid (DHA) with an increase in water temperature of 2.5 °C. Using a previously published estimate of the global production of EPA by diatoms, which contribute to most of the world's supply of EPA, we predict a loss of 14.2 Mt of EPA annually as a result of ocean warming. The n-3 LC-PUFA are vitally important for an array of key physiological functions in aquatic and terrestrial organisms, and these FA are mainly produced by phytoplankton. Therefore, reduced production of these EFA, as a consequence of climate warming, is predicted to negatively affect species that depend on these compounds for optimum physiological function. Such profound changes in the biochemical composition of phytoplankton cell membranes can lead to cascading effects throughout the world's ecosystems. © 2016 John Wiley & Sons Ltd.

  5. Enhancing the accumulation of omega-3 long chain polyunsaturated fatty acids in transgenic Arabidopsis thaliana via iterative metabolic engineering and genetic crossing.

    PubMed

    Ruiz-López, Noemi; Haslam, Richard P; Venegas-Calerón, Mónica; Li, Tianbi; Bauer, Joerg; Napier, Johnathan A; Sayanova, Olga

    2012-12-01

    The synthesis and accumulation of long chain polyunsaturated fatty acids such as eicosapentaenoic acid has previously been demonstrated in the seeds of transgenic plants. However, the obtained levels are relatively low, indicating the need for further studies and the better definition of the interplay between endogenous lipid synthesis and the non-native transgene-encoded activities. In this study we have systematically compared three different transgenic configurations of the biosynthetic pathway for eicosapentaenoic acid, using lipidomic profiling to identify metabolic bottlenecks. We have also used genetic crossing to stack up to ten transgenes in Arabidopsis. These studies indicate several potential approaches to optimize the accumulation of target fatty acids in transgenic plants. Our data show the unexpected channeling of heterologous C20 polyunsaturated fatty acids into minor phospholipid species, and also the apparent negative metabolic regulation of phospholipid-dependent Δ6-desaturases. Collectively, this study confirms the benefits of iterative approaches to metabolic engineering of plant lipid synthesis.

  6. Maternal intake of seafood and supplementary long chain n-3 poly-unsaturated fatty acids and preterm delivery.

    PubMed

    Brantsæter, Anne Lise; Englund-Ögge, Linda; Haugen, Margareta; Birgisdottir, Bryndis Eva; Knutsen, Helle Katrine; Sengpiel, Verena; Myhre, Ronny; Alexander, Jan; Nilsen, Roy M; Jacobsson, Bo; Meltzer, Helle Margrete

    2017-01-19

    Preterm delivery increases the risk of neonatal morbidity and mortality. Studies suggest that maternal diet may affect the prevalence of preterm delivery. The aim of this study was to assess whether maternal intakes of seafood and marine long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) from supplements were associated with preterm delivery. The study population included 67,007 women from the Norwegian Mother and Child Cohort Study. Maternal food and supplement intakes were assessed by a validated self-reported food frequency questionnaire in mid-pregnancy. Information about gestational duration was obtained from the Medical Birth Registry of Norway. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between total seafood, lean fish, fatty fish, and LCn-3PUFA intakes and preterm delivery. Preterm was defined as any onset of delivery before gestational week 37, and as spontaneous or iatrogenic deliveries and as preterm delivery at early, moderate, and late preterm gestations. Lean fish constituted 56%, fatty fish 34% and shellfish 10% of seafood intake. Any intake of seafood above no/rare intake (>5 g/d) was associated with lower prevalence of preterm delivery. Adjusted HRs were 0.76 (CI: 0.66, 0.88) for 1-2 servings/week (20-40 g/d), 0.72 (CI: 0.62, 0.83) for 2-3 servings/week (40-60 g/d), and 0.72 (CI: 0.61, 0.85) for ≥3 servings/week (>60 g/d), p-trend <0.001. The association was seen for lean fish (p-trend: 0.005) but not for fatty fish (p-trend: 0.411). The intake of supplementary LCn-3PUFA was associated only with lower prevalence of early preterm delivery (before 32 gestational weeks), while increasing intake of LCn-3PUFA from food was associated with lower prevalence of overall preterm delivery (p-trend: 0.002). Any seafood intake above no/rare was associated with lower prevalence of both spontaneous and iatrogenic preterm delivery, and with lower prevalence of late preterm delivery. Any

  7. Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome.

    PubMed

    Vargas, M Luisa; Almario, Rogelio U; Buchan, Wendy; Kim, Kyoungmi; Karakas, Sidika E

    2011-12-01

    The objective of the study was to compare the effects of essential vs long-chain omega (n)-3 polyunsaturated fatty acids (PUFAs) in polycystic ovary syndrome. In this 6-week, prospective, double-blinded, placebo (soybean oil)-controlled study, 51 completers received 3.5 g n-3 PUFA per day (essential PUFA from flaxseed oil or long-chain PUFA from fish oil). Anthropometric variables, cardiovascular risk factors, and androgens were measured; oral glucose tolerance test (OGTT) and frequently sampled intravenous GTT (IVGTT) were conducted at baseline and 6 weeks. Between-group comparisons showed significant differences in serum triglyceride response (P = .0368), whereas the changes in disposition index also tended to differ (P = .0621). When within-group changes (after vs before intervention) were considered, fish oil and flaxseed oil lowered serum triglyceride (P = .0154 and P = .0176, respectively). Fish oil increased glucose at 120 minutes of OGTT (P = .0355), decreased the Matsuda index (P = .0378), and tended to decrease acute insulin response during IVGTT (P = .0871). Soybean oil increased glucose at 30 (P = .0030) and 60 minutes (P = .0121) and AUC for glucose (P = .0122) during OGTT, tended to decrease acute insulin response during IVGTT (P = .0848), reduced testosterone (P = .0216), and tended to reduce sex hormone-binding globulin (P = .0858). Fasting glucose, insulin, adiponectin, leptin, or high-sensitivity C-reactive protein did not change with any intervention. Long-chain vs essential n-3 PUFA-rich oils have distinct metabolic and endocrine effects in polycystic ovary syndrome; and therefore, they should not be used interchangeably.

  8. Effect of Long-Chain Polyunsaturated Fatty Acid Supplementation on Neurodevelopmental Outcome in Full-Term Infants

    PubMed Central

    Hadders-Algra, Mijna

    2010-01-01

    It takes more than 20 years before the human brain obtains its complex, adult configuration. Most dramatic developmental changes occur prenatally and early postnatally. During development, long-chain polyunsaturated fatty acids (LCPUFA) such as doxosahexaenoic acid (DHA) and arachidonic acid (AA) are accreted in the brain. Since breastfeeding is associated with a better developmental outcome than formula feeding, and human milk in contrast to traditional standard formula contains LCPUFA, the question arose whether LCPUFA supplementation of infant formula may promote the neurodevelopmental outcome. The current paper reviews the evidence available in full-term infants. It concludes that postnatal supplementation of formula with LCPUFA is associated with a beneficial effect on short-term neurodevelopmental outcome. However, no evidence is available that LCPUFA supplementation enhances neurodevelopmental outcome in full-term infants beyond the age of four months. Nevertheless, it should be realized that very limited information is available on the effect of LCPUFA supplementation on neurodevelopmental outcome at school age or later. It is conceivable that effects of LCPUFA supplementation first emerge or re-emerge at school age when more complex neural functions are expressed. PMID:22254056

  9. Differential levels of long chain polyunsaturated fatty acids in women with preeclampsia delivering male and female babies.

    PubMed

    Roy, Suchitra; Dhobale, Madhavi; Dangat, Kamini; Mehendale, Savita; Wagh, Girija; Lalwani, Sanjay; Joshi, Sadhana

    2014-11-01

    Maternal long chain polyunsaturated fatty acids (LCPUFA) play a key role in fetal growth and development. This study for the first time examines the maternal and cord LCPUFA levels in preeclamptic mothers delivering male and female infants. In this study 122 normotensive control pregnant women (gestation≥37 weeks) and 90 women with preeclampsia were recruited. Results indicate lower maternal plasma docosahexaenoic acid (DHA) levels (p<0.05) in women with preeclampsia delivering male babies as compared to normotensive control women delivering male babies. Similarly, cord nervonic acid levels were lower (p<0.01) in women with preeclampsia delivering male babies as compared to normotensive control group. However, cord nervonic acid levels were comparable in women with preeclampsia and normotensive control women delivering female babies. This data suggests that male babies born to mothers with preeclampsia may be at an increased risk of developing neurodevelopmental disorders as compared to female babies. Future studies need to follow up both male and female children born to mothers with preeclampsia since altered levels of LCPUFA at birth may have differential implications for the growth and development.

  10. A reduced cost strategy for enriching chicken meat with omega-3 long chain polyunsaturated fatty acids using dietary flaxseed oil.

    PubMed

    Kanakri, K; Carragher, J; Hughes, R; Muhlhausler, B; Gibson, R

    2017-06-01

    1. This study aimed to determine the minimal duration required for feeding male broilers (Cobb 500) with a flaxseed oil diet while still retaining long chain omega-3 polyunsaturated fatty acid (n-3 LCPUFA) accumulation in the meat at a desirable level. 2. Three groups of broilers (60 each) were fed on a 3% flaxseed oil (high α-linolenic acid (ALA)) diet for either 6, 4 or 2 weeks prior to slaughter. During the remaining time they were maintained on a 3% macadamia oil (low ALA) diet. A fourth group (control, n = 60) was fed on a commercial diet for 6 weeks. 3. No significant difference was observed in growth performance of broilers between groups. The amounts of total n-3 and n-3 LCPUFA in breast and thigh meat were not different between broilers fed the flaxseed oil diet for 4 and 6 weeks, but they were lower (P < 0.001) in those fed the flaxseed diet for only 2 weeks. 4. These results suggest comparable levels of n-3 LCPUFA in the meat can be achieved by only feeding the flaxseed oil diet in the last 3-4 weeks of the growth period; this would result in a ≥ 9.4% reduction in the use of flaxseed oil compared to 6 weeks of feeding; thereby reducing the cost of the enrichment process.

  11. Test meals rich in marine long-chain n-3 polyunsaturated fatty acids increase postprandial chylomicron response.

    PubMed

    Griffo, E; Di Marino, L; Patti, L; Bozzetto, L; Annuzzi, G; Cipriano, P; Mangione, A; Della Pepa, G; Cocozza, S; Riccardi, G; Rivellese, A A

    2014-08-01

    Postprandial lipid abnormalities are considered an independent cardiovascular risk factor. Hence, it is important to find nutritional strategies that are able to positively influence these abnormalities. Since the effect of n-3 polyunsaturated fatty acids (PUFA) and polyphenols on postprandial lipids in humans is still under debate, we evaluated the acute response of triglyceride-rich lipoproteins to test meals that are naturally rich in polyphenols and/or marine long-chain (LC) n-3 PUFAs. We hypothesized that LC n-3 PUFA would have a different effect on chylomicron and very low density lipoproteins when compared with polyphenols or their combination. We randomly assigned 78 individuals who were at high cardiometabolic risk to 4 isoenergetic diets. These diets only differed in amount of LC n-3 PUFA and/or polyphenols. Prior to starting the intervention, each subject underwent a test meal similar to the type of diet assigned: low in LC n-3 PUFA and polyphenols (control), rich in LC n-3 PUFA and low in polyphenols, rich in polyphenols and low in LC n-3 PUFA, or rich in both. Blood samples were taken before and up to 6 hours after the test meal in order to evaluate cholesterol and triglycerides (plasma and triglyceride-rich lipoprotein), apolipoprotein B-48 (large very low density lipoprotein), glucagon-like peptide-1, and free fatty acid plasma levels. The levels of chylomicron cholesterol and triglyceride in response to the test meal rich in LC n-3 PUFA were significantly higher than after the control meal (P = .037 and P = .018); there was no difference in the other variables. In conclusion, this study indicates that acute administration of marine LC n-3 PUFA increases postprandial chylomicron response in contrast with their lowering chronic effects. These differences underline the importance of understanding the acute and chronic effects of nutritional, as well as of other types of, interventions.

  12. Supplementation with long chain polyunsaturated fatty acids in treatment of atopic dermatitis in children

    PubMed Central

    Kaczmarski, Maciej; Sawicka-Żukowska, Małgorzata; Bobrus-Chociej, Anna

    2013-01-01

    Some recent studies indicate that unsaturated fatty acids, components of cellular membranes and precursors of immunomodulators, play a significant role in the pathogenesis of some symptoms of atopic dermatitis. Since they cannot be synthesized by the human body, they must be provided with nutrition as the so called exogenous fatty acids: linoleic (a precursor of arachidonic acid) and α-linolenic acid (a precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)). Their deficiency facilitates the development of some disorders, e.g. of the cardiovascular system or of the nervous system, or becomes the cause of intensification of ailments in their course e.g. pruritus and dryness in atopic dermatitis. Though clinical examinations to date confirm the efficacy of fatty acid supplementation in treatment of atopic dermatitis, their results are not explicit. PMID:24278056

  13. Long-chain polyunsaturated fatty acid biosynthesis in the euryhaline herbivorous teleost Scatophagus argus: Functional characterization, tissue expression and nutritional regulation of two fatty acyl elongases.

    PubMed

    Xie, Dizhi; Chen, Fang; Lin, Siyuan; You, Cuihong; Wang, Shuqi; Zhang, Qinghao; Monroig, Óscar; Tocher, Douglas R; Li, Yuanyou

    2016-08-01

    Both the spotted scat Scatophagus argus and rabbitfish Siganus canaliculatus belong to the few cultured herbivorous marine teleost, however, their fatty acyl desaturase (Fad) system involved in long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis is different. The S. argus has a △6 Fad, while the rabbitfish has △4 and △6/△5 Fads, which were the first report in vertebrate and marine teleost, respectively. In order to compare the characteristics of elongases of very long-chain fatty acids (Elovl) between them, two Elovl cDNAs were cloned from S. argus in the present study. One has 885bp of open read fragment (ORF) encoding a protein with 294 amino acid (aa) showing Elovl5 activity functionally characterized by heterologous expression in yeast, which was primarily active for the elongation of C18 and C20 PUFAs. The other has 915bp of ORF coding for a 305 aa protein showing Elovl4 activity, which was more efficient in the elongation of C20 and C22 PUFAs. Tissue distribution analyses by RT-PCR showed that elovl5 was highly expressed in the liver compared to other tissues determined, whereas elovl4 transcripts were only detected in the eye. The expression of elovl5 and elovl4 were significantly affected by dietary fatty acid composition, with highest expression of mRNA in the liver and eye of fish fed a diet with an 18:3n-3/18:2n-6 ratio of 1.7:1. These results indicated that the S. argus has a similar Elovl system in the LC-PUFA biosynthetic pathway to that of rabbitfish although their Fad system was different, suggesting that the diversification of fish LC-PUFA biosynthesis specificities is more associated with its Fad system. These new insights expand our knowledge and understanding of the molecular basis and regulation of LC-PUFA biosynthesis in fish. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Hypothalamic fatty acid sensing in Senegalese sole (Solea senegalensis): response to long-chain saturated, monounsaturated, and polyunsaturated (n-3) fatty acids.

    PubMed

    Conde-Sieira, Marta; Bonacic, Kruno; Velasco, Cristina; Valente, Luisa M P; Morais, Sofia; Soengas, José L

    2015-12-15

    We assessed the presence of fatty acid (FA)-sensing mechanisms in hypothalamus of Senegalese sole (Solea senegalensis) and investigated their sensitivity to FA chain length and/or level of unsaturation. Stearate (SA, saturated FA), oleate (OA, monounsaturated FA of the same chain length), α-linolenate [ALA, a n-3 polyunsaturated fatty acid (PUFA) of the same chain length], and eicosapentanoate (EPA, a n-3 PUFA of a larger chain length) were injected intraperitoneally. Parameters related to FA sensing and neuropeptide expression in the hypothalamus were assessed after 3 h and changes in accumulated food intake after 4, 24, and 48 h. Three FA sensing systems characterized in rainbow trout were also found in Senegalese sole and were activated by OA in a way similar to that previously characterized in rainbow trout and mammals. These hypothalamic FA sensing systems were also activated by ALA, differing from mammals, where n-3 PUFAs do not seem to activate FA sensors. This might suggest additional roles and highlights the importance of n-3 PUFA in fish diets, especially in marine species. The activation of FA sensing seems to be partially dependent on acyl chain length and degree of saturation, as no major changes were observed after treating fish with SA or EPA. The activation of FA sensing systems by OA and ALA, but not SA or EPA, is further reflected in the expression of hypothalamic neuropeptides involved in the control of food intake. Both OA and ALA enhanced anorexigenic capacity compatible with the activation of FA sensing systems.

  15. The influence of dietary nucleotides and long-chain polyunsaturated fatty acids on the incorporation of [3H] arachidonic acid on experimental liver cirrhosis.

    PubMed

    Leite, L H; Moreira-Vaz, E; Rosa, G; Pereira, A C; Monteiro, C R; Medeiros, F J; Chagas, V L

    2000-09-01

    The purposes of this study were to determine: a) the incorporation of labeled [3H] arachidonic acid on the intestinal mucosa, the liver and plasma, after 1,3 and 5 hours of administration, b) preferential incorporation by different tissues, c) and the effects on experimental rats with thioacetamide-induced cirrhosis, after four weeks of a dietary supplementation with nucleotides and long-chain polyunsaturated fatty acids. 209 female Wistar rats were divided into two groups (control and TAA group). The TAA group was given 300 mg of thioacetamide/L, in their drinking water for four months. After this period, a sample of 6 rats were taken from each group and examined, to evaluate the biochemical and histological changes of the experimental model, and 36 rats were taken to determine the incorporation of radioactivity by the groups. The rest of the animals were divided into four subgroups. Each group, receiving a supplementary diet with only long-chain polyunsaturated fatty acids and/or nucleotides or neither, for 4 weeks. After four months of thioacetamide, the incorporation of the [3H] arachidonic acid showed: a) an increased within 3 h in the intestinal mucosa, b) a decreased in the liver after 3 to 5 h c) and a drastic decrease in the plasma after 3 to 5 h. With a dietary supplementation of long-chain polyunsaturated fatty acids and nucleotides combined, there was a decrease of accumulate [3H] arachidonic acid in the intestine and a increase in the liver and plasma. The simultaneous supply of dietary polyunsaturated fatty acids and nucleotides was beneficial in the reversal of abnormalities of the lipid metabolism, in this experimental model of liver cirrhosis.

  16. Polyunsaturated fatty acids in emerging psychosis.

    PubMed

    Mossaheb, Nilufar; Schloegelhofer, Monika; Schaefer, Miriam R; Fusar-Poli, Paolo; Smesny, Stefan; McGorry, Pat; Berger, Gregor; Amminger, G Paul

    2012-01-01

    The role of polyunsaturated fatty acids and their metabolites for the cause and treatment of psychotic disorders are widely discussed. The efficacy as an augmenting agent in chronic schizophrenia seems to be small or not present, however epidemiological data, as well as some recent controlled studies in emerging psychosis point towards possible preventive effects of long-chain polyunsaturated fatty acids in early and very early stages of psychotic disorders and some potential secondary or tertiary beneficial long-term effects in later, more chronic stages, in particular for metabolic or extra-pyramidal side effects. In this comprehensive review, we describe the physiology and metabolism of polyunsaturated fatty acids, phospholipases, epidemiological evidence and the effect of these fatty acids on the brain and neurodevelopment. Furthermore, we examine the available evidence in indicated prevention in emerging psychosis, monotherapy, add-on therapy and tolerability. The neuroprotective potential of n-3 LC-PUFAs for indicated prevention, i.e. delaying transition to psychosis in high-risk populations needs to be further explored.

  17. Field trial evaluation of the accumulation of omega-3 long chain polyunsaturated fatty acids in transgenic Camelina sativa: Making fish oil substitutes in plants

    PubMed Central

    Usher, Sarah; Haslam, Richard P.; Ruiz-Lopez, Noemi; Sayanova, Olga; Napier, Johnathan A.

    2015-01-01

    The global consumption of fish oils currently exceeds one million tonnes, with the natural de novo source of these important fatty acids forming the base of marine foodwebs. Here we describe the first field-based evaluation of a terrestrial source of these essential nutrients, synthesised in the seeds of transgenic Camelina sativa plants via the heterologous reconstitution of the omega-3 long chain polyunsaturated fatty acid biosynthetic pathway. Our data demonstrate the robust nature of this novel trait, and the feasibility of making fish oils in genetically modified crops. Moreover, to our knowledge, this is the most complex example of plant genetic engineering to undergo environmental release and field evaluation. PMID:27066395

  18. Human milk polyunsaturated long-chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy.

    PubMed

    Duchén, K; Casas, R; Fagerås-Böttcher, M; Yu, G; Björkstén, B

    2000-02-01

    changes in PUFA serum phospholipids, particularly for the n-6 PUFA. The AA: EPA ratio in maternal milk was related, however, to the AA:EPA only in serum from non-allergic children, while this was not the case in allergic children. The levels of total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-beta-lactoglobulin S-IgA in milk from mothers of allergic, as compared to non-allergic, children were similar through the first 3 months of lactation. Low levels of n-3 PUFA in human milk, and particularly a high AA:EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti-ovalbumin S-IgA and lower total S-IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low alpha-linolenic acid, C18:3 n-3 (LNA) and n-3 long-chain polyunsaturated fatty acids (LCP) 20-22 carbon chains, but not the levels of S-IgA antibodies to allergens, are related to the development of atopy in children.

  19. Neurophysiologic measures of auditory function in fish consumers: associations with long chain polyunsaturated fatty acids and methylmercury

    PubMed Central

    Dziorny, Adam C.; Orlando, Mark S.; Strain, J. J.; Davidson, Philip W.; Myers, Gary J.

    2012-01-01

    Background Determining if associations exist between child neurodevelopment and environmental exposures, especially low level or background ones, is challenging and dependent upon being able to measure specific and sensitive endpoints. Psychometric or behavioral measures of CNS function have traditionally been used in such studies, but do have some limitations. Auditory neurophysiologic measures examine different nervous system structures and mechanisms, have fewer limitations, can more easily by quantified, and might be helpful testing additions. To date, their use in human epidemiological studies has been limited. We reviewed the use of auditory brainstem responses (ABR) and otoacoustic emissions (OAE) in studies designed to determine the relationship of exposures to methyl mercury (MeHg) and nutrients from fish consumption with neurological development. We included studies of experimental animals and humans in an effort to better understand the possible benefits and risks of fish consumption. Objectives We reviewed the literature on the use of ABR and OAE to measure associations with environmental exposures that result from consuming a diet high in fish. We focused specifically on long chain polyunsaturated fatty acids (LCPUFA) and MeHg. Methods We performed a comprehensive review of relevant studies using web-based search tools and appropriate search terms. Results Gestational exposure to both LCPUFA and MeHg has been reported to influence the developing auditory system. In experimental studies supplemental LCPUFA is reported to prolong ABR latencies and human studies also suggest an association. Experimental studies of acute and gestational MeHg exposure are reported to prolong ABR latencies and impair hair cell function. In humans, MeHg exposure is reported to prolong ABR latencies, but the impact on hair cell function is unknown. Conclusion The auditory system can provide objective measures and may be useful in studying exposures to nutrients and toxicants

  20. Neurophysiologic measures of auditory function in fish consumers: associations with long chain polyunsaturated fatty acids and methylmercury.

    PubMed

    Dziorny, Adam C; Orlando, Mark S; Strain, J J; Davidson, Philip W; Myers, Gary J

    2013-09-01

    Determining if associations exist between child neurodevelopment and environmental exposures, especially low level or background ones, is challenging and dependent upon being able to measure specific and sensitive endpoints. Psychometric or behavioral measures of CNS function have traditionally been used in such studies, but do have some limitations. Auditory neurophysiologic measures examine different nervous system structures and mechanisms, have fewer limitations, can more easily be quantified, and might be helpful additions to testing. To date, their use in human epidemiological studies has been limited. We reviewed the use of auditory brainstem responses (ABR) and otoacoustic emissions (OAE) in studies designed to determine the relationship of exposures to methyl mercury (MeHg) and nutrients from fish consumption with neurological development. We included studies of experimental animals and humans in an effort to better understand the possible benefits and risks of fish consumption. We reviewed the literature on the use of ABR and OAE to measure associations with environmental exposures that result from consuming a diet high in fish. We focused specifically on long chain polyunsaturated fatty acids (LCPUFA) and MeHg. We performed a comprehensive review of relevant studies using web-based search tools and appropriate search terms. Gestational exposure to both LCPUFA and MeHg has been reported to influence the developing auditory system. In experimental studies supplemental LCPUFA is reported to prolong ABR latencies and human studies also suggest an association. Experimental studies of acute and gestational MeHg exposure are reported to prolong ABR latencies and impair hair cell function. In humans, MeHg exposure is reported to prolong ABR latencies, but the impact on hair cell function is unknown. The auditory system can provide objective measures and may be useful in studying exposures to nutrients and toxicants and whether they are associated with children

  1. Dietary supplementation with long chain omega-3 polyunsaturated fatty acids and weight loss in obese adults.

    PubMed

    Munro, Irene A; Garg, Manohar L

    2013-01-01

    Obesity is associated with elevated levels of inflammation and metabolic abnormalities, with increased risk of developing insulin resistance, type 2 diabetes, stroke and CVD. Nutrients that can assist in weight loss may also reduce the risk of obesity related co-morbidities. The aim of this study was to investigate whether LCn-3PUFA, combined with a reduced energy diet, facilitated weight loss and improvements in blood lipids and inflammatory mediators. A double blind randomised controlled trial with two parallel groups. Both groups followed a low energy diet for 12 weeks, one group consumed 6 × 1 g capsules/d monounsaturated oil (Placebo) (n = 18), the other 6 × 1 g capsules/d LCn-3PUFA (fish oil) (n = 17). Fasting blood samples, anthropometric measurements and 3-day food diaries were collected at baseline and post intervention. There was a two-fold increase in plasma levels of EPA and DHA in the fish oil group (p < 0.001). There were no significant difference within and between the placebo and the fish oil groups for weight reduction (3.37% and 4.35% respectively), fat mass reduction (8.95% and 9.76% respectively), or changes in inflammatory biomarkers and blood lipids apart from triglycerides, reduced by 27% in fish oil group (p < 0.05). For fish oil group there were significant correlations between leptin and weight loss (p = 0.01) and leptin and EPA and DHA (p < 0.05 for both). Dietary LCn-3PUFA supplementation during a weight loss program does not appear to assist weight loss. Poor dietary compliance may be a contributing factor in accurate assessment of the role of these fatty acids in weight loss. Crown Copyright © 2011 Published by Elsevier Ltd on behalf of Asian Oceanian Association for the Study of Obesity. All rights reserved.

  2. Long-chain polyunsaturated fatty acid supplementation in infants born at term.

    PubMed

    Simmer, K

    2001-01-01

    The n-3 and n-6 fatty acids linolenic acid and linoleic acid are precursors of the n-3 and n-6 longchain fatty acids (LCPUFA). Infant formula has historically only contained the precursor fatty acids. Controversy exists over whether LCPUFA are also essential nutrients in infancy. Over the last few years some manufacturers have added LCPUFA to formulae and marketed them as providing an advantage for the development of term infants. The aim of this review is to assess whether supplementation of formula with LCPUFA is safe and of benefit to term infants. Trials were identified by MEDLINE, checking reference lists of articles and conference proceedings, and by personal communication. All randomised trials of formula supplemented with LCPUFA and with clinical endpoints were reviewed. Ten randomised studies were identified. One of these studies was excluded due to supplementation commencing after three weeks of age. Eight of the nine included trials were assessed to be of good quality. There was insufficient information available to assess the quality of the other included trial. Visual acuity was assessed by visual evoked potentials (VEP) at 4 and 7-8 months in the studies of Makrides et al (1995 & 1996). The supplemented infants had an improved rate of visual maturation at both time points in the first study, but no difference was found between the groups at the same time points in the second study. VEP acuity was also assessed in the study of Austed et al (1997) and no effect of supplementation was found at any time point over the first year. This contrasts with the study of Birch et al (1998) where VEP acuity was better in the supplemented group compared with the control group at 6 weeks, 4 and 12 months but not at 6 months. Visual acuity was assessed by Teller acuity cards in the study of Carlson et al (1996), Clausen et al (1996), Austed et al (1997) and Birch et al (1998). Supplementation had no effect on visual acuity over the first year of life except at one of

  3. Towards the Industrial Production of Omega-3 Long Chain Polyunsaturated Fatty Acids from a Genetically Modified Diatom Phaeodactylum tricornutum

    PubMed Central

    Hamilton, Mary L.; Warwick, Joanna; Terry, Anya; Allen, Michael J.; Napier, Johnathan A.; Sayanova, Olga

    2015-01-01

    The marine diatom Phaeodactylum tricornutum can accumulate up to 30% of the omega-3 long chain polyunsaturated fatty acid (LC-PUFA) eicosapentaenoic acid (EPA) and, as such, is considered a good source for the industrial production of EPA. However, P. tricornutum does not naturally accumulate significant levels of the more valuable omega-3 LC-PUFA docosahexaenoic acid (DHA). Previously, we have engineered P. tricornutum to accumulate elevated levels of DHA and docosapentaenoic acid (DPA) by overexpressing heterologous genes encoding enzyme activities of the LC-PUFA biosynthetic pathway. Here, the transgenic strain Pt_Elo5 has been investigated for the scalable production of EPA and DHA. Studies have been performed at the laboratory scale on the cultures growing in up to 1 L flasks a 3.5 L bubble column, a 550 L closed photobioreactor and a 1250 L raceway pond with artificial illumination. Detailed studies were carried out on the effect of different media, carbon sources and illumination on omega-3 LC-PUFAs production by transgenic strain Pt_Elo5 and wild type P. tricornutum grown in 3.5 L bubble columns. The highest content of DHA (7.5% of total fatty acids, TFA) in transgenic strain was achieved in cultures grown in seawater salts, Instant Ocean (IO), supplemented with F/2 nutrients (F2N) under continuous light. After identifying the optimal conditions for omega-3 LC-PUFA accumulation in the small-scale experiments we compared EPA and DHA levels of the transgenic strain grown in a larger fence-style tubular photobioreactor and a raceway pond. We observed a significant production of DHA over EPA, generating an EPA/DPA/DHA profile of 8.7%/4.5%/12.3% of TFA in cells grown in a photobioreactor, equivalent to 6.4 μg/mg dry weight DHA in a mid-exponentially growing algal culture. Omega-3 LC-PUFAs production in a raceway pond at ambient temperature but supplemented with artificial illumination (110 μmol photons m-2s-1) on a 16:8h light:dark cycle, in natural seawater

  4. Event-related potential differences in children supplemented with long-chain polyunsaturated fatty acids during infancy.

    PubMed

    Liao, Ke; McCandliss, Bruce D; Carlson, Susan E; Colombo, John; Shaddy, D Jill; Kerling, Elizabeth H; Lepping, Rebecca J; Sittiprapaporn, Wichian; Cheatham, Carol L; Gustafson, Kathleen M

    2017-09-01

    Long-chain polyunsaturated fatty acids (LCPUFA) have been shown to be necessary for early retinal and brain development, but long-term cognitive benefits of LCPUFA in infancy have not been definitively established. The present study sought to determine whether LCPUFA supplementation during the first year of life would result in group differences in behavior and event-related potentials (ERPs) while performing a task requiring response inhibition (Go/No-Go) at 5.5 years of age. As newborns, 69 children were randomly assigned to infant formulas containing either no LCPUFA (control) or formula with 0.64% of total fatty acids as arachidonic acid (ARA; 20:4n6) and various concentrations of docosahexaenoic acid (DHA; 22:6n3) (0.32%, 0.64% or 0.96%) for the first 12 months of life. At 5.5 years of age, a task designed to test the ability to inhibit a prepotent response (Go/No-Go) was administered, yielding both event-related potentials (ERPs) and behavioral data. Behavioral measures did not differ between groups, although reaction times of supplemented children were marginally faster. Unsupplemented children had lower P2 amplitude than supplemented children to both Go and No-Go conditions. N2 amplitude was significantly higher on No-Go trials than Go trials, but only for supplemented children, resulting in a significant Group × Condition interaction. Topographical analysis of the ERPs revealed that the LCPUFA-supplemented group developed a novel period of synchronous activation (microstate) involving wider anterior brain activation around 200 ms; this microstate was not present in controls. These findings suggest that LCPUFA supplementation during the first 12 months of life exerts a developmental programming effect that is manifest in brain electrophysiology. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=oM2leg4sevs. © 2016 John Wiley & Sons Ltd.

  5. The impact of long-chain n-3 polyunsaturated fatty acids on human health.

    PubMed

    Ruxton, C H S; Calder, P C; Reed, S C; Simpson, M J A

    2005-06-01

    A considerable literature has been published on the health benefits of fish, oil-rich fish and fish oils and their constituent long-chain (LC) n-3 PUFA. Evidence from epidemiological studies highlights the cardioprotective attributes of diets rich in fish, especially oil-rich fish. Data from intervention trials are consistent in suggesting that LC n-3 PUFA lower the risk of CVD, probably by the multiple mechanisms of lowering serum triacylglycerols, improving the LDL:HDL ratio, anti-arrhythmic effects on heart muscle, improved plaque stability, anti-thrombotic effects and reduced endothelial activation. Research indicates LC n-3 PUFA provision has an impact during development, and there is preliminary evidence that docosahexaenoic acid supplementation during pregnancy could optimise brain and retina development in the infant. LC n-3 PUFA are also postulated to ameliorate behavioural and mental health disturbances such as depression, schizophrenia, dementia and attention deficit hyperactivity disorder. However, despite some positive evidence in each of these areas, use of LC n-3 PUFA in these conditions remains at the experimental stage. In the case of immune function, there is little doubt that LC n-3 PUFA have a positive effect. Although intervention trials in rheumatoid arthritis show strong evidence of benefit, evidence for efficacy in other inflammatory conditions, including Crohn's disease, ulcerative colitis, psoriasis, lupus, multiple sclerosis, cystic fibrosis and asthma, is inconsistent or inadequate. More promising evidence in some conditions may come from studies which attempt to modify the fetal environment using LC n-3 PUFA supplementation during pregnancy.

  6. Polyunsaturated Fatty Acids in Children

    PubMed Central

    2013-01-01

    Polyunsaturated fatty acids (PUFAs) are the major components of brain and retina, and are the essential fatty acids with important physiologically active functions. Thus, PUFAs should be provided to children, and are very important in the brain growth and development for fetuses, newborn infants, and children. Omega-3 fatty acids decrease coronary artery disease and improve blood flow. PUFAs have been known to have anti-inflammatory action and improved the chronic inflammation such as auto-immune diseases or degenerative neurologic diseases. PUFAs are used for metabolic syndrome related with obesity or diabetes. However, there are several considerations related with intake of PUFAs. Obsession with the intake of unsaturated fatty acids could bring about the shortage of essential fatty acids that are crucial for our body, weaken the immune system, and increase the risk of heart disease, arrhythmia, and stroke. In this review, we discuss types, physiologic mechanism of action of PUFAs, intake of PUFAs for children, recommended intake of PUFAs, and considerations for the intake of PUFAs. PMID:24224148

  7. Supplementation with long chain polyunsaturated fatty acids (LCPUFA) to breastfeeding mothers for improving child growth and development.

    PubMed

    Delgado-Noguera, Mario F; Calvache, Jose Andres; Bonfill Cosp, Xavier

    2010-12-08

    Long chain polyunsaturated fatty acids (LCPUFA), especially docosahexaenoic acid (DHA), are the most abundant fatty acids in the brain and are necessary for growth and maturation of the brain and retina. LCPUFA are named "essential" because they cannot be synthesised efficiently by the human body and come from maternal diet. It remains controversial whether LCPUFA supplementation to breastfeeding mothers is beneficial for the development of their infants. To assess the effectiveness and safety of supplementation with LCPUFA in breastfeeding mothers in the cognitive and physical development of their infants as well as safety for the mother and infant. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2009), CENTRAL (2009, Issue 2), PubMed (1966 to July 2009), EMBASE (1974 to June 2009), CINAHL (1984 to June 2009), LILACS (1982 to June 2009), Google Scholar (June 2009) and reference lists of published narrative and systematic reviews. Randomised controlled trials or cluster-randomised controlled trials evaluating the effects of LCPUFA supplementation on breastfeeding mothers and their infants. Two review authors independently assessed eligibility and trial quality and performed data extraction. We included six randomised controlled trials involving 1280 women. We found no significant difference in children's neurodevelopment: language development (standardised mean difference (SMD) -0.14, 95% confidence interval (CI) -0.49 to 0.20; two trials, 349 participants); intelligence or problem-solving ability (two trials, 817 participants; SMD -0.22, 95% CI -0.23 to 0.66); psychomotor development (SMD 0.34, 95% CI -0.11 to 0.78; two trials, 279 participants); motor development (SMD 0.08, 95% CI -0.13 to 0.29; two trials, 349 participants); in child attention there was a significant difference (SMD 0.50, 95% CI 0.24 to 0.77; one study). For child visual acuity there was no significant difference (SMD -0.06, 95% CI -0.26 to 0.14; three trials

  8. Vitamin B12 Deficiency Across Three Generations Adversely Influences Long-chain Polyunsaturated Fatty Acid Status and Cardiometabolic Markers in Rats.

    PubMed

    Khaire, Amrita; Rathod, Richa; Kale, Anvita; Joshi, Sadhana

    2016-08-01

    Vitamin B12 and omega-3 fatty acid deficiency is prevalent in the vegetarian population and is associated with adverse pregnancy outcomes and cardiometabolic risk. The present study investigates the long-term effects of vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids on cardiometabolic profile and long-chain polyunsaturated fatty acid levels (LCPUFA) in the F3 generation offspring. Three generations of rats were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient + omega-3 fatty acid supplemented; vitamin B12 + omega-3 fatty acid supplemented. Animals were sacrificed at 3 months of age. Vitamin B12 deficiency lowered (p <0.01 for both) plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), liver DHA (p <0.05), plasma/liver omega-3 fatty acids (p <0.05 for both), increased triglycerides (p <0.05) and systolic BP (p <0.01) and lowered cholesterol levels (p <0.05) as compared to control. Vitamin B12 deficiency in the presence of omega-3 fatty acids improved plasma/liver EPA, DHA and omega-3 fatty acid profile and maintained cholesterol, triglyceride and BP levels. Vitamin B12 supplementation lowered liver DHA (p <0.05) and cholesterol (p <0.01), whereas BP was similar to control. Combined supplementation of vitamin B12 and omega-3 fatty acids improved omega-3 fatty acid profile, lowered cholesterol/triglyceride levels and maintained the BP similar to that of control. Vitamin B12 deficiency across three generations adversely affects LCPUFA and cardiometabolic profile in the adult offspring. This study provides clues for a combined supplementation of vitamin B12 and omega-3 fatty acids to reduce the risk for noncommunicable diseases. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  9. Dietary n-3 long-chain polyunsaturated fatty acid deprivation, tissue lipid composition, ex vivo prostaglandin production, and stress tolerance in juvenile Dover sole (Solea solea L.).

    PubMed

    Logue, J A; Howell, B R; Bell, J G; Cossins, A R

    2000-07-01

    Larval Dover sole fed an Artemia diet supplemented with n-3 long-chain (C20 + C22) polyunsaturated fatty acids (PUFA) are known to be more resistant to low-temperature injury. Here we explore the relationship between tissue fatty acid composition and tolerance of stressful environmental conditions over the larval and early juvenile periods. Artemia nauplii supplemented with n-3 long-chain PUFA-deficient and PUFA-enriched oil emulsions were fed to two groups of larvae. Whole body tissue samples from the resulting PUFA-deficient and -enriched juveniles possessed 12.1 and 21.9% n-3 long-chain PUFA, respectively. These differences were at the expense of C18 PUFA, while proportions of saturated fatty acids, monounsaturated fatty acids, and total PUFA were unaffected. Brain and eye tissues from the PUFA-deficient fish contained lower levels of 22:6n-3, known to be important for optimal nervous system function, incorporating instead a range of fatty acids of lower unsaturation. PUFA-deprived juveniles showed substantially greater mortality when exposed to a combination of low temperature and low salinity, as well as to high temperature and to hypoxia. After adaptation to the different diets, both dietary groups were fed a common formulated feed high in n-3 long-chain PUFA. Tissue PUFA in both groups progressively increased to the same high value, with a consequent loss of the differences in cold-susceptibility. These correlated changes support a link between dietary manipulation of n-3 long-chain PUFA and development of a stress-sensitive phenotype. PUFA deprivation had no detectable effect upon static hydrocarbon order of purified brain membranes (as assessed by fluorescence polarization) but was associated with an increase in the whole-body content of prostaglandins. We conclude that susceptibility to environmental stress is responsive to dietary n-3 long-chain PUFA manipulation, possibly due to altered tissue development or the overproduction of eicosanoids.

  10. The relationship of dietary omega-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report no. 23.

    PubMed

    SanGiovanni, John Paul; Chew, Emily Y; Agrón, Elvira; Clemons, Traci E; Ferris, Frederick L; Gensler, Gary; Lindblad, Anne S; Milton, Roy C; Seddon, Johanna M; Klein, Ronald; Sperduto, Robert D

    2008-09-01

    To examine the association of dietary omega-3 long-chain polyunsaturated fatty acid and fish intake with incident neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA). Multicenter clinic-based prospective cohort study from a clinical trial including Age-Related Eye Disease Study (AREDS) participants with bilateral drusen at enrollment. Main outcome measures were incident neovascular AMD and CGA, ascertained from annual stereoscopic color fundus photographs (median follow-up, 6.3 years). We estimated nutrient and food intake from a validated food frequency questionnaire (FFQ) at baseline, with intake of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), combined EPA and DHA, and fish as primary exposures. After controlling for known covariates, we observed a reduced likelihood of progression from bilateral drusen to CGA among people who reported the highest levels of EPA (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.23-0.87) and EPA+DHA (OR, 0.45; 95% CI, 0.23-0.90) consumption. Levels of DHA were associated with CGA in age-, sex-, and calorie-adjusted models (OR, 0.51; 95% CI, 0.26-1.00); however, this statistical relationship did not persist in multivariable models. Dietary lipid intake is a modifiable factor that may influence the likelihood of developing sight-threatening forms of AMD. Our findings suggest that dietary omega-3 long-chain polyunsaturated fatty acid intake is associated with a decreased risk of progression from bilateral drusen to CGA.

  11. Cancer Risk and Eicosanoid Production: Interaction between the Protective Effect of Long Chain Omega-3 Polyunsaturated Fatty Acid Intake and Genotype

    PubMed Central

    Lenihan-Geels, Georgia; Bishop, Karen S.; Ferguson, Lynnette R.

    2016-01-01

    Dietary inclusion of fish and fish supplements as a means to improve cancer prognosis and prevent tumour growth is largely controversial. Long chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA), eicosapentaenoic acid and docosahexaenoic acid, may modulate the production of inflammatory eicosanoids, thereby influencing local inflammatory status, which is important in cancer development. Although in vitro studies have demonstrated inhibition of tumour cell growth and proliferation by LCn-3 PUFA, results from human studies have been mainly inconsistent. Genes involved in the desaturation of fatty acids, as well as the genes encoding enzymes responsible for eicosanoid production, are known to be implicated in tumour development. This review discusses the current evidence for an interaction between genetic polymorphisms and dietary LCn-3 PUFA in the risk for breast, prostate and colorectal cancers, in regards to inflammation and eicosanoid synthesis. PMID:26891335

  12. Supplementation with long chain polyunsaturated fatty acids (LCPUFA) to breastfeeding mothers for improving child growth and development.

    PubMed

    Delgado-Noguera, Mario F; Calvache, Jose Andres; Bonfill Cosp, Xavier; Kotanidou, Eleni P; Galli-Tsinopoulou, Assimina

    2015-07-14

    Long chain polyunsaturated fatty acids (LCPUFA), especially docosahexaenoic acid (DHA), are the most abundant fatty acids in the brain and are necessary for growth and maturation of an infant's brain and retina. LCPUFAs are named "essential" because they cannot be synthesised efficiently by the human body and come from maternal diet. It remains controversial whether LCPUFA supplementation to breastfeeding mothers is beneficial for the development of their infants. To assess the effectiveness and safety of supplementation with LCPUFA in breastfeeding mothers in the cognitive and physical development of their infants as well as safety for the mother and infant. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 August 2014), CENTRAL (Cochrane Library 2014, Issue 8), PubMed (1966 to August 2014), EMBASE (1974 to August 2014), LILACS (1982 to August 2014), Google Scholar (August 2014) and reference lists of published narrative and systematic reviews. Randomised controlled trials or cluster-randomised controlled trials evaluating the effects of LCPUFA supplementation on breastfeeding mothers (including the pregnancy period) and their infants. Two review authors independently assessed eligibility and trial quality, performed data extraction and evaluated data accuracy. We included eight randomised controlled trials involving 1567 women. All the studies were performed in high-income countries. The longest follow-up was seven years.We report the results from the longest follow-up time point from included studies. Overall, there was moderate quality evidence as assessed using the GRADE approach from these studies for the following outcomes measured beyond 24 months age of children: language development and child weight. There was low-quality evidence for the outcomes: Intelligence or solving problems ability, psychomotor development, child attention, and child visual acuity.We found no significant difference in children's neurodevelopment at long

  13. 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.

  14. High content of long-chain n-3 polyunsaturated fatty acids in red blood cells of Kenyan Maasai despite low dietary intake.

    PubMed

    Knoll, Nadja; Kuhnt, Katrin; Kyallo, Florence M; Kiage-Mokua, Beatrice N; Jahreis, Gerhard

    2011-08-19

    Increasing land restrictions and a reduced livestock-to-human ratio during the 20th century led the Maasai to lead a more sedentary, market-orientated lifestyle. Although plant-derived food nowadays contributes substantially to their diet, dairy products being high in saturated fatty acids (SFA) and low in polyunsaturated fatty acids (PUFA) still are an important energy source. Since reliable data regarding the Maasai diet date back to the 1980s, the study objective was to document current diet practices in a Kenyan Maasai community and to investigate the fatty acid distribution in diet and red blood cells. A cross-sectional study was conducted among 26 Maasai (20 women, 6 men) from Loodokilani, Kajiado District, Kenya. Food intake was described by the subjects via 24-h recall, and both food and blood samples were analysed. Two main foods--milk and ugali--constituted the Maasai diet in this region. A total of 0.9 L of milk and 0.6 kg of ugali were consumed per person and day to yield an energy intake of 7.6 MJ/d per person. A major proportion of ingested food contributing 58.3% to the total dietary energy (en%) was plant-derived, followed by dairy products representing 41.1 en%. Fat consumed (30.5 en%) was high in SFA (63.8%) and low in PUFA (9.2%). Long-chain n-3 PUFA (EPA, DPA and DHA) made up only 0.15% of the ingested fatty acids, but 5.9% of red blood cell fatty acids. The study indicates the Maasai diet is rich in SFA and low in PUFA. Nevertheless, red blood cells are composed of comparable proportions of long-chain n-3 PUFA to populations consuming higher amounts of this fatty acid group.

  15. Supplementing long-chain n-3 polyunsaturated fatty acids in canned wild Pacific pink salmon with Alaska salmon oil.

    PubMed

    Lapis, Trina J; Oliveira, Alexandra C M; Crapo, Charles A; Himelbloom, Brian; Bechtel, Peter J; Long, Kristy A

    2013-01-01

    Establishing n-3 polyunsaturated fatty acid contents in canned wild Alaska pink salmon products is challenging due to ample natural variation found in lipid content of pink salmon muscle. This study investigated the effect of adding salmon oil (SO) to canned pink salmon produced from fish exhibiting two opposite degrees of skin watermarking, bright (B) and dark (D). Specific goals of the study were to evaluate the benefits of adding SO to canned pink salmon with regard to nutritional value of the product, sensory characteristics, and the oxidative and hydrolytic stability of the lipids over thermal processing. Six groups of canned pink salmon were produced with variable levels of SO, either using bright (with 0, 1, or 2% SO) or dark (with 0, 2, or 4% SO) pink salmon. Compositional analysis revealed highest (P < 0.05) lipid content in sample B2 (8.7%) and lowest (P < 0.05) lipid content in sample D0 (3.5%). Lipid content of samples B0, B1, D2, and D4 was not significantly different (P > 0.05) ranging from 5.7% to 6.8%. Consequently, addition of SO to canned pink salmon allowed for consistent lipid content between bright and dark fish. Addition of 1% or 2% SO to canned bright pink salmon was not detrimental to the sensory properties of the product. It is recommended that canned bright pink salmon be supplemented with at least 1% SO, while supplementation with 2% SO would guarantee a minimum quantity of 1.9 g of n-3 fatty acids per 100 g of product. Addition of 4% SO to canned dark pink salmon was detrimental to product texture and taste, while supplementation with 2% SO did not negatively affect sensorial properties of the product. Accordingly, canned dark pink salmon should be supplemented with 2% SO so that a minimum n-3 fatty acids content of 1.5 g per 100 g of product.

  16. Supplementing long-chain n-3 polyunsaturated fatty acids in canned wild Pacific pink salmon with Alaska salmon oil

    PubMed Central

    Lapis, Trina J; Oliveira, Alexandra C M; Crapo, Charles A; Himelbloom, Brian; Bechtel, Peter J; Long, Kristy A

    2013-01-01

    Establishing n-3 polyunsaturated fatty acid contents in canned wild Alaska pink salmon products is challenging due to ample natural variation found in lipid content of pink salmon muscle. This study investigated the effect of adding salmon oil (SO) to canned pink salmon produced from fish exhibiting two opposite degrees of skin watermarking, bright (B) and dark (D). Specific goals of the study were to evaluate the benefits of adding SO to canned pink salmon with regard to nutritional value of the product, sensory characteristics, and the oxidative and hydrolytic stability of the lipids over thermal processing. Six groups of canned pink salmon were produced with variable levels of SO, either using bright (with 0, 1, or 2% SO) or dark (with 0, 2, or 4% SO) pink salmon. Compositional analysis revealed highest (P < 0.05) lipid content in sample B2 (8.7%) and lowest (P < 0.05) lipid content in sample D0 (3.5%). Lipid content of samples B0, B1, D2, and D4 was not significantly different (P > 0.05) ranging from 5.7% to 6.8%. Consequently, addition of SO to canned pink salmon allowed for consistent lipid content between bright and dark fish. Addition of 1% or 2% SO to canned bright pink salmon was not detrimental to the sensory properties of the product. It is recommended that canned bright pink salmon be supplemented with at least 1% SO, while supplementation with 2% SO would guarantee a minimum quantity of 1.9 g of n-3 fatty acids per 100 g of product. Addition of 4% SO to canned dark pink salmon was detrimental to product texture and taste, while supplementation with 2% SO did not negatively affect sensorial properties of the product. Accordingly, canned dark pink salmon should be supplemented with 2% SO so that a minimum n-3 fatty acids content of 1.5 g per 100 g of product. PMID:24804010

  17. Oxidative stability of fish and algae oils containing long-chain polyunsaturated fatty acids in bulk and in oil-in-water emulsions.

    PubMed

    Frankel, Edwin N; Satué-Gracia, Teresa; Meyer, Anne S; German, J Bruce

    2002-03-27

    The oxidative stability of long-chain polyunsaturated fatty acid (PUFA) and docosahexaenoic acid (DHA)-containing fish and algae oils varies widely according to their fatty acid composition, the physical and colloidal states of the lipids, the contents of tocopherols and other antioxidants, and the presence and activity of transition metals. Fish and algal oils were initially much more stable to oxidation in bulk systems than in the corresponding oil-in-water emulsions. The oxidative stability of emulsions cannot, therefore, be predicted on the basis of stability data obtained with bulk long-chain PUFA-containing fish oils and DHA-containing algal oils. The relatively high oxidative stability of an algal oil containing 42% DHA was completely lost after chromatographic purification to remove tocopherols and other antioxidants. Therefore, this evidence does not support the claim that DHA-rich oils from algae are unusually stable to oxidation. Addition of ethylenediaminetetraacetic acid (EDTA) prevented oxidation of both fish and algal oil emulsions without added iron and at low iron:EDTA molar concentrations. EDTA, however, promoted the oxidation of the corresponding emulsions that contained high iron:EDTA ratios. Therefore, to be effective as a metal chelator, EDTA must be added at molar concentrations higher than that of iron to inhibit oxidation of foods containing long-chain PUFA from either fish or algae and fortified with iron.

  18. Modulation of atherosclerosis by N-3 polyunsaturated fatty acids

    USDA-ARS?s Scientific Manuscript database

    We have reviewed literature regarding the effects of n-3 polyunsaturated fatty acids (PUFA) on risk factors for atherosclerosis in human subjects. Dietary intervention with long chain n-3 PUFA decreased some risk factor (s) for atherosclerosis in most human studies reviewed. These benefits resulted ...

  19. Molecular and functional characterisation of two elovl4 elongases involved in the biosynthesis of very long-chain (>C24) polyunsaturated fatty acids in black seabream Acanthopagrus schlegelii.

    PubMed

    Jin, Min; Monroig, Óscar; Navarro, Juan Carlos; Tocher, Douglas R; Zhou, Qi-Cun

    2017-10-01

    Elongation of very long-chain fatty acid (Elovl) 4 proteins are important fatty acyl elongases that participate in the biosynthesis of long-chain (C20-24) and very long-chain (˃C24) polyunsaturated fatty acids (LC-PUFA and VLC-PUFA, respectively) in teleost fish, especially in marine species. Moreover, knowledge of Elovl4 and other elongases such as Elovl2 has contributed to an advanced understanding of the LC-PUFA biosynthetic pathway in marine fish. In the present study, elovl4a and elovl4b were cloned from black seabream Acanthopagrus schlegelii and functionally characterised using recombinant expression in yeast. The elovl4a and elovl4b cDNA sequences included open reading frames (ORF) of 969 and 918 base pairs (bp), encoding proteins of 322 and 315 amino acids (aa), respectively. The functional characterisation of A. schlegelii Elovl4 proteins showed they were able to utilise all assayed C18-22 PUFA substrates except 22:6n-3. Moreover, it was particularly noteworthy that both A. schlegelii Elovl4a and Elovl4b proteins had the ability to elongate 20:5n-3 and 22:5n-3 to 24:5n-3, which can be potentially desaturated and β-oxidised to 22:6n-3. Tissue transcript abundance analysis showed the highest expression of elovl4a and elovl4b in brain and eye, respectively, suggesting these tissues were major sites for VLC-PUFA biosynthesis in black seabream. The functions of the A. schlegelii Elovl4-like elongases, Elovl4a and Elovl4b, characterised in the present study, along with those of the Elovl5 and fatty acyl desaturase (Fads2) proteins of A. schlegelii characterised previously, provided evidence of the biosynthetic pathways of LC-PUFA and VLC-PUFA in this teleost species. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Very-long-chain polyunsaturated fatty acids accumulate in phosphatidylcholine of fibroblasts from patients with Zellweger syndrome and acyl-CoA oxidase1 deficiency.

    PubMed

    Abe, Yuichi; Honsho, Masanori; Nakanishi, Hiroki; Taguchi, Ryo; Fujiki, Yukio

    2014-04-04

    Peroxisomes are subcellular organelles that function in multiple anabolic and catabolic processes, including β-oxidation of very-long-chain fatty acids (VLCFA) and biosynthesis of ether phospholipids. Peroxisomal disorders caused by defects in peroxisome biogenesis or peroxisomal β-oxidation manifest as severe neural disorders of the central nervous system. Abnormal peroxisomal metabolism is thought to be responsible for the clinical symptoms of these diseases, but their molecular pathogenesis remains to be elucidated. We performed lipidomic analysis to identify aberrant metabolites in fibroblasts from patients with Zellweger syndrome (ZS), acyl-CoA oxidase1 (AOx) deficiency, D-bifunctional protein (D-BP) and X-linked adrenoleukodystrophy (X-ALD), as well as in peroxisome-deficient Chinese hamster ovary cell mutants. In cells deficient in peroxisomal biogenesis, plasmenylethanolamine was remarkably reduced and phosphatidylethanolamine was increased. Marked accumulation of very-long-chain saturated fatty acid and monounsaturated fatty acids in phosphatidylcholine was observed in all mutant cells. Very-long-chain polyunsaturated fatty acid (VLC-PUFA) levels were significantly elevated, whilst phospholipids containing docosahexaenoic acid (DHA, C22:6n-3) were reduced in fibroblasts from patients with ZS, AOx deficiency, and D-BP deficiency, but not in fibroblasts from an X-ALD patient. Because patients with AOx deficiency suffer from more severe symptoms than those with X-ALD, accumulation of VLC-PUFA and/or reduction of DHA may be associated with the severity of peroxisomal diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  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

    USDA-ARS?s Scientific Manuscript database

    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 absolu...

  2. Relative abundance of short chain and polyunsaturated fatty acids in propionic acid-induced autistic features in rat pups as potential markers in autism.

    PubMed

    El-Ansary, Afaf; Al-Ayadhi, Laila

    2014-08-31

    Fatty acids are essential dietary nutrients, and one of their important roles is providing polyunsaturated fatty acids (PUFAs) for the growth and function of nervous tissue. Short chain fatty acids (SCFAs) are a group of compounds derived from the host microbiome that were recently linked to effects on the gut, the brain, and behavior. They are therefore linked to neurodevelopmental disorders such as autism. Reduced levels of PUFAs are associated with impairments in cognitive and behavioral performance, which are particularly important during brain development. Recent studies suggest that omega -3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are involved in neurogenesis, neurotransmission, and protection from oxidative stress. Omega-3 PUFAs mediate some of these effects by antagonizing Omega-6 PUFA (arachidonic acid, AA)-induced proinflammatory prostaglandin E₂ (PGE₂) formation. In this work, the absolute and relative concentrations of propionic (PPA), butyric and acetic acids, as well as PUFAs and their precursors (α-Linolenic and linoleic), were measured in the brain tissue of PPA-neurointoxicated rat pups (receiving 250 mg PPA/Kg body weight for 3 consecutive days) as a rodent model with persistent autistic features compared with healthy controls. The data revealed remarkably lower levels of omega6/omega3, α-Linolenic/Linoleic, α-Linolenic/EPA, α-Linolenic/DHA, EPA/DHA, and AA/Linoleic acid ratios in PPA-intoxicated rats. The role of these impaired ratios is discussed in relation to the activity of desaturases and elongases, which are the two enzymatic groups involved in the synthesis of PUFAs from their precursors. The relationship between the abnormal relative concentrations of the studied fatty acids and oxidative stress, neurotransmission, and neuroinflammation is also discussed in detail. This study demonstrates that fatty acid ratios are useful for understanding the mechanism of PPA neurotoxicity in a rodent model

  3. The Relationship of Dietary ω-3 Long-Chain Polyunsaturated Fatty Acid Intake With Incident Age-Related Macular Degeneration AREDS Report No. 23

    PubMed Central

    SanGiovanni, John Paul; Chew, Emily Y.; Agron, Elvira; Clemons, Traci E.; Ferris, Frederick L.; Gensler, Gary; Lindblad, Anne S.; Milton, Roy C.; Seddon, Johanna M.; Klein, Ronald; Sperduto, Robert D.

    2009-01-01

    Objective To examine the association of dietary ω-3 long-chain polyunsaturated fatty acid and fish intake with incident neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA). Methods Multicenter clinic-based prospective cohort study from a clinical trial including Age-Related Eye Disease Study (AREDS) participants with bilateral drusen at enrollment. Main outcome measures were incident neovascular AMD and CGA, ascertained from annual stereoscopic color fundus photographs (median follow-up, 6.3 years). We estimated nutrient and food intake from a validated food frequency questionnaire (FFQ) at baseline, with intake of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), combined EPA and DHA, and fish as primary exposures. Results After controlling for known covariates, we observed a reduced likelihood of progression from bilateral drusen to CGA among people who reported the highest levels of EPA (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.23-0.87) and EPA+DHA (OR, 0.45; 95% CI, 0.23-0.90) consumption. Levels of DHA were associated with CGA in age-, sex-, and calorie-adjusted models (OR, 0.51; 95% CI, 0.26-1.00); however, this statistical relationship did not persist in multivariable models. Conclusions Dietary lipid intake is a modifiable factor that may influence the likelihood of developing sight-threatening forms of AMD. Our findings suggest that dietary ω-3 long-chain polyunsaturated fatty acid intake is associated with a decreased risk of progression from bilateral drusen to CGA. PMID:18779490

  4. Role of ω3 long-chain polyunsaturated fatty acids in reducing cardio-metabolic risk factors.

    PubMed

    Abeywardena, Mahinda Y; Patten, Glen S

    2011-09-01

    Cardiovascular disease is the leading cause of mortality in many economically developed nations, and its incidence is increasing at a rapid rate in emerging economies. Diet and lifestyle issues are closely associated with a myriad of cardiovascular disease risk factors including abnormal plasma lipids, hypertension, insulin resistance, diabetes and obesity, suggesting that diet-based approaches may be of benefit. Omega-3 longchain-polyunsaturated fatty acids (ω3 LC-PUFA) are increasingly being used in the prevention and management of several cardiovascular risk factors. Both the ω3 and ω6 PUFA families are considered essential, as the human body is itself unable to synthesize them. The conversion of the two precursor fatty acids - linoleic acid (18:2ω6) and α-linoleic acid (α18:3ω3) - of these two pathways to longer (≥C(20)) PUFA is inefficient. Although there is an abundance of ω6 PUFA in the food supply; in many populations the relative intake of ω3 LC-PUFA is low with health authorities advocating increased consumption. Fish oil, rich in eicosapentaenoic (EPA, 20:5ω3) and docosahexaenoic (DHA, 22:6ω3) acids, has been found to cause a modest reduction in blood pressure at a dose level of >3g/d both in untreated and treated hypertensives. Whilst a multitude of mechanisms may contribute to the blood pressure lowering action of ω3 LC-PUFA, improved vascular endothelial cell function appears to play a central role. Recent studies which evaluated the potential benefits of fish oil in type-2 diabetes have helped to alleviate concerns raised in some previous studies which used relatively large dose (5-8 g/d) and reported a worsening of glycemic control. Several meta-analyses have confirmed that the most consistent action of ω3 LC-PUFA in insulin resistance and type-2 diabetes is the reduction in triglycerides. In some studies, fish oil has been found to cause a small rise in LDL-cholesterol, but a change in the LDL particle size, from the smaller more

  5. Biosynthesis of Polyunsaturated Fatty Acids in Octopus vulgaris: Molecular Cloning and Functional Characterisation of a Stearoyl-CoA Desaturase and an Elongation of Very Long-Chain Fatty Acid 4 Protein.

    PubMed

    Monroig, Óscar; de Llanos, Rosa; Varó, Inmaculada; Hontoria, Francisco; Tocher, Douglas R; Puig, Sergi; Navarro, Juan C

    2017-03-21

    Polyunsaturated fatty acids (PUFAs) have been acknowledged as essential nutrients for cephalopods but the specific PUFAs that satisfy the physiological requirements are unknown. To expand our previous investigations on characterisation of desaturases and elongases involved in the biosynthesis of PUFAs and hence determine the dietary PUFA requirements in cephalopods, this study aimed to investigate the roles that a stearoyl-CoA desaturase (Scd) and an elongation of very long-chain fatty acid 4 (Elovl4) protein play in the biosynthesis of essential fatty acids (FAs). Our results confirmed the Octopus vulgaris Scd is a ∆9 desaturase with relatively high affinity towards saturated FAs with ≥ C18 chain lengths. Scd was unable to desaturate 20:1n-15 ((∆5)20:1) suggesting that its role in the biosynthesis of non-methylene interrupted FAs (NMI FAs) is limited to the introduction of the first unsaturation at ∆9 position. Interestingly, the previously characterised ∆5 fatty acyl desaturase was indeed able to convert 20:1n-9 ((∆11)20:1) to (∆5,11)20:2, an NMI FA previously detected in octopus nephridium. Additionally, Elovl4 was able to mediate the production of 24:5n-3 and thus can contribute to docosahexaenoic acid (DHA) biosynthesis through the Sprecher pathway. Moreover, the octopus Elovl4 was confirmed to play a key role in the biosynthesis of very long-chain (>C24) PUFAs.

  6. Biosynthesis of Polyunsaturated Fatty Acids in Octopus vulgaris: Molecular Cloning and Functional Characterisation of a Stearoyl-CoA Desaturase and an Elongation of Very Long-Chain Fatty Acid 4 Protein

    PubMed Central

    Monroig, Óscar; de Llanos, Rosa; Varó, Inmaculada; Hontoria, Francisco; Tocher, Douglas R.; Puig, Sergi; Navarro, Juan C.

    2017-01-01

    Polyunsaturated fatty acids (PUFAs) have been acknowledged as essential nutrients for cephalopods but the specific PUFAs that satisfy the physiological requirements are unknown. To expand our previous investigations on characterisation of desaturases and elongases involved in the biosynthesis of PUFAs and hence determine the dietary PUFA requirements in cephalopods, this study aimed to investigate the roles that a stearoyl-CoA desaturase (Scd) and an elongation of very long-chain fatty acid 4 (Elovl4) protein play in the biosynthesis of essential fatty acids (FAs). Our results confirmed the Octopus vulgaris Scd is a ∆9 desaturase with relatively high affinity towards saturated FAs with ≥ C18 chain lengths. Scd was unable to desaturate 20:1n-15 (∆520:1) suggesting that its role in the biosynthesis of non-methylene interrupted FAs (NMI FAs) is limited to the introduction of the first unsaturation at ∆9 position. Interestingly, the previously characterised ∆5 fatty acyl desaturase was indeed able to convert 20:1n-9 (∆1120:1) to ∆5,1120:2, an NMI FA previously detected in octopus nephridium. Additionally, Elovl4 was able to mediate the production of 24:5n-3 and thus can contribute to docosahexaenoic acid (DHA) biosynthesis through the Sprecher pathway. Moreover, the octopus Elovl4 was confirmed to play a key role in the biosynthesis of very long-chain (>C24) PUFAs. PMID:28335553

  7. Polyunsaturated Fatty Acids in Lipid Bilayers and Tubules

    NASA Astrophysics Data System (ADS)

    Hirst, Linda S.; Yuan, Jing; Pramudya, Yohannes; Nguyen, Lam T.

    2007-03-01

    Omega-3 polyunsaturated fatty acids (PUFAs) are found in a variety of biological membranes and have been implicated with lipid raft formation and possible function, typical molecules include DHA (Docosahexanoic Acid) and AA (Alphalinoleic Acid) which have been the focus of considerable attention in recent years. We are interested in the phase behavior of these molecules in the lipid bilayer. The addition of lipid molecules with polyunsaturated chains has a clear effect on the fluidity and curvature of the membrane and we investigate the effects the addition of polyunsaturated lipids on bilayer structure and tubule formation. Self-assembled cylindrical lipid tubules have attracted considerable attention because of their interesting structures and potential technological applications. Using x-ray diffraction techniques, Atomic Force Microscopy and confocal fluorescence imaging, both symmetric and mixed chain lipids were incorporated into model membranes and the effects on bilayer structure and tubule formation investigated.

  8. Potential therapeutic impact of omega-3 long chain-polyunsaturated fatty acids on inflammation markers in Duchenne muscular dystrophy: A double-blind, controlled randomized trial.

    PubMed

    Rodríguez-Cruz, Maricela; Cruz-Guzmán, Oriana Del Rocío; Almeida-Becerril, Tomás; Solís-Serna, Alan Donovan; Atilano-Miguel, Salvador; Sánchez-González, Juan Raúl; Barbosa-Cortés, Lourdes; Ruíz-Cruz, Eugenia Dolores; Huicochea, Juan Carlos; Cárdenas-Conejo, Alan; Escobar-Cedillo, Rosa Elena; Yam-Ontiveros, Carlos Alberto; Ricárdez-Marcial, Edgar F

    2017-09-23

    Duchenne Muscular Dystrophy (DMD) is the most frequent dystrophy in childhood generated by a deficiency in dystrophin. DMD is a neuromuscular disease and its clinical course comprises chronic inflammation and gradual muscle weakness. Supplementation of omega-3 long chain-Polyunsaturated Fatty Acids (ω-3 long chain-PUFA) reduces inflammatory markers in various disorders. The goal of this research was to analyze the influence of ω-3 long chain-PUFA intake on gene expression and blood inflammatory markers in boys with DMD. In a placebo-controlled, double. Blind, randomized trial, boys with DMD (n = 36) consumed 2.9 g/day of ω-3 long chain-PUFA or sunflower oil as control, in capsules, for a period of 6 months. Blood was analyzed at baseline and at months 1, 2, 3, and 6 of supplementation for expression of inflammatory markers in leukocytes and serum. There was high adherence to capsule intake (control: 95.3% ± 7.2%, and ω-3 long chain-PUFA: 97.4% ± 3.7% at month 6). Enrichment of EicosaPentaenoic Acid (EPA) and DocosaHexaenoic Acid (DHA) in erythrocytes increased significantly in patients supplemented with ω-3 long chain-PUFA compared with the placebo group during the 6 months of supplementation. Messenger RNA (mRNA) of the Nuclear Factor kappa beta (NF-κB) and its target genes InterLeukin 1 beta (IL-1β) and IL-6 was downregulated significantly (p < 0.05) in leukocytes from DMD boys supplemented with ω-3 long chain-PUFA for 6 months, compared to the placebo group. Omega-3 long chain-PUFA intake decreased the serum IL-1β (-59.5%; p = 0.011) and IL-6 (-54.8%; p = 0.041), and increased the serum IL-10 (99.9%, p < 0.005), in relation to those with placebo treatment. Supplementation with ω-3 long chain-PUFA 2.9 g/day is well-tolerated, has a beneficial reductive effect on proinflammatory markers, and increases an anti-inflammatory marker, indicating that ω-3 long chain-PUFA could have a potential therapeutic impact on chronic inflammation in

  9. Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice.

    PubMed

    de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2015-03-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

    Pontes, P V; Torres, A G; Trugo, N M F; Fonseca, V M; Sichieri, R

    2006-02-01

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

  11. Validity of food frequency questionnaire-based estimates of long-term long-chain n-3 polyunsaturated fatty acid intake.

    PubMed

    Wallin, Alice; Di Giuseppe, Daniela; Burgaz, Ann; Håkansson, Niclas; Cederholm, Tommy; Michaëlsson, Karl; Wolk, Alicja

    2014-01-01

    To evaluate how long-term dietary intake of long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs), estimated by repeated food frequency questionnaires (FFQs) over 15 years, is correlated with LCn-3 PUFAs in adipose tissue (AT). Subcutaneous adipose tissue was obtained in 2003-2004 (AT-03) from 239 randomly selected women, aged 55-75 years, after completion of a 96-item FFQ (FFQ-03). All participants had previously returned an identical FFQ in 1997 (FFQ-97) and a 67-item version in 1987-1990 (FFQ-87). Pearson product-moment correlations were used to evaluate associations between intake of total and individual LCn-3 PUFAs as estimated by the three FFQ assessments and AT-03 content (% of total fatty acids). FFQ-estimated mean relative intake of LCn-3 PUFAs (% of total fat intake) increased between all three assessments (FFQ-87, 0.55 ± 0.34; FFQ-97, 0.74 ± 0.64; FFQ-03, 0.88 ± 0.56). Validity, in terms of Pearson correlations between FFQ-03 estimates and AT-03 content, was 0.41 (95% CI 0.30-0.51) for total LCn-3 PUFA and ranged from 0.29 to 0.48 for individual fatty acids; lower correlation was observed among participants with higher percentage body fat. With regard to long-term intake estimates, past dietary intake was also correlated with AT-03 content, with correlation coefficients in the range of 0.21-0.33 and 0.21-0.34 for FFQ-97 and FFQ-87, respectively. The correlations were improved by using average estimates from two or more FFQ assessments. Exclusion of fish oil supplement users (14%) did not alter the correlations. These data indicate reasonable validity of FFQ-based estimates of long-term (up to 15 years) LCn-3 PUFA intake, justifying their use in studies of diet-disease associations.

  12. Long-term intake of dietary long-chain n-3 polyunsaturated fatty acids and risk of rheumatoid arthritis: a prospective cohort study of women.

    PubMed

    Di Giuseppe, Daniela; Wallin, Alice; Bottai, Matteo; Askling, Johan; Wolk, Alicja

    2014-11-01

    To analyse the association between dietary long-chain n-3 polyunsaturated fatty acids (PUFAs) and incidence of rheumatoid arthritis (RA) in middle-aged and older women from the Swedish Mammography Cohort, a population-based prospective study. Data on diet were collected in 1987 and 1997 via a self-administered food-frequency questionnaire (FFQ). The risk of RA associated with dietary long-chain n-3 PUFAs and fish intake was estimated using Cox proportional hazard regression models, adjusted for age, cigarette smoking, alcohol intake, use of aspirin and energy intake. Among 32 232 women born 1914-1948, 205 RA cases were identified during a mean follow-up of 7.5 years (1 January 2003 to 31 December 2010; 2 41 120 person-years). An intake of dietary long-chain n-3 PUFAs (FFQ1997) of more than 0.21 g/day (lowest quintile) was associated with a 35% decreased risk of developing RA (multivariable adjusted relative risk (RR) 0.65; 95% CI 0.48 to 0.90) compared with a lower intake. Long-term intake consistently higher than 0.21 g/day (according to both FFQ1987 and FFQ1997) was associated with a 52% (95% CI 29% to 67%) decreased risk. Consistent long-term consumption (FFQ1987 and FFQ1997) of fish ≥1 serving per week compared with<1 was associated with a 29% decrease in risk (RR 0.71; 95% CI 0.48 to 1.04). This prospective study of women supports the hypothesis that dietary intake of long-chain n-3 PUFAs may play a role in aetiology of RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Polyunsaturated fatty acids and inflammatory diseases.

    PubMed

    Gil, A

    2002-10-01

    Inflammation is overall a protective response, whose main goal is to liberate the human being of cellular lesions caused by micro-organisms, toxins, allergens, etc., as well as its consequences, and of death cells and necrotic tissues. Chronic inflammation, which is detrimental to tissues, is the basic pathogenic mechanism of hypersensitivity reactions against xenobiotics. Other frequent pathologies, for instance atherosclerosis, chronic hepatitis, inflammatory bowel disease (IBD), liver cirrhosis, lung fibrosis, psoriasis, and rheumatoid arthritis are also chronic inflammatory diseases. Chemical mediators of inflammation are derived from blood plasma or different cell-type activity. Biogenic amines, eicosanoids and cytokines are within the most important mediators of inflammatory processes. The different activities of eicosanoids derived from arachidonic acid (20:4 n-6) versus those derived from eicosapentaenoic acid (20:5 n-3) are one of the most important mechanisms to explain why n-3, or omega-3, polyunsaturated fatty acids (PUFA) exhibit anti-inflammatory properties in many inflammatory diseases. Dietary supplements ranging 1-8 g per day of n-3 PUFA have been reportedly beneficial in the treatment of IBD, eczema, psoriasis and rheumatoid arthritis. In addition, recent experimental studies in rats with experimental ulcerative colitis, induced by intrarectal injection of trinitrobenzene sulphonic acid, have documented that treatment with n-3 long-chain PUFA reduces mucosal damage as assessed by biochemical and histological markers of inflammation. Moreover, the defence antioxidant system in this model is enhanced in treated animals, provided that the n-3 PUFA supply is adequately preserved from oxidation.

  14. Change in fatty acid composition of serum lipids in obese females after short-term weight-reducing regimen with the addition of n-3 long chain polyunsaturated fatty acids in comparison to controls.

    PubMed

    Hlavatý, P; Kunesová, M; Gojová, M; Tvrzická, E; Vecka, M; Roubal, P; Hill, M; Hlavatá, K; Kalousková, P; Hainer, V; Zák, A; Drbohlav, J

    2008-01-01

    Short-term weight-reducing regimens were shown to influence fatty acid composition of serum lipids unfavorably. Adding long chain n-3 polyunsaturated fatty acids (n-3 LC PUFA) to a low-calorie diet (LCD) could avoid these changes. The aim of this study was to examine the effect of a short-term in-patient weight-reducing regimen including LCD with yogurt enriched by low doses of n-3 PUFA (n-3 LCD). The enriched yogurt contained 790 mg of fish oil, predominantly eicosapentaenoic (20:5n-3; EPA) and docosahexaenoic (22:6n-3; DHA). Forty obese women were randomly assigned to the group consuming LCD and joghurt either with or without n-3 enrichment. Following the 3-week diet in the n-3 LCD group a significantly higher increase in the proportion of n-3 LC PUFA (sum of n-3 FA, EPA and DHA) in serum lipids was confirmed. In phospholipids (PL) a significant difference in the sum of n-6 fatty acids was found, a decrease in the n-3 LCD group and an increase in LCD group. Significantly higher increase in the PL palmitate (16:0) was shown in the LCD group. The results suggest that low doses of n-3 fatty acid enrichment can help to avoid unfavorable changes in fatty acid composition in serum lipids after a short-term weight-reducing regimen.

  15. The effects of n-3 long-chain polyunsaturated fatty acid supplementation on AGEs and sRAGE in type 2 diabetes mellitus.

    PubMed

    Kurt, Asuman; Andican, Gülnur; Siva, Zeynep Oşar; Andican, Ahat; Burcak, Gülden

    2016-12-01

    In diabetes mellitus, chronic hyperglycemia leads to formation of advanced glycation end products (AGEs). Binding of AGEs to receptors of AGE (RAGE) causes deleterious effects. In populations with a high consumption of n-3 long-chain polyunsaturated fatty acids, a lower prevalence of diabetes mellitus has been reported. We aimed to investigate the effects of n-3 fatty acid (EPA and DHA) supplementation on the levels of AGEs (carboxymethyl lysine (CML) and pentosidine), sRAGE, and nuclear factor kappa B (NF-kB) in type 2 diabetes mellitus (T2DM). T2DM patients (n = 38) treated with oral hypoglycemic agents, without insulin were supplemented with n-3 fatty acids (1.2 g/day) for 2 months. Plasma CML, pentosidine, sRAGE, and NF-kB levels were measured by ELISA both before and after the supplementation. n-3 fatty acid supplementation significantly reduced fasting glucose (p < 0.01), glycated hemoglobin (HbA1c) (p < 0.05), and pentosidine (p < 0.05) levels. The supplementation induced percentage changes in pentosidine and HbA1c and in pentosidine and creatinine were observed to be correlated (r = 0.349, p < 0.05) and (r = 0.377, p < 0.05), respectively. Waist circumference and systolic and diastolic pressures were significantly decreased due to n-3 supplementation (p < 0.001, p < 0.01, p < 0.01), respectively. Our results show that supplementation with n-3 fatty acid has beneficial effects on waist circumference; systolic and diastolic blood pressures; and the levels of glucose, HbA1c, and pentosidine in T2DM patients. However, the supplementation failed to decrease these parameters to the reference ranges for healthy subjects. In addition, the supplementation did not appear to induce any significant differences in CML, sRAGE, or NF-kB.

  16. Long-chain polyunsaturated fatty acid status during pregnancy and maternal mental health in pregnancy and the postpartum period: results from the GUSTO study.

    PubMed

    Chong, Mary F F; Ong, Yi-Lin; Calder, Philip C; Colega, Marjorelee; Wong, Jocelyn X Y; Tan, Chuen Seng; Lim, Ai Lin; Fisk, Helena L; Cai, Shirong; Pang, Wei Wei; Broekman, Birit F P; Saw, Seang Mei; Kwek, Kenneth; Godfrey, Keith M; Chong, Yap-Seng; Gluckman, Peter; Meaney, Michael J; Chen, Helen

    2015-07-01

    Studies have demonstrated a relationship between lower omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) status and anxiety and depression. It is uncertain whether similar associations occur in pregnant women, when anxiety and depression could have long-term effects on the offspring. We examined the associations between plasma LC-PUFA status during pregnancy and perinatal mental health. At 26-28 weeks' gestation, plasma LC-PUFAs were measured in mothers of the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort study, who were recruited between June 2009 and September 2010. Maternal symptoms of anxiety and depression were assessed with the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3 months' postpartum. The STAI-state subscale was used as a continuous measure of current anxiety, while EPDS scores ≥ 15 during pregnancy or ≥ 13 postpartum were indicative of symptoms of probable depression. In adjusted regression analyses (n = 698), lower plasma total omega-3 PUFA concentrations (β = -6.49 STAI-state subscale scores/unit increase of omega-3 fatty acid; 95% CI, -11.90 to -1.08) and higher plasma omega-6:omega-3 PUFA ratios (β = 6.58 scores/unit increase of fatty acid ratio; 95% CI, 1.19 to 12.66), specifically higher arachidonic acid (AA):docosahexaenoic acid, AA:eicosapentaenoic acid, and AA:docosapentaenoic acid ratios, were associated with increased antenatal anxiety (P < .05 for all), but not postpartum anxiety. There was no association between plasma PUFAs and perinatal probable depression. No association was found with probable depression in pregnancy or postpartum. Lower plasma omega-3 fatty acids and higher omega-6:omega-3 fatty acid ratios were associated with higher antenatal anxiety, but not postpartum anxiety. Replication in other studies is needed to confirm the findings and determine the direction of causality. ClinicalTrials.gov identifier: NCT

  17. Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration.

    PubMed

    Janssen, Carola I F; Kiliaan, Amanda J

    2014-01-01

    Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are important components of neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid also affect cardiovascular health and inflammation. In neural development, LCPUFA deficiency can lead to severe disorders like schizophrenia and attention deficit hyperactivity disorder. Perinatal LCPUFA supplementation demonstrated beneficial effects in neural development in humans and rodents resulting in improved cognition and sensorimotor integration. In normal aging, the effect of LCPUFA on prevention of cognitive impairment will be discussed. LCPUFA are important for neuronal membrane integrity and function, and also contribute in prevention of brain hypoperfusion. Cerebral perfusion can be compromised as result of obesity, cerebrovascular disease, hypertension, or diabetes mellitus type 2. Last, we will focus on the role of LCPUFA in most common neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. These disorders are characterized by impaired cognition and connectivity and both clinical and animal supplementation studies have shown the potential of LCPUFA to decrease neurodegeneration and inflammation. This review shows that LCPUFA are essential throughout life.

  18. Lower n-3 long-chain polyunsaturated fatty acid values in patients with phenylketonuria: a systematic review and meta-analysis.

    PubMed

    Lohner, Szimonetta; Fekete, Katalin; Decsi, Tamás

    2013-07-01

    The mainstream of phenylketonuria (PKU) management is lifelong restriction of protein intake; however, this dietary restriction may be accompanied by insufficient dietary intake of long-chain polyunsaturated fatty acids (LCPUFA). The objective of this review was to assess whether significant depletion of LCPUFA can be detected in PKU patients on low-protein diet and whether LCPUFA supplementation is an effective way to increase the availability of LCPUFA in PKU patients. The method included structured search strategy on Ovid MEDLINE, Scopus, LILACS, and the Cochrane Library CENTRAL databases, with formal inclusion/exclusion criteria, data extraction procedure, and meta-analysis. We evaluated 9 case-control studies and 6 randomized controlled trials, dated from the inception of the databases to 2012. The meta-analysis of the case-control studies showed significantly lower values of both eicosapentaenoic acid and docosahexaenoic acid (DHA) in all biomarkers investigated and that of arachidonic acid in total plasma lipids in PKU patients as compared with healthy controls. There were sufficient data to demonstrate that dietary DHA supplementation of patients with PKU significantly increases the contribution of DHA to total plasma lipids. In summary, suboptimal LCPUFA status, especially that of n-3 LCPUFA, can be detected in PKU patients. Supplementing DHA to the diet of PKU patients may improve their LCPUFA status; however, further research is needed to determine the optimal supplementation dosage and to establish beneficial functional outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. 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.

  20. 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

  1. Inflammatory response following heart surgery and association with n-3 and n-6 long-chain polyunsaturated fatty acids in plasma and red blood cell membrane lipids.

    PubMed

    Bjorgvinsdottir, L; Indridason, O S; Heidarsdottir, R; Skogstrand, K; Arnar, D O; Torfason, B; Hougaard, D M; Palsson, R; Skuladottir, G V

    2013-09-01

    Open heart surgery is associated with a systemic inflammatory response. The n-3 long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the n-6 LC-PUFA arachidonic acid (AA) may contribute to modulation of the inflammatory response. We investigated whether the preoperative levels of EPA, DHA and AA in plasma phospholipids (PL) and red blood cell (RBC) membrane lipids in patients (n=168) undergoing open heart surgery were associated with changes in the plasma concentration of selected inflammatory mediators in the immediate postoperative period. The postoperative concentration of TNF-β was lower (P<0.05) and those of hs-CRP, IL-6, IL-8, IL-18 and IL-10 higher (P<0.05) than the respective preoperative concentrations. We observed that the preoperative levels of EPA and AA in plasma PL and RBC membrane lipids were associated with changes in the concentration of pro-inflammatory and anti-inflammatory mediators, suggesting a complex role in the postoperative inflammatory process. © 2013 Elsevier Ltd. All rights reserved.

  2. Associations of Dietary Long-Chain ω-3 Polyunsaturated Fatty Acids and Fish Consumption With Endometrial Cancer Risk in the Black Women's Health Study

    PubMed Central

    Brasky, Theodore M.; Sponholtz, Todd R.; Palmer, Julie R.; Rosenberg, Lynn; Ruiz-Narváez, Edward A.; Wise, Lauren A.

    2016-01-01

    Dietary long-chain (LC) ω-3 polyunsaturated fatty acids (PUFAs), which derive primarily from intakes of fatty fish, are thought to inhibit inflammation and de novo estrogen synthesis. This study prospectively examined the associations of dietary LC ω-3 PUFAs and fish with endometrial cancer risk in 47,602 African-American women living in the United States, aged 21–69 years at baseline in 1995, and followed them until 2013 (n = 282 cases). Multivariable-adjusted Cox regression models estimated hazard ratios and 95% confidence intervals for associations of LC ω-3 PUFA (quintiled) and fish (quartiled) intake with endometrial cancer risk, overall and by body mass index (BMI; weight (kg)/height (m)2). The hazard ratio for quintile 5 of total dietary LC ω-3 PUFAs versus quintile 1 was 0.79 (95% confidence interval (CI): 0.51, 1.24); there was no linear trend. Hazard ratios for the association were smaller among normal-weight women (BMI <25: hazard ratio (HR) = 0.53, 95% CI: 0.18, 1.58) than among overweight/obese women (BMI ≥25: HR = 0.88, 95% CI: 0.54, 1.43), but these differences were not statistically significant. Fish intake was also not associated with risk (quartile 4 vs. quartile 1: HR = 0.86, 95% CI: 0.56, 1.31). Again hazard ratios were smaller among normal-weight women (HR = 0.65) than among overweight/obese women (HR = 0.94). While compatible with no association, the hazard ratios observed among leaner African-American women are similar to those from recent prospective studies conducted in predominantly white populations. PMID:26755676

  3. Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids.

    PubMed Central

    Leonard, A E; Bobik, E G; Dorado, J; Kroeger, P E; Chuang, L T; Thurmond, J M; Parker-Barnes, J M; Das, T; Huang, Y S; Mukerji, P

    2000-01-01

    The Saccharomyces cerevisiae protein ELO2p is involved in the elongation of saturated and monounsaturated fatty acids. Among several sequences with limited identity with the S. cerevisiae ELO2 gene, a consensus cDNA sequence was identified from the LifeSeq(R) database of Incyte Pharmaceuticals, Inc. Human liver cDNA was amplified by PCR using oligonucleotides complementary to the 5' and 3' ends of the putative human cDNA sequence. The resulting full-length sequence, termed HELO1, consisted of 897 bp, which encoded 299 amino acids. However, in contrast with the ELO2 gene, expression of this open reading frame in S. cerevisiae demonstrated that the encoded protein was involved in the elongation of long-chain polyunsaturated fatty acids, as determined by the conversion of gamma-linolenic acid (C(18:3, n-6)) into dihomo-gamma-linolenic acid (C(20:3, n-6)), arachidonic acid (C(20:4, n-6)) into adrenic acid (C(22:4, n-6)), stearidonic acid (C(18:4, n-3)) into eicosatetraenoic acid (C(20:4, n-3)), eicosapentaenoic acid (C(20:5, n-3)) into omega3-docosapentaenoic acid (C(22:5, n-3)) and alpha-linolenic acid (C(18:3, n-3)) into omega3-eicosatrienoic acid (C(20:3, n-3)). The predicted amino acid sequence of the open reading frame had only 29% identity with the yeast ELO2 sequence, contained a single histidine-rich domain and had six transmembrane-spanning regions, as suggested by hydropathy analysis. The tissue expression profile revealed that the HELO1 gene is highly expressed in the adrenal gland and testis. Furthermore, the HELO1 gene is located on chromosome 6, best known for encoding the major histocompatibility complex, which is essential to the human immune response. PMID:10970790

  4. Assessment of a land-locked Atlantic salmon (Salmo salar L.) population as a potential genetic resource with a focus on long-chain polyunsaturated fatty acid biosynthesis.

    PubMed

    Betancor, M B; Olsen, R E; Solstorm, D; Skulstad, O F; Tocher, D R

    2016-03-01

    The natural food for Atlantic salmon (Salmo salar) in freshwater has relatively lower levels of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA) than found in prey for post-smolt salmon in seawater. Land-locked salmon such as the Gullspång population feed exclusively on freshwater type lipids during its entire life cycle, a successful adaptation derived from divergent evolution. Studying land-locked populations may provide insights into the molecular and genetic control mechanisms that determine and regulate n-3 LC-PUFA biosynthesis and retention in Atlantic salmon. A two factorial study was performed comparing land-locked and farmed salmon parr fed diets formulated with fish or rapeseed oil for 8 weeks. The land-locked parr had higher capacity to synthesise n-3 LC-PUFA as indicated by higher expression and activity of desaturase and elongase enzymes. The data suggested that the land-locked salmon had reduced sensitivity to dietary fatty acid composition and that dietary docosahexaenoic acid (DHA) did not appear to suppress expression of LC-PUFA biosynthetic genes or activity of the biosynthesis pathway, probably an evolutionary adaptation to a natural diet lower in DHA. Increased biosynthetic activity did not translate to enhanced n-3 LC-PUFA contents in the flesh and diet was the only factor affecting this parameter. Additionally, high lipogenic and glycolytic potentials were found in land-locked salmon, together with decreased lipolysis which in turn could indicate increased use of carbohydrates as an energy source and a sparing of lipid.

  5. Changes in Plasma and Tissue Long-Chain Polyunsaturated Fatty Acid (LC-PUFA) Content in the Eel Anguilla japonica After External and Internal Osmotic Stress.

    PubMed

    Zhang, Qinghao; Wong, Marty K S; Li, Yiqi; Li, Yuanyou; Takei, Yoshio

    2017-10-01

    We investigated the effect of external and internal osmotic stress on the profile of long-chain polyunsaturated fatty acids (LC-PUFA) in euryhaline eels Anguilla japonica. Freshwater (FW) fish were transferred to seawater (SW) for external osmotic stress or subjected to internal stress through injection with hypertonic saline. FW eels injected with isotonic saline served as controls. Plasma osmolality, Na(+) concentration, and gill Na(+)/K(+) -ATPase activity increased, but hematocrit decreased compared with controls in eels exposed to external or internal osmotic stress. The expression of two major transporter genes for SW adaptation, the Na(+) -K(+) -2Cl - co-transporter 1a (NKCC1a) in the gill and NKCC2b in the intestine, was up-regulated only in SW-transferred eels, suggesting a direct impact of SW on the gill and intestine via SW ingestion. Total LC-PUFA contents and DHA (22:6 n-3) increased in the gill and liver of SW-transferred eels and in the intestine of hypertonic saline-injected eels. However, total LC-PUFA content in plasma decreased after both external and internal osmotic stimuli. In contrast, the gene expression of two key enzymes involved in the LC-PUFA biosynthesis, Δ6 fatty acid desaturase and elongase, did not change in the gill, intestine and liver of osmotically stressed eels. These results indicate that LC-PUFA is possibly involved in osmoregulation and the increased LC-PUFA contents of osmoregulatory organs might be a result of LC-PUFA transport via circulation, rather than through de novo biosynthesis.

  6. Long-chain polyunsaturated fatty acids and the preterm infant: a case study in developmentally sensitive nutrient needs in the United States1234

    PubMed Central

    2016-01-01

    The vast majority of infant formulas in the United States contain the long-chain polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (22:6n–3) and arachidonic acid (20:4n–6), which were first permitted by the US Food and Drug Administration in 2001. As a scientific case study, preclinical animal studies of these nutrients definitively influenced the design and interpretation of human clinical studies. Early studies were tied to the availability of test substances, and in hindsight suggest re-evaluation of the essential fatty acid concept in light of the totality of available evidence. Research in the 1950s established the essentiality of n–6 PUFAs for skin integrity; however, widespread recognition of the essentiality of n–3 PUFAs came decades later despite compelling evidence of their significance. Barriers to an understanding of the essentiality of n–3 PUFAs were as follows: 1) their role is in neural function, which is measured only with difficulty compared with skin lesions and growth faltering that are apparent for n–6 PUFAs; 2) the experimental use of vegetable oils as PUFA sources that contain the inefficiently used C18 PUFAs rather than the operative C20 and C22 PUFAs; 3) the shift from reliance on high-quality animal studies to define mechanisms that established the required nutrients in the first part of the 20th century to inherently challenging human studies. Advances in nutrition of premature infants require the best practices and opinions available, taking into account the totality of preclinical and clinical evidence. PMID:26791188

  7. Long-chain polyunsaturated fatty acids and the preterm infant: a case study in developmentally sensitive nutrient needs in the United States.

    PubMed

    Brenna, J Thomas

    2016-02-01

    The vast majority of infant formulas in the United States contain the long-chain polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6), which were first permitted by the US Food and Drug Administration in 2001. As a scientific case study, preclinical animal studies of these nutrients definitively influenced the design and interpretation of human clinical studies. Early studies were tied to the availability of test substances, and in hindsight suggest re-evaluation of the essential fatty acid concept in light of the totality of available evidence. Research in the 1950s established the essentiality of n-6 PUFAs for skin integrity; however, widespread recognition of the essentiality of n-3 PUFAs came decades later despite compelling evidence of their significance. Barriers to an understanding of the essentiality of n-3 PUFAs were as follows: 1) their role is in neural function, which is measured only with difficulty compared with skin lesions and growth faltering that are apparent for n-6 PUFAs; 2) the experimental use of vegetable oils as PUFA sources that contain the inefficiently used C18 PUFAs rather than the operative C20 and C22 PUFAs; 3) the shift from reliance on high-quality animal studies to define mechanisms that established the required nutrients in the first part of the 20th century to inherently challenging human studies. Advances in nutrition of premature infants require the best practices and opinions available, taking into account the totality of preclinical and clinical evidence.

  8. Up-Regulation of Mitochondrial Antioxidant Superoxide Dismutase Underpins Persistent Cardiac Nutritional-Preconditioning by Long Chain n-3 Polyunsaturated Fatty Acids in the Rat

    PubMed Central

    Abdukeyum, Grace G.; Owen, Alice J.; Larkin, Theresa A.; McLennan, Peter L.

    2016-01-01

    Reactive oxygen species paradoxically underpin both ischaemia/reperfusion (I/R) damage and ischaemic preconditioning (IPC) cardioprotection. Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) are highly susceptible to peroxidation, but are paradoxically cardioprotective. This study tested the hypothesis that LCn-3 PUFA cardioprotection is underpinned by peroxidation, upregulating antioxidant activity to reduce I/R-induced lipid oxidation, and the mechanisms of this nutritional preconditioning contrast to mechanisms of IPC. Rats were fed: fish oil (LCn-3 PUFA); sunflower seed oil (n-6 PUFA); or beef tallow (saturated fat, SF) enriched diets for six weeks. Isolated hearts were subject to: 180 min normoxic perfusion; a 30 min coronary occlusion ischaemia protocol then 120 min normoxic reperfusion; or a 3 × 5 min global IPC protocol, 30 min ischaemia, then reperfusion. Dietary LCn-3 PUFA raised basal: membrane docosahexaenoic acid (22:6n-3 DHA); fatty acid peroxidisability index; concentrations of lipid oxidation products; and superoxide dismutase (MnSOD) activity (but not CuZnSOD or glutathione peroxidase). Infarct size correlated inversely with basal MnSOD activity (r2 = 0.85) in the ischaemia protocol and positively with I/R-induced lipid oxidation (lipid hydroperoxides (LPO), r2 = 0.475; malondialdehyde (MDA), r2 = 0.583) across ischaemia and IPC protocols. While both dietary fish oil and IPC infarct-reduction were associated with reduced I/R-induced lipid oxidation, fish oil produced nutritional preconditioning by prior LCn-3 PUFA incorporation and increased peroxidisability leading to up-regulated mitochondrial SOD antioxidant activity. PMID:26959067

  9. Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids

    PubMed Central

    2011-01-01

    Background The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]). Results Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05). Conclusion These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism. PMID:22018327

  10. Contribution of n-3 long-chain polyunsaturated fatty acids to human milk is still low in Hungarian mothers.

    PubMed

    Mihályi, Krisztina; Györei, Eszter; Szabó, Éva; Marosvölgyi, Tamás; Lohner, Szimonetta; Decsi, Tamás

    2015-03-01

    Maternal diet has decisive influence on the fatty acid composition of human milk. Fifteen years ago, we found outstandingly low contribution of docosahexaenoic acid (DHA) to human milk in a small group of Hungarian mothers. The major aim of the present study was to investigate whether DHA status in human milk in Hungary changed during the last 15 years. We aimed to examine the fatty acid composition of human milk at three different stages of lactation (3rd day, 6th week, and 6th month) in healthy Hungarian mothers. Fatty acid composition of human milk lipids was determined by gas chromatograph with flame ionization detector. Contribution of arachidonic acid to the fatty acid composition of human milk significantly decreased during lactation (0.91 [0.38] in colostrum, 0.53 [0.17] at 6th week, and 0.46 [0.13] at 6th month, p < 0.01). The contribution of DHA significantly decreased from colostrum to the 6th week of lactation (0.29 [0.12] and 0.14 [0.04], p < 0.01), without further changes by 6 months (0.12 [0.10]). The contribution of DHA to the fatty acid composition of mature human milk in Hungarian mothers is still among the lowest values ever reported in the literature.

  11. Effect of a long-chain n-3 polyunsaturated fatty acid-enriched diet on adipose tissue lipid profiles and gene expression in Holstein dairy cows.

    PubMed

    Elis, Sebastien; Desmarchais, Alice; Freret, Sandrine; Maillard, Virginie; Labas, Valérie; Cognié, Juliette; Briant, Eric; Hivelin, Celine; Dupont, Joëlle; Uzbekova, Svetlana

    2016-12-01

    The objective of this study was to determine whether fish oil supplement has an effect on adipose tissue lipid profiles and gene expression in postpartum dairy cows. Holstein cows were supplemented with either long-chain n-3 polyunsaturated fatty acid (PUFA; protected fish oil) or control PUFA (n-6; toasted soybeans) for 2mo after calving (n=23 per diet). These cows showed no difference in milk production or metabolic parameters, but exhibited a tendency toward a decrease in early embryo mortality rate after artificial insemination. We hypothesized that, in addition to this effect, modifications in adipose tissue (AT) gene expression and lipid profiles would occur in response to diet. Subcutaneous AT samples were thus collected from the dewlaps of n-3 and n-6 dairy cows at 1mo antepartum, and 1wk, 2mo, and 5mo postpartum for the analysis of lipids and gene expression. Lipid profiles were obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in both positive and negative modes. We found 37 lipid species in the 200 to 1,200 m/z range, which differed between the n-3 and control groups, suggesting that the n-3 supplement affected the lipid composition through the enrichment of lipids integrating long-chain PUFA from fish oil sources: eicosapentaenoic and docosahexaenoic acid. Moreover, a decrease in triacylglycerolipids was observed in AT of n-3 supplemented cows. The expression of 44 genes involved in fatty acid metabolism and the adipokine system was assessed by real-time reverse-transcription PCR. Hierarchical clustering, according to either postpartum stage or diet, enabled us to group genes exhibiting similar kinetic properties during lactation or by those that varied in similar ways after n-3 supplementation, respectively. Among the genes exhibiting a dietary effect, FABP4, LIPE, CD36, and PLIN1 were overexpressed in n-3 AT samples compared with the control, suggesting an increase in lipolysis due to n-3 supplementation, which

  12. The use of low-EPA fish oil for long-chain polyunsaturated fatty acid supplementation of preterm infants.

    PubMed

    Lapillonne, A; Picaud, J C; Chirouze, V; Goudable, J; Reygrobellet, B; Claris, O; Salle, B L

    2000-12-01

    Because docosahexaenoic acid (DHA) may be an essential nutrient for the visual and early cognitive development of preterm infants, DHA enrichment of preterm formulas has been recommended. This randomized trial was designed to study the n-6 and n-3 fatty acid status of healthy preterm infants fed a formula enriched with a low eicosapentaenoic-fish oil until 4 mo corrected age compared with that of infants fed a standard formula. A reference group of breast-fed infants was studied concurrently. The fatty acid content of red blood cell (RBC) phospholipid was assessed at enrollment, hospital discharge, expected term, and 3 and 6 mo postterm. The DHA content of RBC phospholipid was higher in infants fed the enriched versus the standard formula at hospital discharge, expected term, and 3 and 6 mo postterm. However, compared with infants fed the standard formula, infants fed the enriched formula had also higher RBC phospholipid eicosapentaenoic content (0.69 +/- 0.15% versus 0.25 +/- 0.12%, p < 0.001), and lower RBC phospholipid arachidonic acid content (15.1 +/- 0.93% versus 18.8 +/- 0.89%; p < 0.001). We conclude that supplementing preterm infants with low-eicosapentaenoic fish oil is effective in improving DHA status, but results in worsening of n-6 fatty acid status. We speculate that preterm infants may require a dietary supply of arachidonic acid as well as DHA if the same fatty acid status as that of breast-fed infants is to be achieved.

  13. Bioconversion of α-linolenic acid into n-3 long-chain polyunsaturated fatty acid in hepatocytes and ad hoc cell culture optimisation.

    PubMed

    Alhazzaa, Ramez; Sinclair, Andrew J; Turchini, Giovanni M

    2013-01-01

    This study aimed to establish optimal conditions for a cell culture system that would allow the measurement of 18:3n-3 (ALA) bioconversion into n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA), and to determine the overall pathway kinetics. Using rat hepatocytes (FaO) as model cells, it was established that a maximum 20:5n-3 (EPA) production from 50 µM ALA initial concentration was achieved after 3 days of incubation. Next, it was established that a gradual increase in the ALA concentration from 0 up to 125 µM lead to a proportional increase in EPA, without concomitant increase in further elongated or desaturated products, such as 22:5n-3 (DPA) and 22:6n-3 (DHA) in 3 day incubations. Of interest, ALA bioconversion products were observed in the culture medium. Therefore, in vitro experiments disregarding the medium fatty acid content are underestimating the metabolism efficiency. The novel application of the fatty acid mass balance (FAMB) method on cell culture system (cells with medium) enabled quantifying the apparent enzymatic activities for the biosynthesis of n-3 LC-PUFA. The activity of the key enzymes was estimated and showed that, under these conditions, 50% (Km) of the theoretical maximal (V max = 3654 µmol.g(-1) of cell protein.hour(-1)) Fads2 activity on ALA can be achieved with 81 µM initial ALA. Interestingly, the apparent activity of Elovl2 (20:5n-3 elongation) was the slowest amongst other biosynthesis steps. Therefore, the possible improvement of Elovl2 activity is suggested toward a more efficient DHA production from ALA. The present study proposed and described an ad hoc optimised cell culture conditions and methodology towards achieving a reliable experimental platform, using FAMB, to assist in studying the efficiency of ALA bioconversion into n-3 LC-PUFA in vitro. The FAMB proved to be a powerful and inexpensive method to generate a detailed description of the kinetics of n-3 LC-PUFA biosynthesis enzymes activities in vitro.

  14. Bioconversion of α-Linolenic Acid into n-3 Long-Chain Polyunsaturated Fatty Acid in Hepatocytes and Ad Hoc Cell Culture Optimisation

    PubMed Central

    Alhazzaa, Ramez; Sinclair, Andrew J.; Turchini, Giovanni M.

    2013-01-01

    This study aimed to establish optimal conditions for a cell culture system that would allow the measurement of 18∶3n-3 (ALA) bioconversion into n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA), and to determine the overall pathway kinetics. Using rat hepatocytes (FaO) as model cells, it was established that a maximum 20∶5n-3 (EPA) production from 50 µM ALA initial concentration was achieved after 3 days of incubation. Next, it was established that a gradual increase in the ALA concentration from 0 up to 125µM lead to a proportional increase in EPA, without concomitant increase in further elongated or desaturated products, such as 22∶5n-3 (DPA) and 22∶6n-3 (DHA) in 3 day incubations. Of interest, ALA bioconversion products were observed in the culture medium. Therefore, in vitro experiments disregarding the medium fatty acid content are underestimating the metabolism efficiency. The novel application of the fatty acid mass balance (FAMB) method on cell culture system (cells with medium) enabled quantifying the apparent enzymatic activities for the biosynthesis of n-3 LC-PUFA. The activity of the key enzymes was estimated and showed that, under these conditions, 50% (Km) of the theoretical maximal (Vmax = 3654 µmol.g−1 of cell protein.hour−1) Fads2 activity on ALA can be achieved with 81 µM initial ALA. Interestingly, the apparent activity of Elovl2 (20∶5n-3 elongation) was the slowest amongst other biosynthesis steps. Therefore, the possible improvement of Elovl2 activity is suggested toward a more efficient DHA production from ALA. The present study proposed and described an ad hoc optimised cell culture conditions and methodology towards achieving a reliable experimental platform, using FAMB, to assist in studying the efficiency of ALA bioconversion into n-3 LC-PUFA in vitro. The FAMB proved to be a powerful and inexpensive method to generate a detailed description of the kinetics of n-3 LC-PUFA biosynthesis enzymes activities in vitro

  15. Erythrocyte fatty acids of term infants fed either breast milk, standard formula, or formula supplemented with long-chain polyunsaturates.

    PubMed

    Makrides, M; Neumann, M A; Simmer, K; Gibson, R A

    1995-10-01

    The purpose of our study was to assess whether a supplement of fish oil (FO) and evening primrose oil (EPO) for formula-fed infants was capable of avoiding reductions in erythrocyte docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) associated with standard formula feeding. Healthy, term infants, whose mothers chose to formula feed, were randomized to either a placebo or supplemented formula for their first 30 wk of life. A reference group of beast-fed infants also was enrolled. Erythrocyte fatty acids were measured by capillary gas chromatography on day 5 and in weeks 6, 16, and 30. Supplementation of formula with 0.36% of total fatty acids as DHA resulted in erythrocyte DHA being maintained at or above breast-fed levels for the entire 30-wk study period, and breast feeding (0.21% DHA) resulted in a modest fall in erythrocyte DHA relative to baseline (day 5) values. The level of erythrocyte DHA in placebo formula-fed infants was halved by week 16. AA levels decreased in all infants in the first six weeks, but the levels in breast- and placebo formula-fed infants increased with age and returned to approximate baseline (day 5) values by 16 and 30 wk of age, respectively. Erythrocyte AA in FO+EPO-supplemented infants remained low and below breast- and placebo formula-fed levels. Our data suggest that dietary supplementation with DHA at 0.36% total fatty acids results in erythrocyte DHA levels above those found in breast-fed infants. EPO supplementation was not effective at maintaining erythrocyte AA when given with FO.

  16. Effect of diets rich in either saturated fat or n-6 polyunsaturated fatty acids and supplemented with long-chain n-3 polyunsaturated fatty acids on plasma lipoprotein profiles.

    PubMed

    Dias, C B; Amigo, N; Wood, L G; Correig, X; Garg, M L

    2017-05-10

    Abnormalities in lipoprotein profiles (size, distribution and concentration) play an important role in the pathobiology of atherosclerosis and coronary artery disease. Dietary fat, among other factors, has been demonstrated to modulate lipoprotein profiles. We aimed to investigate if background dietary fat (saturated, SFA versus omega-6 polyunsaturated fatty acids, n-6PUFA) was a determinant of the effects of LCn-3PUFA supplementation on lipoprotein profiles. A randomized controlled clinical intervention trial in a parallel design was conducted. Healthy subjects (n=26) were supplemented with 400 mg eicosapentaenoic acid plus 2000 mg docosahexaenoic acid daily and randomized to consume diets rich in either SFA or n-6PUFA for a period of 6 weeks. Blood samples, collected at baseline and after 6 weeks of intervention, were assessed for plasma lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) determined using nuclear magnetic resonance spectroscopy. Study participants receiving the SFA or the n-6PUFA enriched diets consumed similar percentage energy from fat (41 and 42% respectively, P=0.681). However, subjects on the SFA diet consumed 50% more energy as saturated fat and 77% less as linoleic acid than those consuming the n-6PUFA diet (P<0.001). The diets rich in SFA and n-6PUFA reduced the concentration of total very-low-density lipoprotein (VLDL) particles (P<0.001, both), and their subclasses and increased VLDL (P=0.042 and P=0.007, respectively) and LDL (P=0.030 and 0.027, respectively) particle size. In addition, plasma triglyceride concentration was significantly reduced by LCn-3PUFA supplementation irrespective of the dietary fat. LCn-3PUFA modulated lipoprotein profiles in a similar fashion when supplemented in diets rich in either SFA or n-6PUFA.European Journal of Clinical Nutrition advance online publication, 10 May 2017; doi:10.1038/ejcn.2017.56.

  17. Elevation of the Yields of Very Long Chain Polyunsaturated Fatty Acids via Minimal Codon Optimization of Two Key Biosynthetic Enzymes.

    PubMed

    Xia, Fei; Li, Xueying; Li, Xinzheng; Zheng, Desong; Sun, Quanxi; Liu, Jiang; Li, Yaxiao; Hua, Jinping; Qi, Baoxiu

    2016-01-01

    Eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17) and Docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19) are nutritionally beneficial to human health. Transgenic production of EPA and DHA in oilseed crops by transferring genes originating from lower eukaryotes, such as microalgae and fungi, has been attempted in recent years. However, the low yield of EPA and DHA produced in these transgenic crops is a major hurdle for the commercialization of these transgenics. Many factors can negatively affect transgene expression, leading to a low level of converted fatty acid products. Among these the codon bias between the transgene donor and the host crop is one of the major contributing factors. Therefore, we carried out codon optimization of a fatty acid delta-6 desaturase gene PinD6 from the fungus Phytophthora infestans, and a delta-9 elongase gene, IgASE1 from the microalga Isochrysis galbana for expression in Saccharomyces cerevisiae and Arabidopsis respectively. These are the two key genes encoding enzymes for driving the first catalytic steps in the Δ6 desaturation/Δ6 elongation and the Δ9 elongation/Δ8 desaturation pathways for EPA/DHA biosynthesis. Hence expression levels of these two genes are important in determining the final yield of EPA/DHA. Via PCR-based mutagenesis we optimized the least preferred codons within the first 16 codons at their N-termini, as well as the most biased CGC codons (coding for arginine) within the entire sequences of both genes. An expression study showed that transgenic Arabidopsis plants harbouring the codon-optimized IgASE1 contained 64% more elongated fatty acid products than plants expressing the native IgASE1 sequence, whilst Saccharomyces cerevisiae expressing the codon optimized PinD6 yielded 20 times more desaturated products than yeast expressing wild-type (WT) PinD6. Thus the codon optimization strategy we developed here offers a simple, effective and low-cost alternative to whole gene synthesis for high expression of

  18. Elevation of the Yields of Very Long Chain Polyunsaturated Fatty Acids via Minimal Codon Optimization of Two Key Biosynthetic Enzymes

    PubMed Central

    Zheng, Desong; Sun, Quanxi; Liu, Jiang; Li, Yaxiao; Hua, Jinping

    2016-01-01

    Eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17) and Docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19) are nutritionally beneficial to human health. Transgenic production of EPA and DHA in oilseed crops by transferring genes originating from lower eukaryotes, such as microalgae and fungi, has been attempted in recent years. However, the low yield of EPA and DHA produced in these transgenic crops is a major hurdle for the commercialization of these transgenics. Many factors can negatively affect transgene expression, leading to a low level of converted fatty acid products. Among these the codon bias between the transgene donor and the host crop is one of the major contributing factors. Therefore, we carried out codon optimization of a fatty acid delta-6 desaturase gene PinD6 from the fungus Phytophthora infestans, and a delta-9 elongase gene, IgASE1 from the microalga Isochrysis galbana for expression in Saccharomyces cerevisiae and Arabidopsis respectively. These are the two key genes encoding enzymes for driving the first catalytic steps in the Δ6 desaturation/Δ6 elongation and the Δ9 elongation/Δ8 desaturation pathways for EPA/DHA biosynthesis. Hence expression levels of these two genes are important in determining the final yield of EPA/DHA. Via PCR-based mutagenesis we optimized the least preferred codons within the first 16 codons at their N-termini, as well as the most biased CGC codons (coding for arginine) within the entire sequences of both genes. An expression study showed that transgenic Arabidopsis plants harbouring the codon-optimized IgASE1 contained 64% more elongated fatty acid products than plants expressing the native IgASE1 sequence, whilst Saccharomyces cerevisiae expressing the codon optimized PinD6 yielded 20 times more desaturated products than yeast expressing wild-type (WT) PinD6. Thus the codon optimization strategy we developed here offers a simple, effective and low-cost alternative to whole gene synthesis for high expression of

  19. Validity of a food frequency questionnaire to estimate long-chain polyunsaturated fatty acid intake among Japanese women in early and late pregnancy

    PubMed Central

    Kobayashi, Minatsu; Jwa, Seung Chik; Ogawa, Kohei; Morisaki, Naho

    2016-01-01

    Background The relative validity of food frequency questionnaires for estimating long-chain polyunsaturated fatty acid (LC-PUFA) intake among pregnant Japanese women is currently unclear. The aim of this study was to verify the external validity of a food frequency questionnaire, originally developed for non-pregnant adults, to assess the dietary intake of LC-PUFA using dietary records and serum phospholipid levels among Japanese women in early and late pregnancy. Methods A validation study involving 188 participants in early pregnancy and 169 participants in late pregnancy was conducted. Intake LC-PUFA was estimated using a food frequency questionnaire and evaluated using a 3-day dietary record and serum phospholipid concentrations in both early and late pregnancy. Results The food frequency questionnaire provided estimates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake with higher precision than dietary records in both early and late pregnancy. Significant correlations were observed for LC-PUFA intake estimated using dietary records in both early and late pregnancy, particularly for EPA and DHA (correlation coefficients ranged from 0.34 to 0.40, p < 0.0001). Similarly, high correlations for EPA and DHA in serum phospholipid composition were also observed in both early and late pregnancy (correlation coefficients ranged 0.27 to 0.34, p < 0.0001). Conclusions Our findings suggest that the food frequency questionnaire, which was originally designed for non-pregnant adults and was evaluated in this study against dietary records and biological markers, has good validity for assessing LC-PUFA intake, especially EPA and DHA intake, among Japanese women in early and late pregnancy. PMID:28135195

  20. Infants fed formula with added long chain polyunsaturated fatty acids have reduced incidence of respiratory illnesses and diarrhea during the first year of life.

    PubMed

    Lapillonne, Alexandre; Pastor, Nitida; Zhuang, Weihong; Scalabrin, Deolinda M F

    2014-07-02

    Long chain polyunsaturated fatty acids (LCPUFAs) may influence the immune system. Our objective was to compare the frequency of common illnesses in infants who received formula with or without added LCPUFAs. In this observational, multi-center, prospective study, infants consumed formula with 17 mg DHA and 34 mg ARA/100 kcal (n = 233) or with no added DHA or ARA (n = 92). Pediatricians recorded respiratory illnesses, otitis media, eczema, and diarrhea through 1 year of age. Infants who consumed formula with DHA/ARA had lower incidence of bronchitis/bronchiolitis (P = 0.004), croup (P = 0.044), nasal congestion (P = 0.001), cough (P = 0.014), and diarrhea requiring medical attention (P = 0.034). The odds ratio (OR) of having at least one episode of bronchitis/bronchiolitis (0.41, 95% CI 0.24, 0.70; P = 0.001), croup (0.23, 95% CI 0.05, 0.97; P = 0.045), nasal congestion (0.37, 95% CI 0.20, 0.66; P = 0.001), cough (0.52, 95% CI 0.32, 0.86; P = 0.011), and diarrhea requiring medical attention (0.51, 95% CI 0.28, 0.92; P = 0.026) was lower in infants fed DHA/ARA. The OR of an increased number of episodes of bronchitis/bronchiolitis, croup, nasal congestion, cough, and diarrhea, as well as the hazard ratio for shorter time to first episode of bronchitis/bronchiolitis, nasal congestion, cough, and diarrhea were also significantly lower in the DHA/ARA group. In healthy infants, formula with DHA/ARA was associated with lower incidence of common respiratory symptoms and illnesses, as well as diarrhea.

  1. Development and validation of a food frequency questionnaire to assess omega-3 long chain polyunsaturated fatty acid intake in Australian children aged 9-13 years.

    PubMed

    Rahmawaty, S; Charlton, K; Lyons-Wall, P; Meyer, B J

    2017-08-01

    The present study aimed to develop a food frequency questionnaire (FFQ) assessing dietary omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) intake in Australian children and to validate the FFQ against a 7-day food diary. The investigation comprised a cross-sectional and validation study. The study setting was two private primary schools in the in the Illawarra region of New South Wales. Twenty-two Australian children, aged 9-13 years, who were not on a special diet or receiving medical care that limited their food choice in the 3 months prior to recruitment, were recruited into the study. A total of 131 items, classified according to seven food group categories, was included in the n-3 LCPUFA FFQ, as identified from published dietary surveys and a supermarket survey. Good correlations between the FFQ and the 7-day food diary were observed for eicosapentaenoic acid (EPA) [r = 0.691, 95% confidence interval (CI) = 0.51-0.83, P < 0.001], docosahexaenoic acid (DHA) (r = 0.684, 95% CI = 0.45-0.84, P < 0.001) and total n-3 LCPUFA (r = 0.687, 95% CI = 0.48-0.85, P < 0.001). Bland-Altman plots showed an acceptable limit of agreement between the FFQ and the average 7-day food diary. However, the mean EPA, DHA and total n-3 LCPUFA intakes estimated from the FFQ were significantly higher than those from the average 7-day food diary estimates (P < 0.001). A novel n-3 LCPUFA FFQ that has been developed to estimate dietary n-3 LCPUFA intakes in Australian children has been shown to have relative validity. The FFQ provides a useful contribution to dietary assessment methodology in this age group; however, reproducibility remains to be demonstrated. © 2016 The British Dietetic Association Ltd.

  2. Validity of a food frequency questionnaire to estimate long-chain polyunsaturated fatty acid intake among Japanese women in early and late pregnancy.

    PubMed

    Kobayashi, Minatsu; Jwa, Seung Chik; Ogawa, Kohei; Morisaki, Naho; Fujiwara, Takeo

    2017-01-01

    The relative validity of food frequency questionnaires for estimating long-chain polyunsaturated fatty acid (LC-PUFA) intake among pregnant Japanese women is currently unclear. The aim of this study was to verify the external validity of a food frequency questionnaire, originally developed for non-pregnant adults, to assess the dietary intake of LC-PUFA using dietary records and serum phospholipid levels among Japanese women in early and late pregnancy. A validation study involving 188 participants in early pregnancy and 169 participants in late pregnancy was conducted. Intake LC-PUFA was estimated using a food frequency questionnaire and evaluated using a 3-day dietary record and serum phospholipid concentrations in both early and late pregnancy. The food frequency questionnaire provided estimates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake with higher precision than dietary records in both early and late pregnancy. Significant correlations were observed for LC-PUFA intake estimated using dietary records in both early and late pregnancy, particularly for EPA and DHA (correlation coefficients ranged from 0.34 to 0.40, p < 0.0001). Similarly, high correlations for EPA and DHA in serum phospholipid composition were also observed in both early and late pregnancy (correlation coefficients ranged 0.27 to 0.34, p < 0.0001). Our findings suggest that the food frequency questionnaire, which was originally designed for non-pregnant adults and was evaluated in this study against dietary records and biological markers, has good validity for assessing LC-PUFA intake, especially EPA and DHA intake, among Japanese women in early and late pregnancy. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  3. Protein restriction in the rat negatively impacts long-chain polyunsaturated fatty acid composition and mammary gland development at the end of gestation.

    PubMed

    Bautista, Claudia J; Rodríguez-González, Guadalupe L; Torres, Nimbe; Hernández-Pando, Rogelio; Ramírez, Victoria; Rodríguez-Cruz, Maricela; Nathanielsz, Peter W; Zambrano, Elena

    2013-08-01

    Maternal nutrition during gestation is critical for mammary gland cell proliferation and differentiation and development of optimal delta-6 (Δ6D) and delta-5 (Δ5D) desaturase and elongase 2 and 5 (Elovl 2 and 5) activity for synthesis of the long chain polyunsaturated fatty acids (LC-PUFAs), arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, important for normal fetal and neonatal brain development. We hypothesized that maternal low protein diet (LPD) impairs mammary gland preparation for lactation and PUFA synthesis. The aim of the study was to evaluate consequences of maternal LPD on mammary gland structure and development and expression of enzymes responsible for LC-PUFA production. Pregnant rats were assigned to control or protein restricted, isocaloric diet (R). At 19 days gestation, mammary gland tissue was removed for histological analysis and lipid, AA, EPA and DHA determination by gas chromatography. Gene transcription was quantified by RT-PCR and protein by Western blot. In R mothers, mammary gland lobuloalveolar development was decreased and showed fat cell infiltration. Δ6D, Δ5D, and Elovl 5 mRNA were lower in R, whereas protein levels measured by Western blot were unchanged. This is the first report that detects mammary gland desaturase and elongase protein. Although Elovl 2 mRNA was not detectable by RT-PCR, Elovl 2 protein was not different between groups. AA and DHA were lower and EPA undetectable in the mammary gland of R mothers. Maternal LPD decreased late gestation mammary gland lobuloalveolar development and LC-PUFAs. Protein restriction negatively impacts maternal mammary gland development prior to lactation. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  4. Rapid isolation of omega-3 long-chain polyunsaturated fatty acids using monolithic high performance liquid chromatography columns.

    PubMed

    Fagan, Peter; Wijesundera, Chakra

    2013-06-01

    Eicosapentaenoic and docosahexaenoic acids are important bio-active fatty acids in fish oils. Monolithic HPLC columns both in the polymeric cation exchange (silver-ion) and RP formats were compared with corresponding packed columns for the isolation of these acids from tuna oil ethyl esters. Monolithic columns in both formats enabled rapid (typically 5-10 min) separations compared with packed columns (30 min). Polymeric monolithic silver-ion disc column rapidly furnished mixtures of eicosapentaenoic and docosahexaenoic esters (90% purity) within 5-10 min, but was unable to resolve individual esters. A preparative version of the same column (80 mL bed volume) enabled isolation (>88% purity) of 100 mg quantities of eicosapentaenoic and docosahexaenoic esters from esterified tuna oil within 6 min. Baseline separation of eicosapentaenoic and docosahexaenoic esters was achieved on all RP columns. The results show that there is potential to use polymeric monolithic cation exchange columns for scaled-up preparation of eicosapentaenoic and docosahexaenoic ester concentrates from fish oils. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Long Chain Polyunsaturated Fatty Acid Levels in U.S. Donor Human Milk: Meeting the Needs of Premature Infants?

    PubMed Central

    Baack, Michelle L.; Norris, Andrew W.; Yao, Jianrong; Colaizy, Tarah

    2011-01-01

    Objective To determine fatty acid levels in the US donor milk supply. Study Design Donor human milk samples from Iowa (n=62), Texas (n=5), North Carolina (n=5), and California (n=5) were analyzed by gas chromatography. Levels in Iowa donor milk were compared before and after pasteurization using Student’s t-test. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels were compared among all milk banks using ANOVA. Results ARA (0.4 pre, 0.4 post, p=0.18) and DHA (0.073 pre, 0.073 post, p=0.84) were not affected by pasteurization. DHA varied between banks (p <0.0001), whereas ARA did not (p = 0.3). DHA levels from all banks were lower than published values for maternal milk and infant formula (p<0.0001). Conclusion Pasteurization of breastmilk does not affect DHA or ARA levels. However, DHA content in US donor milk varies with bank location and may not meet the recommended provision for preterm infants. PMID:22323096

  6. The metabolic syndrome of fructose-fed rats: effects of long-chain polyunsaturated ω3 and ω6 fatty acids. II. Time course of changes in food intake, body weight, plasma glucose and insulin concentrations and insulin resistance.

    PubMed

    Mellouk, Zoheir; Hachimi Idrissi, Tarek; Louchami, Karim; Hupkens, Emeline; Sener, Abdullah; Yahia, Dalila Ait; Malaisse, Willy J

    2012-01-01

    The time course for changes in food intake, body weight, plasma glucose and insulin concentrations and HOMA index was monitored over a period of 8 weeks in rats exposed from the 8th week after birth to diets containing either starch or fructose and sunflower oil. In two further groups of rats exposed to the fructose-rich diet part of the sunflower oil was substituted by either salmon oil rich in long-chain polyunsaturated ω3 fatty acids or safflower oil rich in long-chain polyunsaturated ω6 fatty acids. Despite lower food intake, the gain in body weight was higher in fructose-fed rats than in starch-fed rats. The supplementation of the fructose-rich diet by either ω3 or ω6 fatty acids lowered both food intake and body weight gain. The measurements of plasma glucose and insulin concentrations, HOMA index and insulinogenic index performed after overnight starvation were in fair agreement with those recorded at the occasion of an intraperitoneal glucose tolerance test, with higher values for plasma glucose concentration and HOMA index in the fructose-fed rats exposed to the sunflower oil (with or without enrichment with ω6 fatty acids) than in the starch-fed rats exposed to the sunflower oil or fructose-fed rats exposed to a diet enriched with ω3 fatty acids. Such was also the case for the measurements of glycated albumin at sacrifice. Moreover, the insulinogenic index was lower in the fructose-fed rats with or without dietary enrichment in ω6 fatty acids than in the fructose-fed rats with dietary enrichment in ω3 fatty acids. The elucidation of the biochemical determinants of the later difference requires further investigations in isolated pancreatic islets.

  7. Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials

    PubMed Central

    Mazahery, Hajar; Stonehouse, Welma; Delshad, Maryam; Kruger, Marlena C.; Conlon, Cathryn A.; Beck, Kathryn L.; von Hurst, Pamela R.

    2017-01-01

    Omega-3 long chain polyunsaturated fatty acid supplementation (n-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. The results of previous systematic reviews and meta-analyses of n-3 LCPUFA supplementation on ASD outcomes were inconclusive. Two meta-analyses were conducted; meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-3 LCPUFA supplementation to placebo on symptoms of ASD. Case-control studies and randomised controlled trials (RCTs) were identified searching electronic databases up to May, 2016. Mean differences were pooled and analysed using inverse variance models. Heterogeneity was assessed using I2 statistic. Fifteen case-control studies (n = 1193) were reviewed. Compared with typically developed, ASD populations had lower DHA (−2.14 [95% CI −3.22 to −1.07]; p < 0.0001; I2 = 97%), EPA (−0.72 [95% CI −1.25 to −0.18]; p = 0.008; I2 = 88%), and ARA (−0.83 [95% CI, −1.48 to −0.17]; p = 0.01; I2 = 96%) and higher total n-6 LCPUFA to n-3 LCPUFA ratio (0.42 [95% CI 0.06 to 0.78]; p = 0.02; I2 = 74%). Four RCTs were included in meta-analysis 2 (n = 107). Compared with placebo, n-3 LCPUFA improved social interaction (−1.96 [95% CI −3.5 to −0.34]; p = 0.02; I2 = 0) and repetitive and restricted interests and behaviours (−1.08 [95% CI −2.17 to −0.01]; p = 0.05; I2 = 0). Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms. Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA. PMID:28218722

  8. Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants' allergies in first year of life: randomised controlled trial.

    PubMed

    Palmer, D J; Sullivan, T; Gold, M S; Prescott, S L; Heddle, R; Gibson, R A; Makrides, M

    2012-01-30

    To determine whether dietary n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation of pregnant women with a fetus at high risk of allergic disease reduces immunoglobulin E associated eczema or food allergy at 1 year of age. Follow-up of infants at high hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome (DOMInO) randomised controlled trial. Adelaide, South Australia. 706 infants at high hereditary risk of developing allergic disease whose mothers were participating in the DOMInO trial. The intervention group (n=368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n=338) received matched vegetable oil capsules without n-3 LCPUFA. Immunoglobulin E associated allergic disease (eczema or food allergy with sensitisation) at 1 year of age. No differences were seen in the overall percentage of infants with immunoglobulin E associated allergic disease between the n-3 LCPUFA and control groups (32/368 (9%) v 43/338 (13%); unadjusted relative risk 0.68, 95% confidence interval 0.43 to 1.05, P=0.08; adjusted relative risk 0.70, 0.45 to 1.09, P=0.12), although the percentage of infants diagnosed as having atopic eczema (that is, eczema with associated sensitisation) was lower in the n-3 LCPUFA group (26/368 (7%) v 39/338 (12%); unadjusted relative risk 0.61, 0.38 to 0.98, P=0.04; adjusted relative risk 0.64, 0.40 to 1.02, P=0.06). Fewer infants were sensitised to egg in the n-3 LCPUFA group (34/368 (9%) v 52/338 (15%); unadjusted relative risk 0.61, 0.40 to 0.91, P=0.02; adjusted relative risk 0.62, 0.41 to 0.93, P=0.02), but no difference between groups in immunoglobulin E associated food allergy was seen. n-3 LCPUFA supplementation in pregnancy did not reduce the overall incidence of immunoglobulin E associated allergies in the first year of life, although atopic eczema and egg sensitisation were lower. Longer term

  9. Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials.

    PubMed

    Mazahery, Hajar; Stonehouse, Welma; Delshad, Maryam; Kruger, Marlena C; Conlon, Cathryn A; Beck, Kathryn L; von Hurst, Pamela R

    2017-02-19

    Omega-3 long chain polyunsaturated fatty acid supplementation (n-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. The results of previous systematic reviews and meta-analyses of n-3 LCPUFA supplementation on ASD outcomes were inconclusive. Two meta-analyses were conducted; meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-3 LCPUFA supplementation to placebo on symptoms of ASD. Case-control studies and randomised controlled trials (RCTs) were identified searching electronic databases up to May, 2016. Mean differences were pooled and analysed using inverse variance models. Heterogeneity was assessed using I² statistic. Fifteen case-control studies (n = 1193) were reviewed. Compared with typically developed, ASD populations had lower DHA (-2.14 [95% CI -3.22 to -1.07]; p < 0.0001; I² = 97%), EPA (-0.72 [95% CI -1.25 to -0.18]; p = 0.008; I² = 88%), and ARA (-0.83 [95% CI, -1.48 to -0.17]; p = 0.01; I² = 96%) and higher total n-6 LCPUFA to n-3 LCPUFA ratio (0.42 [95% CI 0.06 to 0.78]; p = 0.02; I² = 74%). Four RCTs were included in meta-analysis 2 (n = 107). Compared with placebo, n-3 LCPUFA improved social interaction (-1.96 [95% CI -3.5 to -0.34]; p = 0.02; I² = 0) and repetitive and restricted interests and behaviours (-1.08 [95% CI -2.17 to -0.01]; p = 0.05; I² = 0). Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms. Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA.

  10. Effect of long chain omega-3 polyunsaturated fatty acids on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial

    PubMed Central

    Ellulu, Mohammed S.; Khaza'ai, Huzwah; Patimah, Ismail; Rahmat, Asmah; Abed, Yehia

    2016-01-01

    Background Obesity is a degree of excess weight that predisposes people to metabolic syndromes via an inflammatory mechanism. Hypertensive and diabetic people have higher risks of developing systemic inflammation. Long chain omega-3 polyunsaturated fatty acids (LC ω-3 PUFAs) can reduce the cardiovascular events and help against inflammation. Objective To identify the effects of LC ω-3 PUFAs on reducing the levels of inflammatory markers on hypertensive and/or diabetic obese adults. Materials and methods Sixty-four patients, who were hypertensive and/or diabetic obese with high levels of inflammatory markers, from primary healthcare centers of Gaza City, Palestine, enrolled in two groups of an open-label, parallel, randomized, controlled trial for 8 weeks. Thirty-three patients were in the control group, and 31 patients were in the experimental group. The experimental group was treated with a daily dose of 300 mg eicosapentaenoic acid and 200 mg of docosahexaenoic acid. Results Treatment with LC ω-3 PUFAs significantly reduced the level of high sensitivity C reactive protein (hs-CRP) [14.78±10.7 to 8.49±6.69 mg/L, p<0.001], fasting blood glucose (FBG) [178.13±58.54 to 157.32±59.77 mg/dL, p=0.024], and triglyceride (TG) [209.23±108.3 to 167.0±79.9 mg/dL, p<0.05] after 8 weeks of treatment, whereas no significant changes appeared in interleukin 6 (IL-6) and total cholesterol (TC). In the control group, significant reduction was detected for FBG [187.15±64.8 to 161.91±37.9 mg/dL, p<0.05] and TG [202.91±107.0 to 183.45±95.82 mg/dL, p<0.05], and no changes for hs-CRP, IL-6, or TC. By comparing the experimental group with the changes of control group at the endpoint, LC ω-3 PUFAs did not reach the clinical significance in treating effectiveness for any of the clinical variables. Conclusion LC ω-3 PUFAs have recommended effects on health; the obtained results can improve the role of LC ω-3 PUFAs as a protective factor on inflammation and metabolic

  11. Effect of long chain omega-3 polyunsaturated fatty acids on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial.

    PubMed

    Ellulu, Mohammed S; Khaza'ai, Huzwah; Patimah, Ismail; Rahmat, Asmah; Abed, Yehia

    2016-01-01

    Obesity is a degree of excess weight that predisposes people to metabolic syndromes via an inflammatory mechanism. Hypertensive and diabetic people have higher risks of developing systemic inflammation. Long chain omega-3 polyunsaturated fatty acids (LC ω-3 PUFAs) can reduce the cardiovascular events and help against inflammation. To identify the effects of LC ω-3 PUFAs on reducing the levels of inflammatory markers on hypertensive and/or diabetic obese adults. Sixty-four patients, who were hypertensive and/or diabetic obese with high levels of inflammatory markers, from primary healthcare centers of Gaza City, Palestine, enrolled in two groups of an open-label, parallel, randomized, controlled trial for 8 weeks. Thirty-three patients were in the control group, and 31 patients were in the experimental group. The experimental group was treated with a daily dose of 300 mg eicosapentaenoic acid and 200 mg of docosahexaenoic acid. Treatment with LC ω-3 PUFAs significantly reduced the level of high sensitivity C reactive protein (hs-CRP) [14.78±10.7 to 8.49±6.69 mg/L, p<0.001], fasting blood glucose (FBG) [178.13±58.54 to 157.32±59.77 mg/dL, p=0.024], and triglyceride (TG) [209.23±108.3 to 167.0±79.9 mg/dL, p<0.05] after 8 weeks of treatment, whereas no significant changes appeared in interleukin 6 (IL-6) and total cholesterol (TC). In the control group, significant reduction was detected for FBG [187.15±64.8 to 161.91±37.9 mg/dL, p<0.05] and TG [202.91±107.0 to 183.45±95.82 mg/dL, p<0.05], and no changes for hs-CRP, IL-6, or TC. By comparing the experimental group with the changes of control group at the endpoint, LC ω-3 PUFAs did not reach the clinical significance in treating effectiveness for any of the clinical variables. LC ω-3 PUFAs have recommended effects on health; the obtained results can improve the role of LC ω-3 PUFAs as a protective factor on inflammation and metabolic dysregulation. The time allowed or the dose used could be insufficient

  12. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances

    PubMed Central

    Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung

    2016-01-01

    Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism. PMID:26742061

  13. The capacity for long-chain polyunsaturated fatty acid synthesis in a carnivorous vertebrate: Functional characterisation and nutritional regulation of a Fads2 fatty acyl desaturase with Δ4 activity and an Elovl5 elongase in striped snakehead (Channa striata).

    PubMed

    Kuah, Meng-Kiat; Jaya-Ram, Annette; Shu-Chien, Alexander Chong

    2015-03-01

    The endogenous production of long-chain polyunsaturated fatty acids (LC-PUFA) in carnivorous teleost species inhabiting freshwater environments is poorly understood. Although a predatory lifestyle could potentially supply sufficient LC-PUFA to satisfy the requirements of these species, the nutrient-poor characteristics of the freshwater food web could impede this advantage. In this study, we report the cloning and functional characterisation of an elongase enzyme in the LC-PUFA biosynthesis pathway from striped snakehead (Channa striata), which is a strict freshwater piscivore that shows high deposition of LC-PUFA in its flesh. We also functionally characterised a previously isolated fatty acyl desaturase cDNA from this species. Results showed that the striped snakehead desaturase is capable of Δ4 and Δ5 desaturation activities, while the elongase showed the characteristics of Elovl5 elongases. Collectively, these findings reveal that striped snakehead exhibits the genetic resources to synthesise docosahexaenoic acid (DHA; 22:6n-3) from eicosapentaenoic acid (EPA; 20:5n-3). Both genes are expressed at considerable levels in the brain and the liver. In liver, both genes were up-regulated by dietary C18 PUFA, although this increase did not correspond to a significant rise in the deposition of muscle LC-PUFA. Brain tissue of fish fed with plant oil diets showed higher expression of fads2 gene compared to fish fed with fish oil-based diet, which could ensure DHA levels remain constant under limited dietary DHA intake. This suggests the importance of DHA production from EPA via the ∆4 desaturation step in order to maintain an optimal reserve of DHA in the neuronal tissues of carnivores. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Echium oil increased the expression of a Δ4 Fads2 fatty acyl desaturase and the deposition of n-3 long-chain polyunsaturated fatty acid in comparison with linseed oil in striped snakehead (Channa striata) muscle.

    PubMed

    Jaya-Ram, Annette; Shu-Chien, Alexander Chong; Kuah, Meng-Kiat

    2016-08-01

    Despite the potential of vegetable oils as aquafeed ingredients, a major drawback associated with their utilization is the inferior level of beneficial n-3 long-chain polyunsaturated fatty acids (LC-PUFA). Echium oil (EO), which is rich in stearidonic acid (SDA, 18:4n-3), could potentially improve the deposition of n-3 LC-PUFA as the biosynthesis of LC-PUFA is enhanced through bypassing the rate-limiting ∆6 desaturation step. We report for the first time an attempt to investigate whether the presence of a desaturase (Fads2) capable of ∆4 desaturation activities and an elongase (Elovl5) will leverage the provision of dietary SDA to produce a higher rate of LC-PUFA bioconversion. Experimental diets were designed containing fish oil (FO), EO or linseed oil (LO) (100FO, 100EO, 100LO), and diets which comprised equal mixtures of the designated oils (50EOFO and 50EOLO) were evaluated in a 12-week feeding trial involving striped snakeheads (Channa striata). There was no significant difference in growth and feed conversion efficiency. The hepatic fatty acid composition and higher expression of fads2 and elovl5 genes in fish fed EO-based diets indicate the utilization of dietary SDA for LC-PUFA biosynthesis. Collectively, this resulted in a higher deposition of muscle eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) compared to LO-based diets. Dietary EO improved the ratio of n-3 LC-PUFA to n-6 LC-PUFA in fish muscle, which is desirable for human populations with excessive consumption of n-6 PUFA. This study validates the contribution of SDA in improving the content of n-3 LC-PUFA and the ratio of EPA to arachidonic acid (ARA, 20:4n-6) in a freshwater carnivorous species.

  15. Dried blood spot omega-3 and omega-6 long chain polyunsaturated fatty acid levels in 7-9 year old Zimbabwean children: a cross sectional study.

    PubMed

    Mashavave, Grace; Kuona, Patience; Tinago, Willard; Stray-Pedersen, Babill; Munjoma, Marshall; Musarurwa, Cuthbert

    2016-01-01

    Omega-3 long chain-polyunsaturated fatty acids (LC-PUFAs)-docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA)- and omega-6 LC-PUFA arachidonic acid (ARA), are essential for optimum physical and mental development in children. Prior to this study, the blood omega-3 LC-PUFA levels were unknown in Zimbabwean children, particularly in those aged 7-9 years, despite the documented benefits of LC-PUFAs. Documentation of the LC-PUFA levels in this age group would help determine whether interventions, such as fortification, are necessary. This study aimed to determine dried whole blood spot omega-3 and omega-6 LC-PUFA levels and LC-PUFA reference intervals among a selected group of Zimbabwean children aged 7-9 years old. We conducted a cross sectional study from September 2011 to August 2012 on a cohort of peri-urban, Zimbabwean children aged 7-9 years. The children were born to mothers enrolled at late pregnancy into an HIV prevention program between 2002 and 2004. Dried whole blood spots were sampled on butylated hydroxytoluene antioxidant impregnated filter papers and dried. LC-PUFAs were quantified using gas liquid chromatography. Differences in LC-PUFAs between groups were compared using the Kruskal Wallis test and reference intervals determined using non-parametric statistical methods. LC-PUFAs levels were determined in 297 Zimbabwean children of whom 170 (57.2 %) were girls. The study determined that LC-PUFAs (wt/wt) ranges were EPA 0.06-0.55 %, DPA 0.38-1.98 %, DHA 1.13-3.52 %, ARA 5.58-14.64 % and ARA: EPA ratio 15.47-1633.33. Sixteen participants had omega-3 LC-PUFAs levels below the determined reference intervals, while 18 had higher omega-6 LC-PUFAs. The study did not show gender differences in omega-3 and omega-6 LC-PUFAs levels (all p > 0.05). EPA was significantly higher in the 8 year age group compared to those aged 7 and 9 years (median; 0.20 vs 0.17 vs 0.18, respectively, p = 0.049). ARA: EPA ratio was

  16. A randomised controlled trial investigating the effect of n-3 long-chain polyunsaturated fatty acid supplementation on cognitive and retinal function in cognitively healthy older people: the Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) study protocol [ISRCTN72331636

    PubMed Central

    Dangour, Alan D; Clemens, Felicity; Elbourne, Diana; Fasey, Nicky; Fletcher, Astrid E; Hardy, Pollyanna; Holder, Graham E; Huppert, Felicia A; Knight, Rosemary; Letley, Louise; Richards, Marcus; Truesdale, Ann; Vickers, Madge; Uauy, Ricardo

    2006-01-01

    The number of individuals with age-related cognitive impairment is rising dramatically in the UK and globally. There is considerable interest in the general hypothesis that improving the diet of older people may slow the progression of cognitive decline. To date, there has been little attention given to the possible protective role of n-3 long-chain polyunsaturated fatty acids (n-3 LCPs) most commonly found in oily fish, in age-related loss of cognitive function. The main research hypothesis of this study is that an increased dietary intake of n-3 LCPs will have a positive effect on cognitive performance in older people in the UK. To test this hypothesis, a double-blind randomised placebo-controlled trial will be carried out among adults aged 70–79 years in which the intervention arm will receive daily capsules containing n-3 LCP (0.5 g/day docosahexaenoic acid and 0.2 g/day eicosapentaenoic acid) while the placebo arm will receive daily capsules containing olive oil. The main outcome variable assessed at 24 months will be cognitive performance and a second major outcome variable will be retinal function. Retinal function tests are included as the retina is a specifically differentiated neural tissue and therefore represents an accessible window into the functioning of the brain. The overall purpose of this public-health research is to help define a simple and effective dietary intervention aimed at maintaining cognitive and retinal function in later life. This will be the first trial of its kind aiming to slow the decline of cognitive and retinal function in older people by increasing daily dietary intake of n-3 LCPs. The link between cognitive ability, visual function and quality of life among older people suggests that this novel line of research may have considerable public health importance. PMID:16945130

  17. The effect of fatty acid positioning in dietary triacylglycerols and intake of long-chain n-3 polyunsaturated fatty acids on bone mineral accretion in growing piglets.

    PubMed

    Andersen, Anders D; Ludvig, Stine E; Damsgaard, Camilla T; Pulkkinen, Pasi; Finnilä, Mikko; Mu, Huiling; Thymann, Thomas; Michaelsen, Kim F; Mølgaard, Christian; Lauritzen, Lotte

    2013-09-01

    Long-chain n-3 PUFA (LCPUFA) and palmitate (16:0) positioning in the triacylglycerol (TAG) of infant formula may affect calcium-uptake which could affect bone health. We investigated if a human milk fat substitute (HMFS) with a modified TAG structure holding 16:0 predominantly in the sn-2-position compared with a control (CONT) and if increasing n-3LCPUFA intake giving fish oil (FO) compared with sunflower oil (SO) would affect bone parameters in piglets in two sets of controlled 14d-interventions (n=12/group). We assessed this by dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography and mechanical strength. Bone mineral content (BMC) was higher in the FO compared to the SO-group (p=0.03). Despite similar weight gain in HMFS- and CONT-groups, body fat accumulation was higher with HMFS (p<0.001), and BMC, bone area (BA) and cortical BA in femur were lower (p=0.002, p=0.005, and p=0.02, respectively), indicating importance of both n-3LCPUFA and 16:0 TAG-positioning in infant formulas. © 2013 Elsevier Ltd. All rights reserved.

  18. Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early childhood.

    PubMed

    Gunaratne, Anoja W; Makrides, Maria; Collins, Carmel T

    2015-07-22

    Allergies have become more prevalent globally over the last 20 years. Dietary consumption of n-3 (or omega 3) long chain polyunsaturated fatty acids (LCPUFA) has declined over the same period of time. This, together with the known role of n-3 LCPUFA in inhibiting inflammation, has resulted in speculation that n-3 LCPUFA may prevent allergy development. Dietary n-3 fatty acids supplements may change the developing immune system of the newborn before allergic responses are established, particularly for those with a genetic predisposition to the production of the immunoglobulin E (IgE) antibody. Individuals with IgE-mediated allergies have both the signs and symptoms of the allergic disease and a positive skin prick test (SPT) to the allergen. To assess the effect of n-3 LCPUFA supplementation in pregnant and/or breastfeeding women on allergy outcomes (food allergy, atopic dermatitis (eczema), allergic rhinitis (hay fever) and asthma/wheeze) in their children. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 August 2014), PubMed (1966 to 01 August 2014), CINAHL via EBSCOhost (1984 to 01 August 2014), Scopus (1995 to 01 August 2014), Web of Knowledge (1864 to 01 August 2014) and ClinicalTrials.gov (01 August 2014) and reference lists of retrieved studies. We included randomised controlled trials (RCTs) evaluating the effect of n-3 LCPUFA supplementation of pregnant and/or lactating women (compared with placebo or no treatment) on allergy outcomes of the infants or children. Trials using a cross-over design and trials examining biochemical outcomes only were not eligible for inclusion. Two review authors independently assessed eligibility and trial quality and performed data extraction. Where the review authors were also investigators on trials selected, an independent reviewer assessed trial quality and performed data extraction. Eight trials involving 3366 women and their 3175 children were included in the review. In these trials, women

  19. Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Alleviates Doxorubicin-Induced Depressive-Like Behaviors and Neurotoxicity in Rats: Involvement of Oxidative Stress and Neuroinflammation.

    PubMed

    Wu, Yan-Qin; Dang, Rui-Li; Tang, Mi-Mi; Cai, Hua-Lin; Li, Huan-De; Liao, De-Hua; He, Xin; Cao, Ling-Juan; Xue, Ying; Jiang, Pei

    2016-04-23

    Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long-term use can cause neurobiological side-effects associated with depression. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), the essential fatty acids found in fish oil, possess neuroprotecitve and antidepressant activities. Thus, the aim of this study was to explore the potential protective effects of ω-3 PUFAs against DOX-induced behavioral changes and neurotoxicity. ω-3 PUFAs were given daily by gavage (1.5 g/kg) over three weeks starting seven days before DOX administration (2.5 mg/kg). Open-field test (OFT) and forced swimming test (FST) were conducted to assess exploratory activity and despair behavior, respectively. Our data showed that ω-3 PUFAs supplementation significantly mitigated the behavioral changes induced by DOX. ω-3 PUFAs pretreatment also alleviated the DOX-induced neural apoptosis. Meanwhile, ω-3 PUFAs treatment ameliorated DOX-induced oxidative stress in the prefrontal cortex and hippocampus. Additionally, gene expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and the protein levels of NF-κB and iNOS were significantly increased in brain tissues of DOX-treated group, whereas ω-3 PUFAs supplementation significantly attenuated DOX-induced neuroinflammation. In conclusion, ω-3 PUFAs can effectively protect against DOX-induced depressive-like behaviors, and the mechanisms underlying the neuroprotective effect are potentially associated with its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

  20. Cross-sectional associations of cortical β-amyloid with erythrocyte membrane long-chain polyunsaturated fatty acids in older adults with subjective memory complaints.

    PubMed

    Hooper, Claudie; De Souto Barreto, Philipe; Payoux, Pierre; Salabert, Anne Sophie; Guyonnet, Sophie; Andrieu, Sandrine; Vellas, Bruno

    2017-08-01

    Omega-3 (n-3) and 6 (n-6) polyunsaturated fatty acids (PUFAs) have been associated with reduced cognitive decline in observational studies. Hence, we examined the cross-sectional associations between cortical β-amyloid (Aβ) and erythrocyte membrane PUFAs in 61 non-demented elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial placebo arm. Cortical-to-cerebellar standard uptake value ratios were obtained using [(18) F] florbetapir positron emission tomography. Fatty acids were measured in erythrocyte membranes by gas chromatography. Associations were explored using adjusted multiple linear regression models and were considered significant at p ≤ 0.005 after correction for multiple testing (10 comparisons). We found no significant associations between cortical Aβ and erythrocyte membrane PUFAs. The associations closest to significance after adjustment were those between Aβ and erythrocyte membrane arachidonic acid (without apolipoprotein E status adjustment: B-coefficient, 0.03; CI, 0.01, 0.05; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, 0.03; CI, 0.00, 0.06; p = 0.04) and Aβ and erythrocyte membrane linoleic acid (without apolipoprotein E status adjustment: B-coefficient, -0.02; CI, -0.04, 0.00; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, -0.02; CI, -0.04, 0.00; p = 0.09). Furthermore, the association between Aβ and erythrocyte membrane arachidonic acid seemed to be specific to Apolipoprotein E ε4 non-carriers (B-coefficient 0.03, CI: 0.00, 0.06, p = 0.03, n = 36). In contrast, no association was found between Aβ and erythrocyte membrane linoleic acid in Apolipoprotein E ε4 stratified analysis. Investigating the relationships between Aβ and PUFAs longitudinally would provide further evidence as to whether fatty acids, particularly arachidonic acid and linoleic acid, might modulate cognition through Aβ-dependent mechanisms. © 2017 International

  1. Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).

    PubMed

    Dain, Alejandro; Repossi, Gaston; Diaz-Gerevini, Gustavo T; Vanamala, Jairam; Das, Undurti N; Eynard, Aldo R

    2016-11-25

    Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM. After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls. Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups. eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory

  2. Long-chain polyunsaturated fatty acids are consumed during allergic inflammation and affect T helper type 1 (Th1)- and Th2-mediated hypersensitivity differently

    PubMed Central

    Johansson, S; Lönnqvist, A; Östman, S; Sandberg, A-S; Wold, A E

    2010-01-01

    Studies have shown that atopic individuals have decreased serum levels of n-3 fatty acids. Indicating these compounds may have a protective effect against allergic reaction and/or are consumed during inflammation. This study investigated whether fish (n-3) or sunflower (n-6) oil supplementation affected T helper type 1 (Th1)- and Th2-mediated hypersensitivity in the skin and airways, respectively, and whether the fatty acid serum profile changed during the inflammatory response. Mice were fed regular chow, chow + 10% fish oil or chow + 10% sunflower oil. Mice were immunized with ovalbumin (OVA) resolved in Th1 or Th2 adjuvant. For Th1 hypersensitivity, mice were challenged with OVA in the footpad. Footpad swelling, OVA-induced lymphocyte proliferation and cytokine production in the draining lymph node were evaluated. In the airway hypersensitivity model (Th2), mice were challenged intranasally with OVA and the resulting serum immunoglobulin (Ig)E and eosinophilic lung infiltration were measured. In the Th1 model, OVA-specific T cells proliferated less and produced less interferon (IFN)-γ, tumour necrosis factor (TNF) and interleukin (IL)-6 in fish oil-fed mice versus controls. Footpad swelling was reduced marginally. In contrast, mice fed fish oil in the Th2 model produced more OVA-specific IgE and had slightly higher proportions of eosinophils in lung infiltrate. A significant fall in serum levels of long-chain n-3 fatty acids accompanied challenge and Th2-mediated inflammation in Th2 model. Fish oil supplementation affects Th1 and Th2 immune responses conversely; significant consumption of n-3 fatty acids occurs during Th2-driven inflammation. The latter observation may explain the association between Th2-mediated inflammation and low serum levels of n-3 fatty acids. PMID:20148912

  3. The effect of prostaglandin E(2) (PGE(2)) and long-chain polyunsaturated fatty acids (LC PUFA) on bone formation in piglets: a model for bone growth in nutritional investigation.

    PubMed

    Burke, A; Weiler, H

    2002-10-01

    This research investigates the effects of exogenous prostaglandin E(2) (PGE(2)) treatment and arachidonic acid supplementation on the rate of growth in modelling bone of piglets. The piglet is a good model for the study of infant nutrition and bone growth. PGE(2) and long-chain polyunsaturated fatty acid (LC PUFA) supplementation, alone and in combination, are shown to have little or no effect on cortical bone thickness. Though exogenous PGE(2) supplementation and LC PUFA supplementation may both be effective in promoting bone growth and mass in adults, they do not appear to have the same positive effect on bone growth in infancy over a short term. A dynamic model for bone growth in piglets is proposed here for the first time. This research adds to our knowledge of the relationship between the dynamic histology of bone, the rate of osteogenesis, and the link between nutrition and bone growth.

  4. Facts about polyunsaturated fats

    MedlinePlus

    Polyunsaturated fatty acid; PUFA; Cholesterol - polyunsaturated fat; Atherosclerosis - polyunsaturated fat; Hardening of the arteries - polyunsaturated fat; Hyperlipidemia - polyunsaturated fat; Hypercholesterolemia - polyunsaturated ...

  5. Supplementation with N-3 Long-Chain Polyunsaturated Fatty Acids or Olive Oil in Men and Women with Renal Disease Induces Differential Changes in the DNA Methylation of FADS2 and ELOVL5 in Peripheral Blood Mononuclear Cells

    PubMed Central

    Hoile, Samuel P.; Clarke-Harris, Rebecca; Huang, Rae-Chi; Calder, Philip C.; Mori, Trevor A.; Beilin, Lawrence J.; Lillycrop, Karen A.; Burdge, Graham C.

    2014-01-01

    Background Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans. Methods and Results We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5′ regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts. Conclusions These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function. PMID:25329159

  6. Circulating B-vitamins and smoking habits are associated with serum polyunsaturated Fatty acids in patients with suspected coronary heart disease: a cross-sectional study.

    PubMed

    Skeie, Eli; Strand, Elin; Pedersen, Eva R; Bjørndal, Bodil; Bohov, Pavol; Berge, Rolf K; Svingen, Gard F T; Seifert, Reinhard; Ueland, Per M; Midttun, Øivind; Ulvik, Arve; Hustad, Steinar; Drevon, Christian A; Gregory, Jesse F; Nygård, Ottar

    2015-01-01

    The long-chain polyunsaturated fatty acids are considered to be of major health importance, and recent studies indicate that their endogenous metabolism is influenced by B-vitamin status and smoking habits. We investigated the associations of circulating B-vitamins and smoking habits with serum polyunsaturated fatty acids among 1,366 patients who underwent coronary angiography due to suspected coronary heart disease at Haukeland University Hospital, Norway. Of these, 52% provided information on dietary habits by a food frequency questionnaire. Associations were assessed using partial correlation (Spearman's rho). In the total population, the concentrations of most circulating B-vitamins were positively associated with serum n-3 polyunsaturated fatty acids, but negatively with serum n-6 polyunsaturated fatty acids. However, the associations between B-vitamins and polyunsaturated fatty acids tended to be weaker in smokers. This could not be solely explained by differences in dietary intake. Furthermore, plasma cotinine, a marker of recent nicotine exposure, showed a negative relationship with serum n-3 polyunsaturated fatty acids, but a positive relationship with serum n-6 polyunsaturated fatty acids. In conclusion, circulating B-vitamins are, in contrast to plasma cotinine, generally positively associated with serum n-3 polyunsaturated fatty acids and negatively with serum n-6 polyunsaturated fatty acids in patients with suspected coronary heart disease. Further studies should investigate whether B-vitamin status and smoking habits may modify the clinical effects of polyunsaturated fatty acid intake.

  7. Circulating B-Vitamins and Smoking Habits Are Associated with Serum Polyunsaturated Fatty Acids in Patients with Suspected Coronary Heart Disease: A Cross-Sectional Study

    PubMed Central

    Skeie, Eli; Strand, Elin; Pedersen, Eva R.; Bjørndal, Bodil; Bohov, Pavol; Berge, Rolf K.; Svingen, Gard F. T.; Seifert, Reinhard; Ueland, Per M.; Midttun, Øivind; Ulvik, Arve; Hustad, Steinar; Drevon, Christian A.; Gregory, Jesse F.; Nygård, Ottar

    2015-01-01

    The long-chain polyunsaturated fatty acids are considered to be of major health importance, and recent studies indicate that their endogenous metabolism is influenced by B-vitamin status and smoking habits. We investigated the associations of circulating B-vitamins and smoking habits with serum polyunsaturated fatty acids among 1,366 patients who underwent coronary angiography due to suspected coronary heart disease at Haukeland University Hospital, Norway. Of these, 52% provided information on dietary habits by a food frequency questionnaire. Associations were assessed using partial correlation (Spearman’s rho). In the total population, the concentrations of most circulating B-vitamins were positively associated with serum n-3 polyunsaturated fatty acids, but negatively with serum n-6 polyunsaturated fatty acids. However, the associations between B-vitamins and polyunsaturated fatty acids tended to be weaker in smokers. This could not be solely explained by differences in dietary intake. Furthermore, plasma cotinine, a marker of recent nicotine exposure, showed a negative relationship with serum n-3 polyunsaturated fatty acids, but a positive relationship with serum n-6 polyunsaturated fatty acids. In conclusion, circulating B-vitamins are, in contrast to plasma cotinine, generally positively associated with serum n-3 polyunsaturated fatty acids and negatively with serum n-6 polyunsaturated fatty acids in patients with suspected coronary heart disease. Further studies should investigate whether B-vitamin status and smoking habits may modify the clinical effects of polyunsaturated fatty acid intake. PMID:26039046

  8. Cold-induced accumulation of ω-3 polyunsaturated fatty acid in a liverwort, Marchantia polymorpha L.

    PubMed

    Takemura, Miho; Hamada, Tatsuro; Kida, Haruka; Ohyama, Kanji

    2012-01-01

    The liverwort Marchantia polymorpha L. synthesizes various long-chain polyunsaturated fatty acids including arachidonic acid and eicosapentaenoic acid, neither of which is produced by higher plants. Here we report the effects of temperature on long-chain polyunsaturated fatty acid accumulation in the liverwort. The accumulation of ω-3 polyunsaturated fatty acids increased significantly as the growth temperature decreased. Specifically, the relative content of eicosapentaenoic acid to total fatty acids at 5 °C was approximately 3-fold higher than at 25 °C. On the other hand, the accumulation of ω-6 polyunsaturated fatty acids decreased at low temperatures. An analysis of gene expression indicated that the mRNA of the MpFAD3 gene for ER ω-3 desaturase increased significantly at 5 °C. These results indicate that in the liverwort the n-3 pathway was enhanced at low temperature, mainly via expression of the cold-induced ω-3 desaturase gene, leading to increased accumulation of eicosapentaenoic acid.

  9. Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial.

    PubMed

    Widenhorn-Müller, Katharina; Schwanda, Simone; Scholz, Elke; Spitzer, Manfred; Bode, Harald

    2014-01-01

    To determine whether supplementation with the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) affects behavioral symptoms and cognitive impairments in children 6-12 years of age diagnosed with attention-deficit/hyperactivity disorder (ADHD). The randomized, double-blind placebo-controlled 16 weeks trial was conducted with 95 children diagnosed with ADHD according to DSM-IV criteria. Behavior was assessed by parents, teachers and investigators using standardized rating scales and questionnaires. Further outcome variables were working memory, speed of information processing and various measures of attention. For a subgroup of 81 participants, erythrocyte membrane fatty acid composition was analyzed before and after the intervention. Supplementation with the omega-3 fatty acid mix increased EPA and DHA concentrations in erythrocyte membranes and improved working memory function, but had no effect on other cognitive measures and parent- and teacher-rated behavior in the study population. Improved working memory correlated significantly with increased EPA, DHA and decreased AA (arachidonic acid). Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Cloning and functional expression of the first plant fatty acid elongase specific for Delta(6)-polyunsaturated fatty acids.

    PubMed

    Zank, T K; Zähringer, U; Lerchl, J; Heinz, E

    2000-12-01

    In order to elucidate the biosynthesis of long-chain polyunsaturated fatty acids (PUFAs) in plants we searched for a cDNA encoding a Delta(6)-specific PUFA elongase from Physcomitrella patens, which is known to contain high proportions of arachidonic acid (20:4 Delta(5,8,11,14)). An EST clone from P. patens was identified by its low homology to the yeast gene ELO1, which is required for the elongation of medium-chain fatty acids. We functionally characterized this cDNA by heterologous expression in Saccharomyces cerevisiae grown in the presence of several fatty acids. Analysis of the fatty acid profile of the transgenic yeast revealed that the cDNA encodes a protein that leads to the elongation of the C(18) Delta(6)-polyunsaturated fatty acids gamma-linolenic acid (18:3 Delta(6,9,12)) and stearidonic acid (18:4 Delta(6,9,12,15)), which were recovered to 45-51% as their elongation products. In contrast, linoleic and alpha-linolenic acids were hardly elongated and we could not measure any elongation of saturated and mono-unsaturated fatty acids (including 18:1 Delta(6)), indicating that the elongase is highly specific for the polyunsaturated nature of the fatty acid acting as substrate.

  11. Gas-liquid chromatographic method for analysing complex mixtures of fatty acids including conjugated linoleic acids (cis9trans11 and trans10cis12 isomers) and long-chain (n-3 or n-6) polyunsaturated fatty acids. Application to the intramuscular fat of beef meat.

    PubMed

    Aldai, N; Osoro, K; Barrón, L J R; Nájera, A I

    2006-03-31

    The optimisation and validation of a gas-liquid chromatographic (GLC) method using direct saponification with KOH/methanol followed by a derivatization with (trimethylsilyl)diazomethane was carried out trying to overcome all the difficulties posed by the analysis of complex mixtures of fatty acids (FAs) in animal fat tissues. The presented method allowed sensitive, selective and simultaneous determination of a wide range of different FAs, including short-chain FAs, branched-chain FAs and conjugated linoleic acid isomers in the same GLC run along with other well known saturated, monounsaturated and polyunsaturated FAs. To demonstrate the feasibility of the procedure, the total FA profile of beef meat was characterised.

  12. Dietary intake and status of n-3 polyunsaturated fatty acids in a population of fish-eating and non-fish-eating meat-eaters, vegetarians, and vegans and the product-precursor ratio [corrected] of α-linolenic acid to long-chain n-3 polyunsaturated fatty acids: results from the EPIC-Norfolk cohort.

    PubMed

    Welch, Ailsa A; Shakya-Shrestha, Subodha; Lentjes, Marleen A H; Wareham, Nicholas J; Khaw, Kay-Tee

    2010-11-01

    Intakes of n-3 (omega-3) polyunsaturated fatty acids (PUFAs) are important for health. Because fish is the major source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), non-fish-eaters may have suboptimal n-3 PUFA status, although the importance of the conversion of plant-derived α-linolenic acid (ALA) to EPA and DHA is debated. The objective was to determine intakes, food sources, and status of n-3 PUFAs according to dietary habit (fish-eaters and non-fish-eating meat-eaters, vegetarians, or vegans) and estimated conversion between dietary ALA and circulating long-chain n-3 PUFAs. This study included 14,422 men and women aged 39-78 y from the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk cohort with 7-d diary data and a substudy in 4902 individuals with plasma phospholipid fatty acid measures. Intakes and status of n-3 PUFAs were measured, and the product-precursor ratio [corrected] of ALA to circulating n-3 PUFAs was calculated. Most of the dietary intake of EPA and DHA was supplied by fish; however, meat was the major source in meat-eaters, and spreading fats, soups, and sauces were the major sources in vegetarians. Total n-3 PUFA intakes in non-fish-eaters were 57-80% of those in fish-eaters, but status differences were considerably smaller [corrected]. The estimated product-precursor ratio [corrected] was greater in women than in men and greater in non-fish-eaters than in fish-eaters. Substantial differences in intakes and in sources of n-3 PUFAs existed between the dietary-habit groups, but the differences in status were smaller than expected, possibly because the product-precursor ratio [corrected] was greater in non-fish-eaters than in fish-eaters, potentially indicating increased estimated conversion of ALA. If intervention studies were to confirm these findings, it could have implications for fish requirements.

  13. Long-chain n-3 polyunsaturated fatty acid from fish oil modulates aortic nitric oxide and tocopherol status in the rat.

    PubMed

    López, Diego; Möller, Matías; Denicola, Ana; Casós, Kelly; Rubbo, Homero; Ruiz-Sanz, José Ignacio; Mitjavila, Maria Teresa

    2008-10-01

    In spite of their high oxidisability, long-chain n-3 PUFA protect against CVD. Dietary fatty acids modulate the fatty acid composition of lipoproteins involved in atherosclerosis. We thought that if long-chain n-3 PUFA were able to increase NO production by the aorta, then by its antioxidant activity the NO will prevent lipid peroxidation. However, the beneficial effect of NO in vivo on VLDL + LDL oxidation would only be possible if NO could diffuse to their lipidic core. Rats were fed maize oil- or fish oil as menhaden oil- (MO) rich diets for 8 weeks, to study the effects of MOon aortic NO production, NO diffusion into VLDL + LDL, the extent of oxidation in native VLDL + LDL and their oxidisability ex vivo. Aortic NO production and its alpha-tocopherol content were increased and n-3 PUFA were incorporated into the VLDL + LDL. In spite of the higher peroxidisability and the low alpha-tocopherol in native VLDL + LDL from rats fed MO, native VLDL + LDL from the two groups shared similar electrophoretic patterns, conjugated dienes, thiobarbituric acid-reactive substances, total antioxidant capacity, and NO diffusibility on VLDL + LDL, indicative of an in vivo protection against oxidation. However, these results do not correlate with the ex vivo oxidisability of VLDL+ LDL, as NO is lacking. Thus, the in vivo beneficial effects can be explained by increased a-tocopherol in aorta and by a compensatory effect of NO onVLDL + LDL against the low alpha-tocopherol levels, which may contribute to the anti-atherogenic properties of fish oil.

  14. Metabolic engineering of omega-3 long-chain polyunsaturated fatty acids in plants using an acyl-CoA Delta6-desaturase with omega3-preference from the marine microalga Micromonas pusilla.

    PubMed

    Petrie, James R; Shrestha, Pushkar; Mansour, Maged P; Nichols, Peter D; Liu, Qing; Singh, Surinder P

    2010-05-01

    Long-chain (> or = C20) polyunsaturated fatty acids (LC-PUFA) EPA and DHA (20:5(Delta5,8,11,14,17) and 22:6(Delta4,7,10,13,16,19)) have well-documented health benefits against coronary heart disease, rheumatoid arthritis and other disorders. Currently, the predominant sources of these fatty acids are marine fish and algal oils, but research is being conducted to ensure that a sustainable, land-based production system can be developed. We here describe the metabolic engineering of an artificial pathway that produces 26% EPA in leaf triacylglycerol using a newly-identified Delta6-desaturase from the marine microalga Micromonas pusilla. We also demonstrate that this enzyme appears to function as an acyl-CoA desaturase that has preference for omega3 substrates both in planta and in yeast. Phylogenetic analysis indicates that this desaturase shares highly conserved motifs with previously described acyl-CoA Delta6-desaturases.

  15. Dietary n-3 long-chain polyunsaturated fatty acids modify phosphoenolpyruvate carboxykinase activity and lipid synthesis from glucose in adipose tissue of rats fed a high-sucrose diet.

    PubMed

    Londero, Lisiane G; Rieger, Débora K; Hansen, Fernanda; Silveira, Simone L; Martins, Tiago L; Lulhier, Francisco; da Silva, Roselis S; Souza, Diogo O; Perry, Marcos L S; de Assis, Adriano M

    2013-12-01

    Long-chain polyunsaturated n-3 fatty acids (n-3 LCPUFAs) have hypolipidemic effects and modulate intermediary metabolism to prevent or reverse insulin resistance in a way that is not completely elucidated. Here, effects of these fatty acids on the lipid profile, phosphoenolpyruvate carboxykinase (PEPCK) activity, lipid synthesis from glucose in epididymal adipose tissue (Ep-AT) and liver were investigated. Male rats were fed a high-sucrose diet (SU diet), containing either sunflower oil or a mixture of sunflower and fish oil (SU-FO diet), and the control group was fed a standard diet. After 13 weeks, liver, adipose tissue and blood were harvested and analysed. The dietary n-3 LCPUFAs prevented sucrose-induced increase in adiposity and serum free fat acids, serum and hepatic triacylglycerol and insulin levels. Furthermore, these n-3 LCPUFAs decreased lipid synthesis from glucose and increased PEPCK activity in the Ep-AT of rats fed the SU-FO diet compared to those fed the SU diet, besides reducing lipid synthesis from glucose in hepatic tissue. Thus, the inclusion of n-3 LCPUFAs in the diet may be beneficial for the prevention or attenuation of dyslipidemia and insulin resistance, and for reducing the risk of related chronic diseases.

  16. Interaction between Marine-Derived n-3 Long Chain Polyunsaturated Fatty Acids and Uric Acid on Glucose Metabolism and Risk of Type 2 Diabetes Mellitus: A Case-Control Study.

    PubMed

    Li, Kelei; Wu, Kejian; Zhao, Yimin; Huang, Tao; Lou, Dajun; Yu, Xiaomei; Li, Duo

    2015-08-26

    The present case-control study explored the interaction between marine-derived n-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs) and uric acid (UA) on glucose metabolism and risk of type 2 diabetes mellitus (T2DM). Two hundred and eleven healthy subjects in control group and 268 T2DM subjects in case group were included. Plasma phospholipid (PL) fatty acids and biochemical parameters were detected by standard methods. Plasma PL C22:6n-3 was significantly lower in case group than in control group, and was negatively correlated with fasting glucose (r = -0.177, p < 0.001). Higher plasma PL C22:6n-3 was associated with lower risk of T2DM, and the OR was 0.32 (95% confidence interval (CI), 0.12 to 0.80; p = 0.016) for per unit increase of C22:6n-3. UA was significantly lower in case group than in control group. UA was positively correlated with fasting glucose in healthy subjects, but this correlation became negative in T2DM subjects. A significant interaction was observed between C22:6n-3 and UA on fasting glucose (p for interaction = 0.005): the lowering effect of C22:6n-3 was only significant in subjects with a lower level of UA. In conclusion, C22:6n-3 interacts with UA to modulate glucose metabolism.

  17. Polyunsaturated fatty acid supplementation reverses cystic fibrosis-related fatty acid abnormalities in CFTR-/- mice by suppressing fatty acid desaturases.

    PubMed

    Njoroge, Sarah W; Laposata, Michael; Boyd, Kelli L; Seegmiller, Adam C

    2015-01-01

    Cystic fibrosis patients and model systems exhibit consistent abnormalities in metabolism of polyunsaturated fatty acids that appear to play a role in disease pathophysiology. Recent in vitro studies have suggested that these changes are due to overexpression of fatty acid desaturases that can be reversed by supplementation with the long-chain polyunsaturated fatty acids docosahexaenoate and eicosapentaenoate. However, these findings have not been tested in vivo. The current study aimed to test these results in an in vivo model system, the CFTR(-/-) knockout mouse. When compared with wild-type mice, the knockout mice exhibited fatty acid abnormalities similar to those seen in cystic fibrosis patients and other model systems. The abnormalities were confined to lung, ileum and pancreas, tissues that are affected by the disease. Similar to in vitro models, these fatty acid changes correlated with increased expression of Δ5- and Δ6-desaturases and elongase 5. Dietary supplementation with high-dose free docosahexaenoate or a combination of lower-dose docosahexaenoate and eicosapentaenoate in triglyceride form corrected the fatty acid abnormalities and reduced expression of the desaturase and elongase genes in the ileum and liver of knockout mice. Only the high-dose docosahexaenoate reduced histologic evidence of disease, reducing mucus accumulation in ileal sections. These results provide in vivo support for the hypothesis that fatty acid abnormalities in cystic fibrosis result from abnormal expression and activity of metabolic enzymes in affected cell types. They further demonstrate that these changes can be reversed by dietary n-3 fatty acid supplementation, highlighting the potential therapeutic benefit for cystic fibrosis patients.

  18. Note on the chromatographic analyses of marine polyunsaturated fatty acids

    USGS Publications Warehouse

    Schultz, D.M.; Quinn, J.G.

    1977-01-01

    Gas-liquid chromatography was used to study the effects of saponification/methylation and thin-layer chromatographic isolation on the analyses of polyunsaturated fatty acids. Using selected procedures, the qualitative and quantitative distribution of these acids in marine organisms can be determined with a high degree of accuracy. ?? 1977 Springer-Verlag.

  19. Preservation of polyunsaturated fatty acyl glycerides via intramolecular antioxidant coupling

    USDA-ARS?s Scientific Manuscript database

    Ferulic acid and its esters are known to be effective antioxidants. Feruloyl di-gamma-linolenoylglycerol was assessed for its ability to serve as an antioxidant for preventing the oxidation of its gamma-linolenoyl polyunsaturated fatty acyl groups in model membrane phospholipid vesicles. The molec...

  20. Modifications of proteins by polyunsaturated fatty acid peroxidation products

    NASA Astrophysics Data System (ADS)

    Refsgaard, Hanne H. F.; Tsai, Lin; Stadtman, Earl R.

    2000-01-01

    The ability of unsaturated fatty acid methyl esters to modify amino acid residues in bovine serum albumin (BSA), glutamine synthetase, and insulin in the presence of a metal-catalyzed oxidation system [ascorbate/Fe(III)/O2] depends on the degree of unsaturation of the fatty acid. The fatty acid-dependent generation of carbonyl groups and loss of lysine residues increased in the order methyl linoleate < methyl linolenate < methyl arachidonate. The amounts of alkyl hydroperoxides, malondialdehyde, and a number of other aldehydes that accumulated when polyunsaturated fatty acids were oxidized in the presence of BSA were significantly lower than that observed in the absence of BSA. Direct treatment of proteins with various lipid hydroperoxides led to a slight increase in the formation of protein carbonyl derivatives, whereas treatment with the hydroperoxides together with Fe(II) led to a substantial increase in the formation of protein carbonyls. These results are consistent with the proposition that metal-catalyzed oxidation of polyunsaturated fatty acids can contribute to the generation of protein carbonyls by direct interaction of lipid oxidation products (α,β-unsaturated aldehydes) with lysine residues (Michael addition reactions) and also by interactions with alkoxyl radicals obtained by Fe(II) cleavage of lipid hydroperoxides that are formed. In addition, saturated aldehydes derived from the polyunsaturated fatty acids likely react with lysine residues to form Schiff base adducts.

  1. A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans.

    PubMed

    Wood, K E; Lau, A; Mantzioris, E; Gibson, R A; Ramsden, C E; Muhlhausler, B S

    2014-04-01

    This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake.

  2. Associations between intake of fish and n-3 long-chain polyunsaturated fatty acids and plasma metabolites related to the kynurenine pathway in patients with coronary artery disease.

    PubMed

    Karlsson, Therese; Strand, Elin; Dierkes, Jutta; Drevon, Christian A; Øyen, Jannike; Midttun, Øivind; Ueland, Per M; Gudbrandsen, Oddrun A; Pedersen, Eva Ringdal; Nygård, Ottar

    2017-02-01

    Enhanced tryptophan degradation via the kynurenine pathway has been related to several pathological conditions. However, little is known about the effect of diet on individual metabolites of this pathway. We investigated cross-sectional associations between reported intake of fish and omega-3 (n-3) long-chain PUFA (LC-PUFA) and plasma metabolites related to the kynurenine pathway. Participants were 2324 individuals with coronary artery disease from the Western Norway B Vitamin Intervention Trial. Fish and n-3 LC-PUFA intakes were assessed using a food frequency questionnaire. Plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid, neopterin, and kynurenine-to-tryptophan ratio (KTR) were analyzed. Associations were investigated using partial Spearman's rank correlations and multiple linear regressions. Median age at inclusion was 62 years (80 % males), and 84 % had stable angina pectoris. Intake of fatty fish and n-3 LC-PUFA was inversely associated with plasma 3-hydroxykynurenine. Consumption of total fish, lean fish, and n-3 LC-PUFA was inversely associated with plasma neopterin. Intake of total fish, fatty fish, and n-3 LC-PUFA was inversely associated with KTR. All these correlations were weak (ρ between -0.12 and -0.06, P < 0.01). In 306 patients with diabetes, lean fish intake was positively associated with plasma 3-hydroxyanthranilic acid (ρ = 0.22, P < 0.001, P for interaction = 0.01), and total fish intake was inversely associated with KTR (ρ = -0.17, P < 0.01, P for interaction = 0.02). Fish intake was not an important determinant of individual metabolites in the kynurenine pathway. However, some correlations were stronger in patients with diabetes. The inverse associations of fish or n-3 LC-PUFA with neopterin and KTR may suggest a slightly lower IFN-γ-mediated immune activation with a higher intake.

  3. Polyunsaturated fatty acids in pregnancy and metabolic syndrome: a review.

    PubMed

    Poniedzialek-Czajkowska, Elzbieta; Mierzynski, Radzislaw; Kimber-Trojnar, Zaneta; Leszczynska-Gorzelak, Bozena; Oleszczuk, Jan

    2014-01-01

    This review presents available evidence for possible application of n-3 long chain polyunsaturated fatty acids (PUFAs) in pregnant obese women with metabolic syndrome (MS) and focuses on prophylaxis of pregnancy complications associated with MS such as gestational hypertension, preeclampsia and gestational diabetes. Dietary supplementation with n-3 PUFAs has recently become popular and their adequate intake during pregnancy and early childhood is of clinical importance. The results of experimental and epidemiological investigations reveal that n-3 PUFAs, especially α- linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), may decrease the risk of cardiovascular diseases. It is believed that n-3 PUFAs affect a multitude of molecular pathways, involving regulation of gene expression, alteration of physical and chemical properties of cellular membranes and modulation of membrane channels and proteins. A large body of evidence focuses on anti-inflammatory properties of PUFAs which seem to be fundamental in prevention and reversing of insulin resistance, atherogenic dyslipidemia, hypertension, thromboembolism and in improving vascular function. Despite the potential PUFAs benefits of decreasing insulin resistance, their application in order to prevent preeclampsia, gestational hypertension and gestational diabetes mellitus in pregnant women with MS has not yet been established. Numerous reports have revealed that appropriate fetal development, including neuronal, retinal and immune function depends on EPA and DHA which are crucial also for prevention of preterm birth. Thus the supplementation with EPA and DHA is highly recommended during pregnancy although the optimal dosing and treatment strategies still need to be determined.

  4. Modulation of plant TPC channels by polyunsaturated fatty acids

    PubMed Central

    Gutla, Paul Vijay Kanth; Carpaneto, Armando

    2012-01-01

    Polyunsaturated fatty acids (PUFAs) are powerful modulators of several animal ion channels. It is shown here that PUFAs strongly affect the activity of the Slow Vacuolar (SV) channel encoded by the plant TPC1 gene. The patch-clamp technique was applied to isolated vacuoles from carrot taproots and Arabidopsis thaliana mesophyll cells and arachidonic acid (AA) was chosen as a model molecule for PUFAs. Our study was extended to different PUFAs including the endogenous alpha-linolenic acid (ALA). The addition of micromolar concentrations of AA reversibly inhibited the SV channel decreasing the maximum open probability and shifting the half activation voltage to positive values. Comparing the effects of different PUFAs, it was found that the length of the lipophilic acyl chain, the number of double bonds and the polar head were critical for channel modulation.The experimental data can be reproduced by a simple three-state model, in which PUFAs do not interact directly with the voltage sensors but affect the voltage-independent transition that leads the channel from the open state to the closed configuration. The results indicate that lipids play an important role in co-ordinating ion channel activities similar to what is known from animal cells. PMID:23105130

  5. Polyunsaturated fatty acid status of Dutch vegans and omnivores.

    PubMed

    Fokkema, M R; Brouwer, D A; Hasperhoven, M B; Hettema, Y; Bemelmans, W J; Muskiet, F A

    2000-11-01

    We compared the polyunsaturated fatty acid (PUFA) status of Dutch vegans and omnivores to investigate whether disparities can be explained by different diets and long chain PUFA (LCP) synthesis rates. Dietary intakes and fatty acid compositions of erythrocytes (RBC), platelets (PLT), plasma cholesterol esters (CE) and plasma triglycerides (TG) of 12 strict vegans and 15 age- and sex-matched omnivores were determined. Vegans had higher omega 6 (CE, TG), 18:2 omega 6 (RBC, CE, TG), 18:3 omega 6 (TG), 20:3 omega 6 (TG), 22:4 omega 6 (TG), 22:5 omega 3 (RBC, PLT), 22:5 omega 3/22:6 omega 3 (RBC, PLT) and 22:5 omega 6/22:6 omega 3 (RBC, PLT), and lower 22:4 omega 6 (RBC, PLT), 22:4 omega 6/22:5 omega 6 (RBC, PLT), omega 3 (CE), LCP omega 3 (CE, TG), 20:5 omega 3 (RBC, PLT, CE), 22:5 omega 3 (TG) and 22:6 omega 3 (all compartments). Vegans had lower 20:4 omega 6 (TG) after normalization of PUFA to 100%, and normalization of eicosanoid precursors to 100% revealed similar 20:4 omega 6 (all), higher 20:3 omega 6 (TG) and lower 20:5 omega 3 (all). High omega 6 (notably 18:2 omega 6) and low omega 3 (notably 20:5 omega 3, 22:6 omega 3) status in Dutch vegans derives from low dietary LCP omega 3 and 18:3 omega 3/18:2 omega 6 ratio. Higher 18:3 omega 6 and 20:3 omega 6 in their TG may reflect higher hepatic 20:4 omega 6 production rate, whereas higher 20:4 omega 6 and 22:4 omega 6 in omnivores indicates 20:4 omega 6 intake from meat.

  6. 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.

  7. Microencapsulated krill and tuna oil blend raises plasma long-chain n-3 polyunsaturated fatty acid levels compared to tuna oil with similar increases in ileal contractility in rats.

    PubMed

    Patten, Glen S; Sanguansri, Luz; Augustin, Mary Ann; Abeywardena, Mahinda Y; Bird, Anthony R; Patch, Craig S; Belobrajdic, Damien P

    2017-03-01

    Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may be more bioavailable from krill oil compared to fish oil due to their phospholipid structure. We tested whether a microencapsulated krill and tuna oil blend (ME-TOKO) provided greater LC n-3 PUFA bioavailability, improved blood lipid profiles and increased intestinal contractility compared to microencapsulated tuna oil (ME-TO). Rats were divided into three groups to receive isocaloric diets containing ME-TO, ME-TOKO and microencapsulated olive oil (ME-OO) at 0.3 or 2 g/100 g for 4 weeks. Final body and organ weights, feed intake and waste output were similar. ME-TOKO rats had higher plasma total LC n-3 PUFA levels compared to ME-TO, but liver LC n-3 PUFA levels and plasma triglyceride and cholesterol levels were similar in non-fasted rats. Diets containing 2% ME-TO and ME-TOKO also showed similar increases in ileal contractility. In summary, ME-TO bioavailability of LC n-3 PUFA was similar to ME-TOKO.

  8. Australians are not Meeting the Recommended Intakes for Omega-3 Long Chain Polyunsaturated Fatty Acids: Results of an Analysis from the 2011–2012 National Nutrition and Physical Activity Survey

    PubMed Central

    Meyer, Barbara J.

    2016-01-01

    Health benefits have been attributed to omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA). Therefore it is important to know if Australians are currently meeting the recommended intake for n-3 LCPUFA and if they have increased since the last National Nutrition Survey in 1995 (NNS 1995). Dietary intake data was obtained from the recent 2011–2012 National Nutrition and Physical Activity Survey (2011–2012 NNPAS). Linoleic acid (LA) intakes have decreased whilst alpha-linolenic acid (LNA) and n-3 LCPUFA intakes have increased primarily due to n-3 LCPUFA supplements. The median n-3 LCPUFA intakes are less than 50% of the mean n-3 LCPUFA intakes which highlights the highly-skewed n-3 LCPUFA intakes, which shows that there are some people consuming high amounts of n-3 LCPUFA, but the vast majority of the population are consuming much lower amounts. Only 20% of the population meets the recommended n-3 LCPUFA intakes and only 10% of women of childbearing age meet the recommended docosahexaenoic acid (DHA) intake. Fish and seafood is by far the richest source of n-3 LCPUFA including DHA. PMID:26927162

  9. Short-term supplementation of acute long-chain omega-3 polyunsaturated fatty acids may alter depression status and decrease symptomology among young adults with depression: A preliminary randomized and placebo controlled trial.

    PubMed

    Ginty, Annie T; Conklin, Sarah M

    2015-09-30

    The current study examined the psychological effects of acute and low-dose long-chain omega-3 polyunsaturated fatty acids (LCPUFAs) supplementation on young adults with depressive symptoms. Participants (N=23, M age (SD)=20.2 (1.25), 78% female), with a Beck Depression Inventory (BDI) score of greater than 10, were randomly assigned to a placebo (corn oil) or LCPUFAs group (1.4g of eicosapentaenoic and docosahexaeonic acids) and were instructed to consume the assigned capsules daily for 21-days. BDI was completed prior to supplementation and at day 21. Group differences in depression status on day 21 were analyzed using chi-square tests. After 21-days of supplementation, there was a significant difference in depression status between groups. 67% of the LCPUFAs no longer met criteria for being depressed, while only 20% in the placebo group were no longer depressed. A mixed ANOVA revealed a significant group x time interaction for BDI scores. Post-hoc analyses revealed the LCPFUAs group had a significant reduction in BDI scores over time, while the placebo group's scores did not significantly change. These findings suggest that LCPUFAs may alter depression and depressive symptomology in young adults in a relatively short amount of time.

  10. Ozone and the peroxidation of polyunsaturated fatty acids in vivo

    SciTech Connect

    Goheen, S.C.; O'Rourke, L.; Larkin, E.C.

    1986-06-01

    Two experiments were carried out to determine whether ozone causes significant oxidation of pulmonary polyunsaturated fatty acids in vivo. These involved ad libitum and pair-feeding. In the first experiment, rats were fed fat-free diets and exposed to ozone for 0, 1, 2, and 4 weeks. Lung and liver fatty acids were analyzed to determine if the rats exposed to ozone lost essential fatty acids more rapidly than those exposed to filtered air. In the second experiment, rats were divided into four groups. Two of these groups were fed fat-free diets, and two were fed diets containing essential fatty acids. Rats from the two diet groups (one of each type) were exposed to ozone, while the remaining two groups were exposed to filtered air. In the second experiment, rats were pair-fed. The amounts of lung and liver fatty acids were relatively uninfluenced by breathing ozone. Results from these experiments demonstrate that in the lung, the polyunsaturated fatty acids, linoleic and arachidonic acids, appear to be oxidized by filtered air and ozone at essentially the same rate.

  11. Brain docosahexaenoic acid status and learning in young rats submitted to dietary long-chain polyunsaturated fatty acid deficiency and supplementation limited to lactation.

    PubMed

    García-Calatayud, Salvador; Redondo, Carlos; Martín, Eva; Ruiz, José Ignacio; García-Fuentes, Miguel; Sanjurjo, Pablo

    2005-05-01

    N-3 fatty acid deficiency has been related to decreased docosahexaenoic acid (DHA) and increased docosapentaenoic acid (DPA) levels in brain and to learning disadvantages. The influence of n-3 deficiency and supplementation on brain fatty acids and learning were investigated in young rats. Newborn Wistar rats were assigned to three groups of cross-foster mothers. The control group (C) was nursed by mothers that received essential fatty acids during pregnancy and lactation, and the deficient group (D) was nursed by mothers that did not receive those fatty acids. The supplemental group (S) had the same conditions as D, receiving an additional DHA and arachidonic acid supplement during lactation. Cerebral cortex and hippocampus fatty acid composition was examined using thin-layer and capillary column gas chromatography, and learning was measured by passive-avoidance procedure. D brains showed low DHA and high DPA levels, but S brain composition was similar to C. Learning in the S group was unaffected, but in the D group, it was poorer than C. Learning was directly correlated with DHA levels and inversely with DPA levels in brain. Low DHA and high DPA brain levels both were correlated with poor learning. DPA seems not to be a suitable brain functional analogue of DHA, and DHA supplementation reversed both biochemical and learning adverse effects observed in n-3 deficiency.

  12. Metolachlor-mediated selection of a microalgal strain producing novel polyunsaturated fatty acids.

    PubMed

    Robert, Stanley; Mansour, Maged P; Blackburn, Susan I

    2007-01-01

    Long-chain (> or = C(20)) polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, are nutritionally important and provide protection against cardiovascular disease, stroke, and cancer. Structural variants of these compounds may have the potential to be used as pharmaceuticals. Marine microalgae are the key producers of long-chain polyunsaturated fatty acids in the global food web. Assuming vast biological and biochemical diversity, we devised a screen to identify microalgae that produce novel fatty acids. The herbicide metolachlor, an inhibitor of long-chain fatty acid biosynthesis, was used in microcosms containing field-collected microalgae to identify naturally resistant strains. We show that one diatom, Melosira cf. moniliformis, is naturally resistant to concentrations of metolachlor, which were cytostatic or lethal to all the other microalgae. Gas chromatography and gas chromatography-mass spectrometry revealed three fatty acids that have not previously been described-18:4 (Delta5,8,11,14), 18:4 (Delta5,9,12,15), and 18:5 (Delta5,8,11,14,17). We propose that this type of screen may be generally applicable to the search of novel compounds produced by marine microorganisms.

  13. 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

  14. 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

  15. Conversion of α-linolenic acid to long-chain omega-3 fatty acid derivatives and alterations of HDL density subfractions and plasma lipids with dietary polyunsaturated fatty acids in Monk parrots (Myiopsitta monachus).

    PubMed

    Petzinger, C; Larner, C; Heatley, J J; Bailey, C A; MacFarlane, R D; Bauer, J E

    2014-04-01

    The effect of α-linolenic acid from a flaxseed (FLX)-enriched diet on plasma lipid and fatty acid metabolism and possible atherosclerosis risk factors was studied in Monk parrots (Myiopsitta monachus). Twenty-four Monk parrots were randomly assigned to diets containing either 10% ground SUNs or 10% ground FLXs. Feed intake was calculated daily. Blood samples, body condition scores and body weights were obtained at -5 weeks, day 0, 7, 14, 28, 42 and 70. Plasma samples were analysed for total cholesterol, free cholesterol, triacylglycerols and lipoproteins. Phospholipid subfraction fatty acid profiles were determined. By day 70, the FLX group had significantly higher plasma phospholipid fatty acids including 18:3n-3 (α-linolenic acid), 20:5n-3 (eicosapentaenoic acid) and 22:6n-3 (docosahexaenoic acid). The sunflower group had significantly higher plasma phospholipid levels of 20:4n-6 (arachidonic acid). By day 70, the high-density lipoprotein (HDL) peak shifted resulting in significantly different HDL peak densities between the two experimental groups (1.097 g/ml FLX group and 1.095 g/ml SUN group, p = 0.028). The plasma fatty acid results indicate that Monk parrots can readily convert α-linolenic acid to the long-chain omega-3 derivatives including docosahexaenoic acid and reduce 20:4n-6 accumulation in plasma phospholipids. The reason for a shift in the HDL peak density is unknown at this time.

  16. Effects of lactoferrin, phytic acid, and EDTA on oxidation in two food emulsions enriched with long-chain polyunsaturated fatty acids.

    PubMed

    Nielsen, Nina S; Petersen, Arni; Meyer, Anne S; Timm-Heinrich, Maike; Jacobsen, Charlotte

    2004-12-15

    The influence of the addition of metal chelators on oxidative stability was studied in a milk drink and in a mayonnaise system containing highly polyunsaturated lipids. Milk drinks containing 5% (w/w) of specific structured lipid were supplemented with lactoferrin (6-24 muM) and stored at 2 degrees C for up to 9 weeks. Mayonnaise samples with 16% fish oil and 64% rapeseed oil (w/w) were supplemented with either lactoferrin (8-32 muM), phytic acid (16-124 muM), or EDTA (16-64 muM) and were stored at 20 degrees C for up to 4 weeks. The effect of the metal chelators was evaluated by determination of peroxide values, secondary volatile oxidation products, and sensory analysis. Lactoferrin reduced the oxidation when added in concentrations of 12 muM in the milk drink and 8 muM in the mayonnaise, whereas it was a prooxidant at higher concentrations in both systems. In mayonnaise, EDTA was an effective metal chelator even at 16 muM, whereas phytic acid did not exert a distinct protective effect against oxidation. The differences in the equimolar effects of the metal chelators are proposed to be due to differences in their binding constants to iron and their different stabilities toward heat and low pH.

  17. Dietary intakes of polyunsaturated fatty acids among pregnant Mexican women.

    PubMed

    Parra-Cabrera, Socorro; Stein, Aryeh D; Wang, Meng; Martorell, Reynaldo; Rivera, Juan; Ramakrishnan, Usha

    2011-04-01

    Nutritional demands for docosahexaenoic acid (DHA) are high during pregnancy. Diets low in DHA and long-chain polyunsaturated fatty-acids (LC-PUFA) in pregnancy are associated with poorer DHA status and slower reestablishment of maternal stores. To assess intakes of LC-PUFA among urban pregnant women in Central Mexico, we conducted a cross-sectional survey in Prenatal Clinic at the General Hospital No. 1 of the Mexican Society Security Institute, Cuernavaca, Morelos, Mexico. We ascertained intakes over past three months of 110 food items using a food frequency questionnaire developed for this population. Among 1364 pregnant women 18-35 years of age (mean age 26.2 ± 4.7 years) who were interviewed at 18-22 weeks gestation, median (inter-quartile range) daily intakes of linoleic acid, alpha-linolenic acid (LA), arachidonic acid, eicosapentaenoic acid and DHA were 17.6 (13.6; 22.2) g, 1.4 (1.0; 2.0) g, 137 (102; 174) mg, 18 (10; 38) mg, and 55 (37; 99) mg respectively. The median ratio of n-6 to n-3 PUFA was 11.8:1. The main dietary contributions to DHA intake were eggs, chicken, and fresh canned fish. Intakes of PUFAs were higher among women who had completed high school (p<0.01). We conclude that intakes of DHA were much lower than recommended values; the high n-6 to n-3 ratio suggests a suboptimal balance of these PUFAs. Very few sources of DHA are commonly eaten. © 2010 Blackwell Publishing Ltd.

  18. Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids

    USDA-ARS?s Scientific Manuscript database

    The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 PUFA is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and dependent on cholesterol status. To further elucidate the mechanism(...

  19. Folate and long-chain polyunsaturated fatty acid supplementation during pregnancy has long-term effects on the attention system of 8.5-y-old offspring: a randomized controlled trial.

    PubMed

    Catena, Andrés; Muñoz-Machicao, J Angela; Torres-Espínola, Francisco J; Martínez-Zaldívar, Cristina; Diaz-Piedra, Carolina; Gil, Angel; Haile, Gudrun; Györei, Eszter; Molloy, Anne M; Decsi, Tamás; Koletzko, Berthold; Campoy, Cristina

    2016-01-01

    During fetal and perinatal periods, many nutrients, such as long-chain polyunsaturated fatty acids [contained in fish oil (FO)] and folate, are important in achieving normal brain development. Several studies have shown the benefits of early nutrition on children's neurocognitive development. However, the evidence with regard to the attention system is scarce. The aim of this study was to analyze the long-term effects of FO, 5-methyltetrahydrofolate (5-MTHF), or FO+5-MTHF prenatal supplementation on attention networks. Participants were 136 children born to mothers from the NUHEAL (Nutraceuticals for a Healthy Life) project (randomly assigned to receive FO and/or 5-MTHF or placebo prenatal supplementation) who were recalled for a new examination 8.5 y later. The response conflict-resolution ability (using congruent and incongruent conditions)), alerting, and spatial orienting of attention were evaluated with behavioral measures (Attention Network Test), electroencephalography/event-related potentials (ERPs), and standardized low-resolution brain electromagnetic tomography (sLORETA). Children born to mothers supplemented with 5-MTHF alone solved the response conflict more quickly than did the placebo and the FO+5-MTHF groups (all P < 0.05). Differences between ERP amplitudes for the conflict conditions were also observed. sLORETA analysis showed higher activation of the right midcingulate cortex for the incongruent condition. In addition, a significant slowing down of response speed depending on the warning cue in the 5-MTHF and FO groups was observed. Folate supplementation during pregnancy, rather than FO or FO+5-MTHF supplementation, improves children's ability to solve response conflicts. This advantage seems to be based on the higher activation of the midcingulate cortex, indicating that early nutrition influences the functionality of specific brain areas involved in executive functions. This trial was registered at clinicaltrials.gov as NCT01180933. © 2016

  20. Effect of maternal n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on adiposity in childhood: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Stratakis, N; Gielen, M; Chatzi, L; Zeegers, M P

    2014-12-01

    It is hypothesized that prenatal and early postnatal exposure to n-3 long-chain polyunsaturated fatty acids (LCPUFAs) is negatively associated with adiposity later in life. We conducted a systematic review and meta-analysis to evaluate whether maternal n-3 LCPUFA supplementation in pregnancy and/or lactation exerts a beneficial effect on adiposity status in childhood. We searched six electronic databases till 20 May 2014 for randomized controlled trials (RCTs) of n-3 LCPUFA supplementation to pregnant and/or lactating women that reported data on body mass index (BMI), waist circumference, sum of skinfold thicknesses or body fat mass in children. Adiposity measures were grouped into three age categories: preschool children (<5 years), school-aged children (6-12 years), and adolescents (>13 years). Trial quality was assessed. We conducted fixed-effect and random-effects meta-analyses to combine study-specific estimates of differences between the supplemented and control groups. A total of 6 RCTs (9 publications) involving 2847 participants were included. Summary estimates showed no effect of maternal supplementation on BMI in preschool (standardized mean difference (SMD)=0.07, 95% confidence interval (CI)=-0.22, 0.36, P=0.65) and school-aged children (SMD=0.12, 95% CI=-0.06, 0.30, P=0.20). Because of sparse data, it was not possible to pool study results relating to other adiposity measures. There is currently no evidence to support that n-3 LCPUFA supplementation during pregnancy and/or lactation favourably affects child adiposity. Further high-quality trials are needed.

  1. Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: the effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids.

    PubMed

    Lam, Y Y; Hatzinikolas, G; Weir, J M; Janovská, A; McAinch, A J; Game, P; Meikle, P J; Wittert, G A

    2011-01-01

    The study aims to determine the effect of long-chain saturated and polyunsaturated (PUFA) fatty acids, specifically palmitic acid (PA; 16:0), docosahexaenoic acid (DHA; 22:6n-3) and linoleic acid (LA; 18:2n-6), and their interactions with factors from adipose tissue, on insulin sensitivity and lipid metabolism in skeletal muscle. L6 myotubes were cultured with PA, DHA or LA (0.4mmol/l), with or without conditioned media from human subcutaneous (SC) and visceral (IAB) fat. Insulin-stimulated glucose uptake, lipid content, mRNA expression of key genes involved in nutrient utilization and protein expression of inhibitor protein inhibitor kappa B (IκB)-α and mammalian target of rapamycin (mTOR) were measured. PA and IAB fat reduced insulin-stimulated glucose uptake and their combined effect was similar to that of PA alone. PA-induced insulin resistance was ameliorated by inhibiting the de novo synthesis of ceramide, IκBα degradation or mTOR activation. The PA effect was also partially reversed by DHA and completely by LA in the presence of SC fat. PA increased diacylglycerol content, which was reduced by LA and to a greater extent when either IAB or SC fat was also present. PA increased SCD1 whereas DHA and LA increased AMPKα2 mRNA. In the presence of SC or IAB fat, the combination of PA with either DHA or LA decreased SCD1 and increased AMPKα2 mRNA. PA-induced insulin resistance in skeletal muscle involves inflammatory (nuclear factor kappa B/mTOR) and nutrient (ceramide) pathways. PUFAs promote pathways, at a transcriptional level, that increase fat oxidation and synergize with factors from SC fat to abrogate PA-induced insulin resistance. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Lipids in blood-brain barrier models in vitro I: Thin-layer chromatography and high-performance liquid chromatography for the analysis of lipid classes and long-chain polyunsaturated fatty acids.

    PubMed

    Krämer, Stefanie D; Hurley, Johannah A; Abbott, N Joan; Begley, David J

    2002-01-01

    The objectives of this study were to optimize a sensitive high-performance liquid chromatography (HPLC) method for fatty acid (FA) analysis for the quantification of polyunsaturated FAs (PUFAs) in cell lipid extracts and to analyze the lipid and FA patterns of three cell lines used in blood-brain barrier (BBB) models: RBE4, ECV304, and C6. Thin-layer chromatographic analysis revealed differences in the phosphatidylcholine-phosphatidylethanolamine (PC:PE) ratios and the triglyceride (TG) content. The PC:PE ratio was <1 for RBE4 cells but >1 for ECV304 and C6 cells. ECV304 cells displayed up to 9% TG depending on culture time, whereas the other cell lines contained about 1% TG. The percentages of docosahexaenoic acid were 9.4 +/- 1.7% of the unsaturated FAs in RBE4 cells (n = 5; 4 d in culture; 9.9% after 10 d), 8.1 +/- 2.0% in ECV304 cells (n = 11; 10 to 14 d), and 6.7 +/- 0.6% in C6 cells (n = 6; 10 to 14 d) and were close to the published values for rat brain microvascular endothelium. The percentage of arachidonic acid (C20:4) was about half that in vivo. ECV304 cells contained the highest fraction of C20:4, 17.8 +/- 2.2%; RBE4 cells contained 11.6 +/- 2.4%; and C6 cells 15.8 +/- 1.9%. It is concluded that a sensitive HPLC method for FAs is now optimized for the analysis of long-chain PUFAs. The results provide a useful framework for studies on the effects of lipid modulation and give reference information for the development of further BBB models.

  3. The metabolic syndrome of fructose-fed rats: effects of long-chain polyunsaturated ω3 and ω6 fatty acids. V. Post-mortem findings.

    PubMed

    Mellouk, Zoheir; Louchami, Karim; Hupkens, Emeline; Sener, Abdullah; Ait Yahia, Dalila; Malaisse, Willy J

    2012-12-01

    The present study deals with the possible effects of dietary ω3 and ω6 fatty acids upon the metabolic syndrome found in rats exposed for 8 weeks to a diet containing 64% (w/w) D-fructose instead of starch. Fructose-fed rats were found to display a modest increase in plasma albumin and protein concentration and more pronounced increases in plasma urea, creatinine, phospholipids, triglycerides and cholesterol concentrations, glycated hemoglobin concentration and liver contents of cholesterol, triglycerides and phospholipids. The plasma concentrations of HDL-cholesterol, calcium and iron were decreased, however, in the fructose-fed rats. In general, the partial substitution of sunflower oil by either safflower oil or salmon oil opposed the metabolic perturbations otherwise associated with the fructose-induced metabolic syndrome in the fructose-fed rats, with salmon oil demonstrating particular efficacy. Consideration is given to the possible biological determinants of these perturbations and their attenuation in rats exposed to safflower or salmon oil.

  4. Distinctive lipid composition of the copepod Limnocalanus macrurus with a high abundance of polyunsaturated fatty acids.

    PubMed

    Hiltunen, Minna; Strandberg, Ursula; Keinänen, Markku; Taipale, Sami; Kankaala, Paula

    2014-09-01

    We studied the copepod Limnocalanus macrurus for seasonal variation in the composition of fatty acids, wax esters and sterols in large boreal lakes, where it occurs as a glacial-relict. Vast wax ester reserves of Limnocalanus were accumulated in a period of only two months, and comprised mono- and polyunsaturated fatty acids (PUFA) and saturated fatty alcohols. In winter, the mobilization of wax esters was selective, and the proportion of long-chain polyunsaturated wax esters declined first. PUFA accounted for >50% of all fatty acids throughout the year reaching up to ca. 65% during late summer and fall. Long-chain PUFA 20:5n-3 and 22:6n-3 together comprised 17-40% of all fatty acids. The rarely reported C24 and C26 very-long-chain PUFA (VLC-PUFA) comprised 6.2 ± 3.4 % of all fatty acids in August and 2.1 ± 1.7% in September. The VLC-PUFA are presumably synthesized by Limnocalanus from shorter chain-length precursors because they were not found in the potential food sources. We hypothesize that these VLC-PUFA help Limnocalanus to maximize lipid reserves when food is abundant. Sterol content of Limnocalanus, consisting ca. 90% of cholesterol, did not show great seasonal variation. As a lipid-rich copepod with high abundance of PUFA, Limnocalanus is excellent quality food for fish. The VLC-PUFA were also detected in planktivorous fish, suggesting that these compounds can be used as a trophic marker indicating feeding on Limnocalanus.

  5. Prior supplementation with long chain omega-3 polyunsaturated fatty acids promotes weight loss in obese adults: a double-blinded randomised controlled trial.

    PubMed

    Munro, Irene A; Garg, Manohar L

    2013-04-25

    Obesity has been linked with low levels of ω-3 fatty acids. Generally, intervention studies have failed to establish benefits of supplementation with ω-3PUFA in reducing body weight or fat mass in humans. The aim of this study was to investigate whether supplementation with LCω-3PUFA alone, then consumed concomitantly with a very low energy diet (VLED), facilitated weight loss, improvements in blood lipids and positive changes to inflammatory mediators. This was a double blind randomised controlled trial with two parallel groups. For 4 weeks of prior supplementation, one group consumed 6 × 1 g capsules per day monounsaturated oil (placebo), the other group consumed 6 × 1 g capsules per day LCω-3PUFA (fish oil) each comprising 70 mg EPA and 270 mg DHA, while consuming their usual diet. Each group continued with their supplements for another 4 weeks while both groups followed a VLED regimen (n = 19 placebo, n = 20 fish oil). Fasting blood samples, anthropometric measurements and 3-day food diaries were collected at baseline, at 4 weeks and at 8 weeks. At 4 weeks levels of EPA and DHA increased two-fold in the fish oil group (P < 0.001), with no significant changes to anthropometric measurements for either group. At 8 weeks a significant 3-way interaction between time, group and gender was observed for percentage reduction in weight, F(1,35) = 5.55, P = 0.024, and BMI, F(1,35) = 5.3, P = 0.027 with a greater percentage decrease for females in FO compared to PB for weight (-7.21% vs.-5.82%) and BMI (-7.43% vs.-5.91%) respectively (P < 0.05 for both). It would appear that supplementation with LCω-3PUFA had a time dependent effect on weight loss in females.

  6. Direct and maternal n-3 long-chain polyunsaturated fatty acid supplementation improved triglyceridemia and glycemia through the regulation of hepatic and muscle sphingolipid synthesis in offspring hamsters fed a high-fat diet.

    PubMed

    Kasbi-Chadli, Fatima; Ferchaud-Roucher, Véronique; Krempf, Michel; Ouguerram, Khadija

    2016-03-01

    We recently reported that direct and maternal supplementation with n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) alleviates the metabolic disturbances in adult hamster pups fed with a high-fat diet (HFD). In this study, we hypothesized that these results involved a perinatal modulating effect of sphingolipids by n-3 LC-PUFA. We studied the effect of direct and maternal n-3 LC-PUFA supplementation on sphingolipid contents in liver and muscle, hepatic triglycerides (TG) secretion and glucose tolerance. Offspring male hamsters born from supplemented (Cω) or unsupplemented (C) mothers were subjected after weaning to a HFD during 16 weeks, without (Cω-HF or C-HF) or with direct supplementation with n-3 LC-PUFA (C-HFω). Direct supplementation decreased sphingosine, sphinganine and ceramides in liver and decreased sphingosine, sphinganine, sphingosine-1-phosphate (S1P) and ceramides in muscle in C-HFω compared to C-HF (p < 0.05). Maternal supplementation decreased C20 ceramide and lactosylceramide in liver and sphinganine, S1P and lactosylceramide in muscle (p < 0.05). This supplementation tended to decrease glucosylceramide in liver (p < 0.06) and muscle (p < 0.07) in Cω-HF compared to C-HF. Direct supplementation increased glucose tolerance and decreased hepatic TG secretion and hepatic gene expression levels of diacylglycerol O-acyltransferase 2 (DGAT2), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase, stearoyl-CoA desaturase-1 (SCD1) and tumor necrosis factor α (TNFα). Maternal supplementation decreased basal glycemia and hepatic TG secretion. We observed a positive correlation between hepatic TG secretion and hepatic ceramide (p = 0.0059), and between basal glycemia and hepatic ceramide (p = 0.04) or muscle lactosylceramide contents (p = 0.001). We observed an improvement of lipids and glucose metabolism in hamster with n-3 LC-PUFA direct supplementation and a decrease in glycemia and hepatic TG secretion with maternal

  7. Polyunsaturated Fatty Acids in Male Ruminant Reproduction - A Review.

    PubMed

    Van Tran, Len; Malla, Bilal Ahmad; Kumar, Sachin; Tyagi, Amrish Kumar

    2017-05-01

    Fatty acids such as n-3 and n-6 polyunsaturated fatty acids (PUFA) are critical nutrients, used to improve male reproductive performance through modification of fatty acid profile and maintenance of sperm membrane integrity, especially under cold shock or cryopreservation condition. Also, PUFA provide the precursors for prostaglandin synthesis and can modulate the expression patterns of many key enzymes involved in both prostaglandin and steroid metabolism. Many studies carried out on diets supplemented with PUFA have demonstrated their capability to sustain sperm motility, viability and fertility during chilling and freezing as well as improving testis development and spermatogenesis in a variety of livestock species. In addition to the type and quantity of dietary fatty acids, ways of addition of PUFA to diet or semen extender is very crucial as it has different effects on semen quality in male ruminants. Limitation of PUFA added to ruminant ration is due to biohydrogenation by rumen microorganisms, which causes conversion of unsaturated fatty acids to saturated fatty acids, leading to loss of PUFA quantity. Thus, many strategies for protecting PUFA from biohydrogenation in rumen have been developed over the years. This paper reviews four aspects of PUFA in light of previous research including rumen metabolism, biological roles, influence on reproduction, and strategies to use in male ruminants.

  8. Polyunsaturated Fatty Acids in Male Ruminant Reproduction — A Review

    PubMed Central

    Van Tran, Len; Malla, Bilal Ahmad; Kumar, Sachin; Tyagi, Amrish Kumar

    2017-01-01

    Fatty acids such as n-3 and n-6 polyunsaturated fatty acids (PUFA) are critical nutrients, used to improve male reproductive performance through modification of fatty acid profile and maintenance of sperm membrane integrity, especially under cold shock or cryopreservation condition. Also, PUFA provide the precursors for prostaglandin synthesis and can modulate the expression patterns of many key enzymes involved in both prostaglandin and steroid metabolism. Many studies carried out on diets supplemented with PUFA have demonstrated their capability to sustain sperm motility, viability and fertility during chilling and freezing as well as improving testis development and spermatogenesis in a variety of livestock species. In addition to the type and quantity of dietary fatty acids, ways of addition of PUFA to diet or semen extender is very crucial as it has different effects on semen quality in male ruminants. Limitation of PUFA added to ruminant ration is due to biohydrogenation by rumen microorganisms, which causes conversion of unsaturated fatty acids to saturated fatty acids, leading to loss of PUFA quantity. Thus, many strategies for protecting PUFA from biohydrogenation in rumen have been developed over the years. This paper reviews four aspects of PUFA in light of previous research including rumen metabolism, biological roles, influence on reproduction, and strategies to use in male ruminants. PMID:26954196

  9. Mouse models: the ketogenic diet and polyunsaturated fatty acids.

    PubMed

    Borges, Karin

    2008-11-01

    Literature on the anticonvulsant effects of the ketogenic diet (KD) in mouse seizure models is summarized. Recent data show that a KD balanced in vitamin, mineral, and antioxidant content is anticonvulsant in mice, confirming that the KD's effect in mice can be attributed to the composition of the diet and not other dietary factors. Given that the anticonvulsant mechanism of the KD is still unknown, the anticonvulsant profile of the diet in different seizure models may help to decipher this mechanism. The implications of the findings that the KD is anticonvulsant in electrical seizure models are indicated. Further, the potential involvement of polyunsaturated fatty acids (PUFA) in the KD's anticonvulsant mechanism is discussed.

  10. Independent and interactive effects of plant sterols and fish oil n-3 long-chain polyunsaturated fatty acids on the plasma lipid profile of mildly hyperlipidaemic Indian adults.

    PubMed

    Khandelwal, Shweta; Demonty, Isabelle; Jeemon, Panniyammakal; Lakshmy, Ramakrishnan; Mukherjee, Rajat; Gupta, Ruby; Snehi, Uma; Niveditha, Devasenapathy; Singh, Yogendra; van der Knaap, Henk C M; Passi, Santosh J; Prabhakaran, Dorairaj; Reddy, K Srinath

    2009-09-01

    The present study was designed to evaluate the independent and interactive effects of a once-a-day yoghurt drink providing 2 g plant sterols/d and capsules providing 2 g fish oil n-3 long-chain (LC) PUFA/d on plasma lipids, apolipoproteins and LDL particle size. Following a 2-week run-in period, 200 mildly hypercholesterolaemic Indian adults aged 35-55 years were randomised into one of four groups of a 2 x 2 factorial, double-blind controlled trial. The 4-week treatments consisted of (1) control yoghurt drink and control capsules, (2) control yoghurt drink and fish oil capsules, (3) plant sterol-enriched yoghurt drink and control capsules, or (4) plant sterol-enriched yoghurt drink and fish oil capsules. Blood was drawn before and after the 4-week intervention. Changes in health status, lifestyle and dietary habits, and daily compliance were recorded. The main effects of plant sterols were a 4.5 % reduction in LDL-cholesterol and a 15 % reduction in TAG without a significant change in HDL-cholesterol. Overall, fish oil n-3 LC-PUFA did not significantly affect cholesterol concentrations but reduced TAG by 15 % and increased HDL-cholesterol by 5.4 %. The combination significantly lowered TAG by 15 % v. control. No significant interaction between plant sterols and n-3 LC-PUFA was observed on plasma cholesterol concentrations. In conclusion, once-a-day intake of 2 g plant sterols/d in a yoghurt drink, 2 g fish oil n-3 LC-PUFA/d in capsules, and their combination had beneficial effects on the lipid profile of mildly hypercholesterolaemic Indian adults. The potent hypotriacylglycerolaemic effect of plant sterols observed in the present study and this population warrants additional investigation.

  11. The Groningen LCPUFA study: no effect of postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years.

    PubMed

    de Jong, Corina; Kikkert, Hedwig K; Fidler, Vaclav; Hadders-Algra, Mijna

    2010-08-01

    Long-chain PUFA (LCPUFA) supplementation of formula can have beneficial effects on neurodevelopmental outcome in early infancy, but uncertainty exists regarding effects after 6 months. The present study is the first to investigate whether consumption by term infants of formula containing LCPUFA for the first 2 months after birth improves neurological condition of these children at 9 years of age. A prospective, double-blind, randomised control study was performed in two groups of healthy term infants: a control group with standard formula (n 169) and a LCPUFA-supplemented group (LF; n 146). A breast-fed group (BF; n 159) served as a reference. At age 9 years, children were neurologically assessed according to Touwen, resulting in a Neurological Optimality Score and information on severity and type of minor neurological dysfunction (MND). Information on potential confounders was collected at enrollment and follow-up. Multivariate analyses were carried out to evaluate the effect of nutrition while adjusting for confounders. Attrition (28 %) was selective: drop-outs in the LF group were more often boys and had a significantly lower mental developmental index at 18 months. Neurological optimality and severity and type of MND at 9 years did not differ between the two formula groups. Children in the BF group showed significantly less often fine manipulative dysfunction than formula-fed children. In conclusion, LCPUFA supplementation of formula during the first 2 postnatal months in healthy term infants does not alter neurological function at school age. The study confirmed that breast-fed infants have a slightly better neurodevelopmental outcome than formula-fed infants.

  12. ω-Alkynyl lipid surrogates for polyunsaturated fatty acids: free radical and enzymatic oxidations.

    PubMed

    Beavers, William N; Serwa, Remigiusz; Shimozu, Yuki; Tallman, Keri A; Vaught, Melissa; Dalvie, Esha D; Marnett, Lawrence J; Porter, Ned A

    2014-08-13

    Lipid and lipid metabolite profiling are important parameters in understanding the pathogenesis of many diseases. Alkynylated polyunsaturated fatty acids are potentially useful probes for tracking the fate of fatty acid metabolites. The nonenzymatic and enzymatic oxidations of ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid were compared to that of linoleic and arachidonic acid. There was no detectable difference in the primary products of nonenzymatic oxidation, which comprised cis,trans-hydroxy fatty acids. Similar hydroxy fatty acid products were formed when ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid were reacted with lipoxygenase enzymes that introduce oxygen at different positions in the carbon chains. The rates of oxidation of ω-alkynylated fatty acids were reduced compared to those of the natural fatty acids. Cyclooxygenase-1 and -2 did not oxidize alkynyl linoleic but efficiently oxidized alkynyl arachidonic acid. The products were identified as alkynyl 11-hydroxy-eicosatetraenoic acid, alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid, and alkynyl prostaglandins. This deviation from the metabolic profile of arachidonic acid may limit the utility of alkynyl arachidonic acid in the tracking of cyclooxygenase-based lipid oxidation. The formation of alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid compared to alkynyl prostaglandins suggests that the ω-alkyne group causes a conformational change in the fatty acid bound to the enzyme, which reduces the efficiency of cyclization of dioxalanyl intermediates to endoperoxide intermediates. Overall, ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid appear to be metabolically competent surrogates for tracking the fate of polyunsaturated fatty acids when looking at models involving autoxidation and oxidation by lipoxygenases.

  13. Fish Oil-Derived Long-Chain n-3 Polyunsaturated Fatty Acids Reduce Expression of M1-Associated Macrophage Markers in an ex vivo Adipose Tissue Culture Model, in Part through Adiponectin.

    PubMed

    De Boer, Anna A; Monk, Jennifer M; Liddle, Danyelle M; Power, Krista A; Ma, David W L; Robinson, Lindsay E

    2015-01-01

    Adipose tissue (AT) macrophages (ATM) play a key role in obesity-associated pathologies, and their phenotype can be influenced by the local tissue microenvironment. Interestingly, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and the LC n-3 PUFA-upregulated adipokine, adiponectin (Ad), may mitigate excessive ATM inflammatory M1-polarization responses. However, to what extent LC n-3 PUFA and Ad work in concert to affect macrophage phenotype has not been examined. Thus, we used an established ex vivo AT organ culture model using visceral AT from mice fed a control (CON; 10% w/w safflower oil) n-6 PUFA-rich diet or an isocaloric fish oil (FO; 3% w/w menhaden oil + 7% w/w safflower oil)-derived LC n-3 PUFA-rich diet to generate AT conditioned media (ACM). We then evaluated if CON or FO ACM affected macrophage polarization markers in a model designed to mimic acute [18 h ACM plus lipopolysaccharide (LPS) for the last 6 h] or chronic (macrophages treated with LPS-challenged CON or FO ACM for 24 h) inflammation ± Ad-neutralizing antibody and the LPS-neutralizing agent, polymyxin B. In the acute inflammation model, macrophages treated with FO ACM had decreased lipid uptake and mRNA expression of M1 markers (Nos2, Nfκb, Il6, Il18, Ccl2, and Ccl5) compared with CON ACM (p ≤ 0.05); however, these effects were largely attenuated when Ad was neutralized (p > 0.05). Furthermore, in the chronic inflammation model, macrophages treated with FO ACM had decreased mRNA expression of M1 markers (Nos2, Tnfα, Ccl2, and Il1β) and IL-6 and CCL2 secretion (p ≤ 0.05); however, some of these effects were lost when Ad was neutralized, and were further exacerbated when both Ad and LPS were neutralized. Taken together, this work shows that LC n-3 PUFA and Ad work in concert to suppress certain M1 macrophage responses. Thus, future strategies to modulate the ATM phenotype should consider the role of both LC n-3 PUFA and Ad in mitigating obese AT

  14. Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice.

    PubMed

    Valenzuela, Rodrigo; Echeverria, Francisca; Ortiz, Macarena; Rincón-Cervera, Miguel Ángel; Espinosa, Alejandra; Hernandez-Rodas, María Catalina; Illesca, Paola; Valenzuela, Alfonso; Videla, Luis A

    2017-04-11

    Eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, C20:4n-6) are long-chain polyunsaturated fatty acids (LCPUFAs) with relevant roles in the organism. EPA and DHA are synthesized from the precursor alpha-linolenic acid (ALA, C18:3n-3), whereas AA is produced from linoleic acid (LA, C18:2n-6) through the action of Δ5 and Δ6-desaturases. High-fat diet (HFD) decreases the activity of both desaturases and LCPUFA accretion in liver and other tissues. Hydroxytyrosol (HT), a natural antioxidant, has an important cytoprotective effects in different cells and tissues. Male mice C57BL/6 J were fed a control diet (CD) (10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks. Animals were daily supplemented with saline (CD) or 5 mg HT (HFD), and blood and the studied tissues were analyzed after the HT intervention. Parameters studied included liver histology (optical microscopy), activity of hepatic desaturases 5 and 6 (gas-liquid chromatography of methyl esters derivatives) and antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase by spectrophotometry), oxidative stress indicators (glutathione, thiobarbituric acid reactants, and the antioxidant capacity of plasma), gene expression assays for sterol regulatory element-binding protein 1c (SREBP-1c) (qPCR and ELISA), and LCPUFA profiles in liver, erythrocyte, brain, heart, and testicle (gas-liquid chromatography). HFD led to insulin resistance and liver steatosis associated with SREBP-1c upregulation, with enhancement in plasma and liver oxidative stress status and diminution in the synthesis and storage of n-6 and n-3 LCPUFAs in the studied tissues, compared to animals given control diet. HT supplementation significantly reduced fat accumulation in liver and plasma as well as tissue metabolic alterations induced by HFD. Furthermore, a normalization of desaturase activities

  15. The Association between Marine n-3 Polyunsaturated Fatty Acid Levels and Survival after Renal Transplantation

    PubMed Central

    Jenssen, Trond; Hartmann, Anders; Diep, Lien M.; Dahle, Dag O.; Reisæter, Anna V.; Bjerve, Kristian S.; Christensen, Jeppe H.; Schmidt, Erik B.; Svensson, My

    2015-01-01

    Background and objectives Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants. Design, setting, participants, & measurements In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation. Results There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (≥7.95 weight percentage) compared with low levels (<7.95 weight percentage) for all age categories (pooled mortality rate ratio estimate, 0.69; 95% confidence interval, 0.57 to 0.85). When divided into quartiles according to marine n-3 polyunsaturated fatty acid levels, patients in the upper quartile compared with the lower quartile had a 56% lower risk of death (adjusted hazard ratio, 0.44; 95% confidence interval, 0.26 to 0.75) using multivariable Cox proportional hazard regression analysis. There was a lower hazard ratio for death from cardiovascular disease with high levels of marine n-3 polyunsaturated fatty acid and a lower hazard ratio for death from infectious disease with high levels of the marine n-3 polyunsaturated fatty acid eicosapentaenoic acid, whereas there was no association between total or individual marine n-3 polyunsaturated fatty acid levels and cancer mortality. Conclusions Higher plasma phospholipid marine n-3

  16. Nutrigenomics and nutrigenetics of ω3 polyunsaturated fatty acids.

    PubMed

    Vanden Heuvel, John P

    2012-01-01

    Diets rich in ω3 polyunsaturated fatty acids (ω3-PUFAs) such as alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid are associated with decreased incidence and severity of several chronic diseases including cardiovascular disease (CVD) and cancer. At least some of the beneficial effects of these dietary fatty acids are via metabolites such as prostaglandins, leukotrienes, thromboxanes, and resolvins. The effects of ω3-PUFAs are in contrast to those of fatty acids with virtually identical structures, such as the ω6-PUFAs linoleic acid and arachidonic acid, and their corresponding metabolites. The purpose of this chapter is to discuss both the nutrigenomics (nutrient-gene interactions) and nutrigenetics (genetic variation in nutrition) of dietary fatty acids with a focus on the ω3-PUFAs (Gebauer et al., 2007(1)). Important in the biological response for these fatty acids or their metabolites are cognate receptors that are able to regulate gene expression and coordinately affect metabolic or signaling pathways associated with CVD and cancer. Four nuclear receptor (NR) subfamilies will be emphasized as receptors that respond to dietary and endogenous ligands: (1) peroxisome proliferator-activated receptors, (2) retinoid X receptors, (3) liver X receptors, and (4) farnesoid X receptor. In addition to the different responses elicited by varying structures of fatty acids, responses may vary because of genetic variation in enzymes that metabolize ω3- and ω6 fatty acids or that respond to them. In particular, polymorphisms in the fatty acid desaturases and the aforementioned NRs contribute to the complexity of nutritional effects seen with ω3-PUFAs. Following a brief introduction to the health benefits of ω3-PUFAs, the regulation of gene expression by these dietary fatty acids via NRs will be characterized. Subsequently, the effects of single-nucleotide polymorphisms (SNPs) in key enzymes involved in the metabolism and response to ω3-PUFAs will

  17. TRPA1 Is a Polyunsaturated Fatty Acid Sensor in Mammals

    PubMed Central

    Motter, Arianne L.; Ahern, Gerard P.

    2012-01-01

    Fatty acids can act as important signaling molecules regulating diverse physiological processes. Our understanding, however, of fatty acid signaling mechanisms and receptor targets remains incomplete. Here we show that Transient Receptor Potential Ankyrin 1 (TRPA1), a cation channel expressed in sensory neurons and gut tissues, functions as a sensor of polyunsaturated fatty acids (PUFAs) in vitro and in vivo. PUFAs, containing at least 18 carbon atoms and three unsaturated bonds, activate TRPA1 to excite primary sensory neurons and enteroendocrine cells. Moreover, behavioral aversion to PUFAs is absent in TRPA1-null mice. Further, sustained or repeated agonism with PUFAs leads to TRPA1 desensitization. PUFAs activate TRPA1 non-covalently and independently of known ligand binding domains located in the N-terminus and 5th transmembrane region. PUFA sensitivity is restricted to mammalian (rodent and human) TRPA1 channels, as the drosophila and zebrafish TRPA1 orthologs do not respond to DHA. We propose that PUFA-sensing by mammalian TRPA1 may regulate pain and gastrointestinal functions. PMID:22723860

  18. Atomic determinants of BK channel activation by polyunsaturated fatty acids

    PubMed Central

    Tian, Yutao; Aursnes, Marius; Hansen, Trond Vidar; Tungen, Jørn Eivind; Galpin, Jason D.; Leisle, Lilia; Ahern, Christopher A.; Xu, Rong; Heinemann, Stefan H.; Hoshi, Toshinori

    2016-01-01

    Docosahexaenoic acid (DHA), a polyunsaturated ω-3 fatty acid enriched in oily fish, contributes to better health by affecting multiple targets. Large-conductance Ca2+- and voltage-gated Slo1 BK channels are directly activated by nanomolar levels of DHA. We investigated DHA–channel interaction by manipulating both the fatty acid structure and the channel composition through the site-directed incorporation of unnatural amino acids. Electrophysiological measurements show that the para-group of a Tyr residue near the ion conduction pathway has a critical role. To robustly activate the channel, ionization must occur readily by a fatty acid for a good efficacy, and a long nonpolar acyl tail with a Z double bond present at the halfway position for a high affinity. The results suggest that DHA and the channel form an ion–dipole bond to promote opening and demonstrate the channel druggability. DHA, a marine-derived nutraceutical, represents a promising lead compound for rational drug design and discovery. PMID:27849612

  19. Oxidative stability of omega-3 polyunsaturated fatty acids enriched eggs.

    PubMed

    Ren, Yuan; Perez, Tulia I; Zuidhof, Martin J; Renema, Robert A; Wu, Jianping

    2013-11-27

    Omega-3 polyunsaturated fatty acids (n-3 PUFA) enriched eggs have a growing market share in the egg industry. This study examined the stability of n-3 PUFA enriched eggs fortified with antioxidants (vitamin E or organic Selenium [Sel-Plex] or both) following cooking and storage. The total fat content was not affected by cooking or simulated retail storage conditions, whereas, n-3 fatty acids were reduced. The content of n-3 fatty acids in boiled eggs was higher than in fried eggs. Lipid oxidation was significantly affected by the different cooking methods. Fried eggs contained higher levels of malondialdehyde (MDA, 2.02 μg/kg) and cholesterol oxidation products (COPs, 13.58 μg/g) compared to boiled (1.44 and 10.15 μg/kg) and raw eggs (0.95 and 9.03 μg/kg, respectively, for MDA and COPs). Supplementation of antioxidants reduced the formation of MDA by 40% and COPs by 12% in fried eggs. Although the content of MDA was significantly increased after 28 days of storage, COPs were not affected by storage. Our study indicated that the n-3 PUFA in enriched eggs was relatively stable during storage and home cooking in the presence of antioxidants.

  20. The Role of Omega-3 Polyunsaturated Fatty Acids in Stroke

    PubMed Central

    Bu, Jiyuan; Dou, Yang; Tian, Xiaodi; Wang, Zhong

    2016-01-01

    Stroke is the third commonest cause of death following cardiovascular diseases and cancer. In particular, in recent years, the morbidity and mortality of stroke keep remarkable growing. However, stroke still captures people attention far less than cardiovascular diseases and cancer. Past studies have shown that oxidative stress and inflammation play crucial roles in the progress of cerebral injury induced by stroke. Evidence is accumulating that the dietary supplementation of fish oil exhibits beneficial effects on several diseases, such as cardiovascular diseases, metabolic diseases, and cancer. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), the major component of fish oil, have been found against oxidative stress and inflammation in cardiovascular diseases. And the potential of n-3 PUFAs in stroke treatment is attracting more and more attention. In this review, we will review the effects of n-3 PUFAs on stroke and mainly focus on the antioxidant and anti-inflammatory effects of n-3 PUFAs. PMID:27433289

  1. Fish Lipids as a Valuable Source of Polyunsaturated Fatty Acids

    NASA Astrophysics Data System (ADS)

    Merdzhanova, Albena; Ivanov, Ivaylo; Dobreva, Diana A.; Makedonski, Lyubomir

    2017-03-01

    This article presents information about omega-3 (h-3) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) contents in a broad range of commercially important fish species available on Bulgarian fish markets. The aim is to raise consumers' awareness and encourage them to eat fish. Fish species from the Black Sea coast have relatively high proportion of n-3 PUFAs, of which more than 80% is by EPf (eicosapentaenoic acid, C 20:5 n-3) and DHA (docosahexaenoic acid, C 22:6 n-3). Extensive epidemiological studies show that fish consumption is inversely associated with the incidence of cardiovascular diseases (CVD), stroke and the functioning of the brain. About 0.5 g of omega-3 (EPA+DHA) a day or two savings of oily fish a week are required to reduce the risk of death from CVD. PUFAs needs should be satisfied not only with food additives but with fish lipids containing food.

  2. [Metabolic syndrome reversion by polyunsaturated fatty acids ingestion].

    PubMed

    Campos Mondragón, Martha Gabriela; Oliart Ros, Rosa María; Martínez Martinez, Angélica; Méndez Machado, Gustavo Francisco; Angulo Guerrero, Jesús Ofelia

    2013-12-21

    Metabolic syndrome (MS) frequency is growing and diet has an important influence on its evolution. Our objective was to study the effect of 3 sources of polyunsaturated fatty acids on MS parameters in humans. The MS was diagnosed according to the International Diabetes Federation. Three groups of individuals (n=15/group) were quasi-randomly assigned to one of the following treatments during 6 weeks: a) 1.8 g/d n-3 (1.08g eicosapentoaenoic acid+0.72 g docosahexaenoic acid); b) 2.0 g/d conjugated linoleic acid (CLA, 50:50, cis9:trans11, trans10:cis12), and c) 40 g/d walnut. The clinical and biochemical parameters were evaluated at the beginning and the end of the essay. In the group with n-3 the triglycerides level decreased from 183.9 ± 35.2mg/dl to 149.6 ± 29.0mg/dl (P=.007). In the group with walnut the HDL level rose from 41.7 ± 5.2mg/dl to 47.8 ± 5.4 mg/dl (P=.004) and the Castelli index (total cholesterol/HDL) decreased from 4.86 ± 0.97 to 3.82 ± 0.81 (P=.004). There were not significant changes in the CLA group. At the end of the essay, 46.7% of walnut group patients, 46.7% of n-3 group and 20% of CLA group, had no MS. The groups that consumed polyunsaturated fatty acids n-3 and those in walnut in moderate daily doses during 6 weeks had an improvement of the dyslipidemia component of MS, hypertriglyceridemia and low HDL level. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  3. [Molecular mechanisms of action and health benefits of polyunsaturated fatty acids].

    PubMed

    Rodríguez-Cruz, Maricela; Tovar, Armando R; del Prado, Martha; Torres, Nimbe

    2005-01-01

    Essential polyunsaturated fatty acids (PUFAs), linoleic acid n6 (LA) and linolenic acid (ALA) n3 obtained from the diet are precursors of the long-chain polyunsaturated fatty acids (Lc-PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) respectively. Consumption of PUFAs is related with a better neurological and cognitive development in newborns. It has been demonstrated that consumption of n-6 and n-3 PUFAs decreases blood triglycerides by increasing fatty acid oxidation through activation of PPARalpha or by reducing the activation of SREBP-1 inhibiting lipogenesis. Dietary PUFAs activate PPARalpha and PPARgamma increasing lipid oxidation, and decreasing insulin resistance leading in a reduction of hepatic steatosis. Beneficial effects of PUFAs have been observed in humans and in animals models of diabetes, obesity, cancer, and cardiovascular diseases. It is important to promote the consumption of PUFAs. Main food sources of PUFAs n-6 are corn, soy and safflower oil, and for PUFAs n-3 are fish, soy, canola oil and, flaxseed. Finally FAO/WHO recommends an optimal daily intake of n6/n3 of 5-10:1.

  4. Brain phospholipids as dietary source of (n-3) polyunsaturated fatty acids for nervous tissue in the rat.

    PubMed

    Bourre, J M; Dumont, O; Durand, G

    1993-06-01

    In a previous work, we calculated the dietary alpha-linolenic requirements (from vegetable oil triglycerides) for obtaining and maintaining a physiological level of (n-3) fatty acids in developing animal membranes as determined by the cervonic acid content [22:6(n-3), docosahexaenoic acid]. The aim of the present study was to measure the phospholipid requirement, as these compounds directly provide the very long polyunsaturated fatty acids found in membranes. Two weeks before mating, eight groups of female rats (previously fed peanut oil deficient in alpha-linolenic acid) were fed different semisynthetic diets containing 6% African peanut oil supplemented with different quantities of phospholipids obtained from bovine brain lipid extract, so as to add (n-3) polyunsaturated fatty acids to the diet. An additional group was fed peanut oil with rapeseed oil, and served as control. Pups were fed the same diet as their respective mothers, and were killed at weaning. Forebrain, sciatic nerve, retina, nerve endings, myelin, and liver were analyzed. We conclude that during the combined maternal and perinatal period, the (n-3) fatty acid requirement for adequate deposition of (n-3) polyunsaturated fatty acids in the nervous tissue (and in liver) of pups is lower if animals are fed (n-3) very long chain polyunsaturated fatty acids found in brain phospholipids [this study, approximately 60 mg of (n-3) fatty acids/100 g of diet, i.e., approximately 130 mg/1,000 kcal] rather than alpha-linolenic acid from vegetable oil triglycerides [200 mg of (n-3) fatty acids/100 g of diet, i.e., approximately 440 mg/1,000 kcal].

  5. Content of essential polyunsaturated fatty acids in three canned fish species.

    PubMed

    Gladyshev, Michail I; Sushchik, Nadezhda N; Makhutova, Olesia N; Kalachova, Galina S

    2009-05-01

    Three canned fish species--Pacific saury (Cololabis saira), Pacific herring (Clupea harengus) and Baltic sprat (Sprattus sprattus)--most common and popular in Russia, were analyzed for fatty acids. Special attention was paid to long-chain essential polyunsaturated fatty acids: eicosapentaenoic acid (20:5omega3) and docosahexaenoic acid (22:6omega3). Sums of eicosapentaenoic acid and docosahexaenoic acid in saury, herring and sprat were, on average, 2.42, 1.80 and 1.43 g/100 g product, respectively. Contents of these essential acids in all the canned fish species were found to be very high compared with many other fish reported in the available literature. All the canned fish appeared to be highly valuable products for human nutrition concerning the content of eicosapentaenoic and docosahexaenoic acids.

  6. Omega-3 polyunsaturated fatty acids in the treatment of hypertriglyceridaemia.

    PubMed

    Pirillo, Angela; Catapano, Alberico Luigi

    2013-12-20

    Hypertriglyceridaemia (HTG) is an independent risk factor for cardiovascular disease; high-risk patients with HTG, such as those with metabolic syndrome or diabetes, may benefit from hypolipidaemic therapies. Several lipid-lowering drugs act by reducing triglyceride (TG) levels, including fibrates, nicotinic acid and omega-3 fatty acids. The omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dose-dependently reduce plasma TG levels; the effect tends to be greater in patients with higher TG levels at baseline. Evidence from clinical trials suggests that EPA+DHA doses of ≥ 2 g/day are required to achieve significant effects. The optimal TG-lowering doses of EPA+DHA are 3-4 g/day, with little evidence to support lipid-altering efficacy of doses of EPA and DHA <1g/day. Predicted changes in fasting serum TG levels at the recommended dietary intakes of EPA and/or DHA of 200-500 mg/day are -3.1% to -7.2%. Reductions of plasma TG levels at the optimal doses are from 25-35% up to 45% in the presence of severely elevated TG levels (≥ 500 mg/dl; ≥ 5.65 mmol/l), along with a reduction in non-high-density lipoprotein-cholesterol (non-HDL-C) and an increase in HDL-C. This observation has also been confirmed in statin-treated patients.

  7. The enrichment of n-3 polyunsaturated fatty acids using aminopropyl solid phase extraction columns.

    PubMed

    Wilson, R; James Henderson, R; Burkow, I C; Sargent, J R

    1993-01-01

    A rapid, simple and reliable method is described for the preparation of concentrates of methyl or ethyl esters of n-3 polyunsaturated fatty acids by solid phase extraction using aminopropyl bonded silica columns. After applying mixtures of fatty acid esters in hexane, saturated and monounsaturated fatty acid esters are preferentially eluted with hexane whereas polyunsaturated fatty acids (PUFA) can subsequently be eluted with dichloromethane. Concentrates containing 80-90% n-3 PUFA can thus be obtained using fish oil fatty acids esters as a starting material.

  8. Crystal structure of FAS thioesterase domain with polyunsaturated fatty acyl adduct and inhibition by dihomo-gamma-linolenic acid.

    PubMed

    Zhang, Wei; Chakravarty, Bornali; Zheng, Fei; Gu, Ziwei; Wu, Hongmei; Mao, Jianqiang; Wakil, Salih J; Quiocho, Florante A

    2011-09-20

    Human fatty acid synthase (hFAS) is a homodimeric multidomain enzyme that catalyzes a series of reactions leading to the de novo biosynthesis of long-chain fatty acids, mainly palmitate. The carboxy-terminal thioesterase (TE) domain determines the length of the fatty acyl chain and its ultimate release by hydrolysis. Because of the upregulation of hFAS in a variety of cancers, it is a target for antiproliferative agent development. Dietary long-chain polyunsaturated fatty acids (PUFAs) have been known to confer beneficial effects on many diseases and health conditions, including cancers, inflammations, diabetes, and heart diseases, but the precise molecular mechanisms involved have not been elucidated. We report the 1.48 Å crystal structure of the hFAS TE domain covalently modified and inactivated by methyl γ-linolenylfluorophosphonate. Whereas the structure confirmed the phosphorylation by the phosphonate head group of the active site serine, it also unexpectedly revealed the binding of the 18-carbon polyunsaturated γ-linolenyl tail in a long groove-tunnel site, which itself is formed mainly by the emergence of an α helix (the "helix flap"). We then found inhibition of the TE domain activity by the PUFA dihomo-γ-linolenic acid; γ- and α-linolenic acids, two popular dietary PUFAs, were less effective. Dihomo-γ-linolenic acid also inhibited fatty acid biosynthesis in 3T3-L1 preadipocytes and selective human breast cancer cell lines, including SKBR3 and MDAMB231. In addition to revealing a novel mechanism for the molecular recognition of a polyunsaturated fatty acyl chain, our results offer a new framework for developing potent FAS inhibitors as therapeutics against cancers and other diseases.

  9. Crystal structure of FAS thioesterase domain with polyunsaturated fatty acyl adduct and inhibition by dihomo-[gamma]-linolenic acid

    SciTech Connect

    Zhang, Wei; Chakravarty, Bornali; Zheng, Fei; Gu, Ziwei; Wu, Hongmei; Mao, Jianqiang; Wakil, Salih J.; Quiocho, Florante A.

    2012-05-29

    Human fatty acid synthase (hFAS) is a homodimeric multidomain enzyme that catalyzes a series of reactions leading to the de novo biosynthesis of long-chain fatty acids, mainly palmitate. The carboxy-terminal thioesterase (TE) domain determines the length of the fatty acyl chain and its ultimate release by hydrolysis. Because of the upregulation of hFAS in a variety of cancers, it is a target for antiproliferative agent development. Dietary long-chain polyunsaturated fatty acids (PUFAs) have been known to confer beneficial effects on many diseases and health conditions, including cancers, inflammations, diabetes, and heart diseases, but the precise molecular mechanisms involved have not been elucidated. We report the crystal structure of the hFAS TE domain covalently modified and inactivated by methyl {gamma}-linolenylfluorophosphonate. Whereas the structure confirmed the phosphorylation by the phosphonate head group of the active site serine, it also unexpectedly revealed the binding of the 18-carbon polyunsaturated {gamma}-linolenyl tail in a long groove-tunnel site, which itself is formed mainly by the emergence of an {alpha} helix (the 'helix flap'). We then found inhibition of the TE domain activity by the PUFA dihomo-{gamma}-linolenic acid; {gamma}- and {alpha}-linolenic acids, two popular dietary PUFAs, were less effective. Dihomo-{gamma}-linolenic acid also inhibited fatty acid biosynthesis in 3T3-L1 preadipocytes and selective human breast cancer cell lines, including SKBR3 and MDAMB231. In addition to revealing a novel mechanism for the molecular recognition of a polyunsaturated fatty acyl chain, our results offer a new framework for developing potent FAS inhibitors as therapeutics against cancers and other diseases.

  10. Long-term melatonin administration increases polyunsaturated fatty acid percentage in plasma lipids of hypercholesterolemic rats.

    PubMed

    Pita, Maria L; Hoyos, Marta; Martin-Lacave, Inés; Osuna, Carmen; Fernández-Santos, Jose M; Guerrero, Juan M

    2002-04-01

    This study was designed to investigate the effect of melatonin on the fatty acid composition of plasma and tissue lipids. Melatonin administration to rats fed with a standard diet only increased long-chain n-6 polyunsaturated fatty acids (PUFA) in total plasma lipids and liver phospholipids but induced significant changes in hypercholesterolemic rats. In plasma, palmitoleic and oleic acids increased and n-6 and n-3 PUFA decreased in hypercholesterolemic rats; theses changes were reversed by melatonin administration. The analysis of lipid fractions revealed that only the cholesteryl ester fraction was affected by melatonin. Histological studies of the carotid artery intima revealed the appearance, in hypercholesterolemic rats, of fatty streaks produced by a mass of foam cells covered by the endothelium and by a thin layer of mononucleated cells. These changes were prevented by melatonin. We conclude that long-term melatonin administration modifies the fatty acid composition of rat plasma and liver lipids and ameliorates the arterial fatty infiltration induced by cholesterol.

  11. Polyunsaturated fatty acids are cerebral vasodilators via the TREK-1 potassium channel.

    PubMed

    Blondeau, Nicolas; Pétrault, Olivier; Manta, Stella; Giordanengo, Valérie; Gounon, Pierre; Bordet, Régis; Lazdunski, Michel; Heurteaux, Catherine

    2007-07-20

    Vessel occlusion is the most frequent cause for impairment of local blood flow within the brain resulting in neuronal damage and is a leading cause of disability and death worldwide. Polyunsaturated fatty acids and especially alpha-linolenic acid improve brain resistance against cerebral ischemia. The purpose of the present study was to evaluate the effects of polyunsaturated fatty acids and particularly alpha-linolenic acid on the cerebral blood flow and on the tone of vessels that regulate brain perfusion. alpha-Linolenic acid injections increased cerebral blood flow and induced vasodilation of the basilar artery but not of the carotid artery. The saturated fatty acid palmitic acid did not produce vasodilation. This suggested that the target of the polyunsaturated fatty acids effect was the TREK-1 potassium channel. We demonstrate the presence of this channel in basilar but not in carotid arteries. We show that vasodilations induced by the polyunsaturated fatty acid in the basilar artery as well as the laser-Doppler flow increase are abolished in TREK-1(-/-) mice. Altogether these data indicate that TREK-1 activation elicits a robust dilation that probably accounts for the increase of cerebral blood flow induced by polyunsaturated fatty acids such as alpha-linolenic acid or docosahexanoic acid. They suggest that the selective expression and activation of TREK-1 in brain collaterals could play a significant role in the protective mechanisms of polyunsaturated fatty acids against stroke by providing residual circulation during ischemia.

  12. Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease

    USDA-ARS?s Scientific Manuscript database

    Multiple randomized controlled trials (RCTs) have assessed the effects of supplementation with eicosapentaenoic acid plus docosahexaenoic acid (omega-3 polyunsaturated fatty acids, commonly called fish oils) on the occurrence of clinical cardiovascular diseases. Although the effects of supplementati...

  13. Efficacy of ω-3 polyunsaturated fatty acids for the treatment of refractory hydroa vacciniforme.

    PubMed

    Durbec, Frédérique; Reguiaï, Ziad; Léonard, Fabienne; Pluot, Michel; Bernard, Philippe

    2012-01-01

    Hydroa vacciniforme (HV) is a rare photodermatosis. Several therapies, with sometimes severe side effects, have been used in isolated cases. We report a case of refractory HV successfully treated with dietary fish oil rich in ω-3 polyunsaturated fatty acids.

  14. The Molecular Basis of Polyunsaturated Fatty Acid Interactions with the Shaker Voltage-Gated Potassium Channel

    PubMed Central

    Yazdi, Samira; Stein, Matthias; Elinder, Fredrik; Andersson, Magnus; Lindahl, Erik

    2016-01-01

    Voltage-gated potassium (KV) channels are membrane proteins that respond to changes in membrane potential by enabling K+ ion flux across the membrane. Polyunsaturated fatty acids (PUFAs) induce channel opening by modulating the voltage-sensitivity, which can provide effective treatment against refractory epilepsy by means of a ketogenic diet. While PUFAs have been reported to influence the gating mechanism by electrostatic interactions to the voltage-sensor domain (VSD), the exact PUFA-protein interactions are still elusive. In this study, we report on the interactions between the Shaker KV channel in open and closed states and a PUFA-enriched lipid bilayer using microsecond molecular dynamics simulations. We determined a putative PUFA binding site in the open state of the channel located at the protein-lipid interface in the vicinity of the extracellular halves of the S3 and S4 helices of the VSD. In particular, the lipophilic PUFA tail covered a wide range of non-specific hydrophobic interactions in the hydrophobic central core of the protein-lipid interface, while the carboxylic head group displayed more specific interactions to polar/charged residues at the extracellular regions of the S3 and S4 helices, encompassing the S3-S4 linker. Moreover, by studying the interactions between saturated fatty acids (SFA) and the Shaker KV channel, our study confirmed an increased conformational flexibility in the polyunsaturated carbon tails compared to saturated carbon chains, which may explain the specificity of PUFA action on channel proteins. PMID:26751683

  15. [Reconstitution of polyunsaturated fatty acid synthesis enzymes in mammalian cells to convert LA to DHA].

    PubMed

    Zhu, Guiming; Saleh, Abdulmomen Ali Mohammed; Bahwal, Said Ahmed; Qiu, Lihong; Sun, Jie; Shang, Yu; Jiang, Xudong; Ge, Tangdong; Zhang, Tao

    2015-02-01

    DHA (22:6n-3) is a Ω-3 polyunsaturated fatty acid with 22 carbon atoms and 6 double bonds, which has important biological functions in human body. Human and other mammals synthesize only limited amounts of DHA, more requirements must be satisfied from food resources. However, the natural resources of DHA (Mainly deep-sea fish and other marine products) are prone to depletion. New resources development is still insufficient to satisfy the growing market demand. Previous studies have revealed that the mammals can increase the synthesis of DHA and other long-chain polyunsaturated fatty acids after transgenic procedures. In this study, mammalian cells were transfected with Δ6, Δ5 desaturase, Δ6, Δ5 elongase, Δ15 desaturase (Isolated from nematode Caenorhabditis elegans) and Δ4 desaturase (Isolated from Euglena gracilis), simultaneously. Results show that the expression or overexpression of these 6 enzymes is capable of conversion of the o-6 linoleic acid (LA, 18:2n-6) in DHA (22:6n-3). DHA content has increased from 16.74% in the control group to 25.3% in the experimental group. The strategy and related technology in our research provided important data for future production the valuable DHA (22:6n-3) by using genetically modified animals.

  16. N-3 Polyunsaturated Fatty Acids through the Lifespan: Implication for Psychopathology.

    PubMed

    Pusceddu, Matteo M; Kelly, Philip; Stanton, Catherine; Cryan, John F; Dinan, Timothy G

    2016-12-01

    The impact of lifetime dietary habits and their role in physical, mental, and social well-being has been the focus of considerable recent research. Omega-3 polyunsaturated fatty acids as a dietary constituent have been under the spotlight for decades. Omega-3 polyunsaturated fatty acids constitute key regulating factors of neurotransmission, neurogenesis, and neuroinflammation and are thereby fundamental for development, functioning, and aging of the CNS. Of note is the fact that these processes are altered in various psychiatric disorders, including attention deficit hyperactivity disorder, depression, and Alzheimer's disease. Relevant literature was identified through a search of MEDLINE via PubMed using the following words, "n-3 PUFAs," "EPA," and "DHA" in combination with "stress," "cognition," "ADHD," "anxiety," "depression," "bipolar disorder," "schizophrenia," and "Alzheimer." The principal focus was on the role of omega-3 polyunsaturated fatty acids throughout the lifespan and their implication for psychopathologies. Recommendations for future investigation on the potential clinical value of omega-3 polyunsaturated fatty acids were examined. The inconsistent and inconclusive results from randomized clinical trials limits the usage of omega-3 polyunsaturated fatty acids in clinical practice. However, a body of literature demonstrates an inverse correlation between omega-3 polyunsaturated fatty acid levels and quality of life/ psychiatric diseases. Specifically, older healthy adults showing low habitual intake of omega-3 polyunsaturated fatty acids benefit most from consuming them, showing improved age-related cognitive decline. Although further studies are required, there is an exciting and growing body of research suggesting that omega-3 polyunsaturated fatty acids may have a potential clinical value in the prevention and treatment of psychopathologies. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  17. N-3 Polyunsaturated Fatty Acids through the Lifespan: Implication for Psychopathology

    PubMed Central

    Pusceddu, Matteo M.; Kelly, Philip; Stanton, Catherine; Cryan, John F.

    2016-01-01

    Objective: The impact of lifetime dietary habits and their role in physical, mental, and social well-being has been the focus of considerable recent research. Omega-3 polyunsaturated fatty acids as a dietary constituent have been under the spotlight for decades. Omega-3 polyunsaturated fatty acids constitute key regulating factors of neurotransmission, neurogenesis, and neuroinflammation and are thereby fundamental for development, functioning, and aging of the CNS. Of note is the fact that these processes are altered in various psychiatric disorders, including attention deficit hyperactivity disorder, depression, and Alzheimer’s disease. Design: Relevant literature was identified through a search of MEDLINE via PubMed using the following words, “n-3 PUFAs,” “EPA,” and “DHA” in combination with “stress,” “cognition,” “ADHD,” “anxiety,” “depression,” “bipolar disorder,” “schizophrenia,” and “Alzheimer.” The principal focus was on the role of omega-3 polyunsaturated fatty acids throughout the lifespan and their implication for psychopathologies. Recommendations for future investigation on the potential clinical value of omega-3 polyunsaturated fatty acids were examined. Results: The inconsistent and inconclusive results from randomized clinical trials limits the usage of omega-3 polyunsaturated fatty acids in clinical practice. However, a body of literature demonstrates an inverse correlation between omega-3 polyunsaturated fatty acid levels and quality of life/ psychiatric diseases. Specifically, older healthy adults showing low habitual intake of omega-3 polyunsaturated fatty acids benefit most from consuming them, showing improved age-related cognitive decline. Conclusions: Although further studies are required, there is an exciting and growing body of research suggesting that omega-3 polyunsaturated fatty acids may have a potential clinical value in the prevention and treatment of psychopathologies. PMID:27608809

  18. Predictors of Memory in Healthy Aging: Polyunsaturated Fatty Acid Balance and Fornix White Matter Integrity.

    PubMed

    Zamroziewicz, Marta K; Paul, Erick J; Zwilling, Chris E; Barbey, Aron K

    2017-07-01

    Recent evidence demonstrates that age and disease-related decline in cognition depends not only upon degeneration in brain structure and function, but also on dietary intake and nutritional status. Memory, a potential preclinical marker of Alzheimer's disease, is supported by white matter integrity in the brain and dietary patterns high in omega-3 and omega-6 polyunsaturated fatty acids. However, the extent to which memory is supported by specific omega-3 and omega-6 polyunsaturated fatty acids, and the degree to which this relationship is reliant upon microstructure of particular white matter regions is not known. This study therefore examined the cross-sectional relationship between empirically-derived patterns of omega-3 and omega-6 polyunsaturated fatty acids (represented by nutrient biomarker patterns), memory, and regional white matter microstructure in healthy, older adults. We measured thirteen plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids, memory, and regional white matter microstructure in 94 cognitively intact older adults (65 to 75 years old). A three-step mediation analysis was implemented using multivariate linear regressions, adjusted for age, gender, education, income, depression status, and body mass index. The mediation analysis revealed that a mixture of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids is linked to memory and that white matter microstructure of the fornix fully mediates the relationship between this pattern of plasma phospholipid polyunsaturated fatty acids and memory. These results suggest that memory may be optimally supported by a balance of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids through the preservation of fornix white matter microstructure in cognitively intact older adults. This report provides novel evidence for the benefits of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acid balance on memory and underlying white matter microstructure.

  19. Exacerbation of Alcohol-Induced Oxidative Stress in Rats by Polyunsaturated Fatty Acids and Iron Load

    PubMed Central

    Patere, S. N.; Majumdar, A. S.; Saraf, M. N.

    2011-01-01

    The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography), polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron. PMID:22303057

  20. Polyunsaturated fatty acids: any role in rheumatoid arthritis?

    PubMed

    Navarini, Luca; Afeltra, Antonella; Gallo Afflitto, Gabriele; Margiotta, Domenico Paolo Emanuele

    2017-10-10

    Polyunsaturated fatty acids (PUFAs) are members of the family of fatty acids and are included in the diet. Particularly, western diet is usually low in n-3 PUFAs and high in n-6 PUFAs. PUFAs play a central role in the homeostasis of immune system: n-6 PUFAs have predominantly pro-inflammatory features, while n-3 PUFAs seem to exert anti-inflammatory and pro-resolving properties. Rheumatoid arthritis (RA) is a chronic inflammatory arthritis in which many inflammatory pathways contribute to joint and systemic inflammation, disease activity, and structural damage. Research on PUFAs could represent an important opportunity to better understand the pathogenesis and to improve the management of RA patients. We searched PubMed, Embase, EBSCO-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI and Wanfang to identify primary research reporting the role of n-3 PUFAs in rheumatoid arthritis both in humans and in animal models up to the end of March 2017. Data from animal models allows to hypothesize that n-3 PUFAs supplementation may represent an interesting perspective in future research as much in prevention as in treating RA. In humans, several case-control and prospective cohort studies suggest that a high content of n-3 PUFAs in the diet could have a protective role for incident RA in subjects at risk. Moreover, n-3 PUFAs supplementation has been assessed as a valuable therapeutic option also for patients with RA, particularly in order to improve the pain symptoms, the tender joint count, the duration of morning stiffness and the frequency of NSAIDs assumption. n-3 PUFAs supplementation could represent a promising therapeutic option to better control many features of RA. The impact of n-3 PUFAs on radiographic progression and synovial histopathology has not been yet evaluated, as well as their role in early arthritis and the combination with biologics.

  1. Plasma Polyunsaturated Fatty Acids and the Decline of Renal Function

    PubMed Central

    Lauretani, Fulvio; Semba, Richard D.; Bandinelli, Stefania; Miller, Edgar R.; Ruggiero, Carmelinda; Cherubini, Antonio; Guralnik, Jack M.; Ferrucci, Luigi

    2009-01-01

    Background Recent studies suggest an association between polyunsaturated fatty acids (PUFAs) and the development of chronic kidney disease. The aim of this study was to examine the relationship between PUFAs and renal function in older adults. Methods We performed a cross-sectional and prospective analysis of 931 adults, ≥65 years old, enrolled in the InCHIANTI study, a population-based cohort in Tuscany, Italy. Plasma PUFAs were measured at enrollment, and creatinine clearance was estimated by the Cockcroft-Gault equation at baseline and after 3-year follow-up. Results At enrollment, participants with higher creatinine clearance had higher concentrations of HDL cholesterol, total plasma PUFAs, plasma n-3 fatty acid (FA), and plasma n-6 FA and lower triglycerides. From enrollment to the 3-year follow-up visit, creatinine clearance declined by 7.8 (12.2) mL/min (P <0.0001). Baseline total plasma PUFAs, n-3 FA, n-6 FA, and linoleic, linolenic, and arachidonic acids were strong independent predictors of less steep decline in creatinine clearance from baseline to follow-up (P <0.0001, after adjusting for baseline creatinine clearance). After adjusting for baseline creatinine, baseline total plasma PUFAs, n-3 FA, and linoleic, linolenic, and arachidonic acids were negatively associated with creatinine at 3-year follow-up. Participants with higher plasma PUFAs at enrollment had a lower risk of developing renal insufficiency, defined by a creatinine clearance <60 mL/min, during 3-year follow-up. Conclusion High PUFA concentrations, both n-3 FA and n-6 FA, may attenuate the age-associated decline in renal function among older community-dwelling women and men. PMID:18202159

  2. Omega 3 polyunsaturated fatty acids and the treatment of depression.

    PubMed

    Deacon, Gelinda; Kettle, Christine; Hayes, David; Dennis, Christina; Tucci, Joseph

    2017-01-02

    Depression is a common, recurrent, and debilitating illness that has become more prevalent over the past 100 years. This report reviews the etiology and pathophysiology of depression, and explores the role of omega 3 polyunsaturated fatty acids (n-3 PUFA) as a possible treatment. In seeking to understand depression, genetic factors and environmental influences have been extensively investigated. Research has led to several hypotheses for the pathophysiological basis of depression but a definitive pathogenic mechanism, or group thereof, has hitherto remained equivocal. To date, treatment has been based on the monoamine hypothesis and hence, selective serotonin reuptake inhibitors have been the most widely used class of medication. In the last decade, there has been considerable interest in n-3 PUFAs and their role in depression. These fatty acids are critical for development and function of the central nervous system. Increasing evidence from epidemiological, laboratory, and randomized placebo-controlled trials suggests deficiency of dietary n-3 PUFAs may contribute to development of mood disorders, and supplementation with n-3 PUFAs may provide a new treatment option. Conclusions based on systematic reviews and meta-analyses of published trials to date vary. Research into the effects of n-3 PUFAs on depressed mood is limited. Furthermore, results from such have led to conflicting conclusions regarding the efficacy of n-3 PUFAs in affecting reduction in symptoms of depression. PUFAs are generally well tolerated by adults and children although mild gastrointestinal effects are reported. There is mounting evidence to suggest that n-3 PUFAs play a role in depression and deserve greater research efforts.

  3. Fortification of foods with omega-3 polyunsaturated fatty acids.

    PubMed

    Ganesan, Balasubramanian; Brothersen, Carl; McMahon, Donald J

    2014-01-01

    A $600 million nutritional supplements market growing at 30% every year attests to consumer awareness of, and interests in, health benefits attributed to these supplements. For over 80 years the importance of polyunsaturated fatty acid (PUFA) consumption for human health has been established. The FDA recently approved the use of ω-3 PUFAs in supplements. Additionally, the market for ω-3 PUFA ingredients grew by 24.3% last year, which affirms their popularity and public awareness of their benefits. PUFAs are essential for normal human growth; however, only minor quantities of the beneficial ω-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are synthesized by human metabolism. Rather PUFAs are obtained via dietary or nutritional supplementation and modified into other beneficial metabolites. A vast literature base is available on the health benefits and biological roles of ω-3 PUFAs and their metabolism; however, information on their dietary sources and palatability of foods incorporated with ω-3 PUFAs is limited. DHA and EPA are added to many foods that are commercially available, such as infant and pet formulae, and they are also supplemented in animal feed to incorporate them in consumer dairy, meat, and poultry products. The chief sources of EPA and DHA are fish oils or purified preparations from microalgae, which when added to foods, impart a fishy flavor that is considered unacceptable. This fishy flavor is completely eliminated by extensively purifying preparations of n-3 PUFA sources. While n-3 PUFA lipid autoxidation is considered the main cause of fishy flavor, the individual oxidation products identified thus far, such as unsaturated carbonyls, do not appear to contribute to fishy flavor or odor. Alternatively, various compound classes such as free fatty acids and volatile sulfur compounds are known to impart fishy flavor to foods. Identification of the causative compounds to reduce and eventually eliminate fishy flavor is important

  4. Effects of N-3 Polyunsaturated Fatty Acids on Dementia

    PubMed Central

    Yanai, Hidekatsu

    2017-01-01

    N-3 polyunsaturated fatty acids (PUFAs) including α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory effects and neuronal protective functions and may benefit prevention of dementia; however, the epidemiological evidence is very limited. Therefore, the literature about the association between n-3 PUFA and dementia was searched, by using Pubmed. In the analyses of observational studies, n-3 PUFA has been reported to be beneficially associated with dementia in 17 studies; however, the beneficial association between n-3 PUFA and dementia was denied by three studies. In the analyses of intervention studies, n-3 PUFA supplementation was beneficially associated with dementia in eight studies; however, five studies reported the negligible effect of n-3 PUFA for dementia. N-3 PUFA may improve Alzheimer’s disease by increasing clearance of amyloid-β peptide, neurotrophic and neuroprotective factors, and by anti-inflammatory effects. In conclusion, patients with mild memory and/or cognitive impairment can be treated by a long-term and higher intake of n-3 PUFA. PMID:27924168

  5. Cardioprotective mechanism of omega-3 polyunsaturated fatty acids.

    PubMed

    Endo, Jin; Arita, Makoto

    2016-01-01

    Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid and docosahexaenoic acid, are widely regarded as cardioprotective. Several large-scale, randomized clinical trials have shown that dietary intake of omega-3 PUFAs improves the prognosis of patients with symptomatic heart failure or recent myocardial infarction. Therefore, dietary consumption of omega-3 PUFA is recommended in international guidelines for the general population to prevent the occurrence of cardiovascular diseases (CVDs). However, the precise mechanisms underlying the cardioprotective effects of omega-3 PUFAs are not fully understood. Omega-3 PUFAs can be incorporated into the phospholipid bilayer of cell membranes and can affect membrane fluidity, lipid microdomain formation, and signaling across membranes. Omega-3 PUFAs also modulate the function of membrane ion channels, such as Na and L-type Ca channels, to prevent lethal arrhythmias. Moreover, omega-3 PUFAs also prevent the conversion of arachidonic acid into pro-inflammatory eicosanoids by serving as an alternative substrate for cyclooxygenase or lipoxygenase, resulting in the production of less potent products. In addition, a number of enzymatically oxygenated metabolites derived from omega-3 PUFAs were recently identified as anti-inflammatory mediators. These omega-3 metabolites may contribute to the beneficial effects against CVDs that are attributed to omega-3 PUFAs.

  6. Omega-3 polyunsaturated fatty acids and oxygenated metabolism in atherothrombosis.

    PubMed

    Guichardant, Michel; Calzada, Catherine; Bernoud-Hubac, Nathalie; Lagarde, Michel; Véricel, Evelyne

    2015-04-01

    Numerous epidemiological studies and clinical trials have reported the health benefits of omega-3 polyunsaturated fatty acids (PUFA), including a lower risk of coronary heart diseases. This review mainly focuses on the effects of alpha-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on some risk factors associated with atherothrombosis, including platelet activation, plasma lipid concentrations and oxidative modification of low-density lipoproteins (LDL). Special focus is given to the effects of marine PUFA on the formation of eicosanoids and docosanoids, and to the bioactive properties of some oxygenated metabolites of omega-3 PUFA produced by cyclooxygenases and lipoxygenases. The antioxidant effects of marine omega-3 PUFA at low concentrations and the pro-oxidant effects of DHA at high concentrations on the redox status of platelets and LDL are highlighted. Non enzymatic peroxidation end-products deriving from omega-3 PUFA such as hydroxy-hexenals, neuroketals and EPA-derived isoprostanes are also considered in relation to atherosclerosis. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

  7. Anti-cancer activities of ω-6 polyunsaturated fatty acids.

    PubMed

    Xu, Yi; Qian, Steven Y

    2014-01-01

    The ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are two major families of PUFAs present as essential cellular components which possess diverse bioactivities. The ω-3s, mainly found in seafood, are associated with many beneficial effects on human health, while the ω-6s are more abundant in our daily diet and could be implicated in many pathological processes including cancer development. Increasing evidence suggests that the adverse effects of ω-6s may be largely attributed to arachidonic acid (AA, a downstream ω-6) and the metabolite prostaglandin E2 (PGE2) that stems from its cyclooxygenase (COX)-catalyzed lipid peroxidation. On the other hand, two of AA's upstream ω-6s, γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA), are shown to possess certain anti-cancer activities, including inducing cell apoptosis and inhibiting cell proliferation. In this paper, we review the documented anti-cancer activities of ω-6 PUFAs, including the recent findings regarding the anti-cancer effects of free radical-mediated DGLA peroxidation. The possible mechanisms and applications of DGLA (and other ω-6s) in inducing anti-cancer activity are also discussed. Considering the wide availability of ω-6s in our daily diet, the study of the potential beneficial effect of ω-6 PUFAs may guide us to develop an ω-6-based diet care strategy for cancer prevention and treatment.

  8. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis

    PubMed Central

    Yang, Wan Seok; Kim, Katherine J.; Gaschler, Michael M.; Patel, Milesh; Shchepinov, Mikhail S.

    2016-01-01

    Ferroptosis is form of regulated nonapoptotic cell death that is involved in diverse disease contexts. Small molecules that inhibit glutathione peroxidase 4 (GPX4), a phospholipid peroxidase, cause lethal accumulation of lipid peroxides and induce ferroptotic cell death. Although ferroptosis has been suggested to involve accumulation of reactive oxygen species (ROS) in lipid environments, the mediators and substrates of ROS generation and the pharmacological mechanism of GPX4 inhibition that generates ROS in lipid environments are unknown. We report here the mechanism of lipid peroxidation during ferroptosis, which involves phosphorylase kinase G2 (PHKG2) regulation of iron availability to lipoxygenase enzymes, which in turn drive ferroptosis through peroxidation of polyunsaturated fatty acids (PUFAs) at the bis-allylic position; indeed, pretreating cells with PUFAs containing the heavy hydrogen isotope deuterium at the site of peroxidation (D-PUFA) prevented PUFA oxidation and blocked ferroptosis. We further found that ferroptosis inducers inhibit GPX4 by covalently targeting the active site selenocysteine, leading to accumulation of PUFA hydroperoxides. In summary, we found that PUFA oxidation by lipoxygenases via a PHKG2-dependent iron pool is necessary for ferroptosis and that the covalent inhibition of the catalytic selenocysteine in Gpx4 prevents elimination of PUFA hydroperoxides; these findings suggest new strategies for controlling ferroptosis in diverse contexts. PMID:27506793

  9. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis.

    PubMed

    Yang, Wan Seok; Kim, Katherine J; Gaschler, Michael M; Patel, Milesh; Shchepinov, Mikhail S; Stockwell, Brent R

    2016-08-23

    Ferroptosis is form of regulated nonapoptotic cell death that is involved in diverse disease contexts. Small molecules that inhibit glutathione peroxidase 4 (GPX4), a phospholipid peroxidase, cause lethal accumulation of lipid peroxides and induce ferroptotic cell death. Although ferroptosis has been suggested to involve accumulation of reactive oxygen species (ROS) in lipid environments, the mediators and substrates of ROS generation and the pharmacological mechanism of GPX4 inhibition that generates ROS in lipid environments are unknown. We report here the mechanism of lipid peroxidation during ferroptosis, which involves phosphorylase kinase G2 (PHKG2) regulation of iron availability to lipoxygenase enzymes, which in turn drive ferroptosis through peroxidation of polyunsaturated fatty acids (PUFAs) at the bis-allylic position; indeed, pretreating cells with PUFAs containing the heavy hydrogen isotope deuterium at the site of peroxidation (D-PUFA) prevented PUFA oxidation and blocked ferroptosis. We further found that ferroptosis inducers inhibit GPX4 by covalently targeting the active site selenocysteine, leading to accumulation of PUFA hydroperoxides. In summary, we found that PUFA oxidation by lipoxygenases via a PHKG2-dependent iron pool is necessary for ferroptosis and that the covalent inhibition of the catalytic selenocysteine in Gpx4 prevents elimination of PUFA hydroperoxides; these findings suggest new strategies for controlling ferroptosis in diverse contexts.

  10. Omega-3 Polyunsaturated Fatty Acids and Heart Rate Variability

    PubMed Central

    Christensen, Jeppe Hagstrup

    2011-01-01

    Omega-3 polyunsaturated fatty acids (PUFA) may modulate autonomic control of the heart because omega-3 PUFA is abundant in the brain and other nervous tissue as well as in cardiac tissue. This might partly explain why omega-3 PUFA offer some protection against sudden cardiac death (SCD). The autonomic nervous system is involved in the pathogenesis of SCD. Heart rate variability (HRV) can be used as a non-invasive marker of cardiac autonomic control and a low HRV is a predictor for SCD and arrhythmic events. Studies on HRV and omega-3 PUFA have been performed in several populations such as patients with ischemic heart disease, patients with diabetes mellitus, patients with chronic renal failure, and in healthy subjects as well as in children. The studies have demonstrated a positive association between cellular content of omega-3 PUFA and HRV and supplementation with omega-3 PUFA seems to increase HRV which could be a possible explanation for decreased risk of arrhythmic events and SCD sometimes observed after omega-3 PUFA supplementation. However, the results are not consistent and further research is needed. PMID:22110443

  11. Wastewater recycling technology for fermentation in polyunsaturated fatty acid production.

    PubMed

    Song, Xiaojin; Ma, Zengxin; Tan, Yanzhen; Zhang, Huidan; Cui, Qiu

    2017-07-01

    To reduce fermentation-associated wastewater discharge and the cost of wastewater treatment, which further reduces the total cost of DHA and ARA production, this study first analyzed the composition of wastewater from Aurantiochytrium (DHA) and Mortierella alpina (ARA) fermentation, after which wastewater recycling technology for these fermentation processes was developed. No negative effects of DHA and ARA production were observed when the two fermentation wastewater methods were cross-recycled. DHA and ARA yields were significantly inhibited when the wastewater from the fermentation process was directly reused. In 5-L fed-batch fermentation experiments, using this cross-recycle technology, the DHA and ARA yields were 30.4 and 5.13gL(-1), respectively, with no significant changes (P>0.05) compared to the control group, and the water consumption was reduced by half compared to the traditional process. Therefore, this technology has great potential in industrial fermentation for polyunsaturated fatty acid production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Do we need 'new' omega-3 polyunsaturated fatty acids formulations?

    PubMed

    Cicero, Arrigo F G; Morbini, Martino; Borghi, Claudio

    2015-02-01

    The therapeutic value of omega-3 polyunsaturated fatty acids (PUFAs), mainly (but not only) found in fish oils, eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively), has been extensively studied in a wide variety of disease conditions, predominantly in cardiovascular disease. However, the significant difference in efficacy observed in various conditions with different dosages seems to be at least partly related to the large discrepancy in quality of the product and to the bioavailability of the omega-3 PUFA. The research of new sources (e.g., from arctic Krill oil) and pharmaceutical forms of omega-3 PUFA (e.g., omega-3 carboxylic acids) is needed in order to detect the one with the best bioavailability and efficacy, and with a parallel reduction in the production costs. There is also the need to understand if long-term PUFA supplementation could increase the efficacy of the already-available evidence-based therapies for cardiovascular disease prevention and for the management of the diseases where the use of PUFA could have a possible improving effect.

  13. Effects of N-3 Polyunsaturated Fatty Acids on Dementia.

    PubMed

    Yanai, Hidekatsu

    2017-01-01

    N-3 polyunsaturated fatty acids (PUFAs) including α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory effects and neuronal protective functions and may benefit prevention of dementia; however, the epidemiological evidence is very limited. Therefore, the literature about the association between n-3 PUFA and dementia was searched, by using Pubmed. In the analyses of observational studies, n-3 PUFA has been reported to be beneficially associated with dementia in 17 studies; however, the beneficial association between n-3 PUFA and dementia was denied by three studies. In the analyses of intervention studies, n-3 PUFA supplementation was beneficially associated with dementia in eight studies; however, five studies reported the negligible effect of n-3 PUFA for dementia. N-3 PUFA may improve Alzheimer's disease by increasing clearance of amyloid-β peptide, neurotrophic and neuroprotective factors, and by anti-inflammatory effects. In conclusion, patients with mild memory and/or cognitive impairment can be treated by a long-term and higher intake of n-3 PUFA.

  14. Enhancement of cell viability after treatment with polyunsaturated fatty acids.

    PubMed

    Bartl, J; Walitza, S; Grünblatt, E

    2014-01-24

    Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent in children and adolescents and both environmental and genetic factors play major roles. Polyunsaturated fatty acids (PUFAs) are postulated to contribute to the development of the infant brain and an imbalance in these may increase the risk of ADHD. In recent clinical studies, supplementation with PUFAs improved symptoms of ADHD in some cases. Similarly, some beneficial effects were observed with PUFA treatment in neuronal cell cultures. Therefore, in this study, we hypothesized that a specific PUFA combination (available on the market as Equazen™ [Vifor Pharma, Switzerland]) along with iron, zinc, or vitamin B5 (vitB5) would produce an additive beneficial effect on the viability of rat pheochromocytoma-12 dopaminergic cells. The specific PUFA combination alone, as well as added to each of the three nutrients, was tested in a dose-response manner. The specific PUFAs significantly improved cell viability, starting at very low doses (100pM) from 60h up to 90h; while the combined treatment with vitB5 and minerals did not provide additional benefit. Our results confirmed the beneficial effect of the specific PUFAs on neuronal cell viability; although supplementation with minerals and vitB5 did not enhance this effect. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes.

    PubMed

    Liin, S I; Karlsson, U; Bentzen, B H; Schmitt, N; Elinder, F

    2016-09-01

    Polyunsaturated fatty acids have been reported to reduce neuronal excitability, in part by promoting inactivation of voltage-gated sodium and calcium channels. Effects on neuronal potassium channels are less explored and experimental data ambiguous. The aim of this study was to investigate anti-excitable effects of polyunsaturated fatty acids on the neuronal M-channel, important for setting the resting membrane potential in hippocampal and dorsal root ganglion neurones. Effects of fatty acids and fatty acid analogues on mouse dorsal root ganglion neurones and on the human KV 7.2/3 channel expressed in Xenopus laevis oocytes were studied using electrophysiology. Extracellular application of physiologically relevant concentrations of the polyunsaturated fatty acid docosahexaenoic acid hyperpolarized the resting membrane potential (-2.4 mV by 30 μm) and increased the threshold current to evoke action potentials in dorsal root ganglion neurones. The polyunsaturated fatty acids docosahexaenoic acid, α-linolenic acid and eicosapentaenoic acid facilitated opening of the human M-channel, comprised of the heteromeric human KV 7.2/3 channel expressed in Xenopus oocytes, by shifting the conductance-vs.-voltage curve towards more negative voltages (by -7.4 to -11.3 mV by 70 μm). Uncharged docosahexaenoic acid methyl ester and monounsaturated oleic acid did not facilitate opening of the human KV 7.2/3 channel. These findings suggest that circulating polyunsaturated fatty acids, with a minimum requirement of multiple double bonds and a charged carboxyl group, dampen excitability by opening neuronal M-channels. Collectively, our data bring light to the molecular targets of polyunsaturated fatty acids and thus a possible mechanism by which polyunsaturated fatty acids reduce neuronal excitability. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  16. Feeding long-chain n-3 polyunsaturated fatty acids to obese leptin receptor-deficient JCR:LA- cp rats modifies immune function and lipid-raft fatty acid composition.

    PubMed

    Ruth, Megan R; Proctor, Spencer D; Field, Catherine J

    2009-05-01

    Dietary EPA and DHA modulate immunity and thereby may improve the aberrant immune function in obese states. To determine the effects of feeding fish oil (FO) containing EPA and DHA on splenocyte phospholipid (PL) and lipid-raft fatty acid composition, phenotypes and cytokine production, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp; n 10) were randomised to one of three nutritionally adequate diets for 3 weeks: control (Ctl, 0 % EPA+DHA); low FO (LFO, 0.8 % (w/w) EPA+DHA); high FO (HFO, 1.4 % (w/w) EPA+DHA). Lean JCR:LA-cp (+/ - or +/+) rats (n 5) were fed the Ctl diet. Obese Ctl rats had a higher proportion of n-3 PUFA in splenocyte PL than lean rats fed the same diet (P < 0.05). The lower n-6:n-3 PUFA ratio of splenocyte PL was consistent with the lower mitogen-stimulated interferon (IFN)-gamma and IL-1beta production by cells from obese rats (P < 0.05). Obese rats fed the FO diet had lower mitogen-stimulated Th1 (IFN-gamma) and Th2 (IL-4) cytokine responses, but IL-2 production (concanavalin A; ConA) did not differ (P < 0.05). The HFO diet was more effective in lowering IL-1beta and increasing IL-10 production (ConA, P < 0.05). This lower IL-1beta production was accompanied by a lower proportion of major histocompatability complex class II-positive cells and a higher incorporation of DHA into lipid rafts. This is the first study to demonstrate impaired responses to mitogen stimulation and altered fatty acid incorporation into the membrane PL of JCR:LA-cp rats. Feeding FO lowered the ex vivo inflammatory response, without altering IL-2 production from ConA-stimulated splenocytes which may occur independent of leptin signalling.

  17. Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health.

    PubMed

    Siddiqui, Rafat A; Harvey, Kevin A; Zaloga, Gary P

    2008-07-01

    Epidemiological evidence from Greenland Eskimos and Japanese fishing villages suggests that eating fish oil and marine animals can prevent coronary heart disease. Dietary studies from various laboratories have similarly indicated that regular fish oil intake affects several humoral and cellular factors involved in atherogenesis and may prevent atherosclerosis, arrhythmia, thrombosis, cardiac hypertrophy and sudden cardiac death. The beneficial effects of fish oil are attributed to their n-3 polyunsaturated fatty acid (PUFA; also known as omega-3 fatty acids) content, particularly eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Dietary supplementation of DHA and EPA influences the fatty acid composition of plasma phospholipids that, in turn, may affect cardiac cell functions in vivo. Recent studies have demonstrated that long-chain omega-3 fatty acids may exert beneficial effects by affecting a wide variety of cellular signaling mechanisms. Pathways involved in calcium homeostasis in the heart may be of particular importance. L-type calcium channels, the Na+-Ca2+ exchanger and mobilization of calcium from intracellular stores are the most obvious key signaling pathways affecting the cardiovascular system; however, recent studies now suggest that other signaling pathways involving activation of phospholipases, synthesis of eicosanoids, regulation of receptor-associated enzymes and protein kinases also play very important roles in mediating n-3 PUFA effects on cardiovascular health. This review is therefore focused on the molecular targets and signaling pathways that are regulated by n-3 PUFAs in relation to their cardioprotective effects.

  18. A New Insight to Bone Turnover: Role of ω-3 Polyunsaturated Fatty Acids

    PubMed Central

    López-Frías, Magdalena; López-Aliaga, Inmaculada; Ochoa, Julio J.

    2013-01-01

    Background. Evidence has shown that long-chain polyunsaturated fatty acids (LCPUFA), especially the ω-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial for bone health and turnover. Objectives. This review summarizes findings from both in vivo and in vitro studies and the effects of LC PUFA on bone metabolism, as well as the relationship with the oxidative stress, the inflammatory process, and obesity. Results. Some studies in humans indicate that LCPUFA can increase bone formation, affect peak bone mass in adolescents, and reduce bone loss. However, the cellular mechanisms of action of the LCPUFA are complex and involve modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signaling pathways, cytokines, and growth factors, although in certain aspects there is still some controversy. LCPUFA affect receptor activator of nuclear factor κβ (RANK), a receptor found on the osteoclast, causing bone resorption, which controls osteoclast formation. Conclusions. Since fatty acids are an endogenous source of reactive oxygen species, free radicals alter the process of bone turnover; however, although there are clinical evidences linking bone metabolism and dietary lipids, more clinical trials are necessary to prove whether ω-3 PUFA supplementation plays a major role in bone health. PMID:24302863

  19. A new insight to bone turnover: role of ω-3 polyunsaturated fatty acids.

    PubMed

    Kajarabille, Naroa; Díaz-Castro, Javier; Hijano, Silvia; López-Frías, Magdalena; López-Aliaga, Inmaculada; Ochoa, Julio J

    2013-11-04

    Background. Evidence has shown that long-chain polyunsaturated fatty acids (LCPUFA), especially the ω -3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial for bone health and turnover. Objectives. This review summarizes findings from both in vivo and in vitro studies and the effects of LC PUFA on bone metabolism, as well as the relationship with the oxidative stress, the inflammatory process, and obesity. Results. Some studies in humans indicate that LCPUFA can increase bone formation, affect peak bone mass in adolescents, and reduce bone loss. However, the cellular mechanisms of action of the LCPUFA are complex and involve modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signaling pathways, cytokines, and growth factors, although in certain aspects there is still some controversy. LCPUFA affect receptor activator of nuclear factor κ β (RANK), a receptor found on the osteoclast, causing bone resorption, which controls osteoclast formation. Conclusions. Since fatty acids are an endogenous source of reactive oxygen species, free radicals alter the process of bone turnover; however, although there are clinical evidences linking bone metabolism and dietary lipids, more clinical trials are necessary to prove whether ω -3 PUFA supplementation plays a major role in bone health.

  20. Symbiotic zooxanthellae provide the host-coral Montipora digitata with polyunsaturated fatty acids.

    PubMed

    Papina, M; Meziane, T; van Woesik, R

    2003-07-01

    We compared the fatty acid composition of the host-coral Montipora digitata with the fatty acid composition in the coral's endosymbiotic dinoflagellates (zooxanthellae). Fatty acids as methyl esters were determined using gas chromatography (GC) and verified by GC-mass spectrometry. We found the main difference between the fatty acids in the host and their symbionts were that zooxanthellae supported higher proportions of polyunsaturated fatty acids. The presence of fatty acids specific to dinoflagellates (i.e. 18:4omega3, 22:5omega3 and 22:6omega3) in the host tissue suggests that zooxanthellae provide the coral host not only with saturated fatty acids, but also with diverse polyunsaturated fatty acids.

  1. Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.

    PubMed

    Tan, May Loong; Ho, Jacqueline J; Teh, Keng Hwang

    2016-09-28

    About 5% of school children have a specific learning disorder, defined as unexpected failure to acquire adequate abilities in reading, writing or mathematics that is not a result of reduced intellectual ability, inadequate teaching or social deprivation. Of these events, 80% are reading disorders. Polyunsaturated fatty acids (PUFAs), in particular, omega-3 and omega-6 fatty acids, which normally are abundant in the brain and in the retina, are important for learning. Some children with specific learning disorders have been found to be deficient in these PUFAs, and it is argued that supplementation of PUFAs may help these children improve their learning abilities. 1. To assess effects on learning outcomes of supplementation of polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.2. To determine whether adverse effects of supplementation of PUFAs are reported in these children. In November 2015, we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, 10 other databases and two trials registers. We also searched the reference lists of relevant articles. Randomised controlled trials (RCTs) or quasi-RCTs comparing PUFAs with placebo or no treatment in children younger than 18 years with specific learning disabilities, as diagnosed in accordance with the fifth (or earlier) edition of theDiagnostic and Statistical Manual of Mental Disorders (DSM-5), or the 10th (or earlier) revision of the International Classification of Diseases (ICD-10) or equivalent criteria. We included children with coexisting developmental disorders such as attention deficit hyperactivity disorder (ADHD) or autism. Two review authors (MLT and KHT) independently screened the titles and abstracts of articles identified by the search and eliminated all studies that did not meet the inclusion criteria. We contacted study authors to ask for missing information and clarification, when needed. We used the GRADE approach to assess the quality of evidence. Two small studies

  2. Long-chain n-3 fatty acids - New anabolic compounds improving protein metabolism

    USDA-ARS?s Scientific Manuscript database

    Previous animal studies demonstrated that chronic feeding of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFA) that modifies muscle membrane fatty acid composition promotes protein anabolism by blunting the age-associated deterioration in insulin sensitivity. The current study assessed, as a pr...

  3. Importance of medium chain fatty acids in animal nutrition

    NASA Astrophysics Data System (ADS)

    Baltić, B.; Starčević, M.; Đorđević, J.; Mrdović, B.; Marković, R.

    2017-09-01

    Fats in animal and human nutrition are a common subject of research. These studies most often pay attention to particular fat groups (saturated, unsaturated, polyunsaturated fats or fats grouped by the length of their fatty acid chains into short, medium or long chain fatty acids). Medium chain fatty acids (MCFAs) have two main sources: milk and coconut oil. To date, research has shown these acids have positive effects on health, production, feed digestibility and lower body and muscle fats in broilers and swine. MCFAs possess antibacterial, anticoccidial and antiviral effects. Also, it has been proven that these acids act synergistically if they are used together with organic acids, essential oils, or probiotics. Nowadays, commercial MCFA products are available for use in animal nutrition as feed additives.

  4. Abdominal aortic aneurysm and omega-3 polyunsaturated fatty acids: Mechanisms, animal models, and potential treatment.

    PubMed

    Meital, Lara T; Sandow, Shaun L; Calder, Philip C; Russell, Fraser D

    2017-03-01

    Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with macrophage accumulation in the adventitia, oxidative stress, medial elastin degradation and aortic dilation. Progression of AAA is linked to increased risk of rupture, which carries a high mortality rate. Drug therapies trialled to date lack efficacy and although aneurysm repair is available for patients with large aneurysm, peri-surgical morbidity and mortality have been widely reported. Recent studies using rodent models of AAA suggest that long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) and their metabolites can moderate inflammation and oxidative stress perpetuated by infiltrating macrophages and intervene in the destruction of medial elastin. This review examines evidence from these animal studies and related reports of inhibition of inflammation and arrest of aneurysm development following prophylactic supplementation with LC n-3 PUFAs. The efficacy of LC n-3 PUFAs for management of existing aneurysm is unclear and further investigations involving human clinical trials are warranted.

  5. Effect of polyunsaturated fatty acid supplementation on biophysical parameters and chilling sensitivity of ewe oocytes.

    PubMed

    Zeron, Yoel; Sklan, David; Arav, Amir

    2002-02-01

    Fat supplementation in the diet influences reproductive performance of lactating ruminants. Changes in the fat supply alter fatty acid composition and this can affect physical properties of cell membranes. This study examined the effect of rumen bypass polyunsaturated fatty acid (PUFA) supplementation on oocyte quality, chilling sensitivity, and lipid phase transition in oocytes of the sheep. Ewes were fed a diet supplemented with calcium soaps of fish oil for 13 weeks. More follicles and oocytes were found in the ovaries of ewes supplemented with PUFA than in control ewes. The number of high-quality oocytes was higher in ewes fed PUFA than in control ewes (74.3 and 57.0%, P < 0.05, respectively). Evaluation of phospholipid fatty acid composition indicated that PUFA were present in small proportions in oocytes, and eicosapentaenoic acid and docosahexaenoic acid were absent. Supplementation with PUFA increased the proportion of long chain unsaturated fatty acid in the plasma and cumulus cells phospholipids by 7.4 and 12.7%, respectively (P < 0.05). Integrity of oocyte membranes following chilling (16 degrees C, 15 min) was improved by PUFA supplementation increasing from 62.5 to 90.0% (P < 0.05). Due to changes in the oocyte's fatty acid profile, physical properties of the membrane were changed and the midpoint temperature of lipid transition reduced by 11 degrees C. These results suggest that supplementation of rumen bypass PUFA to ruminant diets can change fatty acid composition of follicle components and influence parameters such as number and quality of oocytes and their chilling resistance.

  6. Lipids rich in ω-3 polyunsaturated fatty acids from microalgae.

    PubMed

    Santos-Sánchez, N F; Valadez-Blanco, R; Hernández-Carlos, B; Torres-Ariño, A; Guadarrama-Mendoza, P C; Salas-Coronado, R

    2016-10-01

    Despite microalgae recently receiving enormous attention as a potential source of biodiesel, their use is still not feasible as an alternative to fossil fuels. Recently, interest in microalgae has focused on the production of bioactive compounds such as polyunsaturated fatty acids (PUFA), which provide microalgae a high added value. Several considerations need to be assessed for optimizing PUFA production from microalgae. Firstly, a microalgae species that produces high PUFA concentrations should be selected, such as Nannochloropsis gaditana, Isochrysis galbana, Phaeodactylum tricornutum, and Crypthecodinium cohnii, with marine species gaining more attention than do freshwater species. Closed cultivation processes, e.g., photobioreactors, are the most appropriate since temperature, pH, and nutrients can be controlled. An airlift column with LEDs or optical fibers to distribute photons into the culture media can be used at small scale to produce inoculum, while tubular and flat panels are used at commercial scale. Depending on the microalgae, a temperature range from 15 to 28 °C and a pH from 7 to 8 can be employed. Relevant conditions for PUFA production are medium light irradiances (50-300 μmol photons m(-2) s(-1)), air enriched with (0-1 % (v/v) CO2, as well as nitrogen and phosphorous limitation. For research purposes, the most appropriate medium for PUFA production is Bold's Basal, whereas mixotrophic cultivation using sucrose or glucose as the carbon source has been reported for industrial processes. For cell harvesting, the use of tangential flow membrane filtration or disk stack centrifugation is advisable at commercial scale. Current researches on PUFA extraction have focused on the use of organic solvents assisted with ultrasound or microwaves, supercritical fluids, and electroporation or are enzyme assisted. Commercial-scale extraction involves mainly physical methods such as bead mills and expeller presses. All these factors should be taken into

  7. Polyunsaturated fatty acids in male and female reproduction.

    PubMed

    Wathes, D Claire; Abayasekara, D Robert E; Aitken, R John

    2007-08-01

    In Westernized societies, average consumption of n-6 polyunsaturated fatty acids (PUFAs) far exceeds nutritional requirements. The ratio of n-6 to n-3 PUFAs is generally >10:1 whereas on a primitive human diet it was closer to 1:1. Diets fed to intensively farmed livestock have followed a similar trend. Both n-6 and n-3 PUFAs can influence reproductive processes through a variety of mechanisms. They provide the precursors for prostaglandin synthesis and can modulate the expression patterns of many key enzymes involved in both prostaglandin and steroid metabolism. They are essential components of all cell membranes. The proportions of different PUFAs in tissues of the reproductive tract reflect dietary consumption. PUFA supplements (particularly n-3 PUFAs in fish oil) are promoted for general health reasons. Fish oils may also benefit fertility in cattle and reduce the risk of preterm labor in women, but in both cases current evidence to support this is inconclusive. Gamma-linolenic acid containing oils can alter the types of prostaglandins produced by cells in vitro, but published data to support claims relating to effects on reproductive health are lacking. Spermatozoa require a high PUFA content to provide the plasma membrane with the fluidity essential at fertilization. However, this makes spermatozoa particularly vulnerable to attack by reactive oxygen species, and lifestyle factors promoting oxidative stress have clear associations with reduced fertility. Adequately powered trials that control for the ratios of different PUFAs consumed are required to determine the extent to which this aspect of our diets does influence our fertility.

  8. Childrens' Learning and Behaviour and the Association with Cheek Cell Polyunsaturated Fatty Acid Levels

    ERIC Educational Resources Information Center

    Kirby, A.; Woodward, A.; Jackson, S.; Wang, Y.; Crawford, M. A.

    2010-01-01

    Increasing interest in the role of omega-3 fatty acids in relation to neurodevelopmental disorders (e.g. ADHD, dyslexia, autism) has occurred as a consequence of some international studies highlighting this link. In particular, some studies have shown that children with ADHD may have lower concentrations of polyunsaturated fatty acids (PUFAs),…

  9. Childrens' Learning and Behaviour and the Association with Cheek Cell Polyunsaturated Fatty Acid Levels

    ERIC Educational Resources Information Center

    Kirby, A.; Woodward, A.; Jackson, S.; Wang, Y.; Crawford, M. A.

    2010-01-01

    Increasing interest in the role of omega-3 fatty acids in relation to neurodevelopmental disorders (e.g. ADHD, dyslexia, autism) has occurred as a consequence of some international studies highlighting this link. In particular, some studies have shown that children with ADHD may have lower concentrations of polyunsaturated fatty acids (PUFAs),…

  10. Role of FADS1 and FADS2 polymorphisms in polyunsaturated fatty acid metabolism.

    PubMed

    Glaser, Claudia; Heinrich, Joachim; Koletzko, Berthold

    2010-07-01

    Tissue availability of polyunsaturated fatty acids (PUFAs) depends on dietary intake and metabolic turnover and has a major impact on human health. Strong associations between variants in the human genes fatty acid desaturase 1 (FADS1, encoding Delta-5 desaturase) and fatty acid desaturase 2 (FADS2, encoding Delta-6 desaturase) and blood levels of PUFAs and long-chain PUFAs (LC-PUFAs) have been reported. The most significant associations and the highest proportion of genetically explained variability (28%) were found for arachidonic acid (20:4n-6), the main precursor of eicosanoids. Subjects carrying the minor alleles of several single nucleotide polymorphisms had a lower prevalence of allergic rhinitis and atopic eczema. Therefore, blood levels of PUFAs and LC-PUFAs are influenced not only by diet, but to a large extent also by genetic variants common in a European population. These findings have been replicated in independent populations. Depending on genetic variants, requirements of dietary PUFA or LC-PUFA intakes to achieve comparable biological effects may differ. We recommend including analyses of FADS1 and FADS2 polymorphism in future cohort and intervention studies addressing biological effects of PUFAs and LC-PUFAs.

  11. N-3 polyunsaturated fatty acids in animal models with neuroinflammation: An update.

    PubMed

    Trépanier, Marc-Olivier; Hopperton, Kathryn E; Orr, Sarah K; Bazinet, Richard P

    2016-08-15

    Neuroinflammation is a characteristic of a multitude of neurological and psychiatric disorders. Modulating inflammatory pathways offers a potential therapeutic target in these disorders. Omega-3 polyunsaturated fatty acids have anti-inflammatory and pro-resolving properties in the periphery, however, their effect on neuroinflammation is less studied. This review summarizes 61 animal studies that tested the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory outcomes in vivo in various models including stroke, spinal cord injury, aging, Alzheimer's disease, Parkinson's disease, lipopolysaccharide and IL-1β injections, diabetes, neuropathic pain, traumatic brain injury, depression, surgically induced cognitive decline, whole body irradiation, amyotrophic lateral sclerosis, N-methyl-D-aspartate-induced excitotoxicity and lupus. The evidence presented in this review suggests anti-neuroinflammatory properties of omega-3 polyunsaturated fatty acids, however, it is not clear by which mechanism omega-3 polyunsaturated fatty acids exert their effect. Future research should aim to isolate the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory signaling in vivo and elucidate the mechanisms underlying these effects. Copyright © 2016. Published by Elsevier B.V.

  12. Enhanced sensitivity of ubiquinone-deficient mutants of Saccharomyces cerevisiae to products of autoxidized polyunsaturated fatty acids.

    PubMed Central

    Do, T Q; Schultz, J R; Clarke, C F

    1996-01-01

    Coenzyme Q (ubiquinone or Q) plays a well known electron transport function in the respiratory chain, and recent evidence suggests that the reduced form of ubiquinone (QH2) may play a second role as a potent lipid-soluble antioxidant. To probe the function of QH2 as an antioxidant in vivo, we have made use of a Q-deficient strain of Saccharomyces cerevisiae harboring a deletion in the COQ3 gene [Clarke, C. F., Williams, W. & Teruya, J. H. (1991) J. Biol. Chem. 266, 16636-16644]. Q-deficient yeast and the wild-type parental strain were subjected to treatment with polyunsaturated fatty acids, which are prone to autoxidation and breakdown into toxic products. In this study we find that Q-deficient yeast are hypersensitive to the autoxidation products of linolenic acid and other polyunsaturated fatty acids. In contrast, the monounsaturated oleic acid, which is resistant to autoxidative breakdown, has no effect. The hypersensitivity of the coq3delta strains can be prevented by the presence of the COQ3 gene on a single copy plasmid, indicating that the sensitive phenotype results solely from the inability to produce Q. As a result of polyunsaturated fatty acid treatment, there is a marked elevation of lipid hydroperoxides in the coq3 mutant as compared with either wild-type or respiratory-deficient control strains. The hypersensitivity of the Q-deficient mutant can be rescued by the addition of butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin E analog. The results indicate that autoxidation products of polyunsaturated fatty acids mediate the cell killing and that QH2 plays an important role in vivo in protecting eukaryotic cells from these products. PMID:8755509

  13. Do long-chain omega-3 fatty acids protect from atopic dermatitis?

    PubMed

    Reese, Imke; Werfel, Thomas

    2015-09-01

    Long-chain polyunsaturated fatty acids are essential for human nutrition. The number of double bonds determines whether a given fatty acid is termed two, three, or x times unsaturated. Depending on the distance of the first double bond from the fatty acid's methyl group, one distinguishes omega-3 fatty acids from omega-6 fatty acids. While the use of gamma linolenic acid, a long-chain fatty acid of the omega-6 family, has proven unsuccessful in the prevention or treatment of atopic dermatitis, supplementation of long-chain omega-3 fatty acids may represent a promising approach in the prevention of allergic disorders, especially atopic dermatitis. Whether the concept of long-chain omega-3 fatty acid administration will also become established in a therapeutic setting, depends on whether the beneficial effects observed so far can be substantiated in randomized controlled intervention studies.

  14. Longchain polyunsaturated fatty acid supplementation in preterm infants.

    PubMed

    Simmer, K; Patole, S

    2004-01-01

    The n-3 and n-6 essential fatty acids alpha linolenic acid (ALA) and linoleic acid (LA) are the precursors of the n-3 and n-6 longchain polyunsaturated fatty acids (LCPUFA). Controversy exists over whether LCPUFA are essential nutrients for preterm infants who may not be able to synthesise sufficient amounts of LCPUFA to satisfy the needs of the developing brain and retina. The aim of this review is to assess whether supplementation of formula with LCPUFA is safe and of benefit to preterm infants. Trials were identified by MEDLINE (October 2003), Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003) and by checking reference lists of relevant articles and conference proceedings. All randomised trials of formula supplemented with LCPUFA and with clinical endpoints were reviewed. Eleven randomised trials assessing the clinical effects of feeding formula supplemented with LCPUFA were included in the review. Of the eleven randomised trials included in the review, two of these were not classified as of high quality despite blinded assessment and complete follow-up, due to problems with assessment methodology. VISUAL ACUITY: Visual acuity over the first year was measured by Teller acuity cards in six studies, by VEP in four studies and by ERG in two studies. Most studies found no significant differences in any visual assessment between supplemented and control infants. Most of the trials have used Bayley Scales of Infant Development (BSID) at 12 to 24 months postterm and shown no significant effect following supplementation. Meta-analysis of BSID of three studies (Fewtrell 2002, O'Connor 2001, van Wezel 2002) shows no significant effect of supplementation on development. Carlson 1993 and Carlson 1996 demonstrated lower novelty preferences (possibly predictive of lower intelligence) in the supplemented compared with the control group. The investigators however concluded that supplemented infants

  15. Polyunsaturated fatty acid inhibition of fatty acid synthase transcription is independent of PPAR activation.

    PubMed

    Clarke, S D; Turini, M; Jump, D B; Abraham, S; Reedy, M

    1998-01-01

    Polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3) families inhibit the rate of gene transcription for a number of hepatic lipogenic and glycolytic genes, e.g., fatty acid synthase (FAS). In contrast, saturated and monounsaturated fatty acids have no inhibitory capability. The suppression of gene transcription resulting from the addition of PUFA to a high carbohydrate diet: occurs quickly (< 3 h) after its addition to a high glucose diet; can be recreated with hepatocytes cultured in a serum-free medium containing insulin and glucocorticoids; can be demonstrated in diabetic rats fed fructose; and is independent of glucagon. While the nature of the intracellular PUFA inhibitor is unclear, it appears that delta-6 desaturation is a required step in the process. Recently, the fatty acid activated nuclear factor, peroxisome-proliferator activated receptor (PPAR) was suggested to be the PUFA-response factor. However, the potent PPAR activators ETYA and Wy-14643 did not suppress hepatic expression of FAS, but did induce the PPAR-responsive gene, acyl-CoA oxidase (AOX). Similarly, treating rat hepatocytes with 20:4 (n-6) suppressed FAS expression but had no effect on AOX. Thus, it appears that the PUFA regulation of gene transcription involves a PUFA-response factor that is independent from PPAR.

  16. Do polyunsaturated fatty acids behave like an endogenous "polypill"?

    PubMed

    Das, Undurti N

    2008-01-01

    Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin - called as polypill - was estimated to reduce cardiovascular events by approximately 80%. Essential fatty acids (EFAs) and their long-chain metabolites and other products prevent platelet aggregation, lower blood pressure, reduce LDL-C, and ameliorate the adverse actions of homocysteine. Thus, EFAs and their metabolites show all the actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules, have no significant side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and children; and have been shown to reduce the incidence cardiovascular diseases. I propose that a rational combination of omega-3 and omega-6 fatty acids is as beneficial as that of the "polypill"; and may even show additional benefit in the prevention of depression, schizophrenia, Alzheimer's disease, and enhance cognitive function.

  17. Cloning and functional characterisation of an enzyme involved in the elongation of Delta6-polyunsaturated fatty acids from the moss Physcomitrella patens.

    PubMed

    Zank, Thorsten K; Zähringer, Ulrich; Beckmann, Christoph; Pohnert, Georg; Boland, Wilhelm; Holtorf, Hauke; Reski, Ralf; Lerchl, Jens; Heinz, Ernst

    2002-08-01

    The moss Physcomitrella patens contains high proportions of polyunsaturated very-long-chain fatty acids with up to 20 carbon atoms. Starting from preformed C18 polyunsaturated fatty acids, their biosynthesis involves a sequence of Delta6-desaturation, Delta6-elongation and Delta5-desaturation. In this report we describe for the first time the characterisation of a cDNA (PSE1) of plant origin with homology to the ELO-genes from Saccharomyces cerevisiae, encoding a component of the Delta6-elongase. Functional expression of PSE1 in S. cerevisiae led to the elongation of exogenously supplied Delta6-polyunsaturated fatty acids. By feeding experiments with different trienoic fatty acids of natural and synthetic origin, both substrate specificity and substrate selectivity of the enzyme were investigated. The activity of Pse1, when expressed in yeast, was not sensitive to the antibiotic cerulenin, which is an effective inhibitor of fatty acid synthesis and elongation. Furthermore, the PSE1 gene was disrupted in the moss by homologous recombination. This led to a complete loss of all C20 polyunsaturated fatty acids providing additional evidence for the function of the cDNA as coding for a component of the Delta6-elongase. The elimination of the elongase was not accompanied by a visible alteration in the phenotype, indicating that C20-PUFAs are not essential for viability of the moss under phytotron conditions.

  18. Reduction of divinyl ether-containing polyunsaturated fatty acids in transgenic potato plants.

    PubMed

    Eschen-Lippold, Lennart; Rothe, Grit; Stumpe, Michael; Göbel, Cornelia; Feussner, Ivo; Rosahl, Sabine

    2007-03-01

    Oxygenated polyunsaturated fatty acids synthesized via the lipoxygenase pathway play a role in plant responses to pathogen attack. In solanaceous plants, the preferential stimulation of the 9-lipoxygenase pathway in response to pathogen infection leads to the formation of the divinyl ether-containing polyunsaturated fatty acids colneleic and colnelenic acid, as well as hydroxy and trihydroxy polyunsaturated fatty acids. To functionally assess the role of divinyl ethers, transgenic potato plants were generated which express an RNA interference construct directed against the pathogen-inducible 9-divinyl ether synthase. Efficient reduction of 9-divinyl ether synthase transcript accumulation correlated with reduced levels of colneleic and colnelenic acid. However, in response to infection with virulent Phytophthora infestans, the causal agent of late blight disease, no significant differences in pathogen biomass could be detected suggesting that the levels of antimicrobial divinyl ethers are not critical for defense against Phytophthora infestans in a compatible interaction.

  19. Interactions between prebiotics, probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention?

    PubMed

    Peluso, Ilaria; Romanelli, Luca; Palmery, Maura

    2014-05-01

    The metabolic syndrome can be prevented by the Mediterranean diet, characterized by fiber, omega-3 polyunsaturated fatty acids and polyphenols. However, the composition of the Mediterranean diet, which can be viewed as a natural multiple supplement, is poorly controlled, and its beneficial effects poorly predictable. The metabolic syndrome is associated with intestinal dysbiosis and the gut microbioma seems to be the main target and player in the interactions occurring between probiotics, prebiotics, omega 3 polyunsaturated fatty acids, and polyphenols. From the reviewed evidence, it is reasonable to manage growth and metabolism of gut microflora with specific prebiotics and polyphenols. Even though the healthy properties of functional foods and nutraceuticals still need to be fully elucidated, available data suggest that well-designed supplements, containing the better ratio of omega-3 polyunsaturated fatty acids and antioxidants, specific probiotic strains, and selected polyphenols and prebiotics, could be useful in metabolic syndrome prevention and treatment.

  20. Polyunsaturated fatty acid supplementation for drug-resistant epilepsy.

    PubMed

    Sarmento Vasconcelos, Vivian; Macedo, Cristiane R; de Souza Pedrosa, Alexsandra; Pereira Gomes Morais, Edna; Porfírio, Gustavo J M; Torloni, Maria R

    2016-08-17

    An estimated 1% to 3% of all individuals will receive a diagnosis of epilepsy during their lives, which corresponds to approximately 50 million affected people worldwide. The real prevalence is possibly higher because epilepsy is underreported in developing countries. Although most will achieve adequate control of their disease though the use of medication, approximately 25% to 30% of all those with epilepsy are refractory to pharmacological treatment and will continue to have seizures despite the use of two or more agents in adequate dosages. Over the last decade, researchers have tested the use of polyunsaturated fatty acid (PUFA) supplements for the treatment of refractory epilepsy, with inconsistent results. There have also been some concerns about the use of omega-3 PUFA compounds because they reduce platelet aggregation and could, in theory, cause bleeding. To assess the effectiveness and tolerability of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid-EPA and docosahexanoic acid-DHA) in the control of seizures in people with refractory epilepsy. We searched the Cochrane Epilepsy Group Specialised Register (from inception up to November 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, issue 11), MEDLINE (1948 to November 2015), EMBASE (1980 to November 2015), SCOPUS (1823 to November 2015); LILACS (Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde) (1982 to November 2015); ClinicalTrials.gov; World Health Organization (WHO) International Clinical Trials Registry Platform (November 2015). No language restrictions were imposed. We contacted study authors for additional and unpublished information and screened the reference lists of retrieved citations for potentially eligible studies not identified through the electronic search. All randomised and quasi-randomised studies using PUFAs for the treatment of drug-resistant epilepsy. Two review authors were involved in study selection, data extraction

  1. The Impact of the 6:3 Polyunsaturated Fatty Acid Ratio on Intermediate Markers of Breast Cancer

    DTIC Science & Technology

    2007-05-01

    polyunsaturated fatty acids (PtIFAs) have been demonstrated to promote breast tumorigenesis and omega -3 PUFAs have been found to prevent breast cancer, the exact...8 I Introduction Extensive experimental evidence has shown that intake of omega -6 polyunsaturated fatty acids ...activity of the omega -6 fatty acids is abrogated by the competitive inhibition ofomega-3 fatty acids (3, 4). Although the.mechanism Uy wl;ctr the O:3

  2. [The effect of polyunsaturated fatty acids on the biochemical indices of bronchial asthma patients].

    PubMed

    Masuev, K A

    1997-01-01

    A placebo-controlled study was made of the efficacy of diet additive of omega-3 polyunsaturated fatty acids (diet oil eiconol) in 27 patients with bronchial asthma (BA). It was found that eiconol causes qualitative changes in the disease course: severe attacks of asphyxia occurred less frequently, drug doses were reduced. Provocative tests with allergen after two-week intake of eiconol versus placebo intake showed a significant decline of late allergic response due to compitative replacement of arachidonic acid in cell membranes of inflammation cell effectors by omega-3 polyunsaturated fatty acids inhibiting production of lipid mediators of inflammation.

  3. Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study

    USDA-ARS?s Scientific Manuscript database

    In osteoarthritis (OA) the synovium is often inflamed and inflammatory cytokines contribute to cartilage damage. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory effects whereas omega-6 polyunsaturated fatty acids (n-6 PUFAs) have, on balance, proinflammatory effects. The goal ...

  4. Analysis of nutritional habits and intake of polyunsaturated fatty acids in veterans with peripheral arterial disease.

    PubMed

    Nosova, Emily V; Bartel, Kevin; Chong, Karen C; Alley, Hugh F; Conte, Michael S; Owens, Christopher D; Grenon, S Marlene

    2015-10-01

    Inadequate nutrient intake may contribute to the development and progression of peripheral arterial disease (PAD). This study's aim was to assess intake of essential fatty acids and nutrients among veterans with PAD. All 88 subjects had ankle-brachial indices of <0.9 and claudication. A validated food frequency questionnaire evaluated dietary intake, and values were compared to guidelines established by the American Heart Association (AHA) and American College of Cardiology (ACC), as well as the AHA/ACC endorsed Dietary Approaches to Stop Hypertension (DASH) eating plan. The mean age was 69 ± 8 years. Compared to the AHA/ACC guidelines, subjects with PAD had an inadequate intake of long-chain polyunsaturated fatty acids (n-3 PUFA; 59% consumed >1 gram daily). Our subjects with PAD had an increased intake of cholesterol (31% met the cut-off established in the DASH plan), total fat (5%) and sodium (53%). They had an inadequate intake of magnesium (3%), calcium (5%), and soluble fiber (3%). Dietary potassium intake met the recommended guidelines. In our subjects with PAD, intake of critical nutrients deviated substantially from the recommended amounts. Further prospective studies should evaluate whether PAD patients experience clinical benefit if diets are modified to meet the AHA/ACC recommendations. © The Author(s) 2015.

  5. Omega-6 and omega-3 polyunsaturated fatty acids and allergic diseases in infancy and childhood.

    PubMed

    Miles, Elizabeth A; Calder, Philip C

    2014-01-01

    There may be a causal relationship between intake of n-6 polyunsaturated fatty acids (PUFAs) and childhood allergic diseases. This can be explained by plausible biological mechanisms involving eicosanoid mediators produced from the n-6 PUFA arachidonic acid. Long chain n-3 PUFAs are found in fish and fish oils. These fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will lower the risk of developing allergic diseases. In support of this, protective associations have been reported between maternal fish intake during pregnancy and allergic outcomes in infants and children from those pregnancies. However, studies of fish intake during infancy and childhood and allergic outcomes in those infants or children are inconsistent, although some reported a protective association. Supplementing pregnant women with fish oil can induce immunologic changes in cord blood. This supplementation has been reported in some studies to decrease sensitisation to common food allergens and to lower the prevalence and severity of atopic dermatitis in the first year of life. The protective effect of maternal n-3 PUFAs may last until adolescence of the offspring. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, although this benefit may not persist. Whether fish oil is a useful therapy in children with asthma receiving standard therapy is not clear from studies performed to date and this requires further exploration.

  6. Biosynthesis of Polyunsaturated Fatty Acids in the Oleaginous Marine Diatom Fistulifera sp. Strain JPCC DA0580

    PubMed Central

    Liang, Yue; Maeda, Yoshiaki; Sunaga, Yoshihiko; Muto, Masaki; Matsumoto, Mitsufumi; Yoshino, Tomoko; Tanaka, Tsuyoshi

    2013-01-01

    Studies of polyunsaturated fatty acid (PUFA) biosynthesis in microalgae are of great importance for many reasons, including the production of biofuel and variable omega 3-long chain PUFAs. The elucidation of the PUFA biosynthesis pathway is necessary for bioengineering to increase or decrease PUFA content in certain microalgae. In this study, we identified the PUFA synthesis pathway in the oleaginous marine diatom, Fistulifera sp. strain JPCC DA0580, a promising candidate for biodiesel production. The data revealed not only the presence of the desaturases and elongases involved in eicosapentaenoic acid (EPA) synthesis, but also the unexpected localization of ω3-desaturase expression in the chloroplast. This suggests that this microalga might perform the final step of EPA synthesis in the chloroplast and not in the endoplasmic reticulum (ER) like other diatoms. The detailed fatty acid profile suggests that the EPA was synthesized only through the ω6-pathway in this strain, which was also different from other diatoms. Finally, the transcriptome analysis demonstrated an overall down-regulation of desaturases and elongases over incubation time. These genetic features might explain the decrease of PUFA percentage over incubation time in this strain. The important insights into metabolite synthesis acquired here will be useful for future metabolic engineering to control PUFA content in this diatom. PMID:24335525

  7. Thermal properties of encapsulated polyunsaturated fatty acid esters

    USDA-ARS?s Scientific Manuscript database

    Solid lipid particles were prepared to inhibit the degradation of polyunsaturated lipids used in food and feed formulations. Encapsulation with solid lipid particles can provide a physical barrier to limit the mass transfer of prooxidant compounds and by the appropriate selection of lipid particle c...

  8. Long-chain saturated and monounsaturated fatty acids associate with development of premature infants up to 18 months of age.

    PubMed

    Strandvik, Birgitta; Ntoumani, Eleni; Lundqvist-Persson, Cristina; Sabel, Karl-Göran

    2016-04-01

    Myelination is important perinatally and highly dependent on long-chain saturated and monounsaturated fatty acids. Long-chain polyunsaturated fatty acids, nowadays often supplemented, inhibit oleic acid synthesis. Using data from a premature cohort, we studied if nervonic, lignoceric and oleic acids correlated to growth and early development up to 18 months corrected age. Small for gestational age infants had lower concentrations than infants appropriate for gestational age. Only oleic acid was negatively correlated to long-chain polyunsaturated fatty acids. Oleic and lignoceric acids correlated to social interaction at one month, and nervonic acid to mental, psychomotor and behavioral development at 6, 10 and 18 months, also when adjusted for several confounders. Negative association between oleic acid and long-chain polyunsaturated fatty acids suggests inhibition of delta-9 desaturase, and nervonic acid´s divergent correlation to lignoceric and oleic acids suggests different metabolism in neonatal period. Our results may have implications for the supplementation of premature infants.

  9. Longchain polyunsaturated fatty acid supplementation in preterm infants.

    PubMed

    Moon, Kwi; Rao, Shripada C; Schulzke, Sven M; Patole, Sanjay K; Simmer, Karen

    2016-12-20

    Controversy exists over whether longchain polyunsaturated fatty acids (LCPUFA) are essential nutrients for preterm infants because they may not be able to synthesise sufficient amounts of LCPUFA to meet the needs of the developing brain and retina. To assess whether supplementation of formula milk with LCPUFA is safe and of benefit to preterm infants. The main areas of interest were the effects of supplementation on the visual function, development and growth of preterm infants. Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2) in the Cochrane Library (searched 28 February 2016), MEDLINE Ovid (1966 to 28 February 2016), Embase Ovid (1980 to 28 February 2016), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1980 to 28 February 2016), MEDLINE In Process & Other Non-indexed Citations (1966 to 28 February 2016) and by checking reference lists of articles and conference proceedings. We also searched ClinicalTrials.gov (13 April 2016). No language restrictions were applied. All randomised trials evaluating the effect of LCPUFA-supplemented formula in enterally-fed preterm infants (compared with standard formula) on visual development, neurodevelopment and physical growth. Trials reporting only biochemical outcomes were not included. All authors assessed eligibility and trial quality, two authors extracted data separately. Study authors were contacted for additional information. Seventeen trials involving 2260 preterm infants were included in the review. The risk of bias varied across the included trials with 10 studies having low risk of bias in a majority of the domains. The median gestational age (GA) in the included trials was 30 weeks and median birth weight (BW) was 1300 g. The median concentration of docosahexaenoic acid (DHA) was 0.33% (range: 0.15% to 1%) and arachidonic acid (AA) 0.37% (range: 0.02% to 0.84%). Visual acuity Visual acuity over the first year was measured by

  10. The Impact of Polyunsaturated Fatty Acids in Reducing Child Attention Deficit and Hyperactivity Disorders

    ERIC Educational Resources Information Center

    Transler, Catherine; Eilander, Ans; Mitchell, Siobhan; van de Meer, Nelly

    2010-01-01

    Objectives: To review the impact of polyunsaturated fatty acids (PUFA) in reducing ADHD symptoms in children. Methods: Peer-reviewed experimental literature published from 1980 to Mai 2009 is consulted (Psychinfo, Medline, and resulting reference lists). Results: Placebo-controlled studies with ADHD or hyperactive children show no effects on…

  11. Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: Pooling project of 19 cohort studies

    USDA-ARS?s Scientific Manuscript database

    The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. This study sought to evaluate biomarkers of seafood-derived eicosapentaenoic acid ...

  12. Formulation of poultry feed with polyunsaturated fatty acids and natural antioxidants to improve meat quality

    USDA-ARS?s Scientific Manuscript database

    Formulation of poultry feed with polyunsaturated fatty acids and natural antioxidants to improve meat quality Ronald Alan Holser* and Arthur Hinton, Jr Russell Research Center, USDA-ARS, 950 College Station Road, Athens, Georgia, 30605 USA *Corresponding author: Tel. +1 706-546-3361; Fax +1 706-546-...

  13. The Impact of Polyunsaturated Fatty Acids in Reducing Child Attention Deficit and Hyperactivity Disorders

    ERIC Educational Resources Information Center

    Transler, Catherine; Eilander, Ans; Mitchell, Siobhan; van de Meer, Nelly

    2010-01-01

    Objectives: To review the impact of polyunsaturated fatty acids (PUFA) in reducing ADHD symptoms in children. Methods: Peer-reviewed experimental literature published from 1980 to Mai 2009 is consulted (Psychinfo, Medline, and resulting reference lists). Results: Placebo-controlled studies with ADHD or hyperactive children show no effects on…

  14. Dietary Supplementation of Polyunsaturated Fatty Acids in Caenorhabditis elegans

    PubMed Central

    Deline, Marshall L.; Vrablik, Tracy L.; Watts, Jennifer L.

    2013-01-01

    Fatty acids are essential for numerous cellular functions. They serve as efficient energy storage molecules, make up the hydrophobic core of membranes, and participate in various signaling pathways. Caenorhabditis elegans synthesizes all of the enzymes necessary to produce a range of omega-6 and omega-3 fatty acids. This, combined with the simple anatomy and range of available genetic tools, make it an attractive model to study fatty acid function. In order to investigate the genetic pathways that mediate the physiological effects of dietary fatty acids, we have developed a method to supplement the C. elegans diet with unsaturated fatty acids. Supplementation is an effective means to alter the fatty acid composition of worms and can also be used to rescue defects in fatty acid-deficient mutants. Our method uses nematode growth medium agar (NGM) supplemented with fatty acidsodium salts. The fatty acids in the supplemented plates become incorporated into the membranes of the bacterial food source, which is then taken up by the C. elegans that feed on the supplemented bacteria. We also describe a gas chromatography protocol to monitor the changes in fatty acid composition that occur in supplemented worms. This is an efficient way to supplement the diets of both large and small populations of C. elegans, allowing for a range of applications for this method. PMID:24326396

  15. Polyunsaturated fatty acid consumption and concentration among South Indian women during pregnancy.

    PubMed

    Dwarkanath, Pratibha; Muthayya, Sumithra; Thomas, Tinku; Vaz, Mario; Parikh, Panam; Mehra, Ruchika; Kurpad, Anura V

    2009-01-01

    In recent years there is growing interest on the role of long chain omega-3 polyunsaturated fatty acids (omega-3 LC-PUFA) in pregnancy and the growth and development of the offspring. We aim to characterize and provide baseline data on the intake of LCPUFA (omega-3 and omega-6) in a prospective cohort of 829 pregnant Indian women and report associations between LCPUFA intake and erythrocyte membrane phospholipid fatty acid concentration in a sub-group at baseline (1st trimester), the 2nd and 3rd trimesters of pregnancy. The dietary intake of all the macronutrients and of alpha-linolenic acid(ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) significantly increased over the 3 trimesters of pregnancy while that of omega-6 fatty acids (FA) remained unchanged. Median omega-3 FA intakes of ALA, EPA and DHA, however, were on average low at 0.56, 0.003 and 0.011 g/d, respectively while LA was 14.6 g/d during pregnancy. Consequently, the intake ratio of ALA to LA in the women in the present study was very low at 1:26. A significant decline in erythrocyte membrane arachidonic acid (AA) concentration but not of DHA was observed throughout pregnancy. This might be due to increased efficiency in terms of elongation of parent omega-3 FA. Dietary methods for improving the consumption of omega-3 FA need to be considered in the diets of young women as well as during pregnancy. As newborns primarily depend on placental transfer of omega-3 FA there is need to examine the omega-3 LC-PUFA concentration in infants of mother's with low intakes of omega-3 FA.

  16. Effects of n-3 polyunsaturated fatty acids in the fetal pulmonary circulation.

    PubMed

    Houeijeh, Ali; Aubry, Estelle; Coridon, Hélène; Montaigne, Karine; Sfeir, Rony; Deruelle, Philippe; Storme, Laurent

    2011-06-01

    Although evidence exists that n-3 polyunsaturated fatty acids may improve the outcome in patients with severe respiratory failure, little is known regarding their pulmonary circulatory effects. This question is clinically relevant in respiratory failure associated with pulmonary hypertension, in particular in newborn infants with persistent pulmonary hypertension. The objective of this study was to investigate the effects of n-3 polyunsaturated fatty acids on the fetal pulmonary circulation. Randomized, placebo-controlled comparative laboratory investigation. University research facility. Fifty-two chronically prepared lamb fetuses. Catheters and ultrasonic flow transducer were placed through a left thoracotomy in the lamb fetus to determine aortic, pulmonary, and left atrial pressures and left pulmonary artery blood flow. We compared the pulmonary vascular responses to 120 mins of Omegaven (lipid emulsions enriched in n-3 polyunsaturated fatty acids) or Intralipide (lipid emulsions enriched in n-6 polyunsaturated fatty acids) infusion. Then we investigated the effects of Omegaven on the pulmonary circulation after nitric oxide synthase inhibition by L-nitro-arginine, potassium channel blockade by tetraethylammonium, and cytochrome P450 epoxygenase inhibition by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Pulmonary artery and aortic pressures as well as blood gases and plasma lactate concentrations did not change during either fat emulsion infusion. Left pulmonary blood flow increased by 30% and pulmonary vascular resistance decreased by 28% during Omegaven infusion, whereas left pulmonary blood flow and pulmonary vascular resistance did not change during Intralipide infusion. This pulmonary vascular response to Omegaven was not altered by l-nitro-arginine. At the opposite, Omegaven induced pulmonary vasodilatation was abolished by tetraethylammonium and markedly attenuated by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Lipid emulsion containing

  17. Aggressive dogs are characterized by low omega-3 polyunsaturated fatty acid status.

    PubMed

    Re, Simona; Zanoletti, Marco; Emanuele, Enzo

    2008-03-01

    Canine aggressive behaviour is one of the most common problems being reported by dog owners. However, the biochemical basis of this phenomenon remains unclear. In humans, alterations in omega-3 plasma polyunsatured fatty acids and elevated omega6/omega-3 ratio have been linked to behavioural alterations, including aggression. Thus far, however, the relationship between plasma polyunsatured fatty acid status and aggression has not been investigated in the dog. In the present study we sought to investigate whether polyunsatured fatty acid status could be altered in plasma of pathologically aggressive Canis familiaris. Eighteen adult male German Shepherd dogs, aged 4.9 +/- 0.9 years, showing no clinical signs but aggression, were investigated. Eighteen healthy male dogs, aged 4.8 +/- 0.7 years, with a negative history of behavioural and neurological disorders served as controls. Baseline fasting plasma polyunsatured fatty acid composition was determined by gas chromatography. Compared to normal dogs, aggressive dogs showed lower docosahexaenoic acid (22:6 n-3) concentrations and a higher omega6/omega-3 ratio. In addition, they showed reduced cholesterol and bilirubin concentrations compared to their normally behaving counterparts. Altogether, our results suggest that low omega-3 fatty acids may adversely impact behaviour in dogs, resulting in greater propensity to aggression. However, given the cross-sectional design of our study, we cannot claim any causal relationship between the presence of alterations in fatty acid status and canine aggressiveness. Whether omega-3 fatty acids supplementation may be useful to reduce aggressive behaviour in the dog deserves further investigation.

  18. Reduced Triacylglycerol Mobilization during Seed Germination and Early Seedling Growth in Arabidopsis Containing Nutritionally Important Polyunsaturated Fatty Acids

    PubMed Central

    Shrestha, Pushkar; Callahan, Damien L.; Singh, Surinder P.; Petrie, James R.; Zhou, Xue-Rong

    2016-01-01

    There are now several examples of plant species engineered to synthesize and accumulate nutritionally important polyunsaturated fatty acids in their seed triacylglycerols (TAG). The utilization of TAG in germinating seeds of such transgenic plants was unknown. In this study, we examined the TAG utilization efficiency during seed germination in transgenic Arabidopsis seeds containing several examples of these fatty acids. Seed TAG species with native fatty acids had higher utilization rate than the TAG species containing transgenically produced polyunsaturated fatty acids. Conversely, quantification of the fatty acid components remaining in the total TAG after early stages of seed germination revealed that the undigested TAGs tended to contain elevated levels of the engineered polyunsaturated fatty acids (PUFA). LC-MS analysis further revealed asymmetrical mobilization rates for the individual TAG species. TAGs which contained multiple PUFA fatty acids were mobilized slower than the species containing single PUFA. The mobilized engineered fatty acids were used in de novo membrane lipid synthesis during seedling development. PMID:27725822

  19. Gene cloning of an efficiency oleate hydratase from Stenotrophomonas nitritireducens for polyunsaturated fatty acids and its application in the conversion of plant oils to 10-hydroxy fatty acids.

    PubMed

    Kang, Woo-Ri; Seo, Min-Ju; Shin, Kyung-Chul; Park, Jin-Byung; Oh, Deok-Kun

    2017-01-01

    Hydroxy fatty acids are used as precursors of lactones and dicarboxylic acids, as starting materials of polymers, and as additives in coatings and paintings. Stenotrophomonas nitritireducens efficiently converts cis-9 polyunsaturated fatty acids (PUFAs) to 10-hydroxy fatty acids. However, gene encoding enzyme involved in this conversion has not been identified to date. We purified a putative fatty acid double-bond hydratase from S. nitritireducens by ultrafiltration and HiPrep DEAE FF and Resource Q ion exchange chromatographies. Peptide sequences of the purified enzyme were obtained by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis. Sequence of the partial gene encoding this putative fatty acid double-bond hydratase was determined by degenerate polymerase chain reaction (PCR) based on the peptide sequences. The remaining gene sequence was identified by rapid amplification of cDNA ends using cDNA of S. nitritireducens as a template, and the full-length gene was cloned subsequently. The expressed enzyme was identified as an oleate hydratase by determining its kinetic parameters toward unsaturated fatty acids. S. nitritireducens oleate hydratase showed higher activity toward PUFAs compared with other available oleate hydratases. This suggested that the enzyme could be used effectively to convert plant oils to 10-hydroxy fatty acids because these oils contained unsaturated fatty acids such as oleic acid (OA) and linoleic acid (LA) and PUFAs such as α-linolenic acid and/or γ-linolenic acid. The enzyme converted soybean oil and perilla seed oil hydrolyzates containing 10 mM total unsaturated fatty acids, including OA, LA, and ALA, to 8.87 and 8.70 mM total 10-hydroxy fatty acids, respectively, in 240 min. To our knowledge, this is the first study on the biotechnological conversion of PUFA-containing oils to hydroxy fatty acids. Biotechnol. Bioeng. 2017;114: 74-82. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Biophysical and biochemical mechanisms by which dietary N-3 polyunsaturated fatty acids from fish oil disrupt membrane lipid rafts.

    PubMed

    Shaikh, Saame Raza

    2012-02-01

    N-3 polyunsaturated fatty acids (PUFAs) from fish oil exert their functional effects by targeting multiple mechanisms. One mechanism to emerge in the past decade is the ability of n-3 PUFA acyl chains to perturb the molecular organization of plasma membrane sphingolipid/cholesterol-enriched lipid raft domains. These domains are nanometer-scale assemblies that coalesce to compartmentalize select proteins for optimal function. Here we review recent evidence on how n-3 PUFAs modify lipid rafts from biophysical and biochemical experiments from several different model systems. A central theme emerges from these studies. N-3 PUFA acyl chains display tremendous conformational flexibility and a low affinity for cholesterol and saturated acyl chains. This unique flexibility of n-3 PUFA acyl chains impacts the organization of inner and outer leaflet lipid rafts by disrupting acyl chain packing and molecular order within rafts. Ultimately, the disruption in raft organization has consequences for protein clustering and thereby signaling. Overall, elucidating the complex mechanisms by which n-3 PUFA acyl chains reorganize membrane architecture will enhance the translation of these fatty acids into the clinic for treating several diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. A role for AMPK in the inhibition of glucose-6-phosphate dehydrogenase by polyunsaturated fatty acids

    SciTech Connect

    Kohan, Alison B.; Talukdar, Indrani; Walsh, Callee M.; Salati, Lisa M.

    2009-10-09

    Both polyunsaturated fatty acids and AMPK promote energy partitioning away from energy consuming processes, such as fatty acid synthesis, towards energy generating processes, such as {beta}-oxidation. In this report, we demonstrate that arachidonic acid activates AMPK in primary rat hepatocytes, and that this effect is p38 MAPK-dependent. Activation of AMPK mimics the inhibition by arachidonic acid of the insulin-mediated induction of G6PD. Similar to intracellular signaling by arachidonic acid, AMPK decreases insulin signal transduction, increasing Ser{sup 307} phosphorylation of IRS-1 and a subsequent decrease in AKT phosphorylation. Overexpression of dominant-negative AMPK abolishes the effect of arachidonic acid on G6PD expression. These data suggest a role for AMPK in the inhibition of G6PD by polyunsaturated fatty acids.

  2. A ROLE FOR AMPK IN THE INHIBITION OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE BY POLYUNSATURATED FATTY ACIDS

    PubMed Central

    Kohan, Alison B.; Talukdar, Indrani; Walsh, Callee M.; Salati, Lisa M.

    2009-01-01

    Both polyunsaturated fatty acids and AMPK promote energy partitioning away from energy consuming processes, such as fatty acid synthesis, towards energy generating processes, such as β-oxidation. In this report, we demonstrate that arachidonic acid activates AMPK in primary rat hepatocytes, and that this effect is p38 MAPK-dependent. Activation of AMPK mimics the inhibition by arachidonic acid of the insulin-mediated induction of G6PD. Similar to intracellular signaling by arachidonic acid, AMPK decreases insulin signal transduction, increasing Ser307 phosphorylation of IRS-1 and a subsequent decrease in AKT phosphorylation. Overexpression of dominant-negative AMPK abolishes the effect of arachidonic acid on G6PD expression. These data suggest a role for AMPK in the inhibition of G6PD by polyunsaturated fatty acids. PMID:19646964

  3. Biosynthesis of Polyunsaturated Fatty Acids in Marine Invertebrates: Recent Advances in Molecular Mechanisms

    PubMed Central

    Monroig, Óscar; Tocher, Douglas R.; Navarro, Juan C.

    2013-01-01

    Virtually all polyunsaturated fatty acids (PUFA) originate from primary producers but can be modified by bioconversions as they pass up the food chain in a process termed trophic upgrading. Therefore, although the main primary producers of PUFA in the marine environment are microalgae, higher trophic levels have metabolic pathways that can produce novel and unique PUFA. However, little is known about the pathways of PUFA biosynthesis and metabolism in the levels between primary producers and fish that are largely filled by invertebrates. It has become increasingly apparent that, in addition to trophic upgrading, de novo synthesis of PUFA is possible in some lower animals. The unequivocal identification of PUFA biosynthetic pathways in many invertebrates is complicated by the presence of other organisms within them. These organisms include bacteria and algae with PUFA biosynthesis pathways, and range from intestinal flora to symbiotic relationships that can involve PUFA translocation to host organisms. This emphasizes the importance of studying biosynthetic pathways at a molecular level, and the continual expansion of genomic resources and advances in molecular analysis is facilitating this. The present paper highlights recent research into the molecular and biochemical mechanisms of PUFA biosynthesis in marine invertebrates, particularly focusing on cephalopod molluscs. PMID:24152561

  4. Biosynthesis of polyunsaturated fatty acids in marine invertebrates: recent advances in molecular mechanisms.

    PubMed

    Monroig, Óscar; Tocher, Douglas R; Navarro, Juan C

    2013-10-21

    Virtually all polyunsaturated fatty acids (PUFA) originate from primary producers but can be modified by bioconversions as they pass up the food chain in a process termed trophic upgrading. Therefore, although the main primary producers of PUFA in the marine environment are microalgae, higher trophic levels have metabolic pathways that can produce novel and unique PUFA. However, little is known about the pathways of PUFA biosynthesis and metabolism in the levels between primary producers and fish that are largely filled by invertebrates. It has become increasingly apparent that, in addition to trophic upgrading, de novo synthesis of PUFA is possible in some lower animals. The unequivocal identification of PUFA biosynthetic pathways in many invertebrates is complicated by the presence of other organisms within them. These organisms include bacteria and algae with PUFA biosynthesis pathways, and range from intestinal flora to symbiotic relationships that can involve PUFA translocation to host organisms. This emphasizes the importance of studying biosynthetic pathways at a molecular level, and the continual expansion of genomic resources and advances in molecular analysis is facilitating this. The present paper highlights recent research into the molecular and biochemical mechanisms of PUFA biosynthesis in marine invertebrates, particularly focusing on cephalopod molluscs.

  5. n-3 Polyunsaturated fatty acids exert immunomodulatory effects on lymphocytes by targeting plasma membrane molecular organization

    PubMed Central

    Shaikh, Saame Raza; Jolly, Christopher A.; Chapkin, Robert S.

    2011-01-01

    Fish oil, enriched in bioactive n-3 polyunsaturated fatty acids (PUFA), has therapeutic value for the treatment of inflammation-associated disorders. The effects of n-3 PUFAs are pleiotropic and complex; hence, an understanding of their cellular targets and molecular mechanisms of action remains incomplete. Here we focus on recent data indicating n-3 PUFAs exert immunosuppressive effects on the function of effector and regulatory CD4+ T cells. In addition, we also present emerging evidence that n-3 PUFAs have immunomodulatory effects on B cells. We then focus on one multifaceted mechanism of n-3 PUFAs, which is the alteration of the biophysical and biochemical organization of the plasma membrane. This mechanism is central for downstream signaling, eicosanoid production, transcriptional regulation and cytokine secretion. We highlight recent work demonstrating n-3 PUFA acyl chains in the plasma membrane target the lateral organization of membrane signaling assemblies (i.e. lipid rafts or signaling networks) and de novo phospholipid biosynthesis. We conclude by proposing new functional and mechanistic questions in this area of research that will aid in the development of fish oil as adjuvant therapy for treating unresolved chronic inflammation. PMID:22020145

  6. Biosynthesis of isoprenoids, polyunsaturated fatty acids and flavonoids in Saccharomyces cerevisiae

    PubMed Central

    Chemler, Joseph A; Yan, Yajun; Koffas, Mattheos AG

    2006-01-01

    Industrial biotechnology employs the controlled use of microorganisms for the production of synthetic chemicals or simple biomass that can further be used in a diverse array of applications that span the pharmaceutical, chemical and nutraceutical industries. Recent advances in metagenomics and in the incorporation of entire biosynthetic pathways into Saccharomyces cerevisiae have greatly expanded both the fitness and the repertoire of biochemicals that can be synthesized from this popular microorganism. Further, the availability of the S. cerevisiae entire genome sequence allows the application of systems biology approaches for improving its enormous biosynthetic potential. In this review, we will describe some of the efforts on using S. cerevisiae as a cell factory for the biosynthesis of high-value natural products that belong to the families of isoprenoids, flavonoids and long chain polyunsaturated fatty acids. As natural products are increasingly becoming the center of attention of the pharmaceutical and nutraceutical industries, the use of S. cerevisiae for their production is only expected to expand in the future, further allowing the biosynthesis of novel molecular structures with unique properties. PMID:16719921

  7. N-3 polyunsaturated fatty acid DHA during IVM affected oocyte developmental competence in cattle.

    PubMed

    Oseikria, Mouhamad; Elis, Sébastien; Maillard, Virginie; Corbin, Emilie; Uzbekova, Svetlana

    2016-06-01

    The positive effect of n-3 polyunsaturated fatty acids (FAs) on fertility in ruminants seems to be partly mediated through direct effects on the oocyte developmental potential. We aimed to investigate whether supplementation with physiological levels of docosahexaenoic acid (DHA, C22:6 n-3 polyunsaturated fatty acids) during IVM has an effect on oocyte maturation and in vitro embryo development in cattle. We reported that DHA (0, 1, 10, or 100 μM) had no effect on oocyte viability or maturation rate after 22-hour IVM. Incubation of oocyte-cumulus complexes with 1-μM DHA during IVM significantly increased (P < 0.05) oocyte cleavage rate as compared with control (86.1% vs. 78.8%, respectively) and the greater than 4-cell embryo rate at Day 2 after parthenogenetic activation (39.1% vs. 29.7%, respectively). Supplementation with 1 μM DHA during IVM also induced a significant increase in the blastocyst rate at Day 7 after IVF as compared with control (30.6% vs. 17.6%, respectively) and tended to increase the number of cells in the blastocysts (97.1 ± 4.9 vs. 81.2 ± 5.3, respectively; P = 0.08). On the contrary, 10-μM DHA had no effects, whereas 100-μM DHA significantly decreased the cleavage rate compared with control (69.5% vs.78.8%, respectively) and the greater than 4-cell embryo rate at Day 2 after parthenogenetic activation (19.5% vs. 29.7%). As was shown by real-time polymerase chain reaction, negative effects of 100-μM DHA were associated with significant increase of progesterone synthesis by oocyte-cumulus complexes, a three-fold increase in expression level of FA transporter CD36 and a two-fold decrease of FA synthase FASN genes in cumulus cells (CCs) of corresponding oocytes. Docosahexaenoic acid at 1 and 10 μM had no effect on expression of those and other key lipid metabolism-related genes in CC. In conclusion, administration of a low physiological dose of DHA (1 μM) during IVM may have beneficial effects on oocyte developmental

  8. Can long chain n-3 fatty acids from feed be converted into very long chain n-3 fatty acids in fillets from farmed rainbow trout (Oncorhynchus mykiss)?

    NASA Astrophysics Data System (ADS)

    Lušnic Polak, M.; Demšar, L.; Luzar, U.; Polak, T.

    2017-09-01

    The link between the basic chemical and fatty acid composition of trout feed on one hand and trout (Oncorhynchus mykiss) meat (fillet) was investigated.. The content of 52 fatty acids from feed and trout meat lipids was determined by in-situ transesterification and capillary column gas-liquid chromatography. On average, 100 g of trout feed contained 7.4 g of moisture, 47.7 g of proteins, 6.09 g of ash, 21.4 g of fat, and as for fatty acid composition, 47.8 wt. % were monounsaturated, 34.0 wt. % were polyunsaturated and 18.1 wt. % were saturated fatty acids, with the PS ratio 1.88, n-6/n-3 ratio 1.74, 0.80 wt. % of trans and 3.28 wt. % of very long chain n-3 fatty acids. On average, 100 g of trout meat contained 76.1 g of moisture, 21.4 g of proteins, 1.34 g of ash, 2.52 g of fat, and in the fatty acid composition 42.1 wt. % were monounsaturated, 38.2 wt. % were polyunsaturated and 18.9 wt. % were saturated fatty acids, with the PS ratio 2.02, n-6/n-3 ratio 0.98, 0.95 wt. % of trans and 13.25 wt. % of very long chain n-3 fatty acids.

  9. Antarctic microorganisms as source of the omega-3 polyunsaturated fatty acids.

    PubMed

    Bianchi, Ana Clara; Olazábal, Laura; Torre, Alejandra; Loperena, Lyliam

    2014-06-01

    Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are long-chain polyunsaturated fatty acids (PUFAs) that belong to the omega-3 group. They are essential fatty acids found in phospholipid of cell membranes. There is strong evidence that these nutrients may also favorably modulate many diseases. Primary sources of omega-3 PUFAs in the human diet are fish and fish-derived products. The fishing industry worldwide, however, is becoming unable to satisfy the growing demand for these PUFAs. A promising cost-effective alternative source of PUFAs is bacterial production. We identified 40 Antarctic marine bacterial isolates by 16S rRNA gene sequence analysis. Fifteen genera in three phyla were represented in the collection. Isolates were tested for ability to produce EPA using a method in which their ability to reduce 2,3,5-triphenyltetrazolium chloride (TTC) is determined and by gas chromatography coupled to mass spectrometry (GC-MS). All isolates could reduce TTC, and GC-MS analysis showed that four produced EPA and that six produced DHA. We show for the first time that isolates identified as Cellulophaga, Pibocella and Polaribacter can produce EPA and DHA, only DHA or only EPA, respectively. One isolate, Shewanella sp. (strain 8-5), is indicated to be a good candidate for further study to optimize growth and EPA production. In conclusion, a rapid method was tested for identification of new EPA producing strains from marine environments. New EPA and DHA producing strains were found as well as a potentially useful PUFA production strain.

  10. [Protective effect of monounsaturated and polyunsaturated fatty acids on the development of cardiovascular disease].

    PubMed

    Aguilera, C M; Ramírez-Tortosa, M C; Mesa, M D; Gil, A

    2001-01-01

    Cardiovascular disease has a multifactorial aetiology, as is illustrated by the existence of numerous risk indicators, many of which can be influenced by dietary means. In this article, the effects of unsaturated fatty acids on cardiovascular disease are reviewed, with special emphasis on the modifications of the lipoprotein profile and the mechanism by which fatty acids may affect the immune response on the development of the atherosclerotic lesion. Atherosclerosis occurs fundamentally in three stages: dysfunction of the vascular endothelium, fatty streak and fibrous cap formation. Each of the three stages is regulated by the action of vasoactive molecules, growth factors and cytokines, mediators of the immune response. Dietary lipid quality can affect the lipoprotein metabolism, altering their concentrations in the blood, permitting a greater or lesser recruitment of them in the artery wall. The replacement of dietary saturated fat by mono- or polyunsaturated fats significantly lowers the plasma-cholesterol and LDL-cholesterol levels. Likewise, an enriched monounsaturated fatty acid diet prevents LDL oxidative modifications more than an enriched polyunsaturated diet, and the oxidation of LDL in patients with peripheral vascular disease mediated by n-3 fatty acids can be reduced by the simultaneous consumption of olive oil. However, strong controversy surrounds the effect of the different unsaturated fatty acids. The type of dietary fat can directly or indirectly influence some of the mediating factors of the immune response; n-3 fatty acids have powerful antiinflammatory properties. Dietary fatty acids strongly determine the susceptibility of lipoproteins to oxidation, which also has an impact on the activation of molecules of adhesion and other inflammatory factors. Moreover, several works have demonstrated a direct effect of fatty acids on the genetic expression of many of those factors. Finally, certain aspects of blood platelet function, blood coagulability

  11. Five Decades with Polyunsaturated Fatty Acids: Chemical Synthesis, Enzymatic Formation, Lipid Peroxidation and Its Biological Effects

    PubMed Central

    Catalá, Angel

    2013-01-01

    I have been involved in research on polyunsaturated fatty acids since 1964 and this review is intended to cover some of the most important aspects of this work. Polyunsaturated fatty acids have followed me during my whole scientific career and I have published a number of studies concerned with different aspects of them such as chemical synthesis, enzymatic formation, metabolism, transport, physical, chemical, and catalytic properties of a reconstructed desaturase system in liposomes, lipid peroxidation, and their effects. The first project I became involved in was the organic synthesis of [1-14C] eicosa-11,14-dienoic acid, with the aim of demonstrating the participation of that compound as a possible intermediary in the biosynthesis of arachidonic acid “in vivo.” From 1966 to 1982, I was involved in several projects that study the metabolism of polyunsaturated fatty acids. In the eighties, we studied fatty acid binding protein. From 1990 up to now, our laboratory has been interested in the lipid peroxidation of biological membranes from various tissues and different species as well as liposomes prepared with phospholipids rich in PUFAs. We tested the effect of many antioxidants such as alpha tocopherol, vitamin A, melatonin and its structural analogues, and conjugated linoleic acid, among others. PMID:24490074

  12. Dual mechanisms for telomerase inhibition in DLD-1 human colorectal adenocarcinoma cells by polyunsaturated fatty acids.

    PubMed

    Eitsuka, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Teruo

    2004-01-01

    Polyunsaturated fatty acids (PUFAs) have been reported to have antitumor activity. In this study, we have tested whether telomerase might be a target for the antitumor effect of fatty acids using DLD-1 colorectal adenocarcinoma cells. In a cell-free approach, fatty acids were added directly to cell lysates, and we confirmed that increasing fatty acid unsaturation correlates with increased inhibition of telomerase activity. Using a cell culture approach, DLD-1 cells were cultured with fatty acids. In a time and dose dependent manner, EPA and DHA suppressed cellular telomerase activity and the mRNAs encoding hTERT (human telomerase reverse transcriptase) and c-myc. Based on these observations, we suggest that PUFAs inhibit telomerase activity through dual mechanisms: direct inhibition of enzymatic activity and down regulation of hTERT, one of the telomerase components.

  13. Drosophila lacks C20 and C22 polyunsaturated fatty acids

    USDA-ARS?s Scientific Manuscript database

    Drosophila melanogaster has been considered an ideal model organism to investigate human diseases and genetic pathways. Whether Drosophila is an ideal model for nutrigenomics, especially for fatty acid metabolism, however, remains to be illustrated. This study was to examine the metabolism of C20 an...

  14. Acyl chain conformations in phospholipid bilayers: a comparative study of docosahexaenoic acid and saturated fatty acids.

    PubMed

    Feller, Scott E

    2008-05-01

    A variety of experimental methods indicate unique biophysical properties of membranes containing the highly polyunsaturated omega-3 fatty acid, docosahexaenoic acid (DHA). In the following we review the atomically detailed picture of DHA acyl chains structure and dynamics that has emerged from computational studies of this system in our lab. A comprehensive approach, beginning with ab-initio quantum chemical studies of model compounds representing segments of DHA and ending with large scale classical molecular dynamics simulations of DHA-containing bilayers, is described with particular attention paid to contrasting the properties of DHA with those of saturated fatty acids. Connection with experiment is made primarily through comparison with Nuclear Magnetic Resonance (NMR) studies, particularly those that probe details of the chain structure and dynamics. Our computational results suggest that low torsional energy barriers, comparable to kT at physiological conditions, for the rotatable bonds in the DHA chain are the key to the differences observed between polyunsaturated and saturated acyl chains.

  15. Interplay Between Different Polyunsaturated Fatty Acids and Risk of Coronary Heart Disease in Men

    PubMed Central

    Mozaffarian, Dariush; Ascherio, Alberto; Hu, Frank B.; Stampfer, Meir J.; Willett, Walter C.; Siscovick, David S.; Rimm, Eric B.

    2005-01-01

    Background—Consumption of polyunsaturated fatty acids (PUFAs) may reduce coronary heart disease (CHD) risk, but n-6 PUFAs may compete with n-3 PUFA metabolism and attenuate benefits. Additionally, seafood-based, long-chain n-3 PUFAs may modify the effects of plant-based, intermediate-chain n-3 PUFAs. However, the interactions of these PUFAs in relation to CHD risk are not well established. Methods and Results—Among 45 722 men free of known cardiovascular disease in 1986, usual dietary intake was assessed at baseline and every 4 years by using validated food-frequency questionnaires. CHD incidence was prospectively ascertained. Over 14 years of follow-up, participants experienced 218 sudden deaths, 1521 nonfatal myocardial infarctions (MIs), and 2306 total CHD events (combined sudden death, other CHD deaths, and nonfatal MI). In multivariate-adjusted analyses, both long-chain and intermediate-chain n-3 PUFA intakes were associated with lower CHD risk, without modification by n-6 PUFA intake. For example, men with ≥ median long-chain n-3 PUFA intake (≥ 250 mg/d) had a reduced risk of sudden death whether n-6 PUFA intake was below (<11.2 g/d; hazard ratio [HR] = 0.52; 95% confidence interval [CI] = 0.34 to 0.79) or above (≥ 11.2 g/d; HR = 0.60; 95% CI = 0.39 to 0.93) the median compared with men with a < median intake of both. In similar analyses, ≥ median intake of intermediate-chain n-3 PUFAs (≥ 1080 mg/d) was associated with a reduced total CHD risk whether n-6 PUFA intake was lower (HR = 0.88; 95% CI = 0.78 to 0.99) or higher (HR = 0.89; 95% CI = 0.79 to 0.99) compared with a < median intake of both. Intermediate-chain n-3 PUFAs were particularly associated with CHD risk when long-chain n-3 PUFA intake was very low (<100 mg/d); among these men, each 1 g/d of intermediate-chain n-3 PUFA intake was associated with an ≈ 50% lower risk of nonfatal MI (HR = 0.42; 95% CI = 0.23 to 0.75) and total CHD (HR = 0.53; 95% CI = 0.34 to 0.83). Conclusions—n-3

  16. Fatty Acid-Related Phylogeny of Myxobacteria as an Approach to Discover Polyunsaturated Omega-3/6 Fatty Acids ▿ †

    PubMed Central

    Garcia, Ronald; Pistorius, Dominik; Stadler, Marc; Müller, Rolf

    2011-01-01

    In an analysis of 47 aerobic myxobacterial strains, representing 19 genera in suborders Cystobacterineae, Nannocystineae, Sorangiineae, and a novel isolate, “Aetherobacter” SBSr008, an enormously diverse array of fatty acids (FAs) was found. The distribution of straight-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) supports the reported clustering of strains in the phylogenetic tree based on 16S rRNA genes. This finding additionally allows the prediction and assignment of the novel isolate SBSr008 into its corresponding taxon. Sorangiineae predominantly contains larger amounts of SCFA (57 to 84%) than BCFA. On the other hand, Cystobacterineae exhibit significant BCFA content (53 to 90%), with the exception of the genus Stigmatella. In Nannocystineae, the ratio of BCFA and SCFA seems dependent on the taxonomic clade. Myxobacteria could also be identified and classified by using their specific and predominant FAs as biomarkers. Nannocystineae is remarkably unique among the suborders for its absence of hydroxy FAs. After the identification of arachidonic (AA) FA in Phaselicystidaceae, eight additional polyunsaturated fatty acids (PUFAs) belonging to the omega-6 and omega-3 families were discovered. Here we present a comprehensive report of FAs found in aerobic myxobacteria. Gliding bacteria belonging to Flexibacter and Herpetosiphon were chosen for comparative analysis to determine their FA profiles in relation to the myxobacteria. PMID:21317327

  17. Convergent and stereospecific synthesis of complex skipped polyenes and polyunsaturated fatty acids.

    PubMed

    Macklin, Todd K; Micalizio, Glenn C

    2010-08-01

    Skipped polyenes (that is, 1,4-dienes and higher homologues) are stereodefined components of a vast array of biologically important natural products, including polyunsaturated fatty acids. Although widespread in nature, these architectures are generally considered to represent significant barriers to efficient chemical synthesis. Partial reduction of skipped poly-ynes provides a pathway to a subset of such structures, but general chemical methods for the preparation of skipped polyenes that contain varied stereochemistries and substitution patterns are lacking. Here, we describe a metal-promoted reductive cross-coupling reaction between vinylcyclopropanes and alkynes (or vinylsilanes) that provides stereoselective access to a diverse array of skipped polyenes through a process that establishes one C-C bond, generates up to three stereodefined alkenes, and can be used to introduce stereogenic centres at the central positions of the skipped polyene motif. We also demonstrate the significance of the present bond construction by preparing substituted and stereodefined polyunsaturated synthetic fatty acids.

  18. Effect of polyunsaturated fatty acids and phospholipids on ( sup 3 H)-vitamin E incorporation into pulmonary artery endothelial cell membranes

    SciTech Connect

    Sekharam, K.M.; Patel, J.M.; Block, E.R. )

    1990-12-01

    Vitamin E, a dietary antioxidant, is presumed to be incorporated into the lipid bilayer of biological membranes to an extent proportional to the amount of polyunsaturated fatty acids or phospholipids in the membrane. In the present study we evaluated the distribution of incorporated polyunsaturated fatty acids (PUFA) and phosphatidylethanolamine (PE) in various membranes of pulmonary artery endothelial cells. We also studied whether incorporation of PUFA or PE is responsible for increased incorporation of (3H)-vitamin E into the membranes of these cells. Following a 24-hr incubation with linoleic acid (18:2), 18:2 was increased by 6.9-, 9.2-, and 13.2-fold in plasma, mitochondrial, and microsomal membranes, respectively. Incorporation of 18:2 caused significant increases in the unsaturation indexes of mitochondrial and microsomal polyunsaturated fatty acyl chains (P less than .01 versus control in both membranes). Incubation with arachidonic acid (20:4) for 24 hr resulted in 1.5-, 2.3-, and 2.4-fold increases in 20:4 in plasma, mitochondrial, and microsomal membranes, respectively. The unsaturation indexes of polyunsaturated fatty acyl chains of mitochondrial and microsomal membranes also increased (P less than .01 versus control in both membranes). Although incubations with 18:2 or 20:4 resulted in several-fold increases in membrane 18:2 or 20:4 fatty acids, incorporation of (3H)-vitamin E into these membranes was similar to that in controls. Following a 24-hr incubation with PE, membrane PE content was significantly increased, and (3H)-vitamin E incorporation was also increased to a comparable degree, i.e., plasma membrane greater than mitochondria greater than microsomes. Endogenous vitamin E content of the cells was not altered because of increased incorporation of PE and (3H)-vitamin E.

  19. Pathways of Polyunsaturated Fatty Acid Utilization: Implications for Brain Function in Neuropsychiatric Health and Disease

    PubMed Central

    Liu, Joanne J.; Green, Pnina; Mann, J. John; Rapoport, Stanley I.; Sublette, M. Elizabeth

    2014-01-01

    Essential polyunsaturated fatty acids (PUFAs) have profound effects on brain development and function. Abnormalities of PUFA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimer’s disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUFA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUFA utilization, highlighting their relevance to neuropsychiatric disease. PMID:25498862

  20. beta-Hematin (hemozoin) mediated decompostion of polyunsaturated fatty acids to 4-hydroxy-2-nonenal.

    PubMed

    Miller, Crystal M; Carney, Clare Kenny; Schrimpe, Alexandra C; Wright, David W

    2005-04-04

    beta-Hematin is an important heme metabolite of malarial infection. Its role as an agent mediating the formation of the reactive electrophile 4-hydroxynonenal (HNE) from polyunsaturated fatty acids was investigated. In vitro formation of HNE was found to be facilitated by the presence of hemozoin in a concentration-dependent fashion. The reactivity of HNE derived from reaction with beta-hematin was confirmed through its ability to form protein adducts on myoglobin.

  1. Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer.

    PubMed

    El-Ashmawy, Nahla E; Khedr, Eman G; El-Bahrawy, Hoda A; Al-Tantawy, Samar M

    2017-02-01

    Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid: 2:3 w/w; 1200 mg/kg) and/or atorvastatin (6 mg/kg) were given orally daily to rats for eight consecutive weeks concomitantly with N-butyl-N-(4-hydroxybutyl)nitrosamine and continued for further 4 weeks after cessation of N-butyl-N-(4-hydroxybutyl)nitrosamine administration. The histopathological examination of rat bladder revealed the presence of tumors and the absence of apoptotic bodies in sections from N-butyl-N-(4-hydroxybutyl)nitrosamine group, while tumors were absent and apoptotic bodies were clearly observed in sections from rat groups treated with omega-3 polyunsaturated fatty acids, atorvastatin, or both drugs. The study of the molecular mechanisms illustrated downregulation of COX-2 and P53 (mutant) genes and suppression of transforming growth factor beta-1 and the lipid peroxidation product malondialdehyde in serum of rats of the three treated groups. This chemopreventive effect was confirmed by and associated with lower level of bladder tumor antigen in urine. However, the combined treatment with both drugs exhibited the major protective effect and nearly corrected the dyslipidemia that has been induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Collectively, omega-3 polyunsaturated fatty acids and atorvastatin, besides having anti-inflammatory properties, proved a chemopreventive effect against bladder cancer, which nominates them to be used as

  2. Depression and adipose polyunsaturated fatty acids in the survivors of the Seven Countries Study population of Crete.

    PubMed

    Mamalakis, George; Kiriakakis, Michael; Tsibinos, George; Kafatos, Anthony

    2004-06-01

    The purpose of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake and depression. The sample consisted of 150 elderly males from the island of Crete. The subjects were survivors of the Greek Seven Countries Study group. The mean age was 84 years. The number of subjects with complete data on all variables studied was 63. Subjects were examined by the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the short form of the Geriatric Depression Scale (GDS-15). Depression correlated negatively with adipose tissue alpha-linolenic acid (C18:3n-3). Depressed subjects had significantly reduced (-10.5%) adipose tissue C18:3n-3 levels than non-depressed subjects. The observed negative relation between adipose tissue C18:3n-3 and depression, in the present study, appears to indicate increasing long-term dietary C18:3n-3 intakes with decreasing depression. This agrees with findings of other studies indicating an inverse relation between depression and consumption of fish and n-3 polyunsaturated fatty acids. This is the first literature report of a relation between adipose tissue C18:3n-3 and depression. Furthermore, this is the first report of a relation between adipose PUFA and depression in an elderly sample. Depression has been reported to be associated with elevated cytokines, such as, IL-1, IL-2, IL-6, INF-gamma and INF-alpha. Fish oil and omega-3 fatty acids, on the other hand, have been reported to inhibit cytokine production. The observed negative relation between adipose C18:3n-3 and depression, therefore, may stem from the inhibiting effect of C18:3n-3 or its long-chain metabolites on cytokine synthesis.

  3. Effect of Sargassum thunbergii on ROS mediated oxidative damage and identification of polyunsaturated fatty acid components.

    PubMed

    Kim, Jung-Ae; Kong, Chang-Suk; Kim, Se-Kwon

    2010-05-01

    In this study, we examined protective effect of Sargassum thunbergii on reactive oxygen species (ROS) mediated oxidative stress in cellular systems. In addition, polyunsaturated fatty acids from S. thunbergii were identified and quantified by gas chromatography mass spectroscopy. Intracellular ROS levels were measured using a oxidation sensitive dye, 2',7'-dichlorofluorescein diacetate (DCFH-DA). Treatment with S. thunbergii significantly reduced intracellular ROS mediated cell damage and inhibited myeloperoxidase (MPO) activity assessed in tumor necrosis factor-alpha (TNF-alpha) stimulated human monocytic leukemia in a concentration-dependent manner. Moreover, antioxidative mechanisms by S. thunbergii were evaluated by measuring the expression levels of antioxidative enzymes such as superoxide dismutase (SOD-1), catalase, glutathione peroxidase and glutathione reductase. SOD-1 and glutathione reductase were up-regulated by S. thunbergii. Furthermore, S. thunbergii contains polyunsaturated fatty acids such as arachidonic acid, arachidic acid, palmitic acid, elaidic acid, linoleic acid, stearic acid and cis-5,8,11,14,17-eicosanoic acid. Therefore, these results suggested that S. thunbergii has nutraceutical effectiveness in prevention of ROS-induced tissue damage and potential natural antioxidant related to oxidative stress, which can be traceable to polyunsaturated fatty acids contained in S. thunbergii.

  4. Dietary Polyunsaturated Fatty Acids and Inflammation: The Role of Phospholipid Biosynthesis

    PubMed Central

    Raphael, William; Sordillo, Lorraine M.

    2013-01-01

    The composition of fatty acids in the diets of both human and domestic animal species can regulate inflammation through the biosynthesis of potent lipid mediators. The substrates for lipid mediator biosynthesis are derived primarily from membrane phospholipids and reflect dietary fatty acid intake. Inflammation can be exacerbated with intake of certain dietary fatty acids, such as some ω-6 polyunsaturated fatty acids (PUFA), and subsequent incorporation into membrane phospholipids. Inflammation, however, can be resolved with ingestion of other fatty acids, such as ω-3 PUFA. The influence of dietary PUFA on phospholipid composition is influenced by factors that control phospholipid biosynthesis within cellular membranes, such as preferential incorporation of some fatty acids, competition between newly ingested PUFA and fatty acids released from stores such as adipose, and the impacts of carbohydrate metabolism and physiological state. The objective of this review is to explain these factors as potential obstacles to manipulating PUFA composition of tissue phospholipids by specific dietary fatty acids. A better understanding of the factors that influence how dietary fatty acids can be incorporated into phospholipids may lead to nutritional intervention strategies that optimize health. PMID:24152446

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

    PubMed

    Gibson, R A; Neumann, M A; Lien, E L; Boyd, K A; Tu, W C

    2013-01-01

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

  6. Comprehensive analysis of phospholipids in the brain, heart, kidney, and liver: brain phospholipids are least enriched with polyunsaturated fatty acids.

    PubMed

    Choi, Jaewoo; Yin, Tai; Shinozaki, Koichiro; Lampe, Joshua W; Stevens, Jan F; Becker, Lance B; Kim, Junhwan

    2017-10-09

    It is commonly accepted that brain phospholipids are highly enriched with long-chain polyunsaturated fatty acids (PUFAs). However, the evidence for this remains unclear. We used HPLC-MS to analyze the content and composition of phospholipids in rat brain and compared it to the heart, kidney, and liver. Phospholipids typically contain one PUFA, such as 18:2, 20:4, or 22:6, and one saturated fatty acid, such as 16:0 or 18:0. However, we found that brain phospholipids containing monounsaturated fatty acids in the place of PUFAs are highly elevated compared to phospholipids in the heart, kidney, and liver. The relative content of phospholipid containing PUFAs is ~ 60% in the brain, whereas it is over 90% in other tissues. The most abundant species of phosphatidylcholine (PC) is PC(16:0/18:1) in the brain, whereas PC(18:0/20:4) and PC(16:0/20:4) are predominated in other tissues. Moreover, several major species of plasmanyl and plasmenyl phosphatidylethanolamine are found to contain monounsaturated fatty acid in the brain only. Overall, our data clearly show that brain phospholipids are the least enriched with PUFAs of the four major organs, challenging the common belief that the brain is highly enriched with PUFAs.

  7. Improvement of Polyunsaturated Fatty Acid Production in Echium acanthocarpum Transformed Hairy Root Cultures by Application of Different Abiotic Stress Conditions

    PubMed Central

    Zárate, Rafael; Cequier-Sánchez, Elena; Rodríguez, Covadonga; Dorta-Guerra, Roberto; El Jaber-Vazdekis, Nabil; Ravelo, Ángel G.

    2013-01-01

    Fatty acids are of great nutritional, therapeutic, and physiological importance, especially the polyunsaturated n-3 fatty acids, possessing larger carbon chains and abundant double bonds or their immediate precursors. A few higher plant species are able to accumulate these compounds, like those belonging to the Echium genus. Here, the novel E. acanthocarpum hairy root system, which is able to accumulate many fatty acids, including stearidonic and α-linolenic acids, was optimized for a better production. The application of abiotic stress resulted in larger yields of stearidonic and α-linolenic acids, 60 and 35%, respectively, with a decrease in linoleic acid, when grown in a nutrient medium consisting of B5 basal salts, sucrose or glucose, and, more importantly, at a temperature of 15°C. The application of osmotic stress employing sorbitol showed no positive influence on the fatty acid yields; furthermore, the combination of a lower culture temperature and glucose did not show a cumulative boosting effect on the yield, although this carbon source was similarly attractive. The abiotic stress also influenced the lipid profile of the cultures, significantly increasing the phosphatidylglycerol fraction but not the total lipid neither their biomass, proving the appropriateness of applying various abiotic stress in this culture to achieve larger yields. PMID:25937970

  8. Inhibition of protein palmitoylation, raft localization, and T cell signaling by 2-bromopalmitate and polyunsaturated fatty acids.

    PubMed

    Webb, Y; Hermida-Matsumoto, L; Resh, M D

    2000-01-07

    The ability of the Src family kinases Fyn and Lck to participate in signaling through the T cell receptor is critically dependent on their dual fatty acylation with myristate and palmitate. Here we identify a palmitate analog, 2-bromopalmitate, that effectively blocks Fyn fatty acylation in general and palmitoylation in particular. Treatment of COS-1 cells with 2-bromopalmitate blocked myristoylation and palmitoylation of Fyn and inhibited membrane binding and localization of Fyn to detergent-resistant membranes (DRMs). In Jurkat T cells, 2-bromopalmitate blocked localization of the endogenous palmitoylated proteins Fyn, Lck, and LAT to DRMs. This resulted in impaired signaling through the T cell receptor as evidenced by reductions in tyrosine phosphorylation, calcium release, and activation of mitogen-activated protein kinase. We also examined the ability of long chain polyunsaturated fatty acids (PUFAs) to inhibit protein fatty acylation. PUFAs have been reported to inhibit T cell signaling by excluding Src family kinases from DRMs. Here we show that the PUFAs arachidonic acid and eicosapentaenoic acid inhibit Fyn palmitoylation and consequently block Fyn localization to DRMs. We propose that inhibition of protein palmitoylation represents a novel mechanism by which PUFAs exert their immunosuppressive effects.

  9. The cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans.

    PubMed

    Zhang, Yuru; Wang, Haizhen; Zhang, Jingjing; Hu, Ying; Zhang, Linqiang; Wu, Xiaoyun; Su, Xiong; Li, Tingting; Zou, Xiaoju; Liang, Bin

    2016-04-01

    Polyunsaturated fatty acids (PUFAs) are fatty acids with backbones containing more than one double bond, which are introduced by a series of desaturases that insert double bonds at specific carbon atoms in the fatty acid chain. It has been established that desaturases need flavoprotein-NADH-dependent cytochrome b5 reductase (simplified as cytochrome b5 reductase) and cytochrome b5 to pass through electrons for activation. However, it has remained unclear how this multi-enzyme system works for distinct desaturases. The model organism Caenorhabditis elegans contains seven desaturases (FAT-1, -2, -3, -4, -5, -6, -7) for the biosynthesis of PUFAS, providing an excellent model in which to characterize different desaturation reactions. Here, we show that RNAi inactivation of predicted cytochrome b5 reductases hpo-19 and T05H4.4 led to increased levels of C18:1n-9 but decreased levels of PUFAs, small lipid droplets, decreased fat accumulation, reduced brood size and impaired development. Dietary supplementation with different fatty acids showed that HPO-19 and T05H4.4 likely affect the activity of FAT-1, FAT-2, FAT-3, and FAT-4 desaturases, suggesting that these four desaturases use the same cytochrome b5 reductase to function. Collectively, these findings indicate that cytochrome b5 reductase HPO-19/T05H4.4 is required for desaturation to biosynthesize PUFAs in C. elegans. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. 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).

  11. Exogenous polyunsaturated fatty acids (PUFAs) impact membrane remodeling and affect virulence phenotypes among pathogenic Vibrio species.

    PubMed

    Moravec, Anna R; Siv, Andrew W; Hobby, Chelsea R; Lindsay, Emily N; Norbash, Layla V; Shults, Daniel J; Symes, Steven J K; Giles, David K

    2017-09-01

    The pathogenic Vibrio species (cholerae, parahaemolyticus and vulnificus) represent a constant threat to human health, causing food-borne and skin wound infections as a result of ingestion or exposure to contaminated water and seafood. Recent studies have highlighted Vibrio's ability to acquire fatty acids from environmental sources and assimilate them into cell membranes. The possession and conservation of such machinery provokes consideration of fatty acids as important factors in the pathogenic lifestyle of Vibrio species. The findings herein link exogenous fatty acid exposure to changes in bacterial membrane phospholipid structure, permeability, phenotypes associated with virulence and consequent stress responses that may impact survival and persistence of pathogenic Vibrio species. Polyunsaturated fatty acids (PUFAs) (ranging in carbon length and unsaturation) supplied in growth medium were assimilated into bacterial phospholipids, as determined by thin-layer chromatography and liquid chromatography-mass spectrometry. The incorporation of fatty acids variably affected membrane permeability as judged by uptake of the hydrophobic compound crystal violet. For each species, certain fatty acids were identified as affecting resistance to antimicrobial peptide treatment. Significant fluctuations were observed with regard to both motility and biofilm formation following growth in the presence of individual PUFAs. Our results illustrate the important and complex roles of exogenous fatty acids in the membrane physiology and virulence of a bacterial genus that inhabits aquatic and host environments containing an abundance of diverse fatty acids.Importance Bacterial responses to fatty acids include, but are not limited to, degradation for metabolic gain, modification of membrane lipids, alteration of protein function and regulation of gene expression. Vibrio species exhibit significant diversity with regard to the machinery known to participate in the uptake and

  12. n-3 polyunsaturated fatty acids: the potential role for supplementation in cancer.

    PubMed

    Murphy, Rachel A; Mourtzakis, Marina; Mazurak, Vera C

    2012-05-01

    n-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid have been implicated as potential mediators in pathways involved in cancer cachexia. This review summarizes recent findings on the n-3 fatty acid status of patients with cancer, the effects of n-3 fatty acid supplementation on weight and lean body mass and the potential role of supplementation during antineoplastic therapy. Due to suboptimal intakes and possible metabolic disturbances, physiological concentrations of n-3 fatty acids are low in patients with cancer. Low n-3 fatty acids are associated with loss of skeletal muscle, suggesting a need for supplementation. Recent trials have shown an effect of n-3 supplementation throughout antineoplastic therapy on weight, lean body mass and treatment outcomes. Attenuation or gain of weight and lean body mass was reported and the first clinical trials of n-3 fatty acids as an adjuvant to chemotherapy treatment suggest improved efficacy and milder treatment toxicity with n-3 fatty acid supplementation. Recent evidence appears to favour providing n-3 fatty acids early in the disease trajectory, during antineoplastic therapy for preservation of muscle and also to improve treatment tolerance. Additional, larger trials are needed to define these relationships further but it appears that fish oil has broad therapeutic potential in patients with cancer.

  13. Fish and n-3 polyunsaturated fatty acid intake and depressive symptoms: Ryukyus Child Health Study.

    PubMed

    Murakami, Kentaro; Miyake, Yoshihiro; Sasaki, Satoshi; Tanaka, Keiko; Arakawa, Masashi

    2010-09-01

    Epidemiologic evidence on the role of fish and long-chain n-3 polyunsaturated fatty acid intake on depression during adolescence is sparse. We examined the association between fish, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) intake and depressive symptoms in a group of adolescents. This cross-sectional study, conducted in all public junior high schools in Naha City and Nago City, Okinawa, Japan, included 3067 boys and 3450 girls aged 12 to 15 years (52.3% of the eligible sample). Dietary intake was assessed by using a validated, self-administered diet-history questionnaire. Depressive symptoms were defined as present when participants had a Center for Epidemiologic Studies Depression scale score of >or=16. The prevalence of depressive symptoms was 22.5% for boys and 31.2% for girls. For boys, fish intake was inversely associated with depressive symptoms (adjusted odds ratio [OR] for depressive symptoms in the highest [compared with the lowest] quintile of intake: 0.73 [95% confidence interval (CI): 0.55-0.97]; P for trend=.04). EPA intake showed an inverse association with depressive symptoms (OR: 0.71 [95% CI: 0.54-0.94]; P=.04). DHA intake also showed a similar inverse, albeit nonsignificant, association (OR: 0.79 [95% CI: 0.59-1.05]; P=.11). In addition, intake of EPA plus DHA was inversely associated with depressive symptoms (OR: 0.72 [95% CI: 0.55-0.96]; P=.08). Conversely, no such associations were observed among girls. Higher intake of fish, EPA, and DHA was independently associated with a lower prevalence of depressive symptoms in early male, but not female, adolescents.

  14. Dietary n-3 polyunsaturated fatty acid intake and risk of amyotrophic lateral sclerosis

    PubMed Central

    Fitzgerald, Kathryn C.; O’Reilly, Éilis J.; Falcone, Guido J.; McCullough, Marjorie L.; Park, Yikyung; Kolonel, Laurence N.; Ascherio, Alberto

    2014-01-01

    Importance Amyotrophic lateral sclerosis (ALS) is a severe progressive disease that cannot be prevented or cured. Diet-derived long chain polyunsaturated fatty acids (PUFA) are incorporated in brain lipids and modulate oxidative and inflammatory processes, and could thus affect ALS risk and progression. Objective To examine the association between n-6 and n-3 PUFA consumption and ALS risk. Design, setting, and participants Longitudinal analyses based on 1,002,082 participants (479,114 women; 522,968 men) in five prospective cohorts: the National Institutes of Health-AARP Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Health Professionals Follow-up Study, the Multiethnic Cohort Study, and the Nurses’ Health Study. Diet was assessed via food frequency questionnaire developed or modified for each cohort. Participants were categorized into cohort-specific quintiles of intake of energy-adjusted dietary variables. Main outcomes and measures Cohort-specific multivariable-adjusted risk ratios (RR) of ALS incidence or death estimated by Cox proportional hazards regression and pooled using random-effects methods. Results A total of 995 ALS cases were documented during the follow-up. A greater n-3 PUFA intake was associated with a reduced risk of ALS – the pooled, multivariable-adjusted RR for the highest to the lowest quintile was 0.66 (95% CI: 0.53–0.81; P trend<0.001). Consumption of both α-linolenic acid (RR = 0.73; 95% CI: 0.59 to 0.89; P trend=0.003) and marine n-3 PUFAs (RR=0.84; 95% CI: 0.65–1.08, P trend=0.03) contributed to this inverse association. Intakes of n-6 PUFA were not associated with ALS risk. Conclusion and relevance Consumption of foods high in n-3 PUFAs may help prevent or delay onset of ALS. PMID:25023276

  15. Isotope-reinforced polyunsaturated fatty acids protect mitochondria from oxidative stress.

    PubMed

    Andreyev, Alexander Y; Tsui, Hui S; Milne, Ginger L; Shmanai, Vadim V; Bekish, Andrei V; Fomich, Maksim A; Pham, Minhhan N; Nong, Yvonne; Murphy, Anne N; Clarke, Catherine F; Shchepinov, Mikhail S

    2015-05-01

    Polyunsaturated fatty acid (PUFA) peroxidation is initiated by hydrogen atom abstraction at bis-allylic sites and sets in motion a chain reaction that generates multiple toxic products associated with numerous disorders. Replacement of bis-allylic hydrogens of PUFAs with deuterium atoms (D-PUFAs), termed site-specific isotope reinforcement, inhibits PUFA peroxidation and confers cell protection against oxidative stress. We demonstrate that structurally diverse deuterated PUFAs similarly protect against oxidative stress-induced injury in both yeast and mammalian (myoblast H9C2) cells. Cell protection occurs specifically at the lipid peroxidation step, as the formation of isoprostanes, immediate products of lipid peroxidation, is drastically suppressed by D-PUFAs. Mitochondrial bioenergetics function is a likely downstream target of oxidative stress and a subject of protection by D-PUFAs. Pretreatment of cells with D-PUFAs is shown to prevent inhibition of maximal uncoupler-stimulated respiration as well as increased mitochondrial uncoupling, in response to oxidative stress induced by agents with diverse mechanisms of action, including t-butylhydroperoxide, ethacrynic acid, or ferrous iron. Analysis of structure-activity relationships of PUFAs harboring deuterium at distinct sites suggests that there may be a mechanism supplementary to the kinetic isotope effect of deuterium abstraction off the bis-allylic sites that accounts for the protection rendered by deuteration of PUFAs. Paradoxically, PUFAs with partially deuterated bis-allylic positions that retain vulnerable hydrogen atoms (e.g., monodeuterated 11-D1-Lin) protect in a manner similar to that of PUFAs with completely deuterated bis-allylic positions (e.g., 11,11-D2-Lin). Moreover, inclusion of just a fraction of deuterated PUFAs (20-50%) in the total pool of PUFAs preserves mitochondrial respiratory function and confers cell protection. The results indicate that the therapeutic potential of D-PUFAs may derive

  16. DNA Methylation Perturbations in Genes Involved in Polyunsaturated Fatty Acid Biosynthesis Associated with Depression and Suicide Risk

    PubMed Central

    Haghighi, Fatemeh; Galfalvy, Hanga; Chen, Sean; Huang, Yung-yu; Cooper, Thomas B.; Burke, Ainsley K.; Oquendo, Maria A.; Mann, J. John; Sublette, M. Elizabeth

    2015-01-01

    Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention. PMID:25972837

  17. The increase of cell-membranous phosphatidylcholines containing polyunsaturated fatty acid residues induces phosphorylation of p53 through activation of ATR

    PubMed Central

    Zhang, Xu Hannah; Zhao, Chunying; Ma, Zhongmin Alex

    2010-01-01

    Summary The G1 phase of the cell cycle is marked by the rapid turnover of phospholipids. This turnover is regulated by CTP:phosphocholine-cytidylyltransferase (CCT) and group VIA Ca2+-independent-phospholipase A2 (iPLA2). We previously reported that inhibition of iPLA2 arrests cells in G1 phase of the cell cycle by activating the p53-p21 checkpoint. Here we further characterize the mechanism of p53 activation. We show that specific inhibition of iPLA2 induces a time dependent phosphorylation of Ser15 in p53 in the absence of DNA damage. This phosphorylation requires the kinase ataxia-telangiectasia and Rad-3-related (ATR) but not the ataxia-telangiectasia-mutated (ATM) kinase. Moreover, we identify in cell membranes a significant increase of phosphatidylcholines (PCs) containing chains of polyunsaturated fatty acids and a decrease of PCs containing saturated fatty acids in response to inhibition of iPLA2. The time course of phosphorylation of Ser15 in p53 correlates with increasing levels of PCs containing polyunsaturated fatty acids. We further demonstrate that the PCs with linoleic acid in their sn-2 position (18:2n6) induce phosphorylation of Ser15 in p53 in an ATR-dependent manner. Our findings establish that cells can regulate the levels of polyunsaturated fatty acids in phospholipids through iPLA2-mediated deacylation of PCs. Disruption of this regulation increases the proportions of PCs containing polyunsaturated fatty acids and activates the ATR-p53 signalling pathway. PMID:18032786

  18. The increase of cell-membranous phosphatidylcholines containing polyunsaturated fatty acid residues induces phosphorylation of p53 through activation of ATR.

    PubMed

    Zhang, Xu Hannah; Zhao, Chunying; Ma, Zhongmin Alex

    2007-12-01

    The G1 phase of the cell cycle is marked by the rapid turnover of phospholipids. This turnover is regulated by CTP:phosphocholine-cytidylyltransferase (CCT) and group VIA Ca(2+)-independent-phospholipase A(2) (iPLA(2)). We previously reported that inhibition of iPLA(2) arrests cells in G1 phase of the cell cycle by activating the p53-p21 checkpoint. Here we further characterize the mechanism of p53 activation. We show that specific inhibition of iPLA(2) induces a time dependent phosphorylation of Ser15 in p53 in the absence of DNA damage. This phosphorylation requires the kinase ataxia-telangiectasia and Rad-3-related (ATR) but not the ataxia-telangiectasia-mutated (ATM) kinase. Moreover, we identify in cell membranes a significant increase of phosphatidylcholines (PCs) containing chains of polyunsaturated fatty acids and a decrease of PCs containing saturated fatty acids in response to inhibition of iPLA(2). The time course of phosphorylation of Ser15 in p53 correlates with increasing levels of PCs containing polyunsaturated fatty acids. We further demonstrate that the PCs with linoleic acid in their sn-2 position (18:2n6) induce phosphorylation of Ser15 in p53 in an ATR-dependent manner. Our findings establish that cells can regulate the levels of polyunsaturated fatty acids in phospholipids through iPLA(2)-mediated deacylation of PCs. Disruption of this regulation increases the proportions of PCs containing polyunsaturated fatty acids and activates the ATR-p53 signalling pathway.

  19. Polyunsaturated fatty acids influence differential biosynthesis of oxylipids and other lipid mediators during bovine coliform mastitis.

    PubMed

    Mavangira, Vengai; Gandy, Jeffery C; Zhang, Chen; Ryman, Valerie E; Daniel Jones, A; Sordillo, Lorraine M

    2015-09-01

    Coliform mastitis is a severe and sometimes fatal disease characterized by an unregulated inflammatory response. The initiation, progression, and resolution of inflammatory responses are regulated, in part, by potent oxylipid metabolites derived from polyunsaturated fatty acids. The purpose of this study was to characterize the biosynthesis and diversity of oxylipid metabolites during acute bovine coliform mastitis. Eleven cows diagnosed with naturally occurring acute systemic coliform mastitis and 13 healthy control cows, matched for lactation number and days in milk, were selected for comparison of oxylipid and free fatty acid concentrations in both milk and plasma. Oxylipids and free fatty acids were quantified using liquid chromatography-tandem mass spectrometry. All polyunsaturated fatty acids quantified in milk were elevated during coliform mastitis with linoleic acid being the most abundant. Oxylipids synthesized through the lipoxygenase and cytochrome P450 pathways accounted for the majority of the oxylipid biosynthesis. This study demonstrated a complex and diverse oxylipid network, most pronounced at the level of the mammary gland. Substrate availability, biosynthetic pathways, and degree of metabolism influence the biosynthesis of oxylipids during bovine coliform mastitis. Further studies are required to identify targets for novel interventions that modulate oxylipid biosynthesis during coliform mastitis to optimize inflammation. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. The influence of dietary docosahexaenoic acid and arachidonic acid on central nervous system polyunsaturated fatty acid composition.

    PubMed

    Brenna, J Thomas; Diau, Guan-Yeu

    2007-01-01

    Numerous studies on perinatal long-chain polyunsaturated fatty acid nutrition have clarified the influence of dietary docosahexaenoic acid (DHA) and arachidonic acid (ARA) on central nervous system PUFA concentrations. In humans, omnivorous primates, and piglets, DHA and ARA plasma and red blood cells concentrations rise with dietary preformed DHA and ARA. Brain and retina DHA are responsive to diet while ARA is not. DHA is at highest concentration in cells and tissues associated with high energy consumption, consistent with high DHA levels in mitochondria and synaptosomes. DHA is a substrate for docosanoids, signaling compounds of intense current interest. The high concentration in tissues with high rates of oxidative metabolism may be explained by a critical role related to oxidative metabolism.

  1. The Influence of Dietary Docosahexaenoic Acid and Arachidonic Acid on Central Nervous System Polyunsaturated Fatty Acid Composition

    PubMed Central

    Brenna, J. Thomas; Diau, Guan-Yeu

    2007-01-01

    Numerous studies on perinatal long chain polyunsaturated fatty acid nutrition have clarified the influence of dietary docosahexaenoic acid (DHA) and arachidonic acid (ARA) on central nervous system PUFA concentrations. In humans, omnivorous primates, and piglets, DHA and ARA plasma and red blood cells concentrations rise with dietary preformed DHA and ARA. Brain and retina DHA are responsive to diet while ARA is not. DHA is at highest concentration cells and tissues associated with high energy consumption, consistent with high DHA levels in mitochondria and synaptosomes. DHA is a substrate for docosanoids, signaling compounds of intense current interest. The high concentration in tissues with high rates of oxidative metabolism may be explained by a critical role related to oxidative metabolism. PMID:18023566

  2. n-3 polyunsaturated fatty acids and mechanisms to mitigate inflammatory paracrine signaling in obesity-associated breast cancer.

    PubMed

    Monk, Jennifer M; Turk, Harmony F; Liddle, Danyelle M; De Boer, Anna A; Power, Krista A; Ma, David W L; Robinson, Lindsay E

    2014-10-30

    Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA) may have utility in mitigating the severity of obesity-associated inflammation and breast cancer.

  3. Recommendations of the Spanish Menopause Society on the consumption of omega-3 polyunsaturated fatty acids by postmenopausal women.

    PubMed

    Sánchez-Borrego, Rafael; von Schacky, Clemens; Osorio, María José Alonso; Llaneza, Plácido; Pinto, Xavier; Losa, Fernando; Navarro, Mª Concepción; Lubián, Daniel; Mendoza, Nicolás

    2017-09-01

    The consumption of long-chain omega-3 polyunsaturated fatty acids (LCO3-PUFAs) has shown a great variety of beneficial effects, including cardiovascular, metabolic and inflammatory effects, which make them interesting for the postmenopausal woman. Because LCO3-PUFAs could be effective and safe during this period, a panel of experts from the Spanish Menopause Society met to establish a set of recommendations for their use in postmenopausal women based on the best available evidence. The decrease in triglycerides is the most consistent effect observed with LCO3-PUFAs (at doses greater than 3g/day). In addition, LCO3-PUFAs have antiarrhythmic effects, reduce blood pressure, improve depressive and psychotic symptoms, and do not increase the risk of cancer. However, further studies are needed to confirm the benefit of LCO3-PUFAs in the relief of menopause symptoms and osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Suppression of rat hepatic fatty acid synthase and S14 gene transcription by dietary polyunsaturated fat.

    PubMed

    Blake, W L; Clarke, S D

    1990-12-01

    The objective of this research was to determine whether dietary polyunsaturated fatty acids suppress hepatic fatty acid synthase (FAS) mRNA levels by altering FAS gene transcription. Male Sprague-Dawley rats were meal-fed for 10 d a high glucose diet supplemented with 20% digestible energy as menhaden oil or tripalmitin. The transcription rate for FAS was determined by nuclear run-on analysis in hepatic nuclei isolated from rats 2 h postmeal. The values for transcription rates of FAS and S14 (a putative lipogenic protein) in rats fed menhaden oil were only 6 and 21%, respectively, of the rates in rats fed the tripalmitin diet (p less than 0.02). Gene transcription for beta-actin and phosphoenolpyruvate carboxykinase did not differ between treatments. The reduction in hepatic FAS mRNA levels caused by dietary polyunsaturated fats appears to be caused primarily by an inhibition of FAS transcription. The control of transcription by polyunsaturated fats appears not to be mediated by cAMP because the transcription rate for phosphoenolpyruvate carboxykinase (whose gene is very sensitive to cAMP stimulation) was unaffected by the source of dietary fat.

  5. Phospholipids that contain polyunsaturated fatty acids enhance neuronal cell mechanics and touch sensation.

    PubMed

    Vásquez, Valeria; Krieg, Michael; Lockhead, Dean; Goodman, Miriam B

    2014-01-16

    Mechanoelectrical transduction (MeT) channels embedded in neuronal cell membranes are essential for touch and proprioception. Little is understood about the interplay between native MeT channels and membrane phospholipids, in part because few techniques are available for altering plasma membrane composition in vivo. Here, we leverage genetic dissection, chemical complementation, and optogenetics to establish that arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, enhances touch sensation and mechanoelectrical transduction activity while incorporated into membrane phospholipids in C. elegans touch receptor neurons (TRNs). Because dynamic force spectroscopy reveals that AA modulates the mechanical properties of TRN plasma membranes, we propose that this polyunsaturated fatty acid (PUFA) is needed for MeT channel activity. These findings establish that polyunsaturated phospholipids are crucial determinants of both the biochemistry and mechanics of mechanoreceptor neurons and reinforce the idea that sensory mechanotransduction in animals relies on a cellular machine composed of both proteins and membrane lipids. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  6. [A Future Perspective on the Involvement of n-3 Polyunsaturated Fatty Acid in the Development of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis].

    PubMed

    Nakamoto, Kazuo; Obata, Tokio; Hirasawa, Akira; Kim, Ke Ih; Kim, Soo Ryang; Tokuyama, Shogo

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by the pathological accumulation of fat in the liver in the absence of any other disease related to liver steatosis, which includes a wide spectrum of liver diseases ranging from mild asymptomatic fatty liver to nonalcoholic steatohepatitis (NASH) and cirrhosis. Recently, it was reported that NAFLD is characterized by the impaired bioavailability of liver n-6 and n-3 long-chain polyunsaturated fatty acids (PUFAs). That is, compared with healthy individuals, steatosis and steatohepatitis patients have higher n-6/n-3 PUFA ratios. Furthermore, per recent research, decreasing the intake of total fats and increasing the intake of n-3 PUFAs may be beneficial in the treatment of NAFLD. In contrast, some reports describe that NASH patients have more metabolic abnormalities than NAFLD patients; however, these are not influenced by dietary fatty acids. Thus, at present, various opinions exist regarding the efficacy of n-3 PUFA in the treatment of NAFLD. In this review, we discuss the considerable interest n-3 PUFA has attracted as a potential treatment for NAFLD.

  7. [Polyunsaturated fatty acids: omega-3 in child development].

    PubMed

    Caramia, G

    2002-01-01

    The understanding of the role of lipids has made major advances following the identification, by George and Mildred Burr, of so-called "essential fatty acids", i.e. linoleic acid (LA) and alpha-linolenic acid (ALA). LA is supplied by animal and vegetal fats, while ALA reaches higher levels in breastmilk, fish, and olive oil. For both LA and ALA, the human body depends exclusively on the dietary supply. These lipids play a major role as structural components of cell membranes, in particular of neurons, nerves, myelinated sheath, retina, vessels, heart, and blood cells; moreover, they act as precursors of several short-life compounds with hormone-like action: prostaglandins, prostacylins, thromboxanes, leukotriens, all with a regulatory effect on several cell functions, and on cholesterol pathway. It has been suggested a "health programming" role for food, due to the impact of the type of feeding on the subsequent neuromotor development, learning abilities, behavior, metabolism, blood pressure, bone mineralization, and degenrative diseases. This is the consequence of changes of the genomic expression, with a guided clone selection. This is in line with the "imprinting hypothesis" proposed by K. Lorenz (1973 Nobel Prize for Physiology and Medicine), who suggested that stimulations at a particular age may drive animal behavior for the rest of their life.

  8. Kinetics of omega-3 polyunsaturated fatty acids when co-administered with saturated or omega-6 fats.

    PubMed

    Dias, Cintia B; Wood, Lisa G; Phang, Melinda; Garg, Manohar Lal

    2015-12-01

    Absorption of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to be potentiated when consumed with a high fat meal. However, the effect of different dietary fats on n-3PUFA absorption and postprandial kinetics has not been previously studied. In a randomized cross-over design intervention, postprandial incorporation of LCn-3PUFA into plasma lipids following consumption of a meal rich in either saturated fat or omega-6 polyunsaturated fatty acids (n-6PUFA) was investigated. Healthy adult male and female subjects (n=26) were fed an isocaloric meal containing equivalent amount of either butter or sunflower seed oil supplemented with 1.8grams of LCn-3PUFA (300mg eicosapentaenoic acid, 20:5n-3 and 1500mg docosahexaenoic acid, 22:6n-3). Postprandial plasma lipids were enriched with saturated fatty acids and linoleic acid (18:2n-6) following consumption of the butter and the sunflower oil containing meals respectively. The increase in plasma 20:5n-3 and 22:6n-3 levels over the 6hour study period was similar in both the saturated and the n-6 fat groups. These results suggest that the expected competition between LCn-3PUFA and n-6PUFA at the absorption level is unlikely; therefore competition at the enzymatic level should be primarily responsible for differences in their metabolic and clinical effects. Trial registered with the Australia New Zealand Trial registry as ACTRN12612000654853. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Omega 3 polyunsaturated fatty acids and body weight.

    PubMed

    Martínez-Victoria, Emilio; Yago, María Dolores

    2012-06-01

    In animal studies, n-3 PUFA have been shown to influence body composition and to reduce the accumulation of body fat, thereby affecting body weight homeostasis. In addition, it has been suggested that an additional supply of n-3 PUFA during pregnancy or lactation, or both, would have a beneficial effect on birth weight and infant growth and development. The purpose of the present study was to systematically review interventional clinical trials on the effects of dietary n-3 PUFA supplementation on body weight in adult subjects and in infants whose mothers were supplemented with these fatty acids during pregnancy and/or lactation. A systematic search, focused on n-3 PUFA and body weight, and limited to controlled clinical trials, was performed in different databases. The quality of all included studies was assessed against set criteria, and results of eligible trials were compared. There were few studies targeting this topic. In adults, all of the five studies included, except for one, show no change in body weight by dietary supplementation with n-3 PUFA. Within those trials conducted in pregnant and/or lactating women in which a main outcome was birth weight or growth in infancy, two showed a modest increase in birth weight and the rest showed no effect. None of the trials showed an effect of maternal n-3 PUFA supplementation on infant's weight at the short term. However, it should be noted that a number of limitations, including a variety of experimental designs, type and doses of n-3 PUFA, and high attrition rates, among others, make impossible to draw robust conclusions from this review.

  10. Phospholipids that contain polyunsaturated fatty acids enhance neuronal cell mechanics and touch sensation

    PubMed Central

    Vásquez, Valeria; Krieg, Michael; Lockhead, Dean; Goodman, Miriam B.

    2014-01-01

    Summary Mechano-electrical transduction (MeT) channels embedded in neuronal cell membranes are essential for touch and proprioception. Little is understood about the interplay between native MeT channels and membrane phospholipids, in part because few techniques are available for altering plasma membrane composition in vivo. Here, we leverage genetic dissection, chemical complementation, and optogenetics to establish that arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, enhances touch sensation and mechanoelectrical transduction activity while incorporated into membrane phospholipids in C. elegans touch receptor neurons (TRNs). Because dynamic force spectroscopy reveals that AA modulates the mechanical properties of TRN plasma membranes, we propose that this PUFA is needed for MeT channel activity. These findings establish that polyunsaturated phospholipids are crucial determinants of both the biochemistry and mechanics of mechanoreceptor neurons and reinforce the idea that sensory mechanotransduction in animals relies on a cellular machine composed of both proteins and membrane lipids. PMID:24388754

  11. Biochemical and genetic engineering of diatoms for polyunsaturated fatty acid biosynthesis.

    PubMed

    Li, Hong-Ye; Lu, Yang; Zheng, Jian-Wei; Yang, Wei-Dong; Liu, Jie-Sheng

    2014-01-07

    The role of diatoms as a source of bioactive compounds has been recently explored. Diatom cells store a high amount of fatty acids, especially certain polyunsaturated fatty acids (PUFAs). However, many aspects of diatom metabolism and the production of PUFAs remain unclear. This review describes a number of technical strategies, such as modulation of environmental factors (temperature, light, chemical composition of culture medium) and culture methods, to influence the content of PUFAs in diatoms. Genetic engineering, a newly emerging field, also plays an important role in controlling the synthesis of fatty acids in marine microalgae. Several key points in the biosynthetic pathway of PUFAs in diatoms as well as recent progresses are also a critical part and are summarized here.

  12. Biochemical and Genetic Engineering of Diatoms for Polyunsaturated Fatty Acid Biosynthesis

    PubMed Central

    Li, Hong-Ye; Lu, Yang; Zheng, Jian-Wei; Yang, Wei-Dong; Liu, Jie-Sheng

    2014-01-01

    The role of diatoms as a source of bioactive compounds has been recently explored. Diatom cells store a high amount of fatty acids, especially certain polyunsaturated fatty acids (PUFAs). However, many aspects of diatom metabolism and the production of PUFAs remain unclear. This review describes a number of technical strategies, such as modulation of environmental factors (temperature, light, chemical composition of culture medium) and culture methods, to influence the content of PUFAs in diatoms. Genetic engineering, a newly emerging field, also plays an important role in controlling the synthesis of fatty acids in marine microalgae. Several key points in the biosynthetic pathway of PUFAs in diatoms as well as recent progresses are also a critical part and are summarized here. PMID:24402175

  13. Polyunsaturated fatty acids moderate the effect of poor sleep on depression risk.

    PubMed

    Lotrich, Francis E; Sears, Barry; McNamara, Robert K

    2016-03-01

    Although potentially modifiable risk factors for interferon-alpha (IFN-α)-associated depression (IFN-MDD) have been identified, it is not currently known how they interact to confer risk. In the present study we prospectively investigated interactions among poor sleep quality, high-stress, pre-existing depressive symptoms, and polyunsaturated fatty acid status. Non-depressed hepatitis C patients (n=104) were followed prospectively during IFN-α therapy. IFN-MDD occurs in 20-40% of patients and was diagnosed using the Structured Clinical Interview of DSM-IV (SCID-IV), with incidence examined using Cox regression. Baseline Pittsburgh Sleep Quality Inventory (PSQI), Perceived Stress Scale (PSS), Beck Depression Inventory (BDI), and a range of plasma long-chain fatty acid levels were measured (gas chromatography) - focusing on the ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (AA/EPA+DHA). The AA/EPA+DHA ratio (Β=0.40 ± 0.16; p=0.006), PSQI (Β=0.12 ± 0.04; p=0.001), PSS (Β=0.07 ± 0.02; p<0.001), and baseline BDI (Β=0.05 ± 0.02; p<0.001) each individually predicted IFN-MDD incidence. In step-wise Cox regression eliminating non-significant variables, two interactions remained significantly predictive: PSQI*AA/EPA+DHA (p=0.008) and PSS*AA/EPA+DHA (p=0.01). Receiver Operator Curves (ROC) were used to examine the specificity and sensitivity of IFN-MDD prediction. When sleep was normal (PSQI<5), AA/EPA+DHA was strongly predictive of IFN-MDD (AUC=91 ± 6; p=0.002). For example, among those with AA/EPA+DHA less than the median (4.15), none with PSQI<5 developed depression. Conversely, neither PSS nor PSQI was statistically associated with depression risk in those with an elevated AA/EPA+DHA ratio. These data demonstrate that the AA/EPA+DHA ratio moderates the effect of poor sleep on risk for developing IFN-MDD and may have broader implications for predicting and preventing MDD associated with inflammation.

  14. [Omega-3 polyunsaturated fatty acids and cardiovascular diseases].

    PubMed

    Marchioli, R

    2003-10-01

    Population studies indicate omega-3 that a high fish intake, such as reported in the early Eskimo and Japanese studies, is associated with a low mortality from coronary heart disease (CHD). These effects have been associated with measurable effects on a series of established and possible risk factors. In most of the later population studies much lower daily intake of fish has been observed, such intake having only small or not even measurable effects on established risk factors. Still, their association with reduced CHD mortality, particularly sudden cardiac death seem to be reasonably well established. Beneficial effects are found at a level of consumption of about 30 g per day or 1 fish meal per week compared with populations rarely or never consuming fish. Such findings are also reflected in studies including analysis of fatty acid composition in adipose tissue and cell membranes. Fish consumption may be a marker for a healthier lifestyle or, alternatively, fish consumers may be at higher self-perceived risk for CHD and are therefore eating fish to reduce their high baseline risk. Despite all these limitations, the population studies seem to indicate that a high fish intake is associated with a low mortality from CHD. GISSI-Prevenzione was conceived as a population, pragmatic trial on patients with recent myocardial infarction and it was conducted in the framework of the Italian public health system. In GISSI-Prevenzione, 11,323 patients were enrolled in a clinical trial aimed at testing the effectiveness of omega-3 PUFA and vitamin E. Patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term omega-3 PUFA 1 g daily, but not vitamin E 300 mg daily, was beneficial for death and for combined death, non-fatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden death. In

  15. Coordinate regulation of glycolytic and lipogenic gene expression by polyunsaturated fatty acids.

    PubMed

    Jump, D B; Clarke, S D; Thelen, A; Liimatta, M

    1994-06-01

    Using a combination of in vivo and in vitro studies, we have investigated the impact of polyunsaturated fatty acids (PUFA) on the expression of several genes encoding proteins involved in hepatic glycolysis and lipogenesis. Meal-training rats to a high glucose diet containing 10% triolein led to a significant induction of hepatic mRNAs encoding glucokinase (GK), pyruvate kinase (PK), fatty acid synthase (FAS), malic enzyme (ME), and the S14 protein (S14), but had no effect on thyroid hormone receptor-beta 1 (TR beta 1) and c/EBP alpha gene expression. Replacing triolein with menhaden oil attenuated (by 50-90%) the induction of mRNA encoding GK, ME, PK, FAS, and S14. This effect was rapid (within hours) and for FAS and S14, directed at the transcriptional level. The mRNAs encoding TR beta 1, c/EBP alpha and beta-actin were unaffected by menhaden oil. Studies with cultured primary hepatocytes showed that C18:3,omega 3 (n-3), C18:3,omega 6 (n-6), C20:4, omega 6 (n-6), and C20:5,omega 3 (n-3) were all equally effective at suppressing the level of mRNAs encoding FAS, S14, and PK. This effect was specific for glycolytic and lipogenic enzymes, as expression of beta-actin was not affected by these fatty acids. Moreover, the fatty acids had only marginal effects on cell viability as judged by lactate dehydrogenase release. These data indicate that polyunsaturated fatty acids coordinately regulate the expression of several enzymes involved in carbohydrate and lipid metabolism. The mechanism of control does not require extrahepatic factors or fatty acid metabolism.

  16. Characterization of three novel desaturases involved in the delta-6 desaturation pathways for polyunsaturated fatty acid biosynthesis from Phytophthora infestans.

    PubMed

    Sun, Quanxi; Liu, Jiang; Zhang, Qin; Qing, Xiaohe; Dobson, Gary; Li, Xinzheng; Qi, Baoxiu

    2013-09-01

    Phytophthora infestans is the causative agent of potato blight that resulted in the great famine in Ireland in the nineteenth century. This microbe can release large amounts of the C20 very long-chain polyunsaturated fatty acids arachidonic acid (ARA; 20:4Δ(5, 8, 11, 14)) and eicosapentaenoic acid (EPA; 20:5Δ(5, 8, 11, 14, 17)) upon invasion that is known to elicit a hypersensitive response to their host plant. In order to identify enzymes responsible for the biosynthesis of these fatty acids, we blasted the recently fully sequenced P. infestans genome and identified three novel putatively encoding desaturase sequences. These were subsequently functionally characterized by expression in Saccharomyces cerevisiae and confirmed that they encode desaturases with Δ12, Δ6 and Δ5 activity, designated here as PinDes12, PinDes6 and PinDes5, respectively. This, together with the combined fatty acid profiles and a previously identified Δ6 elongase activity, implies that the ARA and EPA are biosynthesized predominantly via the Δ6 desaturation pathways in P. infestans. Elucidation of ARA and EPA biosynthetic mechanism may provide new routes to combating this potato blight microbe directly or by means of conferring resistance to important crops.

  17. Omega-3 Polyunsaturated Fatty Acids Intake to Regulate Helicobacter pylori-Associated Gastric Diseases as Nonantimicrobial Dietary Approach

    PubMed Central

    Park, Jong-Min; Jeong, Migyeong; Kim, Eun-Hee; Han, Young-Min; Kwon, Sung Hun; Hahm, Ki-Baik

    2015-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs), commonly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been acknowledged as essential long-chain fatty acids imposing either optimal health promotion or the rescuing from chronic inflammatory diseases such as atherosclerosis, fatty liver, and various inflammatory gastrointestinal diseases. Recent studies dealing with EPA and DHA have sparked highest interests because detailed molecular mechanisms had been documented with the identification of its receptor, G protein coupled receptor, and GPR120. In this review article, we have described clear evidences showing that n-3 PUFAs could reduce various Helicobacter pylori- (H. pylori-) associated gastric diseases and extended to play even cancer preventive outcomes including H. pylori-associated gastric cancer by influencing multiple targets, including proliferation, survival, angiogenesis, inflammation, and metastasis. Since our previous studies strongly concluded that nonantimicrobial dietary approach for reducing inflammation, for instance, application of phytoceuticals, probiotics, natural products including Korean red ginseng, and walnut plentiful of n-3 PUFAs, might be prerequisite step for preventing H. pylori-associated gastric cancer as well as facilitating the rejuvenation of precancerous atrophic gastritis, these beneficial lipids can restore or modify inflammation-associated lipid distortion and correction of altered lipid rafts to send right signaling to maintain healthy stomach even after chronic H. pylori infection. PMID:26339635

  18. Biosynthesis of Polyunsaturated Fatty Acids in Sea Urchins: Molecular and Functional Characterisation of Three Fatty Acyl Desaturases from Paracentrotus lividus (Lamark 1816).

    PubMed

    Kabeya, Naoki; Sanz-Jorquera, Alicia; Carboni, Stefano; Davie, Andrew; Oboh, Angela; Monroig, Oscar

    2017-01-01

    Sea urchins are broadly recognised as a delicacy and their quality as food for humans is highly influenced by their diet. Lipids in general and the long-chain polyunsaturated fatty acids (LC-PUFA) in particular, are essential nutrients that determine not only the nutritional value of sea urchins but also guarantee normal growth and reproduction in captivity. The contribution of endogenous production (biosynthesis) of LC-PUFA in sea urchins remained unknown. Using Paracentrotus lividus as our model species, we aimed to characterise both molecularly and functionally the repertoire of fatty acyl desaturases (Fads), key enzymes in the biosynthesis of LC-PUFA, in sea urchins. Three Fads, namely FadsA, FadsC1 and FadsC2, were characterised. The phylogenetic analyses suggested that the repertoire of Fads within the Echinodermata phylum varies among classes. On one hand, orthologues of the P. lividus FadsA were found in other echinoderm classes including starfishes, brittle stars and sea cucumbers, thus suggesting that this desaturase is virtually present in all echinoderms. Contrarily, the FadsC appears to be sea urchin-specific desaturase. Finally, a further desaturase termed as FadsB exists in starfishes, brittle stars and sea cucumbers, but appears to be missing in sea urchins. The functional characterisation of the P. lividus Fads confirmed that the FadsA was a Δ5 desaturase with activity towards saturated and polyunsaturated fatty acids (FA). Moreover, our experiments confirmed that FadsA plays a role in the biosynthesis of non-methylene interrupted FA, a group of compounds typically found in marine invertebrates. On the other hand, both FadsC desaturases from P. lividus showed Δ8 activity. The present results demonstrate that P. lividus possesses desaturases that account for all the desaturation reactions required to biosynthesis the physiological essential eicosapentaenoic and arachidonic acids through the so-called "Δ8 pathway".

  19. Biosynthesis of Polyunsaturated Fatty Acids in Sea Urchins: Molecular and Functional Characterisation of Three Fatty Acyl Desaturases from Paracentrotus lividus (Lamark 1816)

    PubMed Central

    Carboni, Stefano; Davie, Andrew; Oboh, Angela

    2017-01-01

    Sea urchins are broadly recognised as a delicacy and their quality as food for humans is highly influenced by their diet. Lipids in general and the long-chain polyunsaturated fatty acids (LC-PUFA) in particular, are essential nutrients that determine not only the nutritional value of sea urchins but also guarantee normal growth and reproduction in captivity. The contribution of endogenous production (biosynthesis) of LC-PUFA in sea urchins remained unknown. Using Paracentrotus lividus as our model species, we aimed to characterise both molecularly and functionally the repertoire of fatty acyl desaturases (Fads), key enzymes in the biosynthesis of LC-PUFA, in sea urchins. Three Fads, namely FadsA, FadsC1 and FadsC2, were characterised. The phylogenetic analyses suggested that the repertoire of Fads within the Echinodermata phylum varies among classes. On one hand, orthologues of the P. lividus FadsA were found in other echinoderm classes including starfishes, brittle stars and sea cucumbers, thus suggesting that this desaturase is virtually present in all echinoderms. Contrarily, the FadsC appears to be sea urchin-specific desaturase. Finally, a further desaturase termed as FadsB exists in starfishes, brittle stars and sea cucumbers, but appears to be missing in sea urchins. The functional characterisation of the P. lividus Fads confirmed that the FadsA was a Δ5 desaturase with activity towards saturated and polyunsaturated fatty acids (FA). Moreover, our experiments confirmed that FadsA plays a role in the biosynthesis of non-methylene interrupted FA, a group of compounds typically found in marine invertebrates. On the other hand, both FadsC desaturases from P. lividus showed Δ8 activity. The present results demonstrate that P. lividus possesses desaturases that account for all the desaturation reactions required to biosynthesis the physiological essential eicosapentaenoic and arachidonic acids through the so-called “Δ8 pathway”. PMID:28052125

  20. FADS genetic variants and ω-6 polyunsaturated fatty acid metabolism in a homogeneous island population[S

    PubMed Central

    Mathias, Rasika A.; Vergara, Candelaria; Gao, Li; Rafaels, Nicholas; Hand, Tracey; Campbell, Monica; Bickel, Carol; Ivester, Priscilla; Sergeant, Susan; Barnes, Kathleen C.; Chilton, Floyd H.

    2010-01-01

    Long-chain polyunsaturated fatty acids (PUFA) orchestrate immunity and inflammation through their capacity to be converted to potent inflammatory mediators. We assessed associations of FADS gene cluster polymorphisms and fasting serum PUFA concentrations in a fully ascertained, geographically isolated founder population of European descent. Concentrations of 22 PUFAs were determined by gas chromatography, of which ten fatty acids and five ratios defining FADS1 and FADS2 activity were tested for genetic association against 16 single nucleotide polymorphisms (SNP) in 224 individuals. A cluster of SNPs in tight linkage disequilibrium in the FADS1 gene (rs174537, rs174545, rs174546, rs174553, rs174556, rs174561, rs174568, and rs99780) were strongly associated with arachidonic acid (AA) (P = 5.8 × 10−7 – 1.7 × 10−8) among other PUFAs, but the strongest associations were with the ratio measuring FADS1 activity in the ω-6 series (P = 2.11 × 10−13 – 1.8 × 10−20). The minor allele across all SNPs was consistently associated with decreased ω-6 PUFAs, with the exception of dihomo-γ-linoleic acid (DHGLA), where the minor allele was consistently associated with increased levels. Our findings in a geographically isolated population with a homogenous dietary environment suggest that variants in the Δ-5 desaturase enzymatic step likely regulate the efficiency of conversion of medium-chain PUFAs to potentially inflammatory PUFAs, such as AA. PMID:20562440

  1. Stearidonic acid as a supplemental source of ω-3 polyunsaturated fatty acids to enhance status for improved human health.

    PubMed

    Walker, Celia G; Jebb, Susan A; Calder, Philip C

    2013-02-01

    There is substantial evidence to show that consumption and increased blood levels of the very long-chain (VLC) ω-3 polyunsaturated fatty acids (ω-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with health benefits. The consumption of oily fish is an effective way of increasing EPA and DHA intake and status, but intake in most Western countries remains below the levels recommended for optimal health. The reasons for this include not liking the taste, a concern about sustainability of fish supplies, or potential chemical and heavy metal contamination. Alternative dietary sources of ω-3 fatty acids to enhance EPA and DHA status in the body would therefore be beneficial. There are many non-fish food sources of the essential plant-derived ω-3 fatty acid α-linolenic acid, but conversion from this to longer-chain EPA and especially to DHA is poor. Stearidonic acid (SDA) is an intermediate fatty acid in the biosynthetic pathway from α-linolenic acid to VLC ω-3 PUFAs and the conversion from SDA is more efficient than from α-linolenic acid. However, there are few food sources rich in SDA. Oil crops naturally rich in SDA or enriched through genetic modification may offer an alternative supplemental oil to boost the population status of VLC ω-3 PUFAs. This review discusses the currently available evidence that increased SDA consumption can increase red blood cell EPA content, although this is less than the effect of supplementation directly with EPA. There is now a need for trials specifically designed to assess whether an increased SDA consumption would translate into improved human health outcomes.

  2. [Effects of n-3 polyunsaturated fatty acids on the cardiovascular system. Should their use be recommended?].

    PubMed

    Lahoz, C; Mata, P

    1993-10-01

    The effects of n-3 polyunsaturated fatty acid (n-3 PFA) intake on lipoprotein metabolism, eicosanoid metabolism, coagulation and the fibrinolytic system, mediators of inflammation, and blood pressure are discussed. The possible role such effects may have on the process of atherogenesis is examined. Laboratory animal studies with n-3 PFA supplements are reviewed. Finally, a review of clinical and epidemiological studies in human subjects is made in order to evaluate whether the experimental findings have clinical relevance. The conclusion is that, at the present time, there is insufficient support for the use of n-3 PFA supplements either in prophylaxis or in treating ischemic cardiopathy.

  3. In vitro modulation of caprine monocyte immune functions by ω-3 polyunsaturated fatty acids.

    PubMed

    Lecchi, Cristina; Invernizzi, Guido; Agazzi, Alessandro; Ferroni, Mariella; Pisani, Laura Francesca; Savoini, Giovanni; Ceciliani, Fabrizio

    2011-09-01

    The in vitro effects of the ω-3 polyunsaturated fatty acids (PUFAs) eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on phagocytosis and the extracellular respiratory burst in caprine monocytes were assessed. Blood monocytes incubated with increasing concentrations of EPA or DHA (25-200 μM) demonstrated increased phagocytosis compared to unexposed monocytes. Generation of reactive oxygen species (ROS) was not markedly affected in the presence of EPA and DHA, except at 200 μM, at which concentrations monocyte viability was also reduced.

  4. Polyunsaturated Fatty Acids and Their Derivatives: Therapeutic Value for Inflammatory, Functional Gastrointestinal Disorders, and Colorectal Cancer

    PubMed Central

    Michalak, Arkadiusz; Mosińska, Paula; Fichna, Jakub

    2016-01-01

    Polyunsaturated fatty acids (PUFAs) are bioactive lipids which modulate inflammation and immunity. They gained recognition in nutritional therapy and are recommended dietary supplements. There is a growing body of evidence suggesting the usefulness of PUFAs in active therapy of various gastrointestinal (GI) diseases. In this review we briefly cover the systematics of PUFAs and their metabolites, and elaborate on their possible use in inflammatory bowel disease (IBD), functional gastrointestinal disorders (FGIDs) with focus on irritable bowel syndrome (IBS), and colorectal cancer (CRC). Each section describes the latest findings from in vitro and in vivo studies, with reports of clinical interventions when available. PMID:27990120

  5. n-3 polyunsaturated fatty acids in milk is associate to weight gain and growth in premature infants

    PubMed Central

    Tinoco, Sandra M Barboza; Sichieri, Rosely; Setta, Cecília L; Moura, Anibal S; Carmo, Maria G Tavares do

    2009-01-01

    Background Linoleic 18:2 (n-6) and α-linolenic 18:3 (n-3) essential fatty acids and long-chain polyunsaturated fatty acids (LC-PUFA) are essential nutrients for growth and neonatal development. Consumption of preformed n-3 LC-PUFA has been shown to increase gestational duration and to decrease the incidence of premature birth in human studies. This study evaluated the association of essential fatty acids and LC-PUFA in breast milk on the growth of premature children (weight, height and head circumference). Study design Thirty-seven premature infants with a gestational age of 37 weeks or less were followed until 6 months of gestational age, adjusted for prematurity. The milk from mothers, weight, height and head circumference measures of children were collected during the follow up. The breast milk fatty acids were quantified by gas-liquid chromatography. Results Our results showed that total n-3 PUFA was positively associated with weight gain (p = 0.05), height (p = 0.04) and body mass index (BMI) of children (p = 0.05). Our results also indicate that both linoleic acid and total essential fatty acids were positively associated with BMI and head circumference, whereas oleic acid was positively associated only with head circumference. Conclusion These results suggest that the n-3 PUFA composition of milk may be associated with weight gain and growth. Considering the advantages of n-3 LC-PUFA consumption on infant growth and visual function and its association with reduced incidence of premature birth, dietitians should advise pregnant women to increase their intake of foods high in n-3 LC-PUFA. PMID:19558659

  6. Contribution of polyunsaturated fatty acids to intestinal repair in protein-energy malnutrition.

    PubMed

    Nieto, Natalia; Mesa, María Dolores; López-Pedrosa, José María; Torres, M Isabel; Ríos, Antonio; Suárez, María Dolores; Gil, Angel

    2007-06-01

    The aim of this study was to assess the effect of polyunsaturated fatty acids supplied in the diet on intestinal mucosa repair in a rat model of protein-energy malnutrition. Rats were fed either a standard semipurified diet or the same diet containing lactose as the only source of carbohydrate to cause protein-energy malnutrition. Diarrhea was induced within 24 h and was maintained for 2 weeks, after which both groups of rats were fed for 1 week either the standard diet or the standard diet supplemented with different sources of fatty acids, such as olive oil (OO), fish oil (FO), and purified phospholipids from pig brain (BPL). The lactose-enriched diet caused loss of enterocyte microvilli, lymphocyte infiltration, supranuclear cytoplasmic vesiculation, decreased number of goblet cells, low-density enlarged mitochondria, and less cristae. The FO diet improved the pathology score according to the histological and ultrastructural analysis, with an increased number of goblet cells, ratio of microvilli length to crypt depth, and percentage of intraepithelial lymphocytes compared to those found in rats with protein-energy malnutrition. We previously reported that chronic diarrhea depletes the antioxidant defense in rat intestine; we now show that both, the FO and the BPL diets, increase GSH levels in colon and that some antioxidant enzyme activities vary according to the source of fatty acids, with higher catalase and superoxide dismutase by the FO diet in jejunum, increased catalase by the BPL diet in jejunum, and elevated glutathione peroxidase by the OO diet in colon. The fatty acid profile of intestinal mucosa reflects the source of fat in the diet, with the lowest ratio of n-6/n-3 for rats fed the FO diet. These results suggest that dietary polyunsaturated fatty acids, particularly those in the n-3 series, may play an important role in intestinal repair in chronic diarrhea due to protein-energy malnutrition.

  7. Polyunsaturated fatty acids in various macroalgal species from north Atlantic and tropical seas

    PubMed Central

    2011-01-01

    Background In this study the efficacy of using marine macroalgae as a source for polyunsaturated fatty acids, which are associated with the prevention of inflammation, cardiovascular diseases and mental disorders, was investigated. Methods The fatty acid (FA) composition in lipids from seven sea weed species from the North Sea (Ulva lactuca, Chondrus crispus, Laminaria hyperborea, Fucus serratus, Undaria pinnatifida, Palmaria palmata, Ascophyllum nodosum) and two from tropical seas (Caulerpa taxifolia, Sargassum natans) was determined using GCMS. Four independent replicates were taken from each seaweed species. Results Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs), were in the concentration range of 2-14 mg/g dry matter (DM), while total lipid content ranged from 7-45 mg/g DM. The n-9 FAs of the selected seaweeds accounted for 3%-56% of total FAs, n-6 FAs for 3%-32% and n-3 FAs for 8%-63%. Red and brown seaweeds contain arachidonic (C20:4, n-6) and/or eicosapentaenoic acids (EPA, C20:5, n-3), the latter being an important "fish" FA, as major PUFAs while in green seaweeds these values are low and mainly C16 FAs were found. A unique observation is the presence of another typical "fish" fatty acid, docosahexaenoic acid (DHA, C22:6, n-3) at ≈ 1 mg/g DM in S. natans. The n-6: n-3 ratio is in the range of 0.05-2.75 and in most cases below 1.0. Environmental effects on lipid-bound FA composition in seaweed species are discussed. Conclusion Marine macroalgae form a good, durable and virtually inexhaustible source for polyunsaturated fatty acids with an (n-6) FA: (n-3) FA ratio of about 1.0. This ratio is recommended by the World Health Organization to be less than 10 in order to prevent inflammatory, cardiovascular and nervous system disorders. Some marine macroalgal species, like P. palmata, contain high proportions of the "fish fatty acid" eicosapentaenoic acid (EPA, C20:5, n-3), while in S. natans also docosahexaenoic acid (DHA, C22:6, n-3) was

  8. Delta 5 fatty acid desaturase upregulates the synthesis of polyunsaturated fatty acids in the marine diatom Phaeodactylum tricornutum.

    PubMed

    Peng, Kun-Tao; Zheng, Cun-Ni; Xue, Jiao; Chen, Xiao-Yan; Yang, Wei-Dong; Liu, Jie-Sheng; Bai, Weibin; Li, Hong-Ye

    2014-09-03

    Microalgae are important primary producers in the marine ecosystem and excellent sources of lipids and other bioactive compounds. The marine diatom Phaeodactylum tricornutum accumulates eicosapentaenoic acid (EPA, 20:5n-3) as its major component of fatty acids. To improve the EPA production, delta 5 desaturase, which plays a role in EPA biosynthetic pathway, was characterized in P. tricornutum. An annotated delta 5 desaturase PtD5b gene was cloned and overexpressed in P. tricornutum. The transgene was integrated into the genome demonstrated by Southern blot, and the overexpression of PtD5b was verified by qPCR and Western blot analysis. Fatty acid composition exhibited a significant increase in the unsaturated fatty acids. Monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) showed an increase of 75% and 64%, respectively. In particular, EPA showed an increase of 58% in engineered microalgae. Meanwhile, neutral lipid content showed an increase up to 65% in engineered microalgae. More importantly, engineered cells showed a similar growth rate with the wild type, thus keeping high biomass productivity. This work provides an effective way to improve the production of microalgal value-added bioproducts by metabolic engineering.

  9. Inhibition of rat liver microsomal fatty acid chain elongation by gemfibrozil in vitro.

    PubMed

    Sánchez, R M; Viñals, M; Alegret, M; Vázquez, M; Adzet, T; Merlos, M; Laguna, J C

    1992-03-23

    Gemfibrozil, a hypolipidemic drug mainly used in the treatment of hypertriglyceridemic states, strongly inhibits the rat hepatic microsomal fatty acid chain elongation system in vitro. The inhibition is independent on the reducing cofactor used in the assay. Furthermore, gemfibrozil seems to act by inhibiting the rate-limiting step of the elongation process, the condensing reaction, without discriminating among the proposed three different condensing enzymes, devoted to condensation of saturated, mono-unsaturated and polyunsaturated acyl-CoA substrates.

  10. ω-3 Polyunsaturated fatty acids accelerate airway repair by activating FFA4 in club cells.

    PubMed

    Lee, Kyoung-Pil; Park, Soo-Jin; Kang, Saeromi; Koh, Jung-Min; Sato, Koichi; Chung, Hae-Young; Okajima, Fumikazu; Im, Dong-Soon

    2017-06-01

    A G protein-coupled receptor (GPCR) named free fatty acid receptor 4 (FFA4, also known as GPR120) was found to act as a GPCR for ω-3 polyunsaturated fatty acids. Its expression has been reported in lung epithelial club cells. We investigated whether supplementation of the ω-3 fatty acids benefits lung health. Omacor (7.75 mg/kg), clinically prescribed preparation of ω-3 fatty acids, and FFA4-knockout mice were utilized in a naphthalene-induced mouse model of acute airway injury (1 injection of 30 mg/kg ip). Naphthalene injection induced complete destruction of bronchiolar epithelial cells within a day. Appearance of bronchiolar epithelial cells was observed after 21 days in control mice. It was found, however, that supplementation of Omacor accelerated the recovery. The appearance of bronchiolar epithelial cells was observed between 7 and 14 days after naphthalene injury in Omacor-treated mice. In isolated club cells, ω-3 fatty acids were found to stimulate cell proliferation and migration but to inhibit cell differentiation. With the use of pharmacological tools and FFA4-knockout mice, FFA4 was found to be responsible for ω-3 fatty acids-induced proliferation in vitro in club cells. Furthermore, accelerated recovery from naphthalene-induced airway injury in Omacor-treated mice was not observed in FFA4-knockout mice in vivo. Present findings indicate that ω-3 fatty acids-induced proliferation of bronchiole epithelial cells through FFA4 is responsible for Omacor-induced accelerated recovery from airway injury. Therefore, intermittent administration of Omacor needs to be tested for acute airway injury because ω-3 fatty acids stimulate proliferation but inhibit differentiation of club cells. Copyright © 2017 the American Physiological Society.

  11. Incorporation of polyunsaturated fatty acids into CT-26, a transplantable murine colonic adenocarcinoma.

    PubMed

    Gaposchkin, D P; Zoeller, R A; Broitman, S A

    2000-02-01

    Previous studies in our laboratory have shown that marine oils, with high levels of eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acids (DHA, 22:6n-3), inhibit the growth of CT-26, a murine colon carcinoma cell line, when implanted into the colons of male BALB/c mice. An in vitro model was developed to study the incorporation of polyunsaturated fatty acids (PUFA) into CT-26 cells in culture. PUFA-induced changes in the phospholipid fatty acid composition and the affinity with which different fatty acids enter the various phospholipid species and subspecies were examined. We found that supplementation of cultured CT-26 cells with either 50 microM linoleic acid (LIN, 18:2n-6), arachidonic acid (AA, 20:4n-6), EPA, or DHA significantly alters the fatty acid composition of CT-26 cells. Incorporation of these fatty acids resulted in decreased levels of monounsaturated fatty acids, while EPA and DHA also resulted in lower levels of AA. While significant elongation of both AA and EPA occurred, LIN remained relatively unmodified. Incorporation of radiolabeled fatty acids into different phospholipid species varied significantly. LIN was incorporated predominantly into phosphatidylcholine and had a much lower affinity for the ethanolamine phospholipids. DHA had a higher affinity for plasmenylethanolamine (1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine) than the other fatty acids, while EPA had the highest affinity for phosphatidylethanol-amine (1,2-diacyl-sn-glycero-3-phosphoethanolamine). These results demonstrate that, in vitro, significant differences are seen between the various PUFA in CT-26 cells with respect to metabolism and distribution, and these may help to explain differences observed with respect to their effects on tumor growth and metastasis in the transplantable model.

  12. Polyunsaturated fats attenuate the dietary phytol-induced increase in hepatic fatty acid oxidation in mice.

    PubMed

    Hashimoto, Toru; Shimizu, Naoto; Kimura, Toshinori; Takahashi, Yoko; Ide, Takashi

    2006-04-01

    The effects of dietary phytol and the type of dietary fat on hepatic fatty acid oxidation were examined in male ICR mice. Mice were fed diets containing 0 or 5 g/kg phytol and 100 g/kg palm, safflower, or fish oil for 21 d. Among the groups fed phytol-free diets, the activities and mRNA abundance of various enzymes involved in fatty acid oxidation were greater in mice fed fish oil than in those fed palm or safflower oil. Dietary phytol profoundly increased the activities and mRNA abundance of hepatic fatty acid oxidation enzymes in mice fed palm oil. However, safflower and fish oils, especially the latter, greatly attenuated the phytol-dependent increase in hepatic fatty acid oxidation. The hepatic concentration of phytanic acid, a metabolite of phytol that is the ligand and activator of retinoid X receptors and peroxisome proliferator-activated receptors, was higher in mice fed fish oil than safflower or palm oil, and in those administered safflower oil than palm oil. The hepatic mRNA abundance of sterol carrier protein-2, a lipid-binding protein involved in phytol metabolism, was inversely correlated with the hepatic concentration of phytanic acid. We demonstrated that polyunsaturated fats attenuate the enhancing effect of dietary phytol on hepatic fatty acid oxidation. Dietary fat-dependent changes in the hepatic phytanic acid concentration cannot account for this phenomenon.

  13. High Omega-3 Polyunsaturated Fatty Acids in fat-1 Mice Reduce Inflammatory Pain.

    PubMed

    Zhang, Enji; Kim, Jwa-Jin; Shin, Nara; Yin, Yuhua; Nan, Yongshan; Xu, Yinshi; Hong, Jinpyo; Hsu, Tzung Min; Chung, Woosuk; Ko, Youngkwon; Lee, Wonhyung; Lim, Kyu; Kim, Dong Woon; Lee, Sun Yeul

    2017-06-01

    Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs), such as α-linolenic and linoleic acids, are essential fatty acids in mammals, because they cannot be synthesized de novo. However, fat-1 transgenic mice can synthesize omega-3 PUFAs from omega-6 PUFAs without dietary supplementation of omega-3, leading to abundant omega-3 PUFA accumulation in various tissues. In this study, we used fat-1 transgenic mice to investigate the role of omega-3 PUFAs in response to inflammatory pain. A high omega-3 PUFA tissue content attenuated formalin-induced pain sensitivity, microglial activation, inducible nitric oxide synthase expression, and the phosphorylation of NR2B, a subunit of the N-methyl-d-aspartate (NMDA) receptor. Our findings suggest that elevated omega-3 PUFA levels inhibit NMDA receptor activity in the spinal dorsal horn and modulate inflammatory pain transmission by regulating signal transmission at the spinal dorsal horn, leading to the attenuation of chemically induced inflammatory pain.

  14. Folate administration increases n-3 polyunsaturated fatty acids in rat plasma and tissue lipids.

    PubMed

    Pita, M L; Delgado, M J

    2000-09-01

    It has been shown that folic acid deficiency can modify polyunsaturated fatty acid (PUFA) metabolism and thus could contribute to the development of cardiovascular diseases. We have studied the effect of folate administration on fatty acid composition of plasma, platelet, erythrocyte, intestinal and liver lipids. Two groups of rats were daily injected with either saline solution (control group) or 5-methyl-tetrahydrofolate (MTHF) solution (MTHF group) for 15 days. Changes induced by folate treatment on n-6 PUFA were not very significant. Linoleic acid only decreased in liver and intestinal phospholipids of MTHF rats whereas arachidonic acid was unaffected by folate administration. However, n-3 PUFA significantly increased in plasma lipid fractions and in platelet, erythrocyte and intestinal phospholipids. It is well known that n-3 PUFA show antithrombotic properties. Thus, the increase of n-3 PUFA observed after MTHF administration might contribute to the prevention of vascular disorders.

  15. Unusually high levels of n-6 polyunsaturated fatty acids in whale sharks and reef manta rays.

    PubMed

    Couturier, L I E; Rohner, C A; Richardson, A J; Pierce, S J; Marshall, A D; Jaine, F R A; Townsend, K A; Bennett, M B; Weeks, S J; Nichols, P D

    2013-10-01

    Fatty acid (FA) signature analysis has been increasingly used to assess dietary preferences and trophodynamics in marine animals. We investigated FA signatures of connective tissue of the whale shark Rhincodon typus and muscle tissue of the reef manta ray Manta alfredi. We found high levels of n-6 polyunsaturated fatty acids (PUFA), dominated by arachidonic acid (20:4n-6; 12-17 % of total FA), and comparatively lower levels of the essential n-3 PUFA-eicosapentaenoic acid (20:5n-3; ~1 %) and docosahexaenoic acid (22:6n-3; 3-10 %). Whale sharks and reef manta rays are regularly observed feeding on surface aggregations of coastal crustacean zooplankton during the day, which generally have FA profiles dominated by n-3 PUFA. The high levels of n-6 PUFA in both giant elasmobranchs raise new questions about the origin of their main food source.

  16. Stage of harvest and polyunsaturated essential fatty acid concentrations in purslane (Portulaca oleraceae) leaves.

    PubMed

    Palaniswamy, U R; McAvoy, R J; Bible, B B

    2001-07-01

    Purslane is a nutritious vegetable crop rich in the polyunsaturated essential fatty acids (PUEFA) alpha-linolenic acid (LNA) and linoleic acid (LA), which are essential for normal human growth, health promotion, and disease prevention. Total lipids and fatty acid concentrations at three stages of harvest (6-, 10-, and 14-true-leaf stages) were examined in a cultivated variety of purslane (Portulaca oleraceae L. var. sativa). The 14-true-leaf stage of growth was found to be ideal for harvest because at this stage the leaf area, shoot fresh weight, shoot dry weight, and PUEFA concentrations per gram of leaf fresh weight were higher (P < or = 0.05) than at the 6- and 10-true-leaf stages of growth. The LNA to LA ratio was also highest at the 14-true-leaf stage.

  17. Hypotonic shocks activate rat TRPV4 in Yeast in the Absence of Polyunsaturated Fatty Acids

    PubMed Central

    Loukin, Stephen H.; Su, Zhenwei; Kung, Ching

    2010-01-01

    Transient-receptor-potential channels (TRPs) underlie the sensing of chemicals, heat, and mechanical force. We expressed the rat TRPV1 and TRPV4 subtypes in yeast and monitored their activities in vivo as Ca2+ rise using transgenic aequorin. Heat and capsaicin activate TRPV1 but not TRPV4 in yeast. Hypotonic shocks activate TRPV4 but not TRPV1. Osmotic swelling is modeled to activate enzyme(s), producing polyunsaturated fatty acids (PUFAs) to open TRPV4 in mammalian cells. This model relegates mechanosensitivity to the enzyme and not the channel. Yeast has only a single Δ9 fatty-acid monodesaturase and cannot make PUFAs suggesting an alternative mechanism for TRPV4 activation. We discuss possible explanations of this difference. PMID:19174160

  18. Selective incorporation of various C-22 polyunsaturated fatty acids in Ehrlich ascites tumor cells

    SciTech Connect

    Masuzawa, Y.; Okano, S.; Waku, K.; Sprecher, H.; Lands, W.E.

    1986-11-01

    Three /sup 14/C-labeled 22-carbon polyunsaturated fatty acids, 7,10,13,16-(/sup 14/C)docosatetraenoic acid (22:4(n-6)), 7,10,13,16,19-(/sup 14/C)docosapentaenoic acid (22:5(n-3)), and 4,7,10,13,16,19-(/sup 14/C)docosahexaenoic acid (22:6(n-3)), were compared with (/sup 3/H)arachidonic acid (20:4(n-6) and (14C)linoleic acid (18:2(n-6)) to characterize their incorporation into the lipids of Ehrlich ascites cells. The relatively rapid incorporation of the labeled 22-carbon acids into phosphatidic acid indicated that substantial amounts of these acids may be incorporated through the de novo pathway of phospholipid synthesis. In marked contrast to 20:4(n-6), the 22-carbon acids were incorporated much less into choline glycerophospholipids (CGP) and inositol glycerophospholipids (IGP). No selective preference was apparent for the (n-3) or (n-6) type of fatty acids. The amounts of the acids incorporated into diacylglycerophosphoethanolamine were in the order of: 22:6(n-3) greater than 20:4(n-6) much greater than 22:5(n-3) greater than or equal to 22:4(n-6) greater than 18:2(n-6), whereas for alkylacylglycerophosphoethanolamine they were in the order of: 22:4(n-6) greater than 22:6(n-3) greater than 22:5(n-3) much greater than 20:4(n-6) greater than 18:2(n-6). Of the mechanisms possibly responsible for the selective entry of 22-carbon acids into ethanolamine glycerophospholipids, the most reasonable explanation was that the cytidine-mediated ethanolamine phosphotransferase may have a unique double selectivity: for hexaenoic species of diacylglycerol and for 22-carbon polyunsaturated fatty acid-containing species of alkylacylglycerol. The relative distribution of fatty acids between newly incorporated and already maintained lipid classes suggested that IGP may function in Ehrlich cells as an intermediate pool for the retention of polyunsaturated fatty acids in glycerolipids.

  19. Gene-diet interaction of a common FADS1 variant with marine polyunsaturated fatty acids for fatty acid composition in plasma and erythrocytes among men.

    PubMed

    Takkunen, Markus J; de Mello, Vanessa D; Schwab, Ursula S; Kuusisto, Johanna; Vaittinen, Maija; Ågren, Jyrki J; Laakso, Markku; Pihlajamäki, Jussi; Uusitupa, Matti I J

    2016-02-01

    Limited information exists on how the relationship between dietary intake of fat and fatty acids in erythrocytes and plasma is modulated by polymorphisms in the FADS gene cluster. We examined gene-diet interaction of total marine PUFA intake with a known gene encoding Δ-5 desaturase enzyme (FADS1) variant (rs174550) for fatty acids in erythrocyte membranes and plasma phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG). In this cross-sectional study, fatty acid compositions were measured using GC, and total intake of polyunsaturated fat from fish and fish oil was estimated using a food frequency questionnaire in a subsample (n = 962) of the Metabolic Syndrome in Men Study. We found nominally significant gene-diet interactions for eicosapentaenoic acid (EPA, 20:5n-3) in erythrocytes (pinteraction = 0.032) and for EPA in plasma PL (pinteraction = 0.062), CE (pinteraction = 0.035), and TG (pinteraction = 0.035), as well as for docosapentaenoic acid (22:5n-3) in PL (pinteraction = 0.007). After excluding omega-3 supplement users, we found a significant gene-diet interaction for EPA in erythrocytes (pinteraction < 0.003). In a separate cohort of the Kuopio Obesity Surgery Study, the same locus was strongly associated with hepatic mRNA expression of FADS1 (p = 1.5 × 10(-10) ). FADS1 variants may modulate the relationship between marine fatty acid intake and circulating levels of long-chain omega-3 fatty acids. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Metabolic diversity in biohydrogenation of polyunsaturated fatty acids by lactic acid bacteria involving conjugated fatty acid production.

    PubMed

    Kishino, Shigenobu; Ogawa, Jun; Yokozeki, Kenzo; Shimizu, Sakayu

    2009-08-01

    Lactobacillus plantarum AKU 1009a effectively transforms linoleic acid to conjugated linoleic acids of cis-9,trans-11-octadecadienoic acid (18:2) and trans-9,trans-11-18:2. The transformation of various polyunsaturated fatty acids by washed cells of L. plantarum AKU 1009a was investigated. Besides linoleic acid, alpha-linolenic acid [cis-9,cis-12,cis-15-octadecatrienoic acid (18:3)], gamma-linolenic acid (cis-6,cis-9,cis-12-18:3), columbinic acid (trans-5,cis-9,cis-12-18:3), and stearidonic acid [cis-6,cis-9,cis-12,cis-15-octadecatetraenoic acid (18:4)] were found to be transformed. The fatty acids transformed by the strain had the common structure of a C18 fatty acid with the cis-9,cis-12 diene system. Three major fatty acids were produced from alpha-linolenic acid, which were identified as cis-9,trans-11,cis-15-18:3, trans-9,trans-11,cis-15-18:3, and trans-10,cis-15-18:2. Four major fatty acids were produced from gamma-linolenic acid, which were identified as cis-6,cis-9,trans-11-18:3, cis-6,trans-9,trans-11-18:3, cis-6,trans-10-18:2, and trans-10-octadecenoic acid. The strain transformed the cis-9,cis-12 diene system of C18 fatty acids into conjugated diene systems of cis-9,trans-11 and trans-9,trans-11. These conjugated dienes were further saturated into the trans-10 monoene system by the strain. The results provide valuable information for understanding the pathway of biohydrogenation by anaerobic bacteria and for establishing microbial processes for the practical production of conjugated fatty acids, especially those produced from alpha-linolenic acid and gamma-linolenic acid.

  1. The role of omega-3 polyunsaturated fatty acids in reproduction of sheep and cattle.

    PubMed

    Gulliver, C E; Friend, M A; King, B J; Clayton, E H

    2012-03-01

    The positive effects of fat and energy supplementation on improvements in reproduction are well documented. However, the specific effects of omega-3 polyunsaturated fatty acids (n-3) on reproductive success in ruminants have not been examined in detail. While the link between n-3 and markers associated with reproduction, in particular, prostaglandin F(2α) (PGF(2α)) and the link between PGF(2α) and reproductive outcomes are well established, evidence of a direct effect of high n-3 diets on measurable reproductive outcomes in ruminants is lacking. Therefore, the aim of the current review was to examine the effect of n-3 on a number of reproductive markers and measurable outcomes in sheep and cattle. There is strong evidence linking consumption of diets high in n-3 with reduced circulating peripheral inflammatory markers such as PGF(2α). Inflammatory eicosanoids including PGF(2α), in particular, can significantly affect reproduction outcomes such as the onset of oestrus, embryo survival and parturition. While there is also evidence linking n-3 supplementation with longer time to oestrus and parturition associated with reduced PGF(2α), the effects of n-3 on other measurable outcomes of reproductive success, such as pregnancy rate, embryo survival and intergenerational effects on the health and production of offspring are largely unknown. Similarly, the effects of diets high in n-3 or n-6 polyunsaturated fatty acids on male fertility are also unknown.

  2. Polyunsaturated fatty acids and type 2 diabetes: impact on the glycemic control mechanism.

    PubMed

    Coelho, Olívia Gonçalves Leão; da Silva, Bárbara Pereira; Rocha, Daniela Mayumi Usuda Prado; Lopes, Lílian Lelis; Alfenas, Rita de Cássia Gonçalves

    2016-02-06

    There is a growing mortality related to co-morbidities associated with diabetes mellitus (DM). Polyunsaturated fatty acids (PUFA) intake has been associated with low cardiometabolic risk and reduction of inflammatory process. The objective of this paper is to review the impact of PUFA intake on glycemic control in diabetic patients, as well as elucidate the possible mechanisms involved. Medline/PubMed electronic database was searched to identify studies published within the last 5 years regarding the effect of PUFA intake on glucose metabolism in type 2 diabetics. The search terms used were: "polyunsaturated fatty acid (s)", "PUFA", and "diabetes." We included only intervetion studies that assessed the effects of PUFA intake on glucose metabolism - fasting glucose, serum insulin, HbA1c and HOMA-IR assessment- in type 2 diabetics. Initially, 48 articles were identified, which 1 was not available and 41 did not match the inclusion criteria. Within the selected studies, 3 showed an improvement on fasting blood glucose, 2 showed an increase on fasting glycemia and there was no effect of the intervention in only 1. Based on the analyzed clinical intervention studies, supplementation of 0,42-5,2 g PUFA/day for at least 8 weeks may be an alternative treatment for T2DM, particularly to Asian people.

  3. Efficient generation of sFat-1 transgenic rabbits rich in n-3 polyunsaturated fatty acids by intracytoplasmic sperm injection.

    PubMed

    Zhang, Shun; Lu, Fenghua; Liu, Qingyou; Liu, Yubing; Guan, Xiaomei; Wei, Yingming; Tan, Shijian; Shi, Deshun

    2016-03-01

    N-3 polyunsaturated fatty acids (n-3 PUFAs) have their first double bond at the third carbon from the methyl end of the fatty-acid chain and had been proven to be beneficial to human health. However, mammals cannot produce n-3 PUFAs by themselves because they lack the n-3 fatty-acid desaturase (Fat-1) gene. Thus, the possibility of producing sFat-1 transgenic rabbits was explored in this study. The transgenic cassette of pPGK1-sFat-1-CMV-EGFP was constructed and transgenic rabbit embryos were produced by intracytoplasmic sperm injection (ICSI). When 123 EGFP-positive embryos at the 2-8-cell stage were transplanted into the oviduct of four oestrous-synchronised recipients, two of them became pregnant and gave birth to seven pups. However, transfer of embryos into the uterus of oestrous-synchronised recipients and oviduct or uterus of oocyte donor rabbits did not result in pregnancy. The integration of the sFat-1 gene was confirmed in six of the seven live pups by PCR and Southern blot. The expression of the sFat-1 gene in the six transgenic pups was also detected by reverse transcription polymerase chain reaction (RT-PCR). Gas chromatography-mass spectrometry analysis revealed that transgenic rabbits exhibited an ~15-fold decrease in the ratio of n-6:n-3 PUFAs in muscle compared with wild-type rabbits and non-transgenic rabbits. These results demonstrate that sFat-1 transgenic rabbits can be produced by ICSI and display a low ratio of n-6:n-3 PUFAs.

  4. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota.

    PubMed

    Watson, Henry; Mitra, Suparna; Croden, Fiona C; Taylor, Morag; Wood, Henry M; Perry, Sarah L; Spencer, Jade A; Quirke, Phil; Toogood, Giles J; Lawton, Clare L; Dye, Louise; Loadman, Paul M; Hull, Mark A

    2017-09-26

    Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). A randomised, open-label, cross-over trial of 8 weeks' treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week 'washout' period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. ISRCTN18662143. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless

  5. Biosynthetic production of universally (13)C-labelled polyunsaturated fatty acids as reference materials for natural health product research.

    PubMed

    Le, Phuong Mai; Fraser, Catherine; Gardner, Graeme; Liang, Wei-Wan; Kralovec, Jaroslav A; Cunnane, Stephen C; Windust, Anthony J

    2007-09-01

    Long-chain polyunsaturated fatty acids (LCPUFA) including eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) have become important natural health products with numerous proven benefits related to brain function and cardiovascular health. Not only are omega-3 fatty acids available in a plethora of dietary supplements, but they are also increasingly being incorporated as triglycerides into conventional foods, including bread, milk, yoghurt and confectionaries. Recently, transgenic oil seed crops and livestock have been developed that enhance omega-3 fatty acid content. This diverse array of matrices presents a difficult analytical challenge and is compounded further by samples generated through clinical research. Stable isotope (13)C-labelled LCPUFA standards offer many advantages as research tools because they may be distinguished from their naturally abundant counterparts by mass spectrometry and directly incorporated as internal standards into analytical procedures. Further, (13)C-labelled LCPUFAs are safe to use as metabolic tracers to study uptake and metabolism in humans. Currently, (13)C-labelled LCPUFAs are expensive, available in limited supply and not in triglyceride form. To resolve these issues, marine heterotrophic microorganisms are being isolated and screened for LCPUFA production with a view to the efficient biosynthetic production of U-(13)C-labelled fatty acids using U-(13)C glucose as a carbon source. Of 37 isolates obtained, most were thraustochytrids, and either DHA or omega-6 docosapentaenoic acid (22:5n-6) were produced as the major LCPUFA. The marine protist Hyalochlorella marina was identified as a novel source of EPA and omega-3 docosapentaenoic acid (22:5n-3). As proof of principle, gram-level production of (13)C-labelled DHA has been achieved with high chemical purity ( >99%) and high (13)C incorporation levels (>90%), as confirmed by NMR and MS analyses. Finally, U-(13)C-DHA was enzymatically re-esterified to

  6. Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli

    PubMed Central

    Oyola-Robles, Delise; Rullán-Lind, Carlos; Carballeira, Néstor M.; Baerga-Ortiz, Abel

    2014-01-01

    Increasing the production of fatty acids by microbial fermentation remains an important step towards the generation of biodiesel and other portable liquid fuels. In this work, we report an Escherichia coli strain engineered to overexpress a fragment consisting of four dehydratase domains from the polyunsaturated fatty acid (PUFA) synthase enzyme complex from the deep-sea bacterium, Photobacterium profundum. The DH1-DH2-UMA enzyme fragment was excised from its natural context within a multi-enzyme PKS and expressed as a stand-alone protein. Fatty acids were extracted from the cell pellet, esterified with methanol and quantified by GC-MS analysis. Results show that the E. coli strain expressing the DH tetradomain fragment was capable of producing up to a 5-fold increase (80.31 mg total FA/L culture) in total fatty acids over the negative control strain lacking the recombinant enzyme. The enhancement in production was observed across the board for all the fatty acids that are typically made by E. coli. The overexpression of the DH tetradomain did not affect E. coli cell growth, thus showing that the observed enhancement in fatty acid production was not a result of effects associated with cell density. The observed enhancement was more pronounced at lower temperatures (3.8-fold at 16 °C, 3.5-fold at 22 °C and 1.5-fold at 30 °C) and supplementation of the media with 0.4% glycerol did not result in an increase in fatty acid production. All these results taken together suggest that either the dehydration of fatty acid intermediates are a limiting step in the E. coli fatty acid biosynthesis machinery, or that the recombinant dehydratase domains used in this study are also capable of catalyzing thioester hydrolysis of the final products. The enzyme in this report is a new tool which could be incorporated into other existing strategies aimed at improving fatty acid production in bacterial fermentations towards accessible biodiesel precursors. PMID:24411456

  7. Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli.

    PubMed

    Oyola-Robles, Delise; Rullán-Lind, Carlos; Carballeira, Néstor M; Baerga-Ortiz, Abel

    2014-02-05

    Increasing the production of fatty acids by microbial fermentation remains an important step toward the generation of biodiesel and other portable liquid fuels. In this work, we report an Escherichia coli strain engineered to overexpress a fragment consisting of four dehydratase domains from the polyunsaturated fatty acid (PUFA) synthase enzyme complex from the deep-sea bacterium, Photobacterium profundum. The DH1-DH2-UMA enzyme fragment was excised from its natural context within a multi-enzyme PKS and expressed as a stand-alone protein. Fatty acids were extracted from the cell pellet, esterified with methanol and quantified by GC-MS analysis. Results show that the E. coli strain expressing the DH tetradomain fragment was capable of producing up to a 5-fold increase (80.31 mg total FA/L culture) in total fatty acids over the negative control strain lacking the recombinant enzyme. The enhancement in production was observed across the board for all the fatty acids that are typically made by E. coli. The overexpression of the DH tetradomain did not affect E. coli cell growth, thus showing that the observed enhancement in fatty acid production was not a result of effects associated with cell density. The observed enhancement was more pronounced at lower temperatures (3.8-fold at 16 °C, 3.5-fold at 22 °C and 1.5-fold at 30 °C) and supplementation of the media with 0.4% glycerol did not result in an increase in fatty acid production. All these results taken together suggest that either the dehydration of fatty acid intermediates are a limiting step in the E. coli fatty acid biosynthesis machinery, or that the recombinant dehydratase domains used in this study are also capable of catalyzing thioester hydrolysis of the final products. The enzyme in this report is a new tool which could be incorporated into other existing strategies aimed at improving fatty acid production in bacterial fermentations toward accessible biodiesel precursors.

  8. Differential influence of pre- and post-delta-6-desaturation n6 polyunsaturated fatty acids on fibroblasts in culture, compared to n9 monounsaturated and n3 polyunsaturated fatty acids.

    PubMed

    Davidson, B C; Girao, L A F; Giangregorio, A

    2005-01-01

    There is now considerable evidence that polyunsaturated fatty acids (PUFA) are effective in vitro at limiting the growth of cancer cells while not affecting normal cells to the same extent. Twenty carbon PUFA, especially of the n3 series, have been shown to be particularly potent; while the eighteen carbon n6 fatty acid, linoleic acid has been implicated in growth stimulation of breast cancer. We report here on the comparative effects of a range of eighteen and twenty carbon fatty acids of varying degrees of unsaturation on normal and transformed fibroblasts in culture. All moieties of the n3 series showed high potency in limiting transformed cell growth, while cis and trans monounsaturates and pre-delta-6-desaturation n6 polyunsaturates induced a mixed response, even inducing comparative growth stimulation with some fatty acid concentrations.

  9. Biosynthesis of Essential Polyunsaturated Fatty Acids in Wheat Triggered by Expression of Artificial Gene

    PubMed Central

    Mihálik, Daniel; Klčová, Lenka; Ondreičková, Katarína; Hudcovicová, Martina; Gubišová, Marcela; Klempová, Tatiana; Čertík, Milan; Pauk, János; Kraic, Ján

    2015-01-01

    The artificial gene D6D encoding the enzyme ∆6desaturase was designed and synthesized using the sequence of the same gene from the fungus Thamnidium elegans. The original start codon was replaced by the signal sequence derived from the wheat gene for high-molecular-weight glutenin subunit and the codon usage was completely changed for optimal expression in wheat. Synthesized artificial D6D gene was delivered into plants of the spring wheat line CY-45 and the gene itself, as well as transcribed D6D mRNA were confirmed in plants of T0 and T1 generations. The desired product of the wheat genetic modification by artificial D6D gene was the γ-linolenic acid. Its presence was confirmed in mature grains of transgenic wheat plants in the amount 0.04%–0.32% (v/v) of the total amount of fatty acids. Both newly synthesized γ-linolenic acid and stearidonic acid have been detected also in leaves, stems, roots, awns, paleas, rachillas, and immature grains of the T1 generation as well as in immature and mature grains of the T2 generation. Contents of γ-linolenic acid and stearidonic acid varied in range 0%–1.40% (v/v) and 0%–1.53% (v/v) from the total amount of fatty acids, respectively. This approach has opened the pathway of desaturation of fatty acids and production of essential polyunsaturated fatty acids in wheat. PMID:26694368

  10. Effects of in utero exposure to polychlorinated biphenyls, methylmercury, and polyunsaturated fatty acids on birth size.

    PubMed

    Miyashita, Chihiro; Sasaki, Seiko; Ikeno, Tamiko; Araki, Atsuko; Ito, Sachiko; Kajiwara, Jumboku; Todaka, Takashi; Hachiya, Noriyuki; Yasutake, Akira; Murata, Katsuyuki; Nakajima, Tamie; Kishi, Reiko

    2015-11-15

    The adverse effects of in utero exposure to polychlorinated biphenyls (PCBs) or methylmercury (MeHg), and the beneficial effects of nutrients from maternal fish intake might have opposing influences on fetal growth. In this study, we assessed the effects of in utero exposure to PCBs and MeHg on birth size in the Japanese population, which is known to have a high frequency of fish consumption. The concentrations of PCBs and polyunsaturated fatty acids in maternal blood, and the total mercury in hair (as a biomarker of MeHg exposure) were measured during pregnancy and at delivery. Maternal intakes of fish (subtypes: fatty and lean) and shellfishes were calculated from a food frequency questionnaire administered at delivery. Newborn anthropometric measurement data were obtained from birth records. The associations between chemical exposures and birth size were analyzed by using multiple regression analysis with adjustment for confounding factors among 367 mother-newborn pairs. The birth weight was 3073±37 g (mean±SD). The incidence of babies small for gestational age (SGA) by weight was 4.9%. The median concentrations of total PCBs and hair mercury were 108 ng/g lipid and 1.41 μg/g, respectively. There was no overall association between mercury concentrations and birth weight, birth length, chest circumference, and head circumference. We observed that the risk of SGA by weight decreased with increasing mercury concentration in regression analyses with adjustment for polyunsaturated fatty acids. Our results suggest that the beneficial effect of essential nutrition may mask the adverse effects of MeHg on birth size. The concentrations of PCBs had no association with birth size.

  11. Polyunsaturated Fatty Acids Differentially Modulate Cell Proliferation and Endocannabinoid System in Two Human Cancer Lines.

    PubMed

    Gastón, Repossi; María Eugenia, Pasqualini; Das, Undurti N; Eynard, Aldo R

    2017-01-01

    Evidence suggests that quantity and quality of dietary polyunsaturated fatty acids (PUFAs) play a role in the development of cancer. However, the mechanisms involved in this interaction(s) are not clear. Endocannabinoids are lipid metabolites known to have growth modulatory actions. We studied the effect of supplementation with PUFAs ω-6 and ω-3 (essential fatty acids, EFAs), saturated and monounsaturated fatty acids (non-EFAs) on the growth of tumor cells and modifications in their endocannabinoid content. Cell cultures of human glioblastoma (T98G) and breast cancer (MCF7) were supplemented with 50 or 100 mmol EFAs and non-EFAs for 72 h. Cell proliferation was then determined by MTT, anandamide (AEA) levels by HPLC, total fatty acids profiles by GLC, CB1 receptor expression by WB and FAAH activity by spectrophotometric method. Fatty acids profile reflected the incorporation of the lipids supplemented in each assay. Arachidonic acid (EFA ω-6) supplementation increased AEA levels and inhibited the growth of T98G, whereas palmitic acid (non-EFA) enhanced their proliferation. In breast cancer (MCF7) cells, eicosapentaenoic acid (EFA ω-3) reduced and oleic acid (non-EFA) enhanced their proliferation. CB1 expression was higher in T98G and no differences were observed in FAAH activity. The growth of tumor cells can be differentially modulated by fatty acids and, at least in part, can be attributed to their ability to act on the components of the endocannabinoid system. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  12. Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.

    PubMed

    Taha, Ameer Y; Cheon, Yewon; Faurot, Keturah F; Macintosh, Beth; Majchrzak-Hong, Sharon F; Mann, J Douglas; Hibbeln, Joseph R; Ringel, Amit; Ramsden, Christopher E

    2014-05-01

    Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA. Published by Elsevier Ltd.

  13. Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel.

    PubMed

    Liin, Sara I; Silverå Ejneby, Malin; Barro-Soria, Rene; Skarsfeldt, Mark Alexander; Larsson, Johan E; Starck Härlin, Frida; Parkkari, Teija; Bentzen, Bo Hjorth; Schmitt, Nicole; Larsson, H Peter; Elinder, Fredrik

    2015-05-05

    Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the β-subunit KCNE1 form the cardiac IKs channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as IKs channel modulators. We report that PUFAs open Kv7.1 via an electrostatic mechanism. Both the polyunsaturated acyl tail and the negatively charged carboxyl head group are required for PUFAs to open Kv7.1. We further show that KCNE1 coexpression abolishes the PUFA effect on Kv7.1 by promoting PUFA protonation. PUFA analogs with a decreased pKa value, to preserve their negative charge at neutral pH, restore the sensitivity to open IKs channels. PUFA analogs with a positively charged head group inhibit IKs channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act antiarrhythmically in embryonic rat cardiomyocytes and in isolated perfused hearts from guinea pig.

  14. Serum n-3 polyunsaturated fatty acids and psychological distress in early pregnancy: Adjunct Study of Japan Environment and Children's Study.

    PubMed

    Hamazaki, K; Harauma, A; Otaka, Y; Moriguchi, T; Inadera, H

    2016-02-16

    N-3 polyunsaturated fatty acids (PUFAs), especially long-chain types such as docosahexaenoic acid, are important nutrients in pregnancy, but the relationship between n-3 PUFA levels and perinatal and postnatal depression remains controversial. This study examined the possible relationship between serum n-3 PUFA levels and psychological distress among expectant mothers in early pregnancy. Data and specimen samples were obtained in a birth cohort study started at Toyama Regional Center in July 2012 as an adjunct study of the Japan Environment and Children's Study. Blood samples were collected at 9-14 weeks' gestation (75% of samples) or after 15 weeks (25%). Subjects with a Kessler Psychological Distress Scale score (K6) ⩾ 9 were assigned to the psychological distress group (n=283). The control group (n=283) was matched for age, educational level and family income. Fatty acid composition was determined from serum samples by gas chromatography. Associations between fatty acid levels and incident psychological distress were evaluated by logistic regression. After adjusting for possible confounders, eicosapentaenoic acid showed an inverse association with risk of psychological distress, with an odds ratio of 0.47 (95% confidence interval: 0.30, 0.73) for the highest tertile. This inverse association remained even after applying a higher cutoff score (K6 ⩾ 13) indicating severe psychological distress (74 pairs). We believe this is the first study to reveal the associations between serum n-3 PUFAs and risk of psychological distress in early pregnancy. Further research is required to verify the causality of these associations.

  15. Serum n-3 polyunsaturated fatty acids and psychological distress in early pregnancy: Adjunct Study of Japan Environment and Children's Study

    PubMed Central

    Hamazaki, K; Harauma, A; Otaka, Y; Moriguchi, T; Inadera, H

    2016-01-01

    N-3 polyunsaturated fatty acids (PUFAs), especially long-chain types such as docosahexaenoic acid, are important nutrients in pregnancy, but the relationship between n-3 PUFA levels and perinatal and postnatal depression remains controversial. This study examined the possible relationship between serum n-3 PUFA levels and psychological distress among expectant mothers in early pregnancy. Data and specimen samples were obtained in a birth cohort study started at Toyama Regional Center in July 2012 as an adjunct study of the Japan Environment and Children's Study. Blood samples were collected at 9–14 weeks' gestation (75% of samples) or after 15 weeks (25%). Subjects with a Kessler Psychological Distress Scale score (K6) ⩾9 were assigned to the psychological distress group (n=283). The control group (n=283) was matched for age, educational level and family income. Fatty acid composition was determined from serum samples by gas chromatography. Associations between fatty acid levels and incident psychological distress were evaluated by logistic regression. After adjusting for possible confounders, eicosapentaenoic acid showed an inverse association with risk of psychological distress, with an odds ratio of 0.47 (95% confidence interval: 0.30, 0.73) for the highest tertile. This inverse association remained even after applying a higher cutoff score (K6 ⩾13) indicating severe psychological distress (74 pairs). We believe this is the first study to reveal the associations between serum n-3 PUFAs and risk of psychological distress in early pregnancy. Further research is required to verify the causality of these associations. PMID:26882037

  16. Meta-analysis of erythrocyte polyunsaturated fatty acid biostatus in bipolar disorder

    PubMed Central

    McNamara, Robert K; Welge, Jeffrey A

    2016-01-01

    Objectives Dietary deficiency in polyunsaturated fatty acids (PUFA), including omega-3 fatty acids eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), and excesses in omega-6 fatty acids including linoleic acid (LA, 18:2n-6) and arachidonic acid (AA, 20:4n-6), may be associated with the pathophysiology of bipolar disorder. In an effort to provide clarification regarding the relationship between PUFA biostatus and bipolar disorder, this meta-analysis investigated studies comparing erythrocyte (red blood cell) membrane PUFA composition in patients with bipolar disorder and healthy controls. Methods A meta-analysis was performed on case–control studies comparing erythrocyte PUFA (EPA, DHA, LA, AA) levels in patients with bipolar I disorder. Standardized effect sizes were calculated and combined using a random effects model. Results Six eligible case–control studies comprising patients with bipolar I disorder (n = 118) and healthy controls (n = 147) were included in the analysis. Compared with healthy controls, patients with bipolar I disorder exhibit robust erythrocyte DHA deficits (p = 0.0008) and there was a trend for lower EPA (p = 0.086). There were no significant differences in LA (p = 0.42) or AA (p = 0.64). Conclusions Bipolar I disorder is associated with robust erythrocyte DHA deficits. These findings add to a growing body of evidence implicating omega-3 PUFA deficiency in the pathophysiology of bipolar disorder. PMID:27087497

  17. Lower omega-3 polyunsaturated fatty acids and lower docosahexaenoic acid in men with pedophilia.

    PubMed

    Mincke, Elda; Cosyns, Paul; Christophe, Armand B; De Vriese, Stephanie; Maes, Michael

    2006-12-01

    Previous studies have suggested that abnormalities in plasma phospholipid fatty acids may play a role in aggressive behavior. Recently, it was suggested that a dysfunctional serotonergic turnover in the brain may be involved in the etiopathology of pedophilia. Depletion of n-3 polyunsaturated fatty acids (PUFA) may cause alterations in the serotonergic system that may be related to pedophilia and aggression. This study examines the serum phospholipid n-3 and n-6 PUFA fractions in pedophilia. Twenty-seven pedophilic men and eighteen healthy volunteers participated in this study. In pedophilia there was a significant depletion of the C22:6n-3 (docosahexaenoic acid, DHA), total n-3 fractions and an increase in the total n-6/n-3 and C20:4n-6/C20:5n-3 (arachidonic acid/eicosapentaenoic acid) ratios. Using the NEO Personality Inventory, lower DHA in pedophiles is related to more impulsiveness and lower agreeableness (trust, altruism, straightforwardness, compliance) and conscientiousness (self-discipline). The results of this study suggest that a depletion of the serum phospholipid n-3 higher unsaturated fatty acids (HUFAs) and, in particular, of DHA may take part in the pathophysiology of pedophilia. One hypothesis is that a depletion of n-3 HUFAs and DHA may cause alterations in the serotonergic turnover, which are related to impulse discontrol and aggression-hostility, behaviors which are associated with pedophilia.

  18. Polyunsaturated Fatty Acid Composition of Maternal Diet and Erythrocyte Phospholipid Status in Chilean Pregnant Women

    PubMed Central

    Bascuñán, Karla A.; Valenzuela, Rodrigo; Chamorro, Rodrigo; Valencia, Alejandra; Barrera, Cynthia; Puigrredon, Claudia; Sandoval, Jorge; Valenzuela, Alfonso

    2014-01-01

    Chilean diets are characterized by a low supply of n-3 polyunsaturated fatty acids (n-3 PUFA), which are critical nutrients during pregnancy and lactation, because of their role in brain and visual development. DHA is the most relevant n-3 PUFA in this period. We evaluated the dietary n-3 PUFA intake and erythrocyte phospholipids n-3 PUFA in Chilean pregnant women. Eighty healthy pregnant women (20–36 years old) in the 3rd–6th month of pregnancy were included in the study. Dietary assessment was done applying a food frequency questionnaire, and data were analyzed through the Food Processor SQL® software. Fatty acids of erythrocyte phospholipids were assessed by gas-liquid chromatography. Diet composition was high in saturated fat, low in mono- and PUFA, high in n-6 PUFA (linoleic acid) and low in n-3 PUFA (alpha-linolenic acid and DHA), with imbalance in the n-6/n-3 PUFA ratio. Similar results were observed for fatty acids from erythrocyte phospholipids. The sample of Chilean pregnant women showed high consumption of saturated fat and low consumption of n-3 PUFA, which is reflected in the low DHA content of erythrocyte phospholipids. Imbalance between n-6/n-3 PUFA could negatively affect fetal development. New strategies are necessary to improve n-3 PUFA intake throughout pregnancy and breast feeding periods. Furthermore, it is necessary to develop dietary interventions to improve the quality of consumed foods with particular emphasis on n-3 PUFA. PMID:25386693

  19. Meta-analysis of erythrocyte polyunsaturated fatty acid biostatus in bipolar disorder.

    PubMed

    McNamara, Robert K; Welge, Jeffrey A

    2016-05-01

    Dietary deficiency in polyunsaturated fatty acids (PUFAs), including the omega-3 fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), and excesses in omega-6 fatty acids, including linoleic acid (LA; 18:2n-6) and arachidonic acid (AA; 20:4n-6), may be associated with the pathophysiology of bipolar disorder. In an effort to provide clarification regarding the relationship between PUFA biostatus and bipolar disorder, this meta-analysis investigated studies comparing erythrocyte (red blood cell) membrane PUFA composition in patients with bipolar disorder and healthy controls. A meta-analysis was performed on case-control studies comparing erythrocyte PUFA (EPA, DHA, LA and AA) levels in patients with bipolar I disorder and healthy controls. Standardized effect sizes were calculated and combined using a random effects model. Six eligible case-control studies comprising n = 118 bipolar I patients and n = 147 healthy controls were included in the analysis. Compared with healthy controls, patients with bipolar I disorder exhibited robust erythrocyte DHA deficits (p = 0.0008) and there was a trend for lower EPA (p = 0.086). There were no significant differences in LA (p = 0.42) or AA (p = 0.64). Bipolar I disorder is associated with robust erythrocyte DHA deficits. These findings add to a growing body of evidence implicating omega-3 PUFA deficiency in the pathophysiology of bipolar disorder. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Periodontal condition in relation to intake of omega-3 and omega-6 polyunsaturated fatty acids.

    PubMed

    Jauhiainen, Leena; Ylöstalo, Pekka; Männistö, Satu; Kanerva, Noora; Knuuttila, Matti; Suominen, Anna L

    2016-11-01

    To examine whether the intake of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) is associated with periodontal condition. The study population consisted of non-smoking, non-diabetic and non-rheumatoid individuals in the Health 2000 Survey in Finland. Analyses were made in two age groups: 30-49 years (n = 1212) and 50-79 years (n = 980). Clinically determined sextants with gingival bleeding and teeth with periodontal pockets were used as outcome variables. Dietary data were collected by a validated food frequency questionnaire. Energy-adjusted intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), omega-3 and omega-6 PUFAs, as well as ratios of EPA/AA and of DHA/AA, and omega-3/omega-6 PUFAs were used as exposures. Prevalence rate ratios were estimated using Poisson regression models. In this population, there were no statistically significant associations between the examined omega-3 or omega-6 fatty acids or their ratios and the periodontal outcome variables. This cross-sectional study provided evidence that individual omega-3 or omega-6 fatty acids, their subclasses or ratios are not associated with periodontal health among a non-diabetic, non-rheumatoid and non-smoking population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. ω-3 polyunsaturated fatty acids ameliorate type 1 diabetes and autoimmunity

    PubMed Central

    Bi, Xinyun; Li, Fanghong; Liu, Shanshan; Jin, Yan; Zhang, Xin; Yang, Tao; Dai, Yifan; Li, Xiaoxi; Zhao, Allan Zijian

    2017-01-01

    Despite the benefit of insulin, blockade of autoimmune attack and regeneration of pancreatic islets are ultimate goals for the complete cure of type 1 diabetes (T1D). Long-term consumption of ω-3 polyunsaturated fatty acids (PUFAs) is known to suppress inflammatory processes, making these fatty acids candidates for the prevention and amelioration of autoimmune diseases. Here, we explored the preventative and therapeutic effects of ω-3 PUFAs on T1D. In NOD mice, dietary intervention with ω-3 PUFAs sharply reduced the incidence of T1D, modulated the differentiation of Th cells and Tregs, and decreased the levels of IFN-γ, IL-17, IL-6, and TNF-α. ω-3 PUFAs exerted similar effects on the differentiation of CD4+ T cells isolated from human peripheral blood mononuclear cells. The regulation of CD4+ T cell differentiation was mediated at least in part through ω-3 PUFA eicosanoid derivatives and by mTOR complex 1 (mTORC1) inhibition. Importantly, therapeutic intervention in NOD mice through nutritional supplementation or lentivirus-mediated expression of an ω-3 fatty acid desaturase, mfat-1, normalized blood glucose and insulin levels for at least 182 days, blocked the development of autoimmunity, prevented lymphocyte infiltration into regenerated islets, and sharply elevated the expression of the β cell markers pancreatic and duodenal homeobox 1 (Pdx1) and paired box 4 (Pax4). The findings suggest that ω-3 PUFAs could potentially serve as a therapeutic modality for T1D. PMID:28375156

  2. [Polyunsaturated omega-3 fatty acids and systemic lupus erythematosus: what do we know?].

    PubMed

    Borges, Mariane Curado; Santos, Fabiana de Miranda Moura; Telles, Rosa Weiss; Correia, Maria Isabel Toulson Davisson; Lanna, Cristina Costa Duarte

    2014-01-01

    Various studies have demonstrated the impact of omega-3 fatty acids on the concentration of C reactive protein (CRP), pro-inflammatory eicosanoids, cytokines, chemokines and other inflammatory mediators. Therefore, the supplementation of these types of lipids may represent additional option treatment for chronic systemic diseases, such as Systemic Lupus Erythematous and other rheumatic diseases. The role of these lipids has not been well established, yet. However, it seems there is a direct relationship between its intake and the decrease of the disease clinical manifestations as well as of the inflammatory status of the patients. Thus, the aim of this manuscript is to present a thorough review on the effects of omega-3 fatty acids in patients with SLE. Bibliographic data set as the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) were searched using as key words: systemic lupus erythematous (SLE), polyunsaturated fatty acids omega-3, eicosapentanoic acid (EPA), docosahexanoic acid (DHA), antioxidants and diet. Manuscripts published up to September 2013 were included. There were 43 articles related to the topic, however only 15 pertained human studies, with three review articles and 12 clinical studies. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  3. Anti-inflammatory effects of polyunsaturated fatty acids in THP-1 cells

    SciTech Connect

    Zhao Guixiang; Etherton, Terry D.; Martin, Keith R.; Vanden Heuvel, John P.; Gillies, Peter J.; West, Sheila G.; Kris-Etherton, Penny M. . E-mail: pmk3@psu.edu

    2005-10-28

    The effects of linoleic acid (LA), {alpha}-linolenic acid (ALA), and docosahexaenoic acid (DHA) were compared to that of palmitic acid (PA), on inflammatory responses in human monocytic THP-1 cells. When cells were pre-incubated with fatty acids for 2-h and then stimulated with lipopolysaccharide for 24-h in the presence of fatty acids, secretion of interleukin (IL)-6, IL-1{beta}, and tumor necrosis factor-{alpha} (TNF{alpha}) was significantly decreased after treatment with LA, ALA, and DHA versus PA (P < 0.01 for all); ALA and DHA elicited more favorable effects. These effects were comparable to those for 15-deoxy-{delta}{sup 12,14}-prostaglandin J2 (15d-PGJ2) and were dose-dependent. In addition, LA, ALA, and DHA decreased IL-6, IL-1{beta}, and TNF{alpha} gene expression (P < 0.05 for all) and nuclear factor (NF)-{kappa}B DNA-binding activity, whereas peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) DNA-binding activity was increased. The results indicate that the anti-inflammatory effects of polyunsaturated fatty acids may be, in part, due to the inhibition of NF-{kappa}B activation via activation of PPAR{gamma}.

  4. Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice

    PubMed Central

    Karanth, Santhosh; Tran, Vy My; Kuberan, Balagurunathan; Schlegel, Amnon

    2013-01-01

    SUMMARY Lipid disorders pose therapeutic challenges. Previously we discovered that mutation of the hepatocyte β-hydroxybutyrate transporter Slc16a6a in zebrafish causes hepatic steatosis during fasting, marked by increased hepatic triacylglycerol, but not cholesterol. This selective diversion of trapped ketogenic carbon atoms is surprising because acetate and acetoacetate can exit mitochondria and can be incorporated into both fatty acids and cholesterol in normal hepatocytes. To elucidate the mechanism of this selective diversion of carbon atoms to fatty acids, we fed wild-type and slc16a6a mutant animals high-protein ketogenic diets. We find that slc16a6a mutants have decreased activity of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr), despite increased Hmgcr protein abundance and relative incorporation of mevalonate into cholesterol. These observations suggest the presence of an endogenous Hmgcr inhibitor. We took a candidate approach to identify such inhibitors. First, we found that mutant livers accumulate multiple polyunsaturated fatty acids (PUFAs) and PUFA-CoAs, and we showed that human HMGCR is inhibited by PUFA-CoAs in vitro. Second, we injected mice with an ethyl ester of the PUFA eicosapentaenoic acid and observed an acute decrease in hepatic Hmgcr activity, without alteration in Hmgcr protein abundance. These results elucidate a mechanism for PUFA-mediated cholesterol lowering through direct inhibition of Hmgcr. PMID:24057001

  5. Six Tissue Transcriptomics Reveals Specific Immune Suppression in Spleen by Dietary Polyunsaturated Fatty Acids.

    PubMed

    Svahn, Sara L; Väremo, Leif; Gabrielsson, Britt G; Peris, Eduard; Nookaew, Intawat; Grahnemo, Louise; Sandberg, Ann-Sofie; Wernstedt Asterholm, Ingrid; Jansson, John-Olov; Nielsen, Jens; Johansson, Maria E

    2016-01-01

    Dietary polyunsaturated fatty acids (PUFA) are suggested to modulate immune function, but the effects of dietary fatty acids composition on gene expression patterns in immune organs have not been fully characterized. In the current study we investigated how dietary fatty acids composition affects the total transcriptome profile, and especially, immune related genes in two immune organs, spleen (SPL) and bone marrow cells (BMC). Four tissues with metabolic function, skeletal muscle (SKM), white adipose tissue (WAT), brown adipose tissue (BAT), and liver (LIV), were investigated as a comparison. Following 8 weeks on low fat diet (LFD), high fat diet (HFD) rich in saturated fatty acids (HFD-S), or HFD rich in PUFA (HFD-P), tissue transcriptomics were analyzed by microarray and metabolic health assessed by fasting blood glucose level, HOMA-IR index, oral glucose tolerance test as well as quantification of crown-like structures in WAT. HFD-P corrected the metabolic phenotype induced by HFD-S. Interestingly, SKM and BMC were relatively inert to the diets, whereas the two adipose tissues (WAT and BAT) were mainly affected by HFD per se (both HFD-S and HFD-P). In particular, WAT gene expression was driven closer to that of the immune organs SPL and BMC by HFDs. The LIV exhibited different responses to both of the HFDs. Surprisingly, the spleen showed a major response to HFD-P (82 genes differed from LFD, mostly immune genes), while it was not affected at all by HFD-S (0 genes differed from LFD). In conclusion, the quantity and composition of dietary fatty acids affected the transcriptome in distinct manners in different organs. Remarkably, dietary PUFA, but not saturated fat, prompted a specific regulation of immune related genes in the spleen, opening the possibility that PUFA can regulate immune function by influencing gene expression in this organ.

  6. Childrens' learning and behaviour and the association with cheek cell polyunsaturated fatty acid levels.

    PubMed

    Kirby, A; Woodward, A; Jackson, S; Wang, Y; Crawford, M A

    2010-01-01

    Increasing interest in the role of omega-3 fatty acids in relation to neurodevelopmental disorders (e.g. ADHD, dyslexia, autism) has occurred as a consequence of some international studies highlighting this link. In particular, some studies have shown that children with ADHD may have lower concentrations of polyunsaturated fatty acids (PUFAs), particularly omega-3, in their red blood cells and plasma, and that supplementation with omega-3 fatty acids may alleviate behavioural symptoms in this population. However, in order to compare levels it seems appropriate to establish fatty acid levels in a mainstream school aged population and if levels relate to learning and behaviour. To date no study has established this. For this study, cheek cell samples from 411 typically developing school children were collected and analysed for PUFA content, in order to establish the range in this population. In addition, measures of general classroom attention and behaviour were assessed in these children by teachers and parents. Cognitive performance tests were also administered in order to explore whether an association between behaviour and/or cognitive performance and PUFA levels exists. Relationships between PUFA levels and socio-economic status were also explored. Measures of reading, spelling and intelligence did not show any association with PUFA levels, but some associations were noted with the level of omega-3 fatty acids and teacher and parental reports of behaviour, with some evidence that higher omega-3 levels were associated with decreased levels of inattention, hyperactivity, emotional and conduct difficulties and increased levels of prosocial behaviour. These findings are discussed in relation to previous findings from omega-3 supplementation studies with children.

  7. Six Tissue Transcriptomics Reveals Specific Immune Suppression in Spleen by Dietary Polyunsaturated Fatty Acids

    PubMed Central

    Gabrielsson, Britt G.; Peris, Eduard; Nookaew, Intawat; Grahnemo, Louise; Sandberg, Ann-Sofie; Wernstedt Asterholm, Ingrid; Jansson, John-Olov; Nielsen, Jens

    2016-01-01

    Dietary polyunsaturated fatty acids (PUFA) are suggested to modulate immune function, but the effects of dietary fatty acids composition on gene expression patterns in immune organs have not been fully characterized. In the current study we investigated how dietary fatty acids composition affects the total transcriptome profile, and especially, immune related genes in two immune organs, spleen (SPL) and bone marrow cells (BMC). Four tissues with metabolic function, skeletal muscle (SKM), white adipose tissue (WAT), brown adipose tissue (BAT), and liver (LIV), were investigated as a comparison. Following 8 weeks on low fat diet (LFD), high fat diet (HFD) rich in saturated fatty acids (HFD-S), or HFD rich in PUFA (HFD-P), tissue transcriptomics were analyzed by microarray and metabolic health assessed by fasting blood glucose level, HOMA-IR index, oral glucose tolerance test as well as quantification of crown-like structures in WAT. HFD-P corrected the metabolic phenotype induced by HFD-S. Interestingly, SKM and BMC were relatively inert to the diets, whereas the two adipose tissues (WAT and BAT) were mainly affected by HFD per se (both HFD-S and HFD-P). In particular, WAT gene expression was driven closer to that of the immune organs SPL and BMC by HFDs. The LIV exhibited different responses to both of the HFDs. Surprisingly, the spleen showed a major response to HFD-P (82 genes differed from LFD, mostly immune genes), while it was not affected at all by HFD-S (0 genes differed from LFD). In conclusion, the quantity and composition of dietary fatty acids affected the transcriptome in distinct manners in different organs. Remarkably, dietary PUFA, but not saturated fat, prompted a specific regulation of immune related genes in the spleen, opening the possibility that PUFA can regulate immune function by influencing gene expression in this organ. PMID:27166587

  8. Use of Omega-3 Polyunsaturated Fatty Acids to Treat Inspissated Bile Syndrome: A Case Report.

    PubMed

    Jun, Woo Young; Cho, Min Jeng; Han, Hye Seung; Bae, Sun Hwan

    2016-12-01

    Inspissated bile syndrome (IBS) is a rare condition in which thick intraluminal bile, including bile plugs, sludge, or stones, blocks the extrahepatic bile ducts in an infant. A 5-week-old female infant was admitted for evaluation of jaundice and acholic stool. Diagnostic tests, including ultrasound sonography, magnetic resonance cholangiopancreatography, and a hepatobiliary scan, were not conclusive. Although the diagnosis was unclear, the clinical and laboratory findings improved gradually on administration of urodeoxycholic acid and lipid emulsion containing omega-3 polyunsaturated fatty acids (PUFAs) for 3 weeks. However, a liver biopsy was suggestive of biliary atresia. This finding forced us to perform intraoperative cholangiography, which revealed a patent common bile duct with impacted thick bile. We performed normal saline irrigation and the symptom was improved, the final diagnosis was IBS. Thus, we herein report that IBS can be treated with omega-3 PUFAs as an alternative to surgical intervention.

  9. Inhibitory role of polyunsaturated fatty acids on lysophosphatidic acid-induced cancer cell migration and adhesion.

    PubMed

    Kim, Eun Kyoung; Ha, Jung Min; Kim, Young Whan; Jin, Seo Yeon; Ha, Hong Koo; Bae, Sun Sik

    2014-08-25

    Polyunsaturated fatty acids (PUFAs) have important pharmacological effects on mammalian cells. Here, we show that carboxyl group-containing PUFAs inhibit lysophosphatidic acid (LPA)-induced focal adhesion formation, thereby inhibiting migration and adhesion. Carboxyl group-containing PUFAs inhibit LPA-induced calcium mobilization, whereas ethyl ester-group containing PUFAs have no effect. In addition, carboxyl group-containing PUFAs functionally inhibit LPA-dependent RhoA activation. Given these results, we suggest that PUFAs may inhibit LPA-induced calcium/RhoA signaling pathways leading to focal adhesion formation. Carboxyl group-containing PUFAs may have a functional role in this regulatory mechanism. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. Use of Omega-3 Polyunsaturated Fatty Acids to Treat Inspissated Bile Syndrome: A Case Report

    PubMed Central

    Jun, Woo Young; Cho, Min Jeng; Han, Hye Seung

    2016-01-01

    Inspissated bile syndrome (IBS) is a rare condition in which thick intraluminal bile, including bile plugs, sludge, or stones, blocks the extrahepatic bile ducts in an infant. A 5-week-old female infant was admitted for evaluation of jaundice and acholic stool. Diagnostic tests, including ultrasound sonography, magnetic resonance cholangiopancreatography, and a hepatobiliary scan, were not conclusive. Although the diagnosis was unclear, the clinical and laboratory findings improved gradually on administration of urodeoxycholic acid and lipid emulsion containing omega-3 polyunsaturated fatty acids (PUFAs) for 3 weeks. However, a liver biopsy was suggestive of biliary atresia. This finding forced us to perform intraoperative cholangiography, which revealed a patent common bile duct with impacted thick bile. We performed normal saline irrigation and the symptom was improved, the final diagnosis was IBS. Thus, we herein report that IBS can be treated with omega-3 PUFAs as an alternative to surgical intervention. PMID:28090475

  11. Omega-3 polyunsaturated fatty acids for the prevention of cardiovascular disease: do formulation, dosage & comparator matter?

    PubMed

    DiNicolantonio, James J; Meier, Pascal; O'Keefe, James H

    2013-01-01

    Multiple trials over the past two decades testing omega-3 polyunsaturated fatty acids (PUFAs), containing eicosapentaenoic acid (EPA) and or docosahexaenoic acid (DHA), have shown substantial benefits for reducing major coronary heart disease (CHD) events, all-cause mortality, cardiovascular (CV) death, sudden cardiac death (SCD), and stroke. However, recent trials testing omega-3s have generally failed to confirm these benefits. While increased fish and fish oil intake among the general population, increased use of optimal medical therapy (including statins, aspirin, and modern antihypertensive medications) probably make it more challenging for fish oil supplementation to show additional benefits, there might be further explanations in the formulation, dosage, and comparator used in these recent omega-3 trials.

  12. Role of n-3 Polyunsaturated Fatty Acids and Exercise in Breast Cancer Prevention: Identifying Common Targets

    PubMed Central

    Abdelmagid, Salma A.; MacKinnon, Jessica L.; Janssen, Sarah M.; Ma, David W.L.

    2016-01-01

    Diet and exercise are recognized as important lifestyle factors that significantly influence breast cancer risk. In particular, dietary n-3 polyunsaturated fatty acids (PUFAs) have been shown to play an important role in breast cancer prevention. Growing evidence also demonstrates a role for exercise in cancer and chronic disease prevention. However, the potential synergistic effect of n-3 PUFA intake and exercise is yet to be determined. This review explores targets for breast cancer prevention that are common between n-3 PUFA intake and exercise and that may be important study outcomes for future research investigating the combined effect of n-3 PUFA intake and exercise. These lines of evidence highlight potential new avenues for research and strategies for breast cancer prevention. PMID:27812288

  13. Enhanced baroreceptor control of the cardiovascular system by polyunsaturated Fatty acids in heart failure patients.

    PubMed

    Radaelli, Alberto; Cazzaniga, Maria; Viola, Andrea; Balestri, Giulia; Janetti, Maria Bianchi; Signorini, Maria G; Castiglioni, Paolo; Azzellino, Arianna; Mancia, Giuseppe; Ferrari, Alberto U

    2006-10-17

    The intention of this study was to test the hypothesis that, in heart failure patients, dietary supplementation of polyunsaturated fatty acids (PUFA) enhances arterial baroreceptor control of the cardiovascular system. Administration of PUFA reduces the risk of life-threatening arrhythmias in patients surviving myocardial infarction. This might result from potentiation of arterial baroreflexes, but whether or not PUFA enhance baroreflex function has never been studied in humans. Patients with post-myocardial infarction left ventricular dysfunction underwent beat-to-beat blood pressure (BP) (Finapres, Ohmeda Inc., Englewood, Colorado) and R-R interval (electrocardiogram) recording; baroreceptor reflexes were assessed from the bradycardic and depressor responses to graded neck suction (NS) as well as by computation of the alpha "spontaneous" baroreflex sensitivity index. Assessments were repeated after prolonged treatment with PUFA (2 g/die, n = 15) or placebo (n = 10). Baseline BP and R-R interval were unaffected by PUFA. Both reflex depressor and bradycardic responses to NS increased after PUFA (respectively from -0.09 +/- 0.01 to -0.16 +/- 0.01 mm Hg x mm Hg(-1), p < 0.01, and from 1.25 +/- 0.9 to 1.76 +/- 1.1 ms x mm Hg(-1), p < 0.04) but not after placebo. The spontaneous baroreflex sensitivity increased in the PUFA (from 8.99 +/- 1.4 to 12.2 +/- 1.2 ms x mm Hg(-1), p < 0.02) but not in the placebo group. Polyunsaturated fatty acids (but not placebo) treatment also significantly increased R-R interval total variance and low-frequency and high-frequency spectral powers. Dietary PUFA supplementation markedly potentiates baroreflex function and enhances heart rate variability in patients with stable congestive heart failure.

  14. Combining nutrition, food science and engineering in developing solutions to Inflammatory bowel diseases--omega-3 polyunsaturated fatty acids as an example.

    PubMed

    Ferguson, Lynnette R; Smith, Bronwen G; James, Bryony J

    2010-10-01

    The Inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are debilitating conditions, characterised by lifelong sensitivity to certain foods, and often a need for surgery and life-long medication. The anti-inflammatory effects of long chain omega-3 polyunsaturated acids justify their inclusion in enteral nutrition formulas that have been associated with disease remission. However, there have been variable data in clinical trials to test supplementary omega-3 polyunsaturated fatty acids in inducing or maintaining remission in these diseases. Although variability in trial design has been suggested as a major factor, we suggest that variability in processing and presentation of the products may be equally or more important. The nature of the source, and rapidity of getting the fish or other food source to processing or to market, will affect the percentage of the various fatty acids, possible presence of heavy metal contaminants and oxidation status of the various fatty acids. For dietary supplements or fortified foods, whether the product is encapsulated or not, whether storage is under nitrogen or not, and length of time between harvest, processing and marketing will again profoundly affect the properties of the final product. Clinical trials to test efficacy of these products in IBD to date have utilised the relevant skills of pharmacology and gastroenterology. We suggest that knowledge from food science, nutrition and engineering will be essential to establish the true role of this important group of compounds in these diseases.

  15. Echium acanthocarpum hairy root cultures, a suitable system for polyunsaturated fatty acid studies and production

    PubMed Central

    2011-01-01

    Background The therapeutic and health promoting role of highly unsaturated fatty acids (HUFAs) from fish, i.e. eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) are well known. These same benefits may however be shared by some of their precursors, the polyunsaturated fatty acids (PUFAs), such as stearidonic acid (SDA, 18:4 n-3). In order to obtain alternative sources for the large-scale production of PUFAs, new searches are being conducted focusing on higher plants oils which can contain these n-3 and n-6 C18 precursors, i.e. SDA and GLA (18:3n-6, γ-linolenic acid). Results The establishment of the novel Echium acanthocarpum hairy root cultures represents a powerful tool in order to research the accumulation and metabolism of fatty acids (FAs) in a plant particularly rich in GLA and SDA. Furthermore, this study constitutes the first example of a Boraginaceae species hairy root induction and establishment for FA studies and production. The dominant PUFAs, 18:2n-6 (LA, linoleic acid) and 18:3n-6 (GLA), accounted for about 50% of total FAs obtained, while the n-3 PUFAs, 18:3n-3 (ALA, α-linolenic acid) and 18:4n-3 (SDA), represented approximately 5% of the total. Production of FAs did not parallel hairy root growth, and the optimal productivity was always associated with the highest biomass density during the culture period. Assuming a compromise between FA production and hairy root biomass, it was determined that sampling times 4 and 5 gave the most useful FA yields. Total lipid amounts were in general comparable between the different hairy root lines (29.75 and 60.95 mg/g DW), with the major lipid classes being triacylglycerols. The FAs were chiefly stored in the hairy roots with very minute amounts being released into the liquid nutrient medium. Conclusions The novel results presented here show the utility and high potential of E. acanthocarpum hairy roots. They are capable of biosynthesizing and accumulating a large range of

  16. ω3-Polyunsaturated fatty acids for heart failure: Effects of dose on efficacy and novel signaling through free fatty acid receptor 4.

    PubMed

    O'Connell, Timothy D; Block, Robert C; Huang, Shue P; Shearer, Gregory C

    2017-02-01

    Heart failure (HF) affects 5.7 million in the U.S., and despite well-established pharmacologic therapy, the 5-year mortality rate remains near 50%. Furthermore, the mortality rate for HF has not declined in years, highlighting the need for new therapeutic options. Omega-3 polyunsaturated fatty acids (ω3-PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important regulators of cardiovascular health. However, questions of efficacy and mechanism of action have made the use of ω3-PUFAs in all cardiovascular disease (CVD) controversial. Here, we review recent studies in animal models of HF indicating that ω3-PUFAs, particularly EPA, are cardioprotective, with the results indicating a threshold for efficacy. We also examine clinical studies suggesting that ω3-PUFAs improve outcomes in patients with HF. Due to the relatively small number of clinical studies of ω3-PUFAs in HF, we discuss EPA concentration-dependency on outcomes in clinical trials of CVD to gain insight into the perceived questionable efficacy of ω3-PUFAs clinically, with the results again indicating a threshold for efficacy. Ultimately, we suggest that the main failing of ω3-PUFAs in clinical trials might be a failure to reach a therapeutically effective concentration. We also examine mechanistic studies suggesting that ω3-PUFAs signal through free fatty acid receptor 4 (Ffar4), a G-protein coupled receptor (GPR) for long-chain fatty acids (FA), thereby identifying an entirely novel mechanism of action for ω3-PUFA mediated cardioprotection. Finally, based on mechanistic animal studies suggesting that EPA prevents interstitial fibrosis and diastolic dysfunction, we speculate about a potential benefit for EPA-Ffar4 signaling in heart failure preserved with ejection fraction. Copyright © 2016. Published by Elsevier Ltd.

  17. Altered erythrocyte membrane fatty acid profile in typical Rett syndrome: effects of omega-3 polyunsaturated fatty acid supplementation.

    PubMed

    Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia; Durand, Thierry; Galano, Jean-Marie; Cortelazzo, Alessio; Zollo, Gloria; Guerranti, Roberto; Gonnelli, Stefano; Caffarelli, Carla; Rossi, Marcello; Pecorelli, Alessandra; Valacchi, Giuseppe; Ciccoli, Lucia; Hayek, Joussef

    2014-11-01

    This study mainly aims at examining the erythrocyte membrane fatty acid (FAs) profile in Rett syndrome (RTT), a genetically determined neurodevelopmental disease. Early reports suggest a beneficial effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on disease severity in RTT. A total of 24 RTT patients were assigned to ω-3 PUFAs-containing fish oil for 12 months in a randomized controlled study (average DHA and EPA doses of 72.9, and 117.1mg/kgb.w./day, respectively). A distinctly altered FAs profile was detectable in RTT, with deficient ω-6 PUFAs, increased saturated FAs and reduced trans 20:4 FAs. FAs changes were found to be related to redox imbalance, subclinical inflammation, and decreased bone density. Supplementation with ω-3 PUFAs led to improved ω-6/ω-3 ratio and serum plasma lipid profile, decreased PUFAs peroxidation end-products, normalization of biochemical markers of inflammation, and reduction of bone hypodensity as compared to the untreated RTT group. Our data indicate that a significant FAs abnormality is detectable in the RTT erythrocyte membranes and is partially rescued by ω-3 PUFAs.

  18. Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations.

    PubMed

    Hu, Yao; Li, Huaixing; Lu, Ling; Manichaikul, Ani; Zhu, Jingwen; Chen, Yii-Der I; Sun, Liang; Liang, Shuang; Siscovick, David S; Steffen, Lyn M; Tsai, Michael Y; Rich, Stephen S; Lemaitre, Rozenn N; Lin, Xu

    2016-03-15

    Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) ≥ 6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P = 4.15 × 10(-14) and 4.30 × 10(-12), respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P ≤ 0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR. Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. n-3 Polyunsaturated Fatty Acids and Mechanisms to Mitigate Inflammatory Paracrine Signaling in Obesity-Associated Breast Cancer

    PubMed Central

    Monk, Jennifer M.; Turk, Harmony F.; Liddle, Danyelle M.; De Boer, Anna A.; Power, Krista A.; Ma, David W.L.; Robinson, Lindsay E.

    2014-01-01

    Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA) may have utility in mitigating the severity of obesity-associated inflammation and breast cancer. PMID:25360510

  20. Analytical evaluation of polyunsaturated fatty acids degradation during thermal oxidation of edible oils by Fourier transform infrared spectroscopy.

    PubMed

    Moya Moreno, M C; Mendoza Olivares, D; Amézquita López, F J; Gimeno Adelantado, J V; Bosch Reig, F

    1999-09-13

    The oxidative deterioration of polyunsaturated fatty acids (PUFAs) in culinary oils and fats during episodes of heating associated with normal usage (80-300 degrees C, 20-40 min) has been monitored by Fourier transform infrared spectroscopy (FTIR). The thermal oxidation of PUFAs is a free radical chain reaction, in which hydroperoxides are generally recognized as the primary major products. Hydroperoxides of PUFAs are easily decomposed into a very complex mixture of secondary products with the decrease in unsaturation. The oxidative advance of PUFAs during heating was studied by the determination of unsaturation percentage at different temperatures and heating times. Oils frequently used in food frying such as olive oil, sunflower oil, corn oil and seeds oil (sunflower, safflower and canola seed) were studied. The results show there is a decrease in unsaturation starting at 150 degrees C and becoming more pronounced at temperatures around 250 degrees C. The following variations were found in the unsaturation percentage, expressed as methyl linoleate, between the original sample and the sample heated at 300 degrees C for 40 min: olive oil (19-6%), sunflower oil (29-12%), corn oil (28-18%) and seeds oil (23-11%). This variation in unsaturation grade provides evidence of the transformation of essential PUFAs and subsequent decrease in the oils' nutritional value. The internal standard method is suitably precise when the n-valeronitrile is used as standard as shown by the 1-2% relative standard deviation (R.S.D.) found for seven replicates.

  1. Polyunsaturated fatty acid biosynthesis is involved in phenylephrine-mediated calcium release in vascular smooth muscle cells.

    PubMed

    Irvine, Nicola A; Lillycrop, Karen A; Fielding, Barbara; Torrens, Christopher; Hanson, Mark A; Burdge, Graham C

    2015-10-01

    Stimulation of vascular smooth muscle (VSM) α1-adrenoceptors induces myosin phosphorylation and vasoconstriction via mobilisation of intracellular calcium and production of specific eicosanoids. Polyunsaturated fatty acid (PUFA) biosynthesis in VSM cells is involved, although the precise mechanism is not known. To address this, we characterised PUFA biosynthesis in VSM cells and determined its role in intracellular calcium release and eicosanoid production. Murine VSM cells converted 18:2n-6 to longer chain PUFA including 22:5n-6. Δ6 (D6d) and Δ5 (D5d) desaturase, and elongase (Elovl) 5 were expressed. Elovl2 was not detected in human, mouse or rat VSM cells, or in rat or mouse aortae, but tit was not associated with hypermethylation of its promoter. D6d or D5d inhibition reduced 18:3n-6 and 20:4n-6 synthesis, respectively, and induced concentration-related decrease in phenylephrine-mediated calcium release, and in PGE2 and PGF2α secretion. Together these findings suggest that PUFA biosynthesis in VSM cells is involved in calcium release associated with vasoconstriction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Cloning, expression and functional characterization of the polyunsaturated fatty acid elongase (ELOVL5) gene from sea cucumber (Apostichopus japonicus).

    PubMed

    Li, Wenxia; Feng, Zhengfu; Song, Xiaojun; Zhu, Wei; Hu, Yanjiang

    2016-11-15

    Long chain polyunsaturated fatty acid (PUFA) are beneficial for maintaining the health, growth and development of an organism and could reduce the risk of some diseases. The ability to endogenously produce PUFA, especially in invertebrates, is largely unknown. To study the function of elongase genes in the PUFA biosynthesis of Apostichopus japonicus, we cloned an ELOVL5 homology gene from intestinal cDNA of A. japonicus (Aj-ELOVL5). The Aj-ELOVL5 gene encoded a 318 amino acid (AA) protein that exhibited all the characteristics of the ELOVL5 family, such as a histidine box motif and four putative transmembrane-spanning domains. The results of the tissue expression profile of Aj-ELOVL5 revealed that the body wall exhibited the highest expression level compared with other adult tissues. We also found that the Aj-ELOVL5 enzyme exhibited the ability to elongate γ-linolenic acid (18:3 n-6) and eicosapentaenoic acid (20:5 n-3) to dihomo-γ-linolenic acid (20:3 n-6) and docosapentaenoic acid (22:5 n-3), respectively. Our results indicated that the Aj-ELOVL5 enzyme had the capacity to biosynthesize PUFA from C18/C20 PUFA substrates. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. A perspective on free radical autoxidation: the physical organic chemistry of polyunsaturated fatty acid and sterol peroxidation.

    PubMed

    Porter, Ned A

    2013-04-19

    This Perspective describes advances from the author's laboratory on the free radical reactions of organic compounds with molecular oxygen. Polyunsaturated fatty acids (PUFAs) and sterols are particularly prone to undergo radical chain oxidation, and evidence suggests that this process, known as lipid peroxidation, occurs in vivo under a variety of conditions that are the result of an oxidative stress. Cyclic peroxides, hydroperoxides, and epoxy alcohols are major products formed from peroxidation, and the basic mechanisms of product formation are now reasonably well understood. These mechanisms include reversible addition of oxygen to carbon radicals, rearrangement and cyclization of allyl and pentadienyl peroxyl radicals, and homolytic substitution of carbon radicals on the peroxide bond. A physical organic approach to the problem of free radicals in biology and medicine is highlighted in this Perspective with stereochemical, kinetic, and extrathermodynamic probes applied to the study of mechanism. A radical clock permits the determination of free radical propagation rate constants, and 7-dehydrocholesterol, the immediate biosynthetic precursor of cholesterol, is found by this clock to be one of the most oxidizable lipids known. The consequences of the extreme reactivity of 7-dehydrocholesterol on human health is the focus of a current research theme in the author's laboratory.

  4. A Perspective on Free Radical Autoxidation: The Physical Organic Chemistry of Polyunsaturated Fatty Acid and Sterol Peroxidation

    PubMed Central

    2013-01-01

    This Perspective describes advances from the author’s laboratory on the free radical reactions of organic compounds with molecular oxygen. Polyunsaturated fatty acids (PUFAs) and sterols are particularly prone to undergo radical chain oxidation and evidence suggests that this process, known as lipid peroxidation, occurs in vivo under a variety of conditions that are the result of an oxidative stress. Cyclic peroxides, hydroperoxides, and epoxy-alcohols are major products formed from peroxidation and the basic mechanisms of product formation are now reasonably well understood. These mechanisms include reversible addition of oxygen to carbon radicals, rearrangement and cyclization of allyl and pentadienyl peroxyl radicals and homolytic substitution of carbon radicals on the peroxide bond. A physical organic approach to the problem of free radicals in biology and medicine is highlighted in this Perspective with stereochemical, kinetic and extrathermodynamic probes applied to the study of mechanism. A radical clock permits the determination of free radical propagation rate constants and 7-dehydrocholesterol, the immediate biosynthetic precursor of cholesterol, is found by this clock to be one of the most oxidizable lipids known. The consequences of the extreme reactivity of 7-dehydrocholesterol on human health is the focus of a current research theme in the author’s laboratory. PMID:23445181

  5. Substrate specificity of the agonist-stimulated release of polyunsaturated fatty acids from vascular endothelial cells

    SciTech Connect

    Rosenthal, M.D.; Garcia, M.C.; Sprecher, H. )

    1989-11-01

    Stimulation of vascular endothelial cells with agonists such as histamine and thrombin results in release of arachidonic acid from membrane lipids and subsequent eicosanoid synthesis. As shown previously, the agonist-stimulated deacylation is specific for arachidonate, eicosapentaenoate, and 5,8,11-eicosatrienoate. This study has utilized radiolabeled fatty acids differing in chain length and position of double bonds to further elucidate the fatty acyl specificity of agonist-stimulated deacylation. Replicate wells of confluent human umbilical vein endothelial cells were incubated with 14C-labeled fatty acids and then challenged with histamine, thrombin, or the calcium ionophore A23187. Comparison of the results obtained with isomeric eicosatetraenoic fatty acids with initial double bonds at carbons 4, 5, or 6 indicated that the deacylation induced by all three agonists exhibited marked specificity for the cis-5 double bond. Lack of stringent chain length specificity was indicated by agonist-stimulated release of 5,8,11,14- tetraenoic fatty acids with 18, 19, 20, and 21 carbons. Release of 5,8,14-(14C)eicosatrienoate was two-to threefold that of 5,11,14-(14C)eicosatrienoate, thus indicating that the cis-8 double bond may also contribute to the stringent recognition by the agonist-sensitive phospholipase. The present study has also demonstrated that histamine, thrombin, and A23187 do not stimulate release of docosahexaenoate from endothelial cells.

  6. N-3 polyunsaturated fatty acids attenuates triglyceride and inflammatory factors level in hfat-1 transgenic pigs.

    PubMed

    Liu, Xingxing; Pang, Daxin; Yuan, Ting; Li, Zhuang; Li, Zhanjun; Zhang, Mingjun; Ren, Wenzhi; Ouyang, Hongsheng; Tang, Xiaochun

    2016-05-10

    The consumption of n-3 polyunsaturated fatty acids (PUFAs) is important to human health, especially in cases of cardiovascular disease. Although beneficial effects of n-3 PUFAs have been observed in a number of studies, the mechanisms involved in these effects have yet to be discovered. We generated hfat-1 transgenic pigs with traditional somatic cell nuclear transfer (SCNT) technology. The fatty acid composition in ear tissue of pigs were detected with gas chromatography. The cholesterol, triglycerides (TAG) and inflammation mediators in circulation were investigated. The hfat-1 transgenic pigs were developed which accumulate high levels of n-3 PUFAs than wild-types pigs. Gas chromatography results demonstrated that the total n-3 PUFAs in the ear tissues of the transgenic founders were 2-fold higher than the wild-type pigs. A lipid analysis demonstrated that the levels of TAG in the transgenic pigs were decreased significantly. The basal levels of the inflammation mediators tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in transgenic pigs were inhibited markedly compared with the wild-type pigs. These results suggest that n-3 PUFAs accumulation in vivo may have beneficial effects on vascular and hfat-1 transgenic pigs may be a useful tool for investigating the involved mechanisms.

  7. Polyunsaturated fatty acids induce ovarian cancer cell death through ROS-dependent MAP kinase activation.

    PubMed

    Tanaka, Aiko; Yamamoto, Akane; Murota, Kaeko; Tsujiuchi, Toshifumi; Iwamori, Masao; Fukushima, Nobuyuki

    2017-09-04

    Free fatty acids not only play a role in cell membrane construction and energy production but also exert diverse cellular effects through receptor and non-receptor mechanisms. Moreover, epidemiological and clinical studies have so far suggested that polyunsaturated fatty acids (PUFAs) could have health benefits and the advantage as therapeutic use in cancer treatment. However, the underlying mechanisms of PUFA-induced cellular effects remained to be cleared. Here, we examined the effects of ω-3 and ω-6 PUFAs on cell death in ovarian cancer cell lines. ω-3 PUFA, docosahexaenoic acid (DHA) and ω-6 PUFA, γ-linolenic acid (γ-LNA) induced cell death in KF28 cells at the levels of physiological concentrations, but not HAC2 cells. Pharmacological and biochemical analyses demonstrated that cell death induced by DHA and γ-LNA was correlated with activation of JNK and p38 MAP kinases, and further an upstream MAP kinase kinase, apoptosis signal-regulating kinase 1, which is stimulated by reactive oxygen species (ROS). Furthermore, an antioxidant vitamin E attenuated PUFA-induced cell death and MAP kinase activation. These findings indicate that PUFA-induced cell death involves ROS-dependent MAP kinase activation and is a cell type-specific action. A further study of the underlying mechanisms for ROS-dependent cell death induced by PUFAs will lead to the discovery of a new target for cancer therapy or diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Omega-3 Polyunsaturated Fatty Acids: The Way Forward in Times of Mixed Evidence.

    PubMed

    Weylandt, Karsten H; Serini, Simona; Chen, Yong Q; Su, Hui-Min; Lim, Kyu; Cittadini, Achille; Calviello, Gabriella

    2015-01-01

    Almost forty years ago, it was first hypothesized that an increased dietary intake of omega-3 polyunsaturated fatty acids (PUFA) from fish fat could exert protective effects against several pathologies. Decades of intense preclinical investigation have supported this hypothesis in a variety of model systems. Several clinical cardiovascular studies demonstrated the beneficial health effects of omega-3 PUFA, leading medical institutions worldwide to publish recommendations for their increased intake. However, particularly in recent years, contradictory results have been obtained in human studies focusing on cardiovascular disease and the clinical evidence in other diseases, particularly chronic inflammatory and neoplastic diseases, was never established to a degree that led to clear approval of treatment with omega-3 PUFA. Recent data not in line with the previous findings have sparked a debate on the health efficacy of omega-3 PUFA and the usefulness of increasing their intake for the prevention of a number of pathologies. In this review, we aim to examine the controversies on the possible use of these fatty acids as preventive/curative tools against the development of cardiovascular, metabolic, and inflammatory diseases, as well as several kinds of cancer.

  9. Omega-3 Polyunsaturated Fatty Acids and Oxylipins in Neuroinflammation and Management of Alzheimer Disease12

    PubMed Central

    Leng, Shan; Gabbs, Melissa; Monirujjaman, Md; Aukema, Harold M

    2016-01-01

    Alzheimer disease (AD) is becoming one of the most prevalent neurodegenerative conditions worldwide. Although the disease progression is becoming better understood, current medical interventions can only ameliorate some of the symptoms but cannot slow disease progression. Neuroinflammation plays an important role in the advancement of this disorder, and n–3 (ω-3) polyunsaturated fatty acids (PUFAs) are involved in both the reduction in and resolution of inflammation. These effects may be mediated by the anti-inflammatory and proresolving effects of bioactive lipid mediators (oxylipins) derived from n–3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in fish oil. Although interventions have generally used fish oil containing both EPA and DHA, several studies that used either EPA or DHA alone or specific oxylipins derived from these fatty acids indicate that they have distinct effects. Both DHA and EPA can reduce neuroinflammation and cognitive decline, but EPA positively influences mood disorders, whereas DHA maintains normal brain structure. Fewer studies with a plant-derived n–3 PUFA, α-linolenic acid, suggest that other n–3 PUFAs and their oxylipins also may positively affect AD. Further research identifying the unique anti-inflammatory and proresolving properties of oxylipins from individual n–3 PUFAs will enable the discovery of novel disease-management strategies in AD. PMID:27633106

  10. Omega-3 Polyunsaturated Fatty Acids: The Way Forward in Times of Mixed Evidence

    PubMed Central

    Weylandt, Karsten H.; Serini, Simona; Chen, Yong Q.; Su, Hui-Min; Lim, Kyu; Cittadini, Achille; Calviello, Gabriella

    2015-01-01

    Almost forty years ago, it was first hypothesized that an increased dietary intake of omega-3 polyunsaturated fatty acids (PUFA) from fish fat could exert protective effects against several pathologies. Decades of intense preclinical investigation have supported this hypothesis in a variety of model systems. Several clinical cardiovascular studies demonstrated the beneficial health effects of omega-3 PUFA, leading medical institutions worldwide to publish recommendations for their increased intake. However, particularly in recent years, contradictory results have been obtained in human studies focusing on cardiovascular disease and the clinical evidence in other diseases, particularly chronic inflammatory and neoplastic diseases, was never established to a degree that led to clear approval of treatment with omega-3 PUFA. Recent data not in line with the previous findings have sparked a debate on the health efficacy of omega-3 PUFA and the usefulness of increasing their intake for the prevention of a number of pathologies. In this review, we aim to examine the controversies on the possible use of these fatty acids as preventive/curative tools against the development of cardiovascular, metabolic, and inflammatory diseases, as well as several kinds of cancer. PMID:26301240

  11. Polyunsaturated fatty acids trigger apoptosis of colon cancer cells through a mitochondrial pathway

    PubMed Central

    Zhang, Chengcheng; Yu, Haining; Shen, Yuzhen; Ni, Xiaofeng; Das, Undurti N.

    2015-01-01

    Introduction Colorectal cancer is common in developed countries. Polyunsaturated fatty acids (PUFAs) have been reported to possess tumoricidal action, but the exact mechanism of their action is not clear. Material and methods In the present study, we studied the effect of various n-6 and n-3 fatty acids on the survival of the colon cancer cells LoVo and RKO and evaluated the possible involvement of a mitochondrial pathway in their ability to induce apoptosis. Results It was observed that n-3 α-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid (ALA, EPA and DHA respectively) and n-6 linoleic acid, gamma-linolenic acid and arachidonic acid (LA, GLA and AA respectively) induced apoptosis of the colon cancer cells LoVo and RKO at concentrations above 120 μM (p < 0.01 compared to control). The semi-differentiated colon cancer cell line RKO was more sensitive to the cytotoxic action of PUFAs compared to the undifferentiated colon cancer cell line LoVo. PUFA-treated cells showed an increased number of lipid droplets in their cytoplasm. PUFA-induced apoptosis of LoVo and RKO cells is mediated through a mitochondria-mediated pathway as evidenced by loss of mitochondrial membrane potential, generation of ROS, accumulation of intracellular Ca2+, activation of caspase-9 and caspase-3, decreased ATP level and increase in the Bax/Bcl2 expression ratio. Conclusions PUFAs induced apoptosis of colon cancer cells through a mitochondrial dependent pathway. PMID:26528354

  12. Formation of dopamine adducts derived from brain polyunsaturated fatty acids: mechanism for Parkinson disease.

    PubMed

    Liu, Xuebo; Yamada, Naruomi; Maruyama, Wakako; Osawa, Toshihiko

    2008-12-12

    Oxidative stress appears to be directly involved in the pathogenesis of the neurodegeneration of dopaminergic systems in Parkinson disease. In this study, we formed four dopamine modification adducts derived from docosahexaenoic acid (C22:6/omega-3) and arachidonic acid (C18:4/omega-6), which are known as the major polyunsaturated fatty acids in the brain. Upon incubation of dopamine with fatty acid hydroperoxides and an in vivo experiment using rat brain tissue, all four dopamine adducts were detected. Furthermore, hexanoyl dopamine (HED), an arachidonic acid-derived adduct, caused severe cytotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells, whereas the other adducts were only slightly affected. The HED-induced cell death was found to include apoptosis, which also seems to be mediated by reactive oxygen species generation and mitochondrial abnormality. Additionally, the experiments using monoamine transporter inhibitor and mouse embryonic fibroblast NIH-3T3 cells that lack the monoamine transporter indicate that the HED-induced cytotoxicity might specially occur in the neuronal cells. These data suggest that the formation of the docosahexaenoic acid- and arachidonic acid-derived dopamine adducts in vitro and in vivo, and HED, the arachidonic acid-derived dopamine modification adduct, which caused selective cytotoxicity of neuronal cells, may indicate a novel mechanism responsible for the pathogenesis in Parkinson disease.

  13. Dietary polyunsaturated fatty acids in asthma- and exercise-induced bronchoconstriction.

    PubMed

    Mickleborough, T D; Rundell, K W

    2005-12-01

    Despite progress that has been made in the treatment of asthma, the prevalence and burden of this disease has continued to increase. While pharmacological treatment of asthma is usually highly effective, medications may have significant side effects or exhibit tachyphylaxis. Alternative therapies for treatment that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. Ecological and temporal data suggest that dietary factors may have a role in recent increases in the prevalence of asthma. A possible contributing factor to the increased incidence of asthma in Western societies may be the consumption of a proinflammatory diet. In the typical Western diet, 20- to 25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which promotes the release of proinflammatory arachidonic acid metabolites (leukotrienes and prostanoids). This review will analyze the evidence for the health effects of n-3 PUFA in asthma- and exercise-induced bronchoconstriction (EIB). While clinical data evaluating the effect of omega-3 fatty acid supplementation in asthma has been equivocal, it has recently been shown that fish oil supplementation, rich in n-3 PUFA, reduces airway narrowing, medication use, and proinflammatory mediator generation in nonatopic elite athletes with EIB. These findings are provocative and suggest that dietary fish oil supplementation may be a viable treatment modality and/or adjunct therapy in asthma and EIB.

  14. Regulatory Activity of Polyunsaturated Fatty Acids in T-Cell Signaling

    PubMed Central

    Kim, Wooki; Khan, Naim A.; McMurray, David N.; Prior, Ian A.; Wang, Naisyin; Chapkin, Robert S.

    2010-01-01

    n-3 polyunsaturated fatty acids (PUFA) are considered to be authentic immunosuppressors and appear to exert beneficial ef