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Sample records for decreased polyunsaturated fatty

  1. Long chain n-3 polyunsaturated fatty acids decrease feelings of anger in substance abusers

    PubMed Central

    Buydens-Branchey, Laure; Branchey, Marc

    2008-01-01

    It has been suggested that low levels of n-3 polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology of some psychiatric disorders. In light of the existence of strong associations between high-frequency and high-severity aggressive behaviors and substance use disorders and of our observation that substance abusers have poor dietary habits, the possibility that the administration of supplements of n-3 PUFAs would decrease their anger levels was explored. A life long history of aggressive behaviors and problems with the law was obtained in 24 patients. Thirteen patients received on a daily basis capsules containing 3 g of n-3 PUFAs (EPA+DHA). Eleven patients received placebo capsules. The trial was double-blind, randomized, and lasted 3 months. An anger scale was administered at baseline and every month thereafter. Six PUFA group patients and eight placebo group patients were followed for an additional 3 months after treatment discontinuation. Four patients in each group had a history of assaultive behavior. The baseline fish and n-3 PUFA intakes of these 8 patients were significantly lower than those of the non-aggressive patients. When given for 3 months, n-3 PUFAs were superior to placebo in diminishing anger scores. These scores remained decreased for 3 months following treatment discontinuation. These data provide further support to emerging evidence indicating that supplementation with long-chain n-3 PUFAs could be beneficial in the treatment of some individuals with aggressive tendencies. PMID:17900705

  2. 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

  3. Lower ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Decrease Fat Deposition by Inhibiting Fat Synthesis in Gosling.

    PubMed

    Yu, Lihuai; Wang, Shunan; Ding, Luoyang; Liang, Xianghuan; Wang, Mengzhi; Dong, Li; Wang, Hongrong

    2016-10-01

    The objective of the current study was to investigate the effects of dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on lipid metabolism in goslings. One hundred and sixty 21-day-old Yangzhou geese of similar weight were randomly divided into 4 groups. They were fed different PUFA-supplemented diets (the 4 diets had ω-6/ω-3 PUFA ratios of 12:1, 9:1, 6:1, or 3:1). The geese were slaughtered and samples of liver and muscle were collected at day 70. The activities and the gene expression of enzymes involved in lipid metabolism were measured. The results show that the activities of acetyl coenzyme A carboxylase (ACC), malic enzyme (ME), and fatty acid synthase (FAS) were lower (p<0.05), but the activities of hepatic lipase (HL) and lipoprotein lipase (LPL) were higher (p<0.05), in the liver and the muscle from the 3:1 and 6:1 groups compared with those in the 9:1 and 12:1 groups. Expression of the genes for FAS (p<0.01), ME (p<0.01) and ACC (p<0.05) were higher in the muscle of groups fed diets with higher ω-6/ω-3 PUFA ratios. Additionally, in situ hybridization tests showed that the expression intensities of the high density lipoprotein (HDL-R) gene in the 12:1 and 9:1 groups were significantly lower (p<0.01) than that of the 3:1 group in the muscle of goslings. In conclusion, diets containing lower ω-6/ω-3 PUFA ratios (3:1 or 6:1) could decrease fat deposition by inhibiting fat synthesis in goslings. PMID:27189638

  4. Dietary ω-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose–endoplasmic reticulum stress reduction to increase adiponectin1234

    PubMed Central

    Fu, Zhongjie; Lofqvist, Chatarina A; Shao, Zhuo; Sun, Ye; Joyal, Jean-Sebastien; Hurst, Christian G; Cui, Ricky Z; Evans, Lucy P; Tian, Katherine; SanGiovanni, John Paul; Chen, Jing; Ley, David; Hansen Pupp, Ingrid; Hellstrom, Ann; Smith, Lois EH

    2015-01-01

    Background: Retinopathy of prematurity (ROP) is a vision-threatening disease in premature infants. Serum adiponectin (APN) concentrations positively correlate with postnatal growth and gestational age, important risk factors for ROP development. Dietary ω-3 (n–3) long-chain polyunsaturated fatty acids (ω-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood. Objective: We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary ω-3 LCPUFAs to mediate the protective effect in ROP. Design: Serum APN concentrations were correlated with ROP development and serum ω-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether ω-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy. Results: We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum ω-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by ω-3 LCPUFA feed. White adipose tissue, where APN is produced and assembled in the endoplasmic reticulum, is the major source of serum APN. In mouse OIR, adipose endoplasmic reticulum stress is increased, and APN production is suppressed. ω-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary ω-3 LCPUFA suppression of neovascularization is reduced from 70% to 10% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels. Conclusion: Our findings suggest that increasing APN by ω-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP. PMID:25833984

  5. Polyunsaturated fatty acids and insulin resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have reviewed results from published studies regarding the effects of polyunsaturated fatty acids (PUFA) intake on insulin resistance (IR) in human subjects. Evidence has been gathered from epidemiological, cross-sectional and interventions studies. Increased intake of trans fatty acids (TFA) inc...

  6. Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease.

    PubMed

    Calon, Frédéric; Lim, Giselle P; Morihara, Takashi; Yang, Fusheng; Ubeda, Oliver; Salem, Norman; Frautschy, Sally A; Cole, Greg M

    2005-08-01

    Epidemiological data indicate that low n-3 polyunsaturated fatty acids (PFA) intake is a readily manipulated dietary risk factor for Alzheimer's disease (AD). Studies in animals confirm the deleterious effect of n-3 PFA depletion on cognition and on dendritic scaffold proteins. Here, we show that in transgenic mice overexpressing the human AD gene APPswe (Tg2576), safflower oil-induced n-3 PFA deficiency caused a decrease in N-methyl-D-aspartate (NMDA) receptor subunits, NR2A and NR2B, in the cortex and hippocampus with no loss of the presynaptic markers, synaptophysin and synaptosomal-associated protein 25 (SNAP-25). n-3 PFA depletion also decreased the NR1 subunit in the hippocampus and Ca2+/calmodulin-dependent protein kinase (CaMKII) in the cortex of Tg2576 mice. These effects of dietary n-3 PFA deficiency were greatly amplified in Tg2576 mice compared to nontransgenic mice. Loss of the NR2B receptor subunit was not explained by changes in mRNA expression, but correlated with p85alpha phosphatidylinositol 3-kinase levels. Most interestingly, n-3 PFA deficiency dramatically increased levels of protein fragments, corresponding to caspase/calpain-cleaved fodrin and gelsolin in Tg2576 mice. This effect was minimal in nontransgenic mice suggesting that n-3 PFA depletion potentiated caspase activation in the Tg2576 mouse model of AD. Dietary supplementation with docosahexaenoic acid (DHA; 22 : 6n-3) partly protected from NMDA receptor subunit loss and accumulation of fodrin and gelsolin fragments but fully prevented CaMKII decrease. The marked effect of dietary n-3 PFA on NMDA receptors and caspase/calpain activation in the cortex of an animal model of AD provide new insights into how dietary essential fatty acids may influence cognition and AD risk. PMID:16101743

  7. Polyunsaturated fatty acids and gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose of review. This review focuses on the effect(s) of n-3 polyunsaturated fatty acids (PUFA) on gene transcription as determined from data generated using cDNA microarrays. Introduced within the past decade, this methodology allows detection of the expression of thousands of genes simultaneo...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  9. ASSOCIATIONS BETWEEN INCREASES IN PLASMA N-3 POLYUNSATURATED FATTY ACIDS FOLLOWING SUPPLEMENTATION AND DECREASES IN ANGER AND ANXIETY IN SUBSTANCE ABUSERS

    PubMed Central

    Buydens-Branchey, Laure; Branchey, Marc; Hibbeln, Joseph R.

    2008-01-01

    Objective Mounting evidence indicates that low levels of n-3 polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology of a large number of psychiatric disorders. In light of the suboptimal n-3 PUFAs intake due to poor dietary habits among substance abusers and the strong associations between aggression, anxiety and substance use disorders we examined if insurance of adequate intakes of n-3 PUFAs with supplementation would decrease their anger and anxiety scores. Method Substance abusers (n=22) were assigned to either 3 g of n-3 PUFAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or soybean oil in identically looking capsules. The trial was double-blind, randomized and lasted 3 months. Anger and anxiety scales were administered at baseline and once a month thereafter. Blood samples were collected at baseline and at the end of the trial. Results Patients' dietary intakes of n-3 PUFAs fell below recommended levels. Assignment to n-3 PUFA treatment was accompanied by significant decreases in anger and anxiety scores compared to placebo assignment. These changes were associated with increases in plasma levels of both EPA and DHA but an increase in EPA was more robustly correlated with low end-of-trial anxiety scores and an increase in DHA was more robustly correlated with low end-of-trial anger scores. Conclusion These pilot data indicate that ensuring adequate n-3 PUFA intake via supplementation benefits substance abusers by reducing their anger and anxiety levels. The strong correlations between an increase in plasma EPA and lower anxiety scores and between an increase in plasma DHA and lower anger scores suggests a need for the further exploration of the differential responses to these two n-3 PUFAs in different psychiatric conditions. PMID:18060675

  10. Anorexia nervosa, seasonality, and polyunsaturated fatty acids.

    PubMed

    Scolnick, Barbara; Mostofsky, David I

    2015-09-01

    Anorexia nervosa is a serious neurobehavioral disorder marked by semistarvation, extreme fear of weight gain, frequently hyperactivity, and low body temperature. The etiology remains unknown. We present a speculation that a primary causative factor is that polyunsaturated fatty acids are skewed to prevent oxidative damage in phospholipid membranes. This causes a change in the trade off of oxidation protection vs homeoviscous adaptation to lower temperatures, which sets off a metabolic cascade that leads to the rogue state of anorexia nervosa. PMID:25981875

  11. Lipidomics of oxidized polyunsaturated fatty acids

    PubMed Central

    Massey, Karen A.; Nicolaou, Anna

    2013-01-01

    Lipid mediators are produced from the oxidation of polyunsaturated fatty acids through enzymatic and free radical-mediated reactions. When subject to oxygenation via cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases, polyunsaturated fatty acids give rise to an array of metabolites including eicosanoids, docosanoids, and octadecanoids. These potent bioactive lipids are involved in many biochemical and signaling pathways, with inflammation being of particular importance. Moreover, because they are produced by more than one pathway and substrate, and are present in a variety of biological milieus, their analysis is not always possible with conventional assays. Liquid chromatography coupled to electrospray mass spectrometry offers a versatile and sensitive approach for the analysis of bioactive lipids, allowing specific and accurate quantitation of multiple species present in the same sample. Here we explain the principles of this approach to mediator lipidomics and present detailed protocols for the assay of enzymatically produced oxygenated metabolites of polyunsaturated fatty acids that can be tailored to answer biological questions or facilitate assessment of nutritional and pharmacological interventions. PMID:22940496

  12. Polyunsaturated fatty acid relatively decreases cholesterol content in THP-1 macrophage-derived foam cell: partly correlates with expression profile of CIDE and PAT members

    PubMed Central

    2013-01-01

    Background Polyunsaturated fatty acids (PUFAs) have positive effect on the regulation of plasma lipids. But the mechanism for them to modulate lipid homeostasis in macrophage is still unclear. In this study, we employed PUFA to pretreat macrophages and evaluated the variations of lipid droplet (LD) content, lipid composition, and expressions of LD-associated genes in macrophage-derived foam cells. Method THP-1-derived macrophages or human peripheral blood monocyte-derived macrophages were pre-treated with four non-esterified fatty acids (NEFAs) separately: saturated fatty acid (SFA)-palmitic acid (PA), monounsaturated fatty acids (MUFAs)-oleic acid (OA), PUFAs-linoleic acid (LA) and eicosapentaenoic acid (EPA). Intracellular lipid content and cholesterol efflux were analyzed in THP-1 macrophage-derived foam cells. Related gene expressions were detected by quantitative real-time PCR. Results PUFA pre-treatment reduced cholesterol content in foam cells and increased cholesterol efflux to lipid-free apoAI in conditioned medium compared with PA or OA group. Cell death-inducing DFF45 like effector (CIDE) and Perilipin-Adipophilin-TIP47 (PAT) family members, as LD-associated proteins, showed specific gene expression profiles after PUFA pre-treatment. These results may help to explain the process of lipid metabolism within foam cells. Conclusion PUFA (LA or EPA) had a potential protective effect against cholesterol accumulation. The specific expressions of CIDE and PAT genes may provide clues to explore the protective mechanism of PUFA in foam cells. PMID:23879935

  13. Omega-3 polyunsaturated fatty acids: photoprotective macronutrients.

    PubMed

    Pilkington, Suzanne M; Watson, Rachel E B; Nicolaou, Anna; Rhodes, Lesley E

    2011-07-01

    Ultraviolet radiation (UVR) in sunlight has deleterious effects on skin, while behavioural changes have resulted in people gaining more sun exposure. The clinical impact includes a year-on-year increase in skin cancer incidence, and topical sunscreens alone provide an inadequate measure to combat overexposure to UVR. Novel methods of photoprotection are being targeted as additional measures, with growing interest in the potential for systemic photoprotection through naturally sourced nutrients. Omega-3 polyunsaturated fatty acids (n-3 PUFA) are promising candidates, showing potential to protect the skin from UVR injury through a range of mechanisms. In this review, we discuss the biological actions of n-3 PUFA in the context of skin protection from acute and chronic UVR overexposure and describe how emerging new technologies such as nutrigenomics and lipidomics assist our understanding of the contribution of such nutrients to skin health. PMID:21569104

  14. 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

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

    PubMed

    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

  16. Use of tocopherol with polyunsaturated fatty acids in poultry feeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tocopherol can inhibit the oxidative degradation of polyunsaturated fatty acids by stabilizing lipid radicals that form at elevated temperatures or pro-oxidant conditions. This is particularly relevant for feeds formulated with fatty acids such as docosahexaenoic acid (DHA) or linolenic acid (ALA) T...

  17. [Omega-3 polyunsaturated fatty acids in the prevention of atherosclerosis].

    PubMed

    Varga, Zsuzsa

    2008-04-01

    Cardioprotective action of omega-3 polyunsaturated fatty acids such as eicosapentaenoic and docosahexaenoic acid in fish and alpha-linolenic acid in plants was demonstrated in primary and secondary clinical trials. Fish oil therapy causes a marked decrease in serum triacylglycerol and very low density lipoprotein levels and increases moderately high density lipoprotein levels without any adverse effects. Omega-3 fatty acids decrease slightly, but significantly blood pressure, enhance endothelial function, they have anti-aggregator, anti-thrombotic and anti-inflammatory effects as well. These beneficial effects are in connection with modification of gene transcription levels of some key molecules such as nuclear factor-kappaB and sterol element binding receptor protein-1c, which regulate for example expression of adhesion molecules or several receptors involved in triglyceride synthesis (hepatocyte X receptor, hepatocyte nuclear factor 4alpha, farnesol X receptor, and peroxisome proliferator-activated receptors). On the basis of these observations, the supplementation of the diet with omega-3 fatty acids (fish, fish oil, linseed, and linseed oil or canola oil) is advisable in primary and secondary prevention. PMID:18375362

  18. Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism

    PubMed Central

    Spector, Arthur A.; Kim, Hee-Yong

    2014-01-01

    Polyunsaturated fatty acids (PUFA) are oxidized by cytochrome P450 epoxygenases to PUFA epoxides which function as potent lipid mediators. The major metabolic pathways of PUFA epoxides are incorporation into phospholipids and hydrolysis to the corresponding PUFA diols by soluble epoxide hydrolase. Inhibitors of soluble epoxide hydrolase stabilize PUFA epoxides and potentiate their functional effects. The epoxyeicosatrienoic acids (EETs) synthesized from arachidonic acid produce vasodilation, stimulate angiogenesis, have anti-inflammatory actions, and protect the heart against ischemia-reperfusion injury. EETs produce these functional effects by activating receptor-mediated signaling pathways and ion channels. The epoxyeicosatetraenoic acids synthesized from eicosapentaenoic acid and epoxydocosapentaenoic acids synthesized from docosahexaenoic acid are potent inhibitors of cardiac arrhythmias. Epoxydocosapentaenoic acids also inhibit angiogenesis, decrease inflammatory and neuropathic pain, and reduce tumor metastasis. These findings indicate that a number of the beneficial functions of PUFA may be due to their conversion to PUFA epoxides. PMID:25093613

  19. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  1. 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.

  2. Modifications of proteins by polyunsaturated fatty acid peroxidation products

    PubMed Central

    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. PMID:10639127

  3. 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.

  4. 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

  5. Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans

    PubMed Central

    Watts, Jennifer L.; Browse, John

    2002-01-01

    Polyunsaturated fatty acids (PUFAs) are important membrane components and precursors of signaling molecules. To investigate the roles of these fatty acids in growth, development, and neurological function in an animal system, we isolated Caenorhabditis elegans mutants deficient in PUFA synthesis by direct analysis of fatty acid composition. C. elegans possesses all the desaturase and elongase activities to synthesize arachidonic acid and eicosapentaenoic acid from saturated fatty acid precursors. In our screen we identified mutants with defects in each fatty acid desaturation and elongation step of the PUFA biosynthetic pathway. The fatty acid compositions of the mutants reveal the substrate preferences of the desaturase and elongase enzymes and clearly demarcate the steps of this pathway. The mutants show that C. elegans does not require n3 or Δ5-unsaturated PUFAs for normal development under laboratory conditions. However, mutants with more severe PUFA deficiencies display growth and neurological defects. The mutants provide tools for investigating the roles of PUFAs in membrane biology and cell function in this animal model. PMID:11972048

  6. Correlation of polyunsaturated fatty acids with the cold adaptation of Rhodotorula glutinis.

    PubMed

    He, Jing; Yang, Zhaojie; Hu, Binbin; Ji, Xiuling; Wei, Yunlin; Lin, Lianbing; Zhang, Qi

    2015-11-01

    This study aimed to investigate the correlation between the cold adaptation of Rhodotorula glutinis YM25079 and the membrane fluidity, content of polyunsaturated fatty acids and mRNA expression level of the Δ(12)-desaturase gene. The optimum temperature for YM25079 growth was analysed first, then the composition changes of membrane lipid in YM25079 were detected by GC-MS and membrane fluidity was evaluated by 1-anilinonaphthalene-8-sulphonate (ANS) fluorescence. Meanwhile, the encoding sequence of Δ(12)-fatty acid desaturase in YM25079 was cloned and further transformed into Saccharomyces cerevisiae INVScl for functional analysis. The mRNA expression levels of Δ(12)-fatty acid desaturase at 15°C and 25°C were analysed by real-time PCR. YM25079 could grow at 5-30°C, with the optimum temperature of 15°C. The membrane fluidity of YM25079 was not significantly reduced when the culture temperature decreased from 25°C to 15°C, but the content of polyunsaturated fatty acids (PUFAs), including linoleic acid and α-Linolenic acid increased significantly from 29.4% to 55.39%. Furthermore, a novel Δ(12)-fatty acid desaturase gene YM25079RGD12 from YM25079 was successfully identified and characterized, and the mRNA transcription level of the Δ(12)-desaturase gene was about five-fold higher in YM25079 cells grown at 15°C than that at 25°C. These results suggests that the cold adaptation of Rhodotorula glutinis YM25079 might result from higher expression of genes, especially the Δ(12)-fatty acid desaturase gene, during polyunsaturated fatty acids biosynthesis, which increased the content of PUFAs in the cell membrane and maintained the membrane fluidity at low temperature. PMID:26284451

  7. 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

  8. Heterologous Reconstitution of Omega-3 Polyunsaturated Fatty Acids in Arabidopsis

    PubMed Central

    Kim, Sun Hee; Roh, Kyung Hee; Park, Jong-Sug; Kim, Kwang-Soo; Kim, Hyun Uk; Lee, Kyeong-Ryeol; Kang, Han-Chul; Kim, Jong-Bum

    2015-01-01

    Reconstitution of nonnative, very-long-chain polyunsaturated fatty acid (VLC-PUFA) biosynthetic pathways in Arabidopsis thaliana was undertaken. The introduction of three primary biosynthetic activities to cells requires the stable coexpression of multiple proteins within the same cell. Herein, we report that C22 VLC-PUFAs were synthesized from C18 precursors by reactions catalyzed by Δ6-desaturase, an ELOVL5-like enzyme involved in VLC-PUFA elongation, and Δ5-desaturase. Coexpression of the corresponding genes (McD6DES, AsELOVL5, and PtD5DES) under the control of the seed-specific vicilin promoter resulted in production of docosapentaenoic acid (22:5 n-3) and docosatetraenoic acid (22:4 n-6) as well as eicosapentaenoic acid (20:5 n-3) and arachidonic acid (20:4 n-6) in Arabidopsis seeds. The contributions of the transgenic enzymes and endogenous fatty acid metabolism were determined. Specifically, the reasonable synthesis of omega-3 stearidonic acid (18:4 n-3) could be a useful tool to obtain a sustainable system for the production of omega-3 fatty acids in seeds of a transgenic T3 line 63-1. The results indicated that coexpression of the three proteins was stable. Therefore, this study suggests that metabolic engineering of oilseed crops to produce VLC-PUFAs is feasible. PMID:26339641

  9. 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. PMID:24164329

  10. 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

  11. 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

  12. Long-chain polyunsaturated fatty acids stimulate cellular fatty acid uptake in human placental choriocarcinoma (BeWo) cells.

    PubMed

    Johnsen, G M; Weedon-Fekjaer, M S; Tobin, K A R; Staff, A C; Duttaroy, A K

    2009-12-01

    Supplementation of long-chain polyunsaturated fatty acids (LCPUFAs) is advocated during pregnancy in some countries although very little information is available on their effects on placental ability to take up these fatty acids for fetal supply to which the fetal growth and development are critically dependent. To identify the roles of LCPUFAs on placental fatty acid transport function, we examined the effects of LCPUFAs on the uptake of fatty acids and expression of fatty acid transport/metabolic genes using placental trophoblast cells (BeWo). Following 24 h incubation of these cells with 100 microM of LCPUFAs (arachidonic acid, 20:4n-6, eicosapentaenoic acid, 20:5n-3, or docosahexaenoic acid, 22:6n-3), the cellular uptake of [(14)C] fatty acids was increased by 20-50%, and accumulated fatty acids were preferentially incorporated into phospholipid fractions. Oleic acid (OA, 18:1n-9), on the other hand, could not stimulate fatty acid uptake. LCPUFAs and OA increased the gene expression of ADRP whilst decreased the expression of ASCL3, ACSL4, ACSL6, LPIN1, and FABP3 in these cells. However, LCPUFAs but not OA increased expression of ACSL1 and ACSL5. Since acyl-CoA synthetases are involved in cellular uptake of fatty acids via activation for their channelling to lipid metabolism and/or for storage, the increased expression of ACSL1 and ACLS5 by LCPUFAs may be responsible for the increased fatty acid uptake. These findings demonstrate that LCPUFA may function as an important regulator of general fatty acid uptake in trophoblast cells and may thus have impact on fetal growth and development. PMID:19880178

  13. Odd-chain polyunsaturated fatty acids in thraustochytrids.

    PubMed

    Chang, Kim Jye Lee; Mansour, Maged P; Dunstan, Graeme A; Blackburn, Susan I; Koutoulis, Anthony; Nichols, Peter D

    2011-08-01

    A series of unusual odd-chain fatty acids (OC-FA) were identified in two thraustochytrid strains, TC 01 and TC 04, isolated from waters off the south east coast of Tasmania, Australia. FA compositions were determined by capillary GC and GC-MS, with confirmation of polyunsaturated fatty acids (PUFA) structure performed by analysis of 4,4-dimethyloxazoline derivatives. PUFA constituted 68-74% of the total FA, with the essential PUFA; eicosapentaenoic acid (20:5ω3, EPA), arachidonic acid (20:4ω6, AA) and docosahexaenoic acid (22:6ω3, DHA), accounting for 42-44% of the total FA. High proportions of the saturated OC-FA 15:0 (7.1% in TC 01) and 17:0 (6.2% in TC 04) were detected. The OC-FA 17:1ω8 was present at 2.8% in TC 01. Of particular interest, the C₂₁ PUFA 21:5ω5 and 21:4ω7 were detected at 3.5% and 4.1%, respectively, in TC 04. A proposed biosynthesis pathway for these OC-PUFA is presented. It is possible that the unsaturated OC-PUFA found previously in a number of marine animals were derived from dietary thraustochytrids and they could be useful biomarkers in environmental and food web studies. PMID:21546043

  14. Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition

    PubMed Central

    Kishino, Shigenobu; Takeuchi, Michiki; Park, Si-Bum; Hirata, Akiko; Kitamura, Nahoko; Kunisawa, Jun; Kiyono, Hiroshi; Iwamoto, Ryo; Isobe, Yosuke; Arita, Makoto; Arai, Hiroyuki; Ueda, Kazumitsu; Shima, Jun; Takahashi, Satomi; Yokozeki, Kenzo; Shimizu, Sakayu; Ogawa, Jun

    2013-01-01

    In the representative gut bacterium Lactobacillus plantarum, we identified genes encoding the enzymes involved in a saturation metabolism of polyunsaturated fatty acids and revealed in detail the metabolic pathway that generates hydroxy fatty acids, oxo fatty acids, conjugated fatty acids, and partially saturated trans-fatty acids as intermediates. Furthermore, we observed these intermediates, especially hydroxy fatty acids, in host organs. Levels of hydroxy fatty acids were much higher in specific pathogen-free mice than in germ-free mice, indicating that these fatty acids are generated through polyunsaturated fatty acids metabolism of gastrointestinal microorganisms. These findings suggested that lipid metabolism by gastrointestinal microbes affects the health of the host by modifying fatty acid composition. PMID:24127592

  15. Synthesis and antiaggregant properties of Stabilized analogues of polyunsaturated fatty acid metabolites.

    PubMed

    Hachem, Ali; Roussel, Patrick; Ménager, Eric; Grée, Danielle; Le Floc'h, Yves; Grée, René; Cerletti, Chiara; Rolland, Yves; Simonet, Serge; Verbeuren, Tony

    2002-09-16

    New aromatic and heteroaromatic analogues of polyunsaturated fatty acid metabolites have been prepared using short and versatile strategies. Preliminary studies of their activity as inhibitors of platelet aggregation are reported. PMID:12182849

  16. Preservation Methods for Retaining n-3 Polyunsaturated Fatty Acids in Alaska Coho Salmon (Oncorhynchus kisutch) Products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coho salmon (Oncorhynchus kisutch) fillets were processed using five different methods (smoking, canning, freezing, acidifying, and salting) to evaluate the effect of preservation choice on the quality of polyunsaturated fatty acids (PUFA). Salmon preserved by smoking, canning, or freezing retained ...

  17. Effect of polyunsaturated fatty acids on drug-sensitive and resistant tumor cells in vitro

    PubMed Central

    2011-01-01

    Previous studies showed that γ-linolenic acid (GLA, 18: 3 ω-6), arachidonic acid (AA, 20:4 ω -6), eicosapentaenoic acid (EPA, 20: 5 ω -3) and docosahexaenoic acid (DHA, 22:6 ω -3) have selective tumoricidal action. In the present study, it was observed that dihomo-gamma-linolenic acid (DGLA) and AA, EPA and DHA have cytotoxic action on both vincristine-sensitive (KB-3-1) and resistant (KB-ChR-8-5) cancer cells in vitro that appeared to be a free-radical dependent process but not due to the formation of prostaglandins, leukotrienes and thromboxanes. Uptake of vincristine and fatty acids was higher while their efflux was lower in KB-3-1 cells compared with KB-ChR-8-5 cells, suggesting that drug resistant cells have an effective efflux pump. GLA, DGLA, AA, EPA and DHA enhanced the uptake and decreased efflux in both drug-sensitive and drug-resistant cells and augmented the susceptibility of tumor cells especially, of drug-resistant cells to the cytotoxic action of vincristine. These results suggest that certain polyunsaturated fatty acids have tumoricidal action and are capable of enhancing the cytotoxic action of anti-cancer drugs specifically, on drug-resistant cells by enhancing drug uptake and reducing its efflux. Thus, polyunsaturated fatty acids either by themselves or in combination with chemotherapeutic drugs have the potential as anti-cancer molecules. PMID:21917129

  18. 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. PMID:25474717

  19. Targeted lipidomics strategies for oxygenated metabolites of polyunsaturated fatty acids

    PubMed Central

    Astarita, Giuseppe; Kendall, Alexandra C.; Dennis, Edward A.; Nicolaou, Anna

    2014-01-01

    Oxidation of polyunsaturated fatty acids (PUFA) through enzymatic or non-enzymatic free radical-mediated reactions can yield an array of lipid metabolites including eicosanoids, octadecanoids, docosanoids and related species. In mammals, these oxygenated PUFA mediators play prominent roles in the physiological and pathological regulation of many key biological processes in the cardiovascular, renal, reproductive and other systems including their pivotal contribution to inflammation. Mass spectrometry-based technology platforms have revolutionized our ability to analyze the complex mixture of lipid mediators found in biological samples, with increased numbers of metabolites that can be simultaneously quantified from a single sample in few analytical steps. The recent development of high-sensitivity and high-throughput analytical tools for lipid mediators affords a broader view of these oxygenated PUFA species, and facilitates research into their role in health and disease. In this review, we illustrate current analytical approaches for a high-throughput lipidomic analysis of eicosanoids and related mediators in biological samples. PMID:25486530

  20. 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. PMID:24269370

  1. 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. PMID:27506793

  2. 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

  3. 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. PMID:12831773

  4. Polyunsaturated Fatty Acids Modify the Gating of Kv Channels

    PubMed Central

    Moreno, Cristina; Macias, Alvaro; Prieto, Angela; De La Cruz, Alicia; Valenzuela, Carmen

    2012-01-01

    Polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, which are attributed to their capability to modulate ion channels. This PUFAs ability has been reported to be due to their effects on the gating properties of ion channels. In the present review, we will focus on the role of PUFAs on the gating of two Kv channels, Kv1.5 and Kv11.1. Kv1.5 channels are blocked by n−3 PUFAs of marine [docosahexaenoic acid (DHA) and eicosapentaenoic acid] and plant origin (alpha-linolenic acid, ALA) at physiological concentrations. The blockade of Kv1.5 channels by PUFAs steeply increased in the range of membrane potentials coinciding with those of Kv1.5 channel activation, suggesting that PUFAs-channel binding may derive a significant fraction of its voltage sensitivity through the coupling to channel gating. A similar shift in the activation voltage was noted for the effects of n–6 arachidonic acid (AA) and DHA on Kv1.1, Kv1.2, and Kv11.1 channels. PUFAs-Kv1.5 channel interaction is time-dependent, producing a fast decay of the current upon depolarization. Thus, Kv1.5 channel opening is a prerequisite for the PUFA-channel interaction. Similar to the Kv1.5 channels, the blockade of Kv11.1 channels by AA and DHA steeply increased in the range of membrane potentials that coincided with the range of Kv11.1 channel activation, suggesting that the PUFAs-Kv channel interactions are also coupled to channel gating. Furthermore, AA regulates the inactivation process in other Kv channels, introducing a fast voltage-dependent inactivation in non-inactivating Kv channels. These results have been explained within the framework that AA closes voltage-dependent potassium channels by inducing conformational changes in the selectivity filter, suggesting that Kv channel gating is lipid dependent. PMID:22973228

  5. 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. PMID:25448610

  6. 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),…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Polyunsaturated fatty acids affect the localization and signaling of PIP3/AKT in prostate cancer cells.

    PubMed

    Gu, Zhennan; Wu, Jiansheng; Wang, Shihua; Suburu, Janel; Chen, Haiqin; Thomas, Michael J; Shi, Lihong; Edwards, Iris J; Berquin, Isabelle M; Chen, Yong Q

    2013-09-01

    AKT is a serine-threonine protein kinase that plays important roles in cell growth, proliferation and apoptosis. It is activated after binding to phosphatidylinositol phosphates (PIPs) with phosphate groups at positions 3,4 and 3,4,5 on the inositol ring. In spite of extensive research on AKT, one aspect has been largely overlooked, namely the role of the fatty acid chains on PIPs. PIPs are phospholipids composed of a glycerol backbone with fatty acids at the sn-1 and sn-2 position and inositol at the sn-3 position. Here, we show that polyunsaturated fatty acids (PUFAs) modify phospholipid content. Docosahexaenoic acid (DHA), an ω3 PUFA, can replace the fatty acid at the sn-2 position of the glycerol backbone, thereby changing the species of phospholipids. DHA also inhibits AKT(T308) but not AKT(S473) phosphorylation, alters PI(3,4,5)P3 (PIP3) and phospho-AKT(S473) protein localization, decreases pPDPK1(S241)-AKT and AKT-BAD interaction and suppresses prostate tumor growth. Our study highlights a potential novel mechanism of cancer inhibition by ω3 PUFA through alteration of PIP3 and AKT localization and affecting the AKT signaling pathway. PMID:23633519

  9. 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. PMID:26036964

  10. 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}.

  11. 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

  12. Polyunsaturated fatty acids in the food chain in Europe.

    PubMed

    Sanders, T A

    2000-01-01

    Intakes of partially hydrogenated fish oil and animal fats have declined and those of palm, soybean, sunflower, and rapeseed oils have increased in northern Europe in the past 30 y. Soybean and rapeseed oils are currently the most plentiful liquid vegetable oils and both have desirable ratios of n-6 to n-3 fatty acids. However, soybean and rapeseed oils are commonly partially hydrogenated for use in commercial frying to decrease susceptibility to oxidative degradation. This process leads to selective losses of alpha-linolenic acid (18:3n-3). Intake of linoleic acid (18:2n-6) has risen in many northern European countries. In the United Kingdom, intakes have increased from approximately 10 g/d in the late 1970s to approximately 15 g/d in the 1990s. The intake of alpha-linolenic acid is estimated to be approximately 1-2 g/d but varies with the type of culinary oil used. There are few reliable estimates of the intake of long-chain n-3 fatty acids, but those are generally approximately 0.1-0.5 g/d. The increased use of intensive, cereal-based livestock production systems has resulted in a lower proportion of n-3 fatty acids in meat compared with traditional extensive production systems. Overall, there has been a shift in the balance between n-6 and n-3 fatty acids over the past 30 y. This shift is reflected in the declining concentrations of docosahexaenoic acid and rising concentrations of linoleic acid in breast milk. PMID:10617968

  13. 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. PMID:24467635

  14. PREECLAMPSIA IS ASSOCIATED WITH COMPROMISED MATERNAL SYNTHESIS OF LONG CHAIN POLYUNSATURATED FATTY ACIDS LEADING TO OFFSPRING DEFICIENCY

    PubMed Central

    Mackay, Vanessa A; Huda, Shahzya S; Stewart, Frances M; Tham, Kahmeng; McKenna, Louise A; Martin, Iain; Jordan, Fiona; Brown, E Ann; Hodson, Leanne; Greer, Ian A; Meyer, Barbara J; Freeman, Dilys J

    2013-01-01

    Obesity and excessive lipolysis are implicated in preeclampsia. Intrauterine growth restriction is associated with low maternal body mass index and decreased lipolysis. Our aim was to assess how maternal and offspring fatty acid metabolism is altered in mothers in the third trimester of pregnancy with preeclampsia (n=62) or intrauterine growth restriction (n=23) compared to healthy pregnancies (n=164). Markers of lipid metabolism and erythrocyte fatty acid concentrations were measured. Maternal adipose tissue fatty acid composition and mRNA expression of adipose tissue fatty acid metabolizing enzymes and placental fatty acid transporters were compared. Mothers with preeclampsia had higher plasma triglyceride (21%, p<0.001) and non-esterified fatty acid (50%, p<0.001) concentrations than Controls. Concentrations of major n-6 and n-3 long chain polyunsaturated fatty acids in erythrocytes were 23-60% lower (all p<0.005) in preeclampsia and intrauterine growth restriction mothers and offspring compared to Controls. Subcutaneous adipose tissue Δ-5 and Δ-6 desaturase and very long chain fatty acid elongase mRNA expression was lower in preeclampsia than Controls [Control 3.38(2.96) vs preeclampsia 1.83(1.91), p=0.030; 3.33(2.25) vs 1.03(0.96), p<0.001; 0.40 (0.81) vs 0.00 (0.00), p=0.038 (square root) expression relative to control gene respectively]. Low maternal and fetal long chain polyunsaturated fatty acid concentrations in preeclampsia may be the result of decreased maternal synthesis. PMID:22949531

  15. Neutrophil migration inhibitory properties of polyunsaturated fatty acids. The role of fatty acid structure, metabolism, and possible second messenger systems.

    PubMed Central

    Ferrante, A; Goh, D; Harvey, D P; Robinson, B S; Hii, C S; Bates, E J; Hardy, S J; Johnson, D W; Poulos, A

    1994-01-01

    The n-3 polyunsaturated fatty acids (PUFA) appear to have antiinflammatory properties that can be partly explained by their biological activity on leukocytes. Since leukocyte emigration is an essential component of the inflammatory response, we have examined the effects of the n-3 PUFA (eicosapentaenoic and docosahexaenoic acids) on neutrophil random and chemotactic movement. Preexposure of neutrophils for 15-30 min to 1-10 micrograms/ml PUFA reduced the random and chemotactic migration to both FMLP- and fungi-activated complement. The inhibitory effect diminished with increasing saturation and carbon chain length, and methylation abolished this activity. Arachidonic and docosahexaenoic acids were the most active fatty acids. The PUFA concentration required to inhibit migration was dependent on cell number, suggesting that the fatty acid effects on leukocyte migration in vivo may be governed by the stage of the inflammatory response. It was concluded that the PUFA rather than their metabolites were responsible for the inhibition since: (a) antioxidants did not prevent the PUFA-induced migration inhibition and the hydroxylated intermediates were less active, and (b) inhibitors of the cyclooxygenase and lipoxygenase pathways were without effect. Inhibitors of protein kinases and calmodulin-dependent enzyme system did not prevent the PUFA-induced migration inhibition, which was also independent of phospholipase D-catalyzed hydrolysis of phospholipids. It is also shown that PUFA decrease the FMLP-induced Ca2+ mobilization. Images PMID:8132744

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  17. Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel

    PubMed Central

    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

    2015-01-01

    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. PMID:25901329

  18. N-3 Polyunsaturated Fatty Acids of Marine Origin and Multifocality in Human Breast Cancer

    PubMed Central

    Ouldamer, Lobna; Goupille, Caroline; Vildé, Anne; Arbion, Flavie; Body, Gilles; Chevalier, Stephan; Cottier, Jean Philippe; Bougnoux, Philippe

    2016-01-01

    Objective The microenvironment of breast epithelial tissue may contribute to the clinical expression of breast cancer. Breast epithelial tissue, whether healthy or tumoral, is directly in contact with fat cells, which in turn could influence tumor multifocality. In this pilot study we investigated whether the fatty acid composition of breast adipose tissue differed according to breast cancer focality. Methods Twenty-three consecutive women presenting with non-metastatic breast cancer underwent breast-imaging procedures including Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during breast surgery. We established a biochemical profile of adipose tissue fatty acids by gas chromatography. We assessed whether there were differences according to breast cancer focality. Results We found that decreased levels in breast adipose tissue of docosahexaenoic and eicosapentaenoic acids, the two main polyunsaturated n-3 fatty acids of marine origin, were associated with multifocality. Discussion These differences in lipid content may contribute to mechanisms through which peritumoral adipose tissue fuels breast cancer multifocality. PMID:26812254

  19. [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. PMID:25445629

  20. Regulation of polyunsaturated fatty acid biosynthesis by seaweed fucoxanthin and its metabolite in cultured hepatocytes.

    PubMed

    Aki, Tsunehiro; Yamamoto, Masaya; Takahashi, Toshiaki; Tomita, Kohki; Toyoura, Rieko; Iwashita, Kazuhiro; Kawamoto, Seiji; Hosokawa, Masashi; Miyashita, Kazuo; Ono, Kazuhisa

    2014-02-01

    The effects of a seaweed carotenoid, fucoxanthin, and its physiological metabolite, fucoxanthinol, on the biosynthesis of polyunsaturated fatty acids (PUFA) were investigated using cultured rat hepatoma BRL-3A. The metabolism of α-linolenic acid (18:3n-3) was suppressed by the addition of these carotenoids, resulting in a decrease in the content of eicosapentaenoic acid (20:5n-3), which suggested a down-regulation of metabolic enzymes such as fatty acid desaturase and elongase. An increase in the content of docosahexaenoic acid (22:6n-3), as observed in previous studies in vivo, might be a buffering action to maintain the membrane fluidity. The suppressive effect of fucoxanthinol on ∆6 fatty acid desaturase was not at the level of gene expression but due to specific modifications of the protein via a ubiquitin-proteasome system. A proteomic analysis revealed several factors such as phosphatidylethanolamine-binding protein that might be involved in the observed action of fucoxanthin. These findings will contribute to studies on the elucidation of the precise molecular mechanisms underlying the regulation of PUFA biosynthesis by fucoxanthin. PMID:24174374

  1. 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. PMID:20172688

  2. Thermal properties of encapsulated polyunsaturated fatty acid esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. Expression profile of polyunsaturated fatty acids in colorectal cancer

    PubMed Central

    Yang, Kai; Li, Hong; Dong, Jin; Dong, Yan; Wang, Chang-Zheng

    2015-01-01

    AIM: To investigate the relationship between the metabolism of polyunsaturated fatty acids (PUFAs) and tumor-associated factors for predicting the outcome of colorectal carcinoma (CRC) in Chinese patients. METHODS: Fresh-frozen malignant and normal tissues from 82 Chinese patients with CRC were analyzed for PUFA composition using gas-liquid chromatography. The levels of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), prostaglandin E2 and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunosorbent assay, and the levels of VEGF, p53 and Ki-67 were measured by immunohistochemistry. RESULTS: In malignant tissue, compared with normal tissue, the levels of total ω-6 PUFAs (24.64% ± 3.41% vs 26.77% ± 3.37%, P = 0.00) and linoleic acid (LA) (15.46% ± 3.51% vs 18.30% ± 2.83%, P < 0.01) were lower, whereas the levels of total ω-3 PUFAs (1.58% ± 0.74% vs 1.35% ± 0.60%, P < 0.01) and dihomo-gamma-linolenic acid (DGLA) (1.32% ± 0.69% vs 0.85% ± 0.29%, P < 0.01) were significantly higher. The ratios of arachidonic acid (AA)/LA (0.53 ± 0.22 vs 0.42 ± 0.19, P < 0.01) and AA/total ω-6 PUFAs (0.31 ± 0.09 vs 0.27 ± 0.10, P < 0.01) were also significantly higher in malignant tissue. The levels of PDGF (353.10 ± 148.85 pg/mL vs 286.09 ± 104.91 pg/mL, P < 0.01), COX-2 (125.21 ± 70.29 ng/mL vs 67.06 ± 42.22 ng/mL, P < 0.01) and VEGF (357.11 ± 128.76 pg/mL vs 211.38 ± 99.47 pg/mL, P < 0.01) were also higher in malignant tissue compared to normal tissue. COX-2 was inversely correlated with LA (R = -0.3244, P < 0.05) and positively correlated with AA/total ω-6 PUFAs (R = 0.3083, P < 0.05) and AA/LA (R = 0.3001, P < 0.05). The tissue level of LA was highest in poorly differentiated tumors (19.9% ± 6.3%, P < 0.05), while the ratio of AA/ω-3 PUFAs was lowest in these tumors (10.8 ± 2.6, P < 0.05). In VEGF-positive tumors, the level of LA was higher (16.2% ± 3.7% vs 13.9% ± 2.7%, P < 0.01), while the AA/ω-3PUFA, AA/ω-6

  4. 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. PMID:25240461

  5. 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

  6. Facts about polyunsaturated fats

    MedlinePlus

    ... gov/ency/patientinstructions/000747.htm Facts about polyunsaturated fats To use the sharing features on this page, ... Alternative names Polyunsaturated fatty acid; PUFA How Polyunsaturated Fats Affect Your Health Polyunsaturated fats can help lower ...

  7. 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

  8. 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. PMID:23701554

  9. Dietary omega-3 and polyunsaturated fatty acids modify fatty acyl composition and insulin binding in skeletal-muscle sarcolemma.

    PubMed

    Liu, S; Baracos, V E; Quinney, H A; Clandinin, M T

    1994-05-01

    Feeding animals with diets high in saturated fat induces insulin resistance, and replacing saturated fat isocalorically with poly-unsaturated fat, especially long-chain omega-3 fatty acids, will prevent the development of insulin resistance in skeletal-muscle tissue. To investigate the mechanism, rats were fed on high-fat (20%, w/w) semipurified diets for 6 weeks. Diets containing ratios of polyunsaturated/saturated (P/S) fatty acid of 0.25 (low-P/S diet) and 1.0 (high-P/S diet) were used to study the effect of the level of saturated fat. To study the effects of omega-3 fatty acids, diets with a low-P/S ratio containing either 0 (low-omega-3 diet) or 3.3% (high-omega-3 diet) long-chain omega-3 fatty acids from fish oil were fed. Plasma membrane from skeletal muscle was purified. The content of fatty acids in sarcolemmal phospholipid was significantly related to the dietary composition. Insulin binding to intact sarcolemmal vesicles prepared from rats fed on diets high in omega-3 fatty acids increased 14-fold compared with animals fed on the low-omega-3 diet (P < 0.0001). Feeding rats on a diet with a high P/S ratio increased sarcolemmal insulin binding by 2.3-fold (P < 0.05). Increased insulin binding was due to increased receptor number at the low-affinity high-capacity binding site. Dietary effects on insulin binding were eliminated when studies were carried out on detergent-solubilized membranes, indicating the importance of the phospholipid fatty acyl composition for insulin binding. The results suggest that dietary omega-3 and polyunsaturated fatty acids increase insulin binding to sarcolemma by changing the fatty acyl composition of phospholipid surrounding the insulin receptor, and this might be the mechanism by which dietary fatty acids modify insulin action. PMID:8192673

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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-...

  11. 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…

  12. Long-Term Treatment with n-3 Polyunsaturated Fatty Acids as a Monotherapy in Children with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Boyraz, Mehmet; Pirgon, Özgür; Dündar, Bumin; Çekmez, Ferhat; Hatipoğlu, Nihal

    2015-01-01

    Objective: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) treatment in obese children with nonalcoholic fatty liver disease (NAFLD). Methods: One hundred and eight obese (body mass index (BMI) >95th percentile for age and sex) adolescents with NAFLD were included in the study. Mean age of the subjects was 13.8±3.9 years (9-17 yrs). The diagnosis of NAFLD was based on the presence of liver steatosis with high transaminases. The subjects were randomly divided into two groups. Group 1 (PUFA group, n=52) received a 1000 mg dose of PUFA once daily for 12 months and lifestyle intervention. Group 2 (placebo group, n=56) received a recommended diet plus placebo and lifestyle intervention for 12 months. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) from fasting samples. Results: BMI, fasting insulin levels and HOMA-IR values in both groups decreased significantly at the end of the study. In group 1, 67.8% of the patients had a decrease from baseline in the prevalence of steatosis (p<0.001). Frequency of elevated alanine aminotransferase (ALT) levels (39.2% to 14.2%; p<0.01) and elevated aspartate aminotransferase (AST) levels (25% to 17.8%; p=0.01) decreased significantly in the PUFA group. Following a 12-month diet plus placebo and lifestyle intervention treatment, 40.3% (21) of the patients in the placebo group also showed a decrease in frequency of steatosis (p=0.04) and slight decreases in frequency of elevated ALT levels (38.4% to 28.8%; p=0.01) and AST levels (30.7% to 28.8%; p>0.05). Conclusion: Our results indicated that n-3 PUFA treatment is safe and efficacious in obese children with NAFLD and can improve ultrasonographic findings and the elevated transaminase levels. PMID:26316434

  13. Immobilized phospholipase A1-catalyzed modification of phosphatidylcholine with n-3 polyunsaturated fatty acid.

    PubMed

    Zhao, TingTing; No, Da Som; Kim, Byung Hee; Garcia, Hugo S; Kim, Yangha; Kim, In-Hwan

    2014-08-15

    n-3 Polyunsaturated fatty acids (n-3 PUFA)-enriched phosphatidylcholine (PC) was successfully produced with fatty acid from fish oil and PC from soybean by immobilized phospholipase A1-catalyzed acidolysis. Detailed studies of immobilization were carried out, and Lewatit VP OC 1600 was selected as a carrier for preparation of immobilized phospholipase A1, which was used for modification of PC by acidolysis. For acidolysis of PC with n-3 PUFA, the effects of several parameters, namely, water content, temperature, and enzyme loading on the reaction time course were investigated to determine optimum conditions. The optimum water content, temperature, and enzyme loading were 1.0%, 55 °C, and 20%, respectively. The highest incorporation (57.4 mol%) of n-3 PUFA into PC was obtained at 24h and the yield of PC was 16.7 mol%. The yield of PC increased significantly by application of vacuum, even though a slight decrease of n-3 PUFA incorporation was observed. PMID:24679762

  14. Hepatoprotective activity of polyherbal formulation (Normeta) in oxidative stress induced by alcohol, polyunsaturated fatty acids and iron in rats.

    PubMed

    Patere, Shilpa N; Saraf, Madhusudan N; Majumdar, Anuradha S

    2009-09-01

    In recent years, oxidative stress has been implicated in the pathophysiology of a large number of diseases or disorders which are initiated and/or exacerbated by pro-oxidants such as various drugs including alcohol and food additives. The present study was carried out to evaluate the effects of oral treatment with polyherbal formulation Normeta (2 ml and 4 ml/kg) on hepatic damage induced by alcohol 10-30% (blood alcohol was maintained at levels between 150 and 350 mg/dl), thermally oxidized oil (polyunsaturated fatty acids) (15% of diet) and carbonyl iron (1.5-2% of diet) for 30 days in rats. In vitro studies with 1, 1-Diphenyl, 2-Picrylhydrazyl (DPPH), Nitric oxide and Ferric chloride (Fe(+3) ions) showed that Normeta possesses antioxidant and metal chelating activity. Alcohol, polyunsaturated fatty acids and iron feeding produced an increase in serum levels of iron, serum glutamate pyruvate transaminase and decrease in serum proteins. It was also associated with elevated lipid peroxidation (thiobarbituric acid reactive substances) and disruption of antioxidant defence mechanism in liver, decreased body weight and increased liver to body weight ratio. Oral administration of Normeta along with alcohol, polyunsaturated fatty acids and iron decreased the serum iron, serum glutamate pyruvate transaminase levels and increased serum protein levels. The levels of liver thiobarbituric acid reactive substances were decreased and the activities of antioxidant enzymes superoxide dismutase and catalase were increased. Improvement in body weight and liver to body weight ratio was also observed. The effects of Normeta on physico-metabolic parameters were comparable with silymarin. This indicates that Normeta has favourable effect in bringing down the severity of hepatotoxicity. PMID:19486336

  15. Transgenic expression of delta-6 and delta-15 fatty acid desaturases enhances omega-3 polyunsaturated fatty acid accumulation in Synechocystis sp. PCC6803

    PubMed Central

    2014-01-01

    Background Polyunsaturated fatty acids (PUFAs), which contain two or more double bonds in their backbone, are the focus of intensive global research, because of their nutritional value, medicinal applications, and potential use as biofuel. However, the ability to produce these economically important compounds is limited, because it is both expensive and technically challenging to separate omega-3 polyunsaturated fatty acids (ω-3 PUFAs) from natural oils. Although the biosynthetic pathways of some plant and microalgal ω-3 PUFAs have been deciphered, current understanding of the correlation between fatty acid desaturase content and fatty acid synthesis in Synechocystis sp. PCC6803 is incomplete. Results We constructed a series of homologous vectors for the endogenous and exogenous expression of Δ6 and Δ15 fatty acid desaturases under the control of the photosynthesis psbA2 promoter in transgenic Synechocystis sp. PCC6803. We generated six homologous recombinants, harboring various fatty acid desaturase genes from Synechocystis sp. PCC6803, Gibberella fujikuroi and Mortierella alpina. These lines produced up to 8.9 mg/l of α-linolenic acid (ALA) and 4.1 mg/l of stearidonic acid (SDA), which are more than six times the corresponding wild-type levels, at 20°C and 30°C. Thus, transgenic expression of Δ6 and Δ15 fatty acid desaturases enhances the accumulation of specific ω-3 PUFAs in Synechocystis sp. PCC6803. Conclusions In the blue-green alga Synechocystis sp. PCC6803, overexpression of endogenous and exogenous genes encoding PUFA desaturases markedly increased accumulation of ALA and SDA and decreased accumulation of linoleic acid and γ-linolenic acid. This study lays the foundation for increasing the fatty acid content of cyanobacteria and, ultimately, for producing nutritional and medicinal products with high levels of essential ω-3 PUFAs. PMID:24581179

  16. Effect of Marine Polyunsaturated Fatty Acids on Biofilm Formation of Candida albicans and Candida dubliniensis

    PubMed Central

    Thibane, Vuyisile S.; Kock, Johan L. F.; Ells, Ruan; van Wyk, Pieter W. J.; Pohl, Carolina H.

    2010-01-01

    The effect of marine polyunsaturated fatty acids on biofilm formation by the human pathogens Candida albicans and Candida dubliniensis was investigated. It was found that stearidonic acid (18:4 n-3), eicosapentaenoic acid (20:5 n-3), docosapentaenoic acid (22:5 n-3) and docosahexaenoic acid (22:6 n-3) have an inhibitory effect on mitochondrial metabolism of both C. albicans and C. dubliniensis and that the production of biofilm biomass by C. dubliniensis was more susceptible to these fatty acids than C. albicans. Ultrastructural differences, which may be due to increased oxidative stress, were observed between treated and untreated cells of C. albicans and C. dubliniensis with formation of rough cell walls by both species and fibrillar structures in C. dubliniensis. These results indicate that marine polyunsaturated fatty acids may be useful in the treatment and/or prevention of biofilms formed by these pathogenic yeasts. PMID:21116408

  17. 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

  18. Microplanktonic Polyunsaturated Fatty Acid Markers: a Mesocosm Trial

    NASA Astrophysics Data System (ADS)

    Pond, D. W.; Bell, M. V.; Harris, R. P.; Sargent, J. R.

    1998-02-01

    The fatty acid composition of total lipid was determined in microplankton (<200 μm) from control, diatom-dominated and coccolithophore-dominated mesocosms. There was a good correlation between the abundances of chlorophyll aand total fatty acids in the three mesocosms. Analyses of fatty acid markers characteristic of diatoms (16:1n-7, 16:2n-3, 16:3n-3, 16:4n-1 and 20:5n-3) and of coccolithophores (18:5n-3 and 22:6n-3) established that in the diatom-dominated mesocosm, an increase in coccolithophore biomass, preceded the diatom bloom. Similarly, an increase in the levels of diatom fatty acids preceded the coccolithophore bloom in the coccolithophore-dominated mesocom. These transient increases in microplanktonic marker fatty acids levels were not evident from measures chlorophyll a, or estimated carbon contribution derived from cell counts. There was appreciable 22:6n-3 derived from coccolithophores in the diatom-dominated bloom suggesting that the amount of this key nutrient at the base of the marine food-web may often be underestimated, with important consequences for higher trophic levels.

  19. Polyunsaturated Fatty Acid-Derived Lipid Mediators and T Cell Function

    PubMed Central

    Nicolaou, Anna; Mauro, Claudio; Urquhart, Paula; Marelli-Berg, Federica

    2014-01-01

    Fatty acids are involved in T cell biology both as nutrients important for energy production as well as signaling molecules. In particular, polyunsaturated fatty acids are known to exhibit a range of immunomodulatory properties that progress through T cell mediated events, although the molecular mechanisms of these actions have not yet been fully elucidated. Some of these immune activities are linked to polyunsaturated fatty acid-induced alteration of the composition of cellular membranes and the consequent changes in signaling pathways linked to membrane raft-associated proteins. However, significant aspects of the polyunsaturated fatty acid bioactivities are mediated through their transformation to specific lipid mediators, products of cyclooxygenase, lipoxygenase, or cytochrome P450 enzymatic reactions. Resulting bioactive metabolites including prostaglandins, leukotrienes, and endocannabinoids are produced by and/or act upon T leukocytes through cell surface receptors and have been shown to alter T cell activation and differentiation, proliferation, cytokine production, motility, and homing events. Detailed appreciation of the mode of action of these lipids presents opportunities for the design and development of therapeutic strategies aimed at regulating T cell function. PMID:24611066

  20. 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

  1. 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

  2. Dietary polyunsaturated fatty acids from flaxseed affect immune responses of dairy sheep around parturition.

    PubMed

    Caroprese, Mariangela; Ciliberti, Maria Giovanna; Albenzio, Marzia; Annicchiarico, Giovanni; Sevi, Agostino

    2015-11-15

    The objective of the study was to characterize the immune profile of dairy ewes fed flaxseed, rich in polyunsaturated fatty acids (PUFA), around parturition. The hypothesis to be verified was that a physiological stressor, such as parturition, could be overcome with a nutritional manipulation in the diet of the animal in order to guarantee welfare of animals and to sustain their immune responses. Twenty Comisana ewes were divided in two groups (10 ewes/group), and fed a supplementation of whole flaxseed in the diet (FS group) or no supplementation (CON group). Blood samples were collected at parturition and then 7, 14, 21, 28, and 42 day post partum. Plasma samples were used to assess the humoral immune response after ovalbumin (OVA) immunization. At parturition, at 14 day, and 42 day post partum the level of plasma cytokines was assessed. The sheep showed a reduced responsiveness to OVA immunization. In FS ewes the IL-6 level remained unchanged until 14 day post partum and then significantly decreased from 14 day to 42 day post partum. IL-10 level was significantly higher in FS ewes than in CON ewes at 14 day. At parturition IL-1β level was significantly lower in FS ewes than in CON ewes and significantly decreased in both groups from parturition to 42 day. In conclusion, PUFA from flaxseed, as supplement in the diet of ewes around parturition can modulate sheep immune reactivity by influencing cytokine production. PMID:26347035

  3. Drosophila lacks C20 and C22 polyunsaturated fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. The effects of nutritional polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats.

    PubMed

    Hauser, Joachim; Makulska-Gertruda, Ewelina; Reissmann, Andreas; Sontag, Thomas-A; Tucha, Oliver; Lange, Klaus W

    2014-06-01

    The present study investigated the effects of nutritional omega-3 polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats (SHRs), which are used as an animal model of attention-deficit/hyperactivity disorder (ADHD). For 6 weeks, two groups of randomly assigned SHRs received food either enriched with or deficient in omega-3 fatty acids (based on the American Institute of Nutrition-93 G/AIN93G). Using an open field, locomotor activity was subsequently assessed for 6 days. A marked difference in locomotor activity as assessed by the distance travelled in the open field was found between the two groups of rats. In comparison with rats fed with omega-3 fatty acid-enriched food, the animals on the omega-3 fatty acid-deficient diet showed a significantly higher locomotor activity. The present findings demonstrated that nutritional enrichment with omega-3 fatty acids was associated with reduced motor activity in an established animal model of ADHD and support the notion that omega-3 polyunsaturated fatty acids may play a role in the pathophysiology of ADHD. PMID:24415401

  5. Enrichment of eggs in n-3 polyunsaturated fatty acids by feeding hens with different amount of linseed oil in diet.

    PubMed

    Petrović, Marinko; Gačić, Milica; Karačić, Veseljko; Gottstein, Zeljko; Mazija, Hrvoje; Medić, Helga

    2012-12-01

    The production of n-3 polyunsaturated fatty acid enriched eggs by addition of linseed oil to the laying hens' diet has been evaluated in terms of production parameters and n-6/n-3 ratio. A total of 150 18weeks old Lohmann Brown laying hens were housed in cages and fed with basal diet and four experimental diets containing 1%, 2%, 3% or 4% of linseed oil added to the basal diet. The effect of the altered level of linseed oil on hens laying performance, fatty acid content and composition and cholesterol content in egg yolk has been evaluated during 13weeks of experiment. Egg weight, yolk fat content, yolk weight, yolk percentage and shape index were not influenced by dietary treatment. The ratio between n-6 and n-3 polyunsaturated fatty acids in eggs decreased in first 5weeks and then remained stable until the end of the experiment for all experimental groups. Different contents of linseed oil in feed highly influenced the n-6/n-3 ratio (P<0.0001). Addition of linseed oil did not influence the cholesterol content in yolks (P=0.5200) while the only factor affecting the cholesterol content was the hens age (P<0.0001). PMID:22953894

  6. Endogenous ω-3 polyunsaturated fatty acid production confers resistance to obesity, dyslipidemia, and diabetes in mice.

    PubMed

    Li, Jie; Li, Fanghong R; Wei, Dong; Jia, Wei; Kang, Jing X; Stefanovic-Racic, Maja; Dai, Yifan; Zhao, Allan Z

    2014-08-01

    Despite the well-documented health benefits of ω-3 polyunsaturated fatty acids (PUFAs), their use in clinical management of hyperglycemia and obesity has shown little success. To better define the mechanisms of ω-3 PUFAs in regulating energy balance and insulin sensitivity, we deployed a transgenic mouse model capable of endogenously producing ω-3 PUFAs while reducing ω-6 PUFAs owing to the expression of a Caenorhabditis elegans fat-1 gene encoding an ω-3 fatty acid desaturase. When challenged with high-fat diets, fat-1 mice strongly resisted obesity, diabetes, hypercholesterolemia, and hepatic steatosis. Endogenous elevation of ω-3 PUFAs and reduction of ω-6 PUFAs did not alter the amount of food intake but led to increased energy expenditure in the fat-1 mice. The requirements for the levels of ω-3 PUFAs as well as the ω-6/ω-3 ratios in controlling blood glucose and obesity are much more stringent than those in lipid metabolism. These metabolic phenotypes were accompanied by attenuation of the inflammatory state because tissue levels of prostaglandin E2, leukotriene B4, monocyte chemoattractant protein-1, and TNF-α were significantly decreased. TNF-α-induced nuclear factor-κB signaling was almost completely abolished. Consistent with the reduction in chronic inflammation and a significant increase in peroxisome proliferator-activated receptor-γ activity in the fat-1 liver tissue, hepatic insulin signaling was sharply elevated. The activities of prolipogenic regulators, such as liver X receptor, stearoyl-CoA desaturase-1, and sterol regulatory element binding protein-1 were sharply decreased, whereas the activity of peroxisome proliferator-activated receptor-α, a nuclear receptor that facilitates lipid β-oxidation, was markedly increased. Thus, endogenous conversion of ω-6 to ω-3 PUFAs via fat-1 strongly protects against obesity, diabetes, inflammation, and dyslipidemia and may represent a novel therapeutic modality to treat these prevalent

  7. 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

    2005-04-01

    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. PMID:15792445

  8. 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

  9. 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

  10. The scope for manipulating the polyunsaturated fatty acid content of beef: a review.

    PubMed

    Vahmani, Payam; Mapiye, Cletos; Prieto, Nuria; Rolland, David C; McAllister, Tim A; Aalhus, Jennifer L; Dugan, Michael E R

    2015-01-01

    Since 1950, links between intake of saturated fatty acids and heart disease have led to recommendations to limit consumption of saturated fatty acid-rich foods, including beef. Over this time, changes in food consumption patterns in several countries including Canada and the USA have not led to improvements in health. Instead, the incidence of obesity, type II diabetes and associated diseases have reached epidemic proportions owing in part to replacement of dietary fat with refined carbohydrates. Despite the content of saturated fatty acids in beef, it is also rich in heart healthy cis-monounsaturated fatty acids, and can be an important source of long-chain omega-3 (n-3) fatty acids in populations where little or no oily fish is consumed. Beef also contains polyunsaturated fatty acid biohydrogenation products, including vaccenic and rumenic acids, which have been shown to have anticarcinogenic and hypolipidemic properties in cell culture and animal models. Beef can be enriched with these beneficial fatty acids through manipulation of beef cattle diets, which is now more important than ever because of increasing public understanding of the relationships between diet and health. The present review examines recommendations for beef in human diets, the need to recognize the complex nature of beef fat, how cattle diets and management can alter the fatty acid composition of beef, and to what extent content claims are currently possible for beef fatty acids. PMID:26199725

  11. Polyunsaturated fatty acids and their metabolites in the pathobiology of schizophrenia.

    PubMed

    Das, Undurti N

    2013-04-01

    Schizophrenia can be considered as a low-grade systemic inflammatory disease with its origins in the perinatal period. It is likely that genetic, environmental, and nutritional factors interact to induce excess production of pro-inflammatory cytokines that, in turn, damage fetal neurons leading to the adult onset of schizophrenia. Polyunsaturated fatty acids (PUFAs) and their metabolites such as lipoxins, resolvins, protectins, maresins and nitrolipids not only have potent neuroprotective action but also are capable of inhibiting the production of pro-inflammatory cytokines. Decreased formation of PUFAs as a result of low activity of Δ(6) and Δ(5) desaturases can result in an increase in the production of pro-inflammatory cytokines due to the absence of negative control exerted by PUFAs and their anti-inflammatory metabolites that, in turn, may predispose to neuronal damage and development of schizophrenia in adult life. Furthermore, PUFAs are essential for brain growth and development. If this proposal is correct, this implies that perinatal and adult supplementation of PUFAs not only prevents but also helps in the treatment of schizophrenia. Furthermore, synthetic analogs of lipoxins, resolvins, and protectins may be of significant benefit in schizophrenia. PMID:22735394

  12. Long-chain polyunsaturated fatty acid status in obesity: a systematic review and meta-analysis.

    PubMed

    Fekete, K; Györei, E; Lohner, S; Verduci, E; Agostoni, C; Decsi, T

    2015-06-01

    Long-chain polyunsaturated fatty acid (LCPUFA) status has recently been related to the pathogenesis of obesity. Our aims were to systematically review observational studies investigating LCPUFA status from different blood compartments in overweight or obese subjects and to assess the relationship between LCPUFA profile and obesity. The Ovid MEDLINE, Scopus and Cochrane Library CENTRAL databases were searched from inception to January 2014. The meta-analysis showed significant differences in the LCPUFA composition of total plasma lipids, plasma phospholipids and plasma cholesteryl esters between overweight or obese subjects and controls. Dihomo-γ-linolenic acid (DGLA) values were significantly higher in overweight or obese subjects compared with controls in all the investigated biomarkers. In addition, the DGLA/linoleic acid ratio (surrogate parameter for Δ6 desaturase activity) in plasma phospholipids was significantly elevated (mean difference [MD]: 0.05; 95% confidence interval [CI]: 0.02, 0.08; n = 280), while the arachidonic acid/DGLA ratio (surrogate parameter for Δ5 desaturase activity) was significantly decreased (MD: -0.55; 95% CI: -0.71, -0.39; n = 347) in overweight or obese subjects compared with controls. The results of the present meta-analysis confirm that LCPUFA profile is altered in obesity and suggest that the differences observed in desaturase activities may be responsible for the disturbed LCPUFA metabolism in obesity. PMID:25828602

  13. n-3 Polyunsaturated fatty acids inhibit Fc ε receptor I-mediated mast cell activation.

    PubMed

    Wang, Xiaofeng; Ma, David W L; Kang, Jing X; Kulka, Marianna

    2015-12-01

    In vivo models show that n-3 polyunsaturated fatty acids (PUFA) inhibit some of the processes associated with allergic inflammation but the direct effect of n-3 PUFA on mast cells, the major effector cells in allergy, is poorly understood. We sought to determine the effect and mechanism of n-3 PUFA on Fc ε receptor I (FcεRI)-mediated signal transduction and mast cell activation. Bone marrow-derived mast cells (BMMC) were differentiated from bone marrow obtained from C57BL/6 wild-type (WT) and fat-1 transgenic mice. The fat-1 mice express fatty acid n-3 desaturase and produce endogenous n-3 PUFA. For comparison, exogenous n-3 PUFA were supplemented to WT BMMC and human mast cell (LAD2) cultures. Fat-1 BMMC released less β-hexosaminidase (β-hex) and cysteinyl leukotrienes and produced less tumor necrosis factor and chemokine (C-C motif) ligand 2. n-3 PUFA supplementation reduced LAD2 and BMMC degranulation (β-hex release) following FcεRI activation. Fat-1 BMMC expressed less constitutive Lyn and linker of activated T cells (LAT), and FcεRI-mediated phosphorylation of Lyn, spleen tyrosine kinase and LAT were reduced in fat-1 BMMC. Although the expression of surface and whole cell FcεRI was similar in WT and fat-1 BMMC, unstimulated fat-1 BMMC showed reduced FcεRI localization to lipid rafts, and stimulation with antigen resulted in aberrant FcεRI shuttling to the rafts. Our results show that n-3 PUFA suppress FcεRI-mediated activation of mast cells, which results in reduced mediator release. This effect is associated with a decrease in LAT and Lyn expression as well as abnormal shuttling of FcεRI to lipid rafts. PMID:26363927

  14. Serum long-chain omega-3 polyunsaturated fatty acids and risk of orthostatic hypotension.

    PubMed

    Nyantika, Asenath N; Tuomainen, Tomi-Pekka; Kauhanen, Jussi; Voutilainen, Sari; Virtanen, Jyrki K

    2016-07-01

    Long-chain omega-3 polyunsaturated fatty acids (PUFAs) from fish have been shown to lower blood pressure. However, there is little information about the association with orthostatic hypotension, for which hypertension is a risk factor. We investigated the associations between serum long-chain omega-3 PUFAs and orthostatic hypotension in 1666 middle-aged or older men and women free of cardiovascular disease (CVD), diabetes or hypertension in 1998-2001 in the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) in eastern Finland. We also investigated the associations with mercury exposure, a major source of which is fish, and which has been associated with higher CVD risk in KIHD. Orthostatic hypotension was defined as decrease in systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 1 min of standing. Orthostatic hypotension was found in 146 participants (8.8%). The mean serum concentrations were 1.67% (s.d. 0.92) for eicosapentaenoic acid, 0.79% (s.d. 0.16) for docosapentaenoic acid (DPA) and 2.78 (s.d. 0.92) for docosahexaenoic acid of all serum fatty acids. The mean pubic hair mercury concentration was 1.5 μg g(-1) (s.d. 1.6). We did not find statistically significant associations between the serum long-chain omega-3 PUFAs or pubic hair mercury and risk of orthostatic hypotension, except for DPA. Those in the highest vs. the lowest serum DPA tertile had multivariate-adjusted 41% lower odds for orthostatic hypotension (95% confidence interval 7-63%, P-trend=0.02). Serum long-chain omega-3 PUFAs or mercury exposure were not associated with the risk of orthostatic hypotension, except for the inverse association with DPA. PMID:26911234

  15. 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. PMID:17624683

  16. Omega-3 polyunsaturated fatty acids and vegetarian diets.

    PubMed

    Saunders, Angela V; Davis, Brenda C; Garg, Manohar L

    2013-08-19

    While intakes of the omega-3 fatty acid α-linolenic acid (ALA) are similar in vegetarians and non-vegetarians, intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low in vegetarians and virtually absent in vegans. Plasma, blood and tissue levels of EPA and DHA are lower in vegetarians than in non-vegetarians, although the clinical significance of this is unknown. Vegetarians do not exhibit clinical signs of DHA deficiency, but further research is required to ascertain whether levels observed in vegetarians are sufficient to support optimal health. ALA is endogenously converted to EPA and DHA, but the process is slow and inefficient and is affected by genetics, sex, age and dietary composition. Vegetarians can take practical steps to optimise conversion of ALA to EPA and DHA, including reducing intake of linoleic acid. There are no official separate recommendations for intake of fatty acids by vegetarians. However, we suggest that vegetarians double the current adequate intake of ALA if no direct sources of EPA and DHA are consumed. Vegetarians with increased needs or reduced conversion ability may receive some advantage from DHA and EPA supplements derived from microalgae. A supplement of 200-300 mg/day of DHA and EPA is suggested for those with increased needs, such as pregnant and lactating women, and those with reduced conversion ability, such as older people or those who have chronic disease (eg, diabetes). PMID:25369925

  17. Astrocytes Release Polyunsaturated Fatty Acids by Lipopolysaccharide Stimuli.

    PubMed

    Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

    2016-01-01

    We previously reported that levels of long-chain fatty acids (FAs) including docosahexaenoic acids (DHA) increase in the hypothalamus of inflammatory pain model mice. However, the precise mechanisms underlying the increment of free fatty acids (FFAs) in the brain during inflammation remains unknown. In this study, we characterized FFAs released by inflammatory stimulation in rat primary cultured astrocytes, and tested the involvement of phospholipase A2 (PLA2) on these mechanisms. Lipopolysaccharide (LPS) stimulation significantly increased the levels of several FAs in the astrocytes. Under these conditions, mRNA expression of cytosolic PLA2 (cPLA2) and calcium-independent PLA2 (iPLA2) in LPS-treated group increased compared with the control group. Furthermore, in the culture media, the levels of DHA and arachidonic acid (ARA) significantly increased by LPS stimuli compared with those of a vehicle-treated control group whereas the levels of saturated FAs (SFAs), namely palmitic acid (PAM) and stearic acid (STA), did not change. In summary, our findings suggest that astrocytes specifically release DHA and ARA by inflammatory conditions. Therefore astrocytes might function as a regulatory factor of DHA and ARA in the brain. PMID:27374285

  18. 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

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

    PubMed

    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

  20. 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. PMID:26806391

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

    NASA Astrophysics Data System (ADS)

    Saiz, Leonor; Klein, Michael L.

    2001-03-01

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

  2. [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. PMID:12494533

  3. 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

  4. 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

    2014-01-01

    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

  5. 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

  6. Blocking effects of polyunsaturated fatty acids on Na+ channels of neonatal rat ventricular myocytes.

    PubMed Central

    Xiao, Y F; Kang, J X; Morgan, J P; Leaf, A

    1995-01-01

    Recent evidence indicates that polyunsaturated long-chain fatty acids (PUFAs) prevent lethal ischemia-induced cardiac arrhythmias in animals and probably in humans. To increase understanding of the mechanism(s) of this phenomenon, the effects of PUFAs on Na+ currents were assessed by the whole-cell patch-clamp technique in cultured neonatal rat ventricular myocytes. Extracellular application of the free 5,8,11,14,17-eicosapentaenoic acid (EPA) produced a concentration-dependent suppression of ventricular, voltage-activated Na+ currents (INa). After cardiac myocytes were treated with 5 or 10 microM EPA, the peak INa (elicited by a single-step voltage change with pulses from -80 to -30 mV) was decreased by 51% +/- 8% (P < 0.01; n = 10) and 64% +/- 5% (P < 0.001; n = 21), respectively, within 2 min. Likewise, the same concentrations of 4,7,10,16,19-docosahexaenoic acid produced the same inhibition of INa. By contrast, 5 and 10 microM arachidonic acid (AA) caused less inhibition of INa, but both n - 6 and n - 3 PUFAs inhibited INa significantly. A monounsaturated fatty acid and a saturated fatty acid did not. After washing out EPA, INa returned to the control level. Raising the concentration of EPA to 40 microM completely blocked INa. The IC50 of EPA was 4.8 microM. The inhibition of this Na+ channel was found to be dose and time, but not use dependent. Also, the EPA-induced inhibition of INa was voltage dependent, since 10 microM EPA produced 83% +/- 7% and 29% +/- 5% inhibition of INa elicited by pulses from -80 to -30 mV and from -150 to -30 mV, respectively, in single-step voltage changes. A concentration of 10 microM EPA shifted the steady-state inactivation curve of INa by -19 +/- 3 mV (n = 7; P < 0.01). These effects of PUFAs on INa may be important for their antiarrhythmic effect in vivo. PMID:7479925

  7. Who's afraid of n-6 polyunsaturated fatty acids? Methodological considerations for assessing whether they are harmful.

    PubMed

    Berry, E M

    2001-06-01

    N-6 fatty acids are essential for normal growth, development and health, and so extreme care is necessary before deciding that they are harmful. Theoretical and epidemiological evidence suggests the involvement of n-6 polyunsaturated fatty acids (PUFAs) in disease progression or prevention; however, n-6 function cannot be considered in isolation but needs to be seen as part of the complex of nutrient interactions with n-3 fatty acids (which compete for the same enzymatic pathways) and antioxidants. Insulin sensitivity might be the common factor relating disease to fatty acid metabolism both within and between the fatty acid pathways. High linoleate to arachidonate concentrations have been observed in insulin resistance, diabetic complications and some tumours, but these are multifactorial processes that include many lifestyle determinants and it is therefore wrong to condemn only n-6 fatty acids in their etiology. The results based on the criteria for assessing diet and disease are still insufficient to declare n-6 fatty acids a serious health risk; at most, the verdict should be "not proven". The question may never be conclusively answered not only because prospective dietary intervention trials (unlike those with n-3 fish oil capsules) are fraught with dosage and compliance problems, but also because of high background linoleate consumption. Tissue fatty acid composition may be a suitable biomarker for PUFA intake but there are many theoretical and methodological problems concerning other suitable markers because of the multiplicity of their biological effects. Before making evidence-based dietary recommendations, future research should consider: 1) how n-3 and n-6 dietary PUFAs affect the physiological balance (dose-response) of their derivatives such as eicosanoids and the newly-discovered fatty acid amides; 2) the metabolic interactions between n-6 and n-3 fatty acid pathways (including gene-nutrient effects); 3) the need for antioxidant cover (quantity and

  8. The effect of modifying dietary LA and ALA intakes on omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) status in human adults: a systematic review and commentary.

    PubMed

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

    2015-04-01

    This paper presents a systematic review of human studies investigating the effect of altering dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) alpha-linolenic acid (ALA) and omega-6 polyunsaturated fatty acid (n-6 PUFA) linoleic acid (LA) intakes on n-3 long-chain polyunsaturated fatty acid (LCPUFA) status in adult humans. The results suggest that it is possible to increase n-3 LCPUFA status by reducing LA and/or increasing ALA intake in humans, although decreasing LA intake to below 2.5%E may be required to specifically increase levels of the n-3 LCPUFA docosahexaenoic acid (DHA). The majority of studies in this area to date have been relatively poor in quality, which limits the ability to draw robust conclusions, and we present a series of recommendations to improve the quality of future studies in fatty acid nutrition in humans. PMID:25687496

  9. 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

  10. Long-chain polyunsaturated fatty acids and the pathophysiology of myalgic encephalomyelitis (chronic fatigue syndrome).

    PubMed

    Puri, B K

    2007-02-01

    Evidence is put forward to suggest that myalgic encephalomyelitis, also known as chronic fatigue syndrome, may be associated with persistent viral infection. In turn, such infections are likely to impair the ability of the body to biosynthesise n-3 and n-6 long-chain polyunsaturated fatty acids by inhibiting the delta-6 desaturation of the precursor essential fatty acids--namely, alpha-linolenic acid and linoleic acid. This would, in turn, impair the proper functioning of cell membranes, including cell signalling, and have an adverse effect on the biosynthesis of eicosanoids from the long-chain polyunsaturated fatty acids dihomo-gamma-linolenic acid, arachidonic acid and eicosapentaenoic acid. These actions might offer an explanation for some of the symptoms and signs of myalgic encephalomyelitis. A potential therapeutic avenue could be offered by bypassing the inhibition of the enzyme delta-6-desaturase by treatment with virgin cold-pressed non-raffinated evening primrose oil, which would supply gamma-linolenic acid and lipophilic pentacyclic triterpenes, and with eicosapentaenoic acid. The gamma-linolenic acid can readily be converted into dihomo-gamma-linolenic acid and thence arachidonic acid, while triterpenes have important free radical scavenging, cyclo-oxygenase and neutrophil elastase inhibitory activities. Furthermore, both arachidonic acid and eicosapentaenoic acid are, at relatively low concentrations, directly virucidal. PMID:16935966

  11. Medium-chain triglyceride and n-3 polyunsaturated fatty acid-containing emulsions in intravenous nutrition.

    PubMed

    Chan, S; McCowen, K C; Bistrian, B

    1998-03-01

    Medium-chain triglycerides and n-3 polyunsaturated fatty acid emulsions as a physical mixture have attracted increasing interest for use in parenteral nutrition and may play an important role in the development of structured triglycerides in a future generation of new lipids. Over the past two decades, the clinical use of intravenous emulsion for the nutritional support of hospitalized patients has relied exclusively on long-chain triglycerides providing both a safe, calorically dense alternative to dextrose and a source of essential fatty acids needed for biological membranes and maintenance of the immune function. During the past decade, the development of new triglycerides (medium- and long-chain triglyceride emulsions and structured triglyceride emulsions) for parenteral use have provided useful advances and opportunities to enhance nutritional and metabolic support. Medium-chain triglycerides and n-3 polyunsaturated fatty acid emulsions possess unique physical, chemical, and metabolic properties that make them theoretically advantageous over the conventional long-chain triglycerides. The physical mixture of medium- and long-chain triglycerides have been used clinically in patients with critical illness, liver disease, immunosuppression, pulmonary disease, and in premature infants, with good tolerance and the avoidance of some of the problems encountered with long-chain triglycerides alone. PMID:10565343

  12. Omega-3 polyunsaturated fatty acids: a necessity for a comprehensive secondary prevention strategy

    PubMed Central

    Patel, Jeetesh V; Tracey, Inessa; Hughes, Elizabeth A; Lip, Gregory YH

    2009-01-01

    Long-chain omega-3 polyunsaturated fatty acid (PUFA) supplementation has been used for the secondary prevention of fatal and nonfatal myocardial infarction (MI). However, the benefit of this therapy is frequently confused with other established treatments in the therapeutic strategy among such patients. We review the data on omega-3 PUFA use in secondary care and consider indications for its use which include post-MI and raised triglycerides. We suggest that the available evidence supports the use of omega-3 supplementation as part of the comprehensive secondary care package for post-MI patients. PMID:19812692

  13. Magnetoliposomes Loaded with Poly-Unsaturated Fatty Acids as Novel Theranostic Anti-Inflammatory Formulations

    PubMed Central

    Calle, Daniel; Negri, Viviana; Ballesteros, Paloma; Cerdán, Sebastián

    2015-01-01

    We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning 1H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved 1H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may become

  14. Magnetoliposomes loaded with poly-unsaturated fatty acids as novel theranostic anti-inflammatory formulations.

    PubMed

    Calle, Daniel; Negri, Viviana; Ballesteros, Paloma; Cerdán, Sebastián

    2015-01-01

    We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning (1)H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved (1)H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may

  15. 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

  16. Short term effects of dietary medium-chain fatty acids and n-3 long-chain polyunsaturated fatty acids on the fat metabolism of healthy volunteers

    PubMed Central

    Beermann, Christopher; Jelinek, J; Reinecker, T; Hauenschild, A; Boehm, G; Klör, H-U

    2003-01-01

    Background The amount and quality of dietary fatty acids can modulate the fat metabolism. Objective This dietary intervention is based on the different metabolic pathways of long-chain saturated fatty acids (LCFA), which are mostly stored in adipocytic triacylglycerols, medium-chain fatty acids (MCFA) which are preferentially available for hepatic mitochondrial β-oxidation and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) suggested to modulate fat oxidation and storage by stimulating the peroxisomal β-oxidation. Combined dietary MCFA and n-3 LCPUFA without LCFA may synergistically stimulate fatty acid oxidation resulting in blood lipid clearance and LCFA release from adipocytes. Design In a short term, parallel, randomized, double-blind trial effects on the fatty acid metabolism of 10 healthy volunteers (Body Mass Index 25–30) of a formula containing 72% MCFA and 22% n-3 LCPUFA without LCFA (intake: 1.500 kcal/day; fat: 55.5% of energy) were measured in comparison to an isoenergetic formula with equal fat amount and LCFA dominated lipid profile. Results The plasma triacylglycerol (p < 0.1) and cholesterol (p < 0.05) content decreased in the test group. The n-3/n-6 LCPUFA (≥ C 20) ratio increased (p < 0.0001) after 4 days treatment. The LCFA content was similar in both groups despite missing LCFA in the test formula indicating LCFA release from adipocytes into the plasma. Both groups significantly reduced body weight considerably 4 kg (p < 0.01) and fat mass up to 50% of weight loss (p < 0.05). Conclusion Combined dietary 72% MCFA and 22% n-3 LCPUFA without LCFA stimulate the fatty acid oxidation and release from adipocytes without affecting any safety parameters measured. PMID:14622442

  17. 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

    2014-09-01

    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. PMID:25109502

  18. Polyunsaturated fatty acid supplementation: effects of seaweed Ascophyllum nodosum and flaxseed on milk production and fatty acid profile of lactating ewes during summer.

    PubMed

    Caroprese, Mariangela; Ciliberti, Maria Giovanna; Marino, Rosaria; Santillo, Antonella; Sevi, Agostino; Albenzio, Marzia

    2016-08-01

    The research reported in this Research Communication was undertaken to evaluate the effects of different sources of polyunsaturated fatty acids (PUFA) supplemented in the diet on milk production and milk fatty acid profile of lactating ewes exposed to long term heat stress. The experiment was conducted during summer, involved 32 ewes divided into 4 groups of 8 each, and lasted 6 weeks. The ewes in all groups were fed twice daily and received 1·8 kg/d of oat hay and 1 kg/d of concentrate. Flaxseed group (FS) was supplemented with 250 g/d of whole flaxseed, Ascophyllum nodosum group (AG) was supplemented with 25 g/d of seaweed Ascophyllum nodosum, and the combination group (FS + AG) received both flaxseed and Ascophyllum nodosum supplementation. The control group (CON) was fed with 1 kg/d of pelleted concentrate without PUFA supplementation. Milk samples were collected twice daily per week, and analysed for fat, total protein, casein, and lactose content. At the beginning and then at 2, 4 and 6 week of the experiment each milk sample was analysed for milk fatty acids. Temperature-humidity index (THI) was calculated daily. Supplementation of flaxseed and of the combination of flaxseed and Ascophyllum nodosum increased milk yield. The total content of saturated fatty acids (SFA) in milk decreased for ewes fed FS, followed by FS + AG. On the contrary, monounsaturated fatty acids (MUFA) increased for ewes fed FS and FS + AG. The total n-3 FA was found higher in FS and FS + AG than in AG and CON groups mainly because of the increase in C 18 : 3 n-3 in FS and FS + AG milk. Milk from FS + AG resulted in the highest n-3/n-6 ratio and decreases in atherogenic and thrombogenic indices. The combination of seaweed Ascophyllum nodosum and flaxseed can be suggested as an adequate supplementation to sustain milk production and milk fatty acid profile of sheep during summer season. PMID:27600962

  19. Ingestion of a single serving of saury alters postprandial levels of plasma n-3 polyunsaturated fatty acids and long-chain monounsaturated fatty acids in healthy human adults

    PubMed Central

    2012-01-01

    Background Saury oil contains considerable amounts of n-3 polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) with long aliphatic tails (>18C atoms). Ingestion of saury oil reduces the risk of developing metabolic syndrome concomitant with increases in n-3 PUFA and long-chain MUFA in plasma and organs of mice. We therefore evaluated changes in postprandial plasma fatty acid levels and plasma parameters in healthy human subjects after ingestion of a single meal of saury. Findings Five healthy human adults ingested 150 g of grilled saury. Blood was collected before the meal and at 2, 6, and 24 hr after the meal, and plasma was prepared. Plasma levels of eicosapentaenoic acid, docosahexaenoic acid, and long-chain MUFA (C20:1 and C22:1 isomers combined) increased significantly throughout the postprandial period compared with the pre-meal baseline. Postprandial plasma insulin concentration increased notably, and plasma levels of glucose and free fatty acids decreased significantly and subsequently returned to the pre-meal levels. Conclusions Our study suggests that a single saury meal may alter the postprandial plasma levels of n-3 PUFA and long-chain MUFA in healthy human subjects. PMID:22846384

  20. Polyunsaturated fatty acid-enriched diet therapy for a child with epilepsy.

    PubMed

    Yoon, Jung-Rim; Lee, Eun Joo; Kim, Heung Dong; Lee, Jae Hwan; Kang, Hoon-Chul

    2014-02-01

    The ketogenic diet (KD) is a high-fat, low-carbohydrate diet with an established efficacy for treating medically refractory epilepsy in children. Fatty acids are the most important constituent of the KD in all aspects of efficacy and complications. Among fatty acids, polyunsaturated fatty acids (PUFAs) increase anticonvulsant properties and reduce the complications associated with the high-fat diet. Here, we report a 7-year-old boy with Lennox-Gastaut syndrome combined with mitochondrial respiratory chain complex I deficiency, whose medically intractable seizures have been successfully controlled with a PUFA-enriched modified Atkins diet without any significant adverse events. The diet consists of canola oil and diverse menu items like fish and nuts instead of olive oil and has an ideal 1:2.8 ratio of omega-3 to omega-6. In addition, fractionation of this boy's plasma showed normal levels of fatty acids, including omega-3 (alpha-linoleic acid, eicosapentaenoic acid) and omega-6 (linoleic acid, arachidonic acid) as well as monounsaturated fatty acids (oleic acid). Plasma docosahexanoic acid remained low after PUFA-enriched diet therapy. PUFA-enriched diet therapy is likely to increase the efficacy of diet therapy and reduce complications of a high-fat diet in children with refractory epilepsy. PMID:23465587

  1. 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. PMID:18608541

  2. 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. PMID:23975574

  3. Cell proliferation and long chain polyunsaturated fatty acid metabolism in a cell line from southern bluefin tuna (Thunnus maccoyii).

    PubMed

    Scholefield, Andrew M; Schuller, Kathryn A

    2014-07-01

    Southern bluefin tuna (SBT, Thunnus maccoyii) aquaculture is a highly valuable industry, but research on these fish is hampered by strict catch quotas and the limited success of captive breeding. To address these limitations, we have developed a SBT cell line (SBT-E1) and here we report on fatty acid metabolism in this cell line. The SBT-E1 cells proliferated well in standard Leibovitz's L-15 cell culture medium containing fetal bovine serum (FBS) as the source of fatty acids. Decreasing the FBS concentration decreased the cell proliferation. Addition of the C(18) polyunsaturated fatty acids (PUFA) α-linolenic acid (ALA, 18:3n-3) or linoleic acid (LNA, 18:2n-6) to the cell culture medium had little effect on the proliferation of the cells, whereas addition of the long-chain PUFA (LC-PUFA) arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3) or docosahexaenoic acid (DHA, 22:6n-3) significantly reduced the proliferation of the cells, especially at higher concentrations and especially for DHA. Addition of vitamin E to the culture medium overcame this effect, suggesting that it was due to oxidative stress. The fatty acid profiles of the total lipid from the cells reflected those of the respective culture media with little evidence for desaturation or elongation of any of the fatty acids. The only exceptions were EPA and ARA, which showed substantial elongation to 22:5n-3 and 22:4n-6, respectively, and DHA, which was significantly enriched in the cells compared with the culture medium. The results are discussed in light of the dietary PUFA requirements of SBT in the wild and in aquaculture. PMID:24825740

  4. Deregulated balance of omega-6 and omega-3 polyunsaturated fatty acids following infection by the zoonotic pathogen Streptococcus suis.

    PubMed

    Lachance, Claude; Segura, Mariela; Dominguez-Punaro, Maria C; Wojewodka, Gabriella; De Sanctis, Juan B; Radzioch, Danuta; Gottschalk, Marcelo

    2014-05-01

    Streptococcus suis is an important swine pathogen and an emergent zoonotic pathogen. Excessive inflammation caused by S. suis is responsible for early high mortality in septic shock-like syndrome cases. Polyunsaturated fatty acids (PUFAs) may contribute to regulating inflammatory processes. This study shows that mouse infection by S. suis is accompanied by an increase of arachidonic acid, a proinflammatory omega-6 (ω-6) PUFA, and by a decrease of docosahexaenoic acid, an anti-inflammatory ω-3 PUFA. Macrophages infected with S. suis showed activation of mitogen-activated protein kinase pathways and cyclooxygenase-2 upregulation. Fenretinide, a synthetic vitamin A analog, reduced in vitro expression of inflammatory mediators. Pretreatment of mice with fenretinide significantly improved their survival by reducing systemic proinflammatory cytokines during the acute phase of an S. suis infection. These findings indicate a beneficial effect of fenretinide in diminishing the expression of inflammation and improving survival during an acute infection by a virulent S. suis strain. PMID:24549326

  5. Use of raw glycerol to produce oil rich in polyunsaturated fatty acids by a thraustochytrid.

    PubMed

    Scott, Spencer D; Armenta, Roberto E; Berryman, Kevin T; Norman, Andrew W

    2011-03-01

    Glucose is the typical carbon source for producing microbial polyunsaturated fatty acids (PUFA) with single cell microorganisms such as thraustochytrids. We assessed the use of a fish oil derived glycerol by-product (raw glycerol), produced by a fish oil processing plant, as a carbon source to produce single cell oil rich in polyunsaturated fatty acids (PUFA), notably docosahexaenoic acid (DHA). These results were compared to those obtained when using analytical grade glycerol, and glucose. The thraustochytrid strain tested produced similar amounts of oil and PUFA when grown with both types of glycerol, and results were also similar to those obtained using glucose. After 6 days of fermentation, approximately 320 mg/g of oil, and 145 mg/g of PUFA were produced with all carbon sources tested. All oils produced by our strain were 99.95% in the triacylglycerol form. To date, this is the first report of using raw glycerol derived from fish oil for producing microbial triglyceride oil rich in PUFA. PMID:22112910

  6. 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

  7. Periodontal disease: modulation of the inflammatory cascade by dietary n-3 polyunsaturated fatty acids.

    PubMed

    Sculley, D V

    2014-06-01

    Periodontal disease, including gingivitis and periodontitis, is caused by the interaction between pathogenic bacteria and the host immune system. The ensuing oxidative stress and inflammatory cascade result in the destruction of gingival tissue, alveolar bone and periodontal ligament. This article reviews the underlying mechanisms and host-bacteria interactions responsible for periodontal disease and evidence that nutritional supplementation with fish oil may provide a protective effect. Historical investigations of diet and disease have highlighted an inverse relationship between ingestion of fish oil, which is high in n-3 polyunsaturated fatty acids, and the incidence of typical inflammatory diseases such as arthritis and coronary heart disease. Ingestion of n-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, results in their incorporation into membrane phospholipids, which can alter eicosanoid production after stimulation during the immune response. These eicosanoids promote a reduction in chronic inflammation, which has led to the proposal that fish oil is a possible modulator of inflammation and may reduce the severity of periodontal diseases. Tentative animal and human studies have provided an indication of this effect. Further human investigation is needed to establish the protective effects of fish oil in relation to periodontal disease. PMID:23889472

  8. [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. PMID:26062349

  9. Biochemical characterization of polyunsaturated fatty acid synthesis in Schizochytrium: release of the products as free fatty acids.

    PubMed

    Metz, James G; Kuner, Jerry; Rosenzweig, Bradley; Lippmeier, James C; Roessler, Paul; Zirkle, Ross

    2009-06-01

    In marine bacteria and some thraustochytrids (marine stramenopiles) long-chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are produced de novo by PUFA synthases. These large, multi-domain enzymes carry out the multitude of individual reactions required for conversion of malonyl-CoA to the final LC-PUFA products. Here we report on the release of fatty acids from the PUFA synthase found in Schizochytrium, a thraustochytrid that has been developed as a commercial source for DHA-enriched biomass and oil. Data from in vitro activity assays indicate that the PUFAs are released from the enzyme as free fatty acids (FFAs). Addition of ATP and Mg(2+) to in vitro assays facilitates appearance of radiolabel from (14)C-malonyl-CoA in a triacylglycerol fraction, suggesting the involvement of acyl-CoA synthetases (ACS). Furthermore, addition of triascin C, an inhibitor of ACSs, to the assays blocks this conversion. When the Schizochytrium PUFA synthase is expressed in Escherichia coli, the products of the enzyme accumulate as FFAs, suggesting that the thioesterase activity required for fatty acid release is an integral part of the PUFA synthase. PMID:19272783

  10. Enrichment of anhydrous milk fat in polyunsaturated fatty acid residues from linseed and rapeseed oils through enzymatic interesterification.

    PubMed

    Aguedo, Mario; Hanon, Emilien; Danthine, Sabine; Paquot, Michel; Lognay, Georges; Thomas, Annick; Vandenbol, Micheline; Thonart, Philippe; Wathelet, Jean-Paul; Blecker, Christophe

    2008-03-12

    Lipozyme TL IM was used in a solvent-free batch and microaqueous system for enzymatic interesterification of anhydrous milkfat (AMF) with linseed oil (LO) in binary blends and with rapeseed oil (RO) in one ternary blend. The aim was to obtain and characterize physicochemically fats enriched with unsaturated C 18 fatty acids (oleic, linoleic, and, especially, linolenic acids) from natural vegetable oils. Binary blends of AMF/LO 100/0, 90/10, 80/20, 70/30, and 60/40 (w/w) were interesterified. The change in triacylglycerol (TAG) profiles showed that quasi-equilibrium conditions were reached after 4-6 h of reaction. Free fatty acid contents <1%. The decrease in solid fat content and in dropping point temperature obtained with increasing content of LO and interesterification resulted in good plastic properties for the products originating from the blends 70/30 and 60/40. This was confirmed by textural measurements. Melting profiles determined by differential scanning calorimetry showed complete disappearance of low-melting TAGs from LO and the formation of intermediary species with a lower melting temperature. Oxidative stability of the interesterified products was diminished with increasing LO content, resulting in low oxidation induction times. A ternary blend composed of AMF/RO/LO 70/20/10 gave satisfactory rheological and oxidative properties, fulfilling the requirements for a marketable spread and, moreover, offering increased potential health benefits due to the enriched content in polyunsaturated fatty acid residues. PMID:18271538

  11. 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

  12. 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

    2014-02-01

    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. PMID:24411456

  13. 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

  14. Specific effect of polyunsaturated fatty acids on the cholesterol-poor membrane domain in a model membrane.

    PubMed

    Onuki, Yoshinori; Hagiwara, Chihiro; Sugibayashi, Ko; Takayama, Kozo

    2008-08-01

    To understand more fully the effect of polyunsaturated fatty acids (PUFAs) on lipid bilayers, we investigated the effects of treatment with fatty acids on the properties of a model membrane. Three kinds of liposomes comprising dipalmitoylphosphatidylcholine (DPPC), dioleylphosphatidylcholine (DOPC), and cholesterol (Ch) were used as the model membrane, and the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and detergent insolubility were determined. Characterization of the liposomes clarified that DPPC, DPPC/Ch, and DPPC/DOPC/Ch existed as solid-ordered phase (L beta), liquid-ordered phase (l o), and a mixture of l o and liquid-disordered phase (L alpha) membranes at room temperature. Treatment with unsaturated fatty acids such as oleic acid (OA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) markedly decreased the fluorescence anisotropy value and detergent insolubility. PUFAs and OA had different effects on the model membranes. In DPPC liposomes, the most prominent change was induced by PUFAs, whereas, in DPPC/Ch and DPPC/DOPC/Ch liposomes, OA had a stronger effect than PUFAs. The effect of PUFAs was strongly affected by the amount of Ch in the membrane, which confirmed a specific effect of PUFAs on the Ch-poor membrane domain. We further explored the effect of fatty acids dispersed in a water-in-oil-in-water multiple emulsion and found that unsaturated fatty acids acted on the membranes even when incorporated in emulsion form. These findings suggest that treatment with PUFAs increases the segregation of ordered and disordered phase domains in membranes. PMID:18670110

  15. 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

  16. Polyunsaturated Fatty Acids of Marine Macroalgae: Potential for Nutritional and Pharmaceutical Applications

    PubMed Central

    Pereira, Hugo; Barreira, Luísa; Figueiredo, Filipe; Custódio, Luísa; Vizetto-Duarte, Catarina; Polo, Cristina; Rešek, Eva; Engelen, Aschwin; Varela, João

    2012-01-01

    As mammals are unable to synthesize essential polyunsaturated fatty acids (PUFA), these compounds need to be taken in through diet. Nowadays, obtaining essential PUFA in diet is becoming increasingly difficult; therefore this work investigated the suitability of using macroalgae as novel dietary sources of PUFA. Hence, 17 macroalgal species from three different phyla (Chlorophyta, Phaeophyta and Rhodophyta) were analyzed and their fatty acid methyl esters (FAME) profile was assessed. Each phylum presented a characteristic fatty acid signature as evidenced by clustering of PUFA profiles of algae belonging to the same phylum in a Principal Components Analysis. The major PUFA detected in all phyla were C18 and C20, namely linoleic, arachidonic and eicosapentaenoic acids. The obtained data showed that rhodophytes and phaeophytes have higher concentrations of PUFA, particularly from the n-3 series, thereby being a better source of these compounds. Moreover, rhodophytes and phaeophytes presented “healthier” ∑n-6/∑n-3 and PUFA/saturated fatty acid ratios than chlorophytes. Ulva was an exception within the Chlorophyta, as it presented high concentrations of n-3 PUFA, α-linolenic acid in particular. In conclusion, macroalgae can be considered as a potential source for large-scale production of essential PUFA with wide applications in the nutraceutical and pharmacological industries. PMID:23118712

  17. Biosynthesis of Essential Polyunsaturated Fatty Acids in Wheat Triggered by Expression of Artificial Gene.

    PubMed

    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

  18. High contents of very long-chain polyunsaturated fatty acids in different moss species.

    PubMed

    Beike, Anna K; Jaeger, Carsten; Zink, Felix; Decker, Eva L; Reski, Ralf

    2014-02-01

    Polyunsaturated fatty acids (PUFAs) are important cellular compounds with manifold biological functions. Many PUFAs are essential for the human diet and beneficial for human health. In this study, we report on the high amounts of very long-chain (vl) PUFAs (≥C₂₀) such as arachidonic acid (AA) in seven moss species. These species were established in axenic in vitro culture, as a prerequisite for comparative metabolic studies under highly standardized laboratory conditions. In the model organism Physcomitrella patens, tissue-specific differences in the fatty acid compositions between the filamentous protonema and the leafy gametophores were observed. These metabolic differences correspond with differential gene expression of fatty acid desaturase (FADS)-encoding genes in both developmental stages, as determined via microarray analyses. Depending on the developmental stage and the species, AA amounts for 6-31 %, respectively, of the total fatty acids. Subcellular localization of the corresponding FADS revealed the endoplasmic reticulum as the cellular compartment for AA synthesis. Our results show that vlPUFAs are highly abundant metabolites in mosses. Standardized cultivation techniques using photobioreactors along with the availability of the P. patens genome sequence and the high rate of homologous recombination are the basis for targeted metabolic engineering in moss. The potential of producing vlPUFAs of interest from mosses will be highlighted as a promising area in plant biotechnology. PMID:24170342

  19. 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

  20. 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

  1. Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression.

    PubMed

    Chhetry, Binod Thapa; Hezghia, Adrienne; Miller, Jeffrey M; Lee, Seonjoo; Rubin-Falcone, Harry; Cooper, Thomas B; Oquendo, Maria A; Mann, J John; Sublette, M Elizabeth

    2016-04-01

    White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = -1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity. PMID:26802812

  2. Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children.

    PubMed

    Schuchardt, Jan Philipp; Huss, Michael; Stauss-Grabo, Manuela; Hahn, Andreas

    2010-02-01

    omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) play a central role in the normal development and functioning of the brain and central nervous system. Long-chain PUFAs (LC-PUFAs) such as eicosapentaenoic acid (EPA, C20:5omega-3), docosahexaenoic acid (DHA, C22:6omega-3) and arachidonic acid (AA, C20:4omega-6), in particular, are involved in numerous neuronal processes, ranging from effects on membrane fluidity to gene expression regulation. Deficiencies and imbalances of these nutrients, not only during the developmental phase but throughout the whole life span, have significant effects on brain function. Numerous observational studies have shown a link between childhood developmental disorders and omega-6:omega-3 fatty acid imbalances. For instance, neurocognitive disorders such as attention-deficit hyperactivity disorder (ADHD), dyslexia, dyspraxia and autism spectrum disorders are often associated with a relative lack of omega-3 fatty acids. In addition to a high omega-6 fatty acid intake and, in many cases, an insufficient supply of omega-3 fatty acids among the population, evidence is increasing to suggest that PUFA metabolism can be impaired in individuals with ADHD. In this context, PUFA imbalances are being discussed as potential risk factors for neurodevelopmental disorders. Another focus is whether the nutritive PUFA requirements-especially long-chain omega-3 fatty acid requirements-are higher among some individuals. Meanwhile, several controlled studies investigated the clinical benefits of LC-PUFA supplementation in affected children and adolescents, with occasionally conflicting results. PMID:19672626

  3. Effect of Polyunsaturated Fatty Acids on Homocysteine Metabolism through Regulating the Gene Expressions Involved in Methionine Metabolism

    PubMed Central

    Huang, Tao; Hu, Xiaojie; Khan, Nicholas; Yang, Jing; Li, Duo

    2013-01-01

    The objective was to investigate the regulatory effect of polyunsaturated fatty acids (PUFAs) on mRNA expression of key genes involved in homocysteine (Hcy) metabolism. Eighty male Sprague Dawley rats were randomly divided into eight groups. The oils were orally administered daily for 8 weeks. Plasma Hcy, phospholipids fatty acids, and mRNA expression were determined. Compared with the control group, plasma Hcy was significantly decreased in the 22:6n-3 and conjugated linoleic acid (CLA) groups; mRNA expression of Mthfr was significantly upregulated in the 22:6n-3, 20:5n-3, and 18:3n-3 groups and downregulated in the 18:2n-6 and stearolic acid (SO) groups. Mat1a was upregulated in the 22:6n-3, 20:5n-3, 18:3n-3, and CLA groups. In addition, Cbs was upregulated in the 22:6n-3, 20:5n-3, 18:3n-3 and CLA groups while downregulated in 18:2n-6 and SO groups. Dietary 22:6n-3 and CLA decrease the plasma concentration of Hcy. mRNA expression of Mthfr, Mat1a, Cbs and Pemt, Gnmt, Mtrr, and Bad is upregulated by n-3 PUFA and downregulated by n-6 PUFA. CLA upregulates mRNA expression of Mat1a and Cbs. PMID:23766724

  4. Draft Genome Sequence of Cutaneotrichosporon curvatus DSM 101032 (Formerly Cryptococcus curvatus), an Oleaginous Yeast Producing Polyunsaturated Fatty Acids.

    PubMed

    Hofmeyer, Thomas; Hackenschmidt, Silke; Nadler, Florian; Thürmer, Andrea; Daniel, Rolf; Kabisch, Johannes

    2016-01-01

    Cutaneotrichosporon curvatus DSM 101032 is an oleaginous yeast that can be isolated from various habitats and is capable of producing substantial amounts of polyunsaturated fatty acids. Here, we present the first draft genome sequence of any C. curvatus species. PMID:27174275

  5. Effect of feeding system and breed on n-3 and n-6 polyunsaturated fatty acid content of lamb muscles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Katahdin (KK, n=6), Katahdin x Suffolk (KS, n=6), Suffolk x Katahdin (SK, n=6) and Suffolk (SS, n=6) wethers were used to evaluate omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acid content, and the ratio of n-6 to n-3 in muscles of these lambs, raised on concentrate or forage diets. Lambs ...

  6. Draft Genome Sequence of Cutaneotrichosporon curvatus DSM 101032 (Formerly Cryptococcus curvatus), an Oleaginous Yeast Producing Polyunsaturated Fatty Acids

    PubMed Central

    Hofmeyer, Thomas; Hackenschmidt, Silke; Nadler, Florian; Thürmer, Andrea; Daniel, Rolf

    2016-01-01

    Cutaneotrichosporon curvatus DSM 101032 is an oleaginous yeast that can be isolated from various habitats and is capable of producing substantial amounts of polyunsaturated fatty acids. Here, we present the first draft genome sequence of any C. curvatus species. PMID:27174275

  7. PTH1 Receptor Is Involved in Mediating Cellular Response to Long-Chain Polyunsaturated Fatty Acids

    PubMed Central

    Chachisvilis, Mirianas

    2012-01-01

    The molecular pathways by which long chain polyunsaturated fatty acids (LCPUFA) influence skeletal health remain elusive. Both LCPUFA and parathyroid hormone type 1 receptor (PTH1R) are known to be involved in bone metabolism while any direct link between the two is yet to be established. Here we report that LCPUFA are capable of direct, PTH1R dependent activation of extracellular ligand-regulated kinases (ERK). From a wide range of fatty acids studied, varying in chain length, saturation, and position of double bonds, eicosapentaenoic (EPA) and docosahexaenoic fatty acids (DHA) caused the highest ERK phosphorylation. Moreover, EPA potentiated the effect of parathyroid hormone (PTH(1–34)) in a superagonistic manner. EPA or DHA dependent ERK phosphorylation was inhibited by the PTH1R antagonist and by knockdown of PTH1R. Inhibition of PTH1R downstream signaling molecules, protein kinases A (PKA) and C (PKC), reduced EPA and DHA dependent ERK phosphorylation indicating that fatty acids predominantly activate G-protein pathway and not the β-arrestin pathway. Using picosecond time-resolved fluorescence microscopy and a genetically engineered PTH1R sensor (PTH-CC), we detected conformational responses to EPA similar to those caused by PTH(1–34). PTH1R antagonist blocked the EPA induced conformational response of the PTH-CC. Competitive binding studies using fluorescence anisotropy technique showed that EPA and DHA competitively bind to and alter the affinity of PTH1 receptor to PTH(1–34) leading to a superagonistic response. Finally, we showed that EPA stimulates protein kinase B (Akt) phosphorylation in a PTH1R-dependent manner and affects the osteoblast survival pathway, by inhibiting glucocorticoid-induced cell death. Our findings demonstrate for the first time that LCPUFAs, EPA and DHA, can activate PTH1R receptor at nanomolar concentrations and consequently provide a putative molecular mechanism for the action of fatty acids in bone. PMID:23300710

  8. 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. PMID:27166587

  9. Effect of dietary polyunsaturated fatty acids on the expression of peroxisomal ABC transporters.

    PubMed

    Leclercq, Sabrina; Skrzypski, Jérémy; Courvoisier, Anne; Gondcaille, Catherine; Bonnetain, Franck; André, Agnès; Chardigny, Jean-Michel; Bellenger, Sandrine; Bellenger, Jérôme; Narce, Michel; Savary, Stéphane

    2008-10-01

    Peroxisomal ABC transporters encoded by the ABCD genes are thought to participate in the import of specific fatty acids in the peroxisomal matrix. ABCD1 deficiency is associated with X-linked adrenoleukodystrophy (X-ALD), the most frequent peroxisomal disorder which is characterized by the accumulation of saturated very-long-chain fatty acids (VLCFA). ABCD2 (the closest homolog of ABCD1) and ABCD3 have been shown to have partial functional redundancy with ABCD1; only when overexpressed, they can compensate for VLCFA accumulation. Other lipids, for instance polyunsaturated fatty acids (PUFA), should be possible candidate substrates for the ABCD2 and ABCD3 gene products, ALDRP and PMP70 respectively. Moreover, PUFA, which are known regulators of gene expression, could therefore represent potent inducers of the ABCD genes. To test this hypothesis, littermates of n-3-deficient rats were subjected to an n-3-deficient diet or equilibrated diets containing ALA (alpha-linolenic acid, 18:3n-3) as unique source of n-3 fatty acids or ALA plus DHA (docosahexaenoic acid, 22:6n-3) at two different doses. We analyzed the expression of peroxisomal ABC transporters and of the peroxisomal acyl-CoA oxidase gene 1 (Acox1) in adrenals, brain and liver. Whatever the diet, we did not observe any difference in gene expression in adrenals and brain. However, the hepatic expression level of Abcd2 and Abcd3 genes was found to be significantly higher in the n-3-deficient rats than in the rats fed the ALA diet or the DHA supplemented diets. This was accompanied by important changes in hepatic fatty acid composition. In summary, the hepatic expression of Abcd2 and Abcd3 but not of Abcd1 and Abcd4 appears to be highly sensitive towards dietary PUFA. This difference could be linked to the substrate specificity of the peroxisomal ABC transporters and a specific involvement of Abcd2 and Abcd3 in PUFA metabolism. PMID:18585430

  10. 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

  11. Genome-Wide Association Study of Plasma Polyunsaturated Fatty Acids in the InCHIANTI Study

    PubMed Central

    Tanaka, Toshiko; Shen, Jian; Abecasis, Gonçalo R.; Kisialiou, Aliaksei; Ordovas, Jose M.; Guralnik, Jack M.; Singleton, Andrew; Bandinelli, Stefania; Cherubini, Antonio; Arnett, Donna; Tsai, Michael Y.; Ferrucci, Luigi

    2009-01-01

    Polyunsaturated fatty acids (PUFA) have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3). The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; p = 5.95×10−46). Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; p = 6.78×10−9) and eicosapentanoic acid (EPA; p = 1.07×10−14). Participants carrying the allele associated with higher AA, EDA, and EPA also had higher low-density lipoprotein (LDL-C) and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2). In this region, association was observed with EPA (rs953413; p = 1.1×10−6). The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids. PMID:19148276

  12. 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

  13. Increased tissue levels of omega-3 polyunsaturated fatty acids prevents pathological preterm birth

    PubMed Central

    Yamashita, Aki; Kawana, Kei; Tomio, Kensuke; Taguchi, Ayumi; Isobe, Yosuke; Iwamoto, Ryo; Masuda, Koji; Furuya, Hitomi; Nagamatsu, Takeshi; Nagasaka, Kazunori; Arimoto, Takahide; Oda, Katsutoshi; Wada-Hiraike, Osamu; Yamashita, Takahiro; Taketani, Yuji; Kang, Jing X.; Kozuma, Shiro; Arai, Hiroyuki; Arita, Makoto; Osuga, Yutaka; Fujii, Tomoyuki

    2013-01-01

    Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have anti-inflammatory effects. Preterm birth is an important problem in modern obstetrics and one of the main causes is an inflammation. We here showed that abundance of omega-3 fatty acids reduced the incidence of preterm birth induced by LPS with fat-1 mice, capable of converting omega-6 to omega-3 fatty acids. We also indicated that the gene expression of IL-6 and IL-1β in uteruses and the number of cervical infiltrating macrophages were reduced in fat-1 mice. The analyses of lipid metabolomics showed the high level of 18-hydroxyeicosapentaenoate in fat-1 mice, which was derived from EPA and was metabolized to anti-inflammatory product named resolvin E3 (RvE3). We finally showed that the administration of RvE3 to LPS-exposed pregnant wild type mice lowered the incidence of preterm birth. Our data suggest that RvE3 could be a potential new therapeutic for the prevention of preterm birth. PMID:24177907

  14. Increased tissue levels of omega-3 polyunsaturated fatty acids prevents pathological preterm birth.

    PubMed

    Yamashita, Aki; Kawana, Kei; Tomio, Kensuke; Taguchi, Ayumi; Isobe, Yosuke; Iwamoto, Ryo; Masuda, Koji; Furuya, Hitomi; Nagamatsu, Takeshi; Nagasaka, Kazunori; Arimoto, Takahide; Oda, Katsutoshi; Wada-Hiraike, Osamu; Yamashita, Takahiro; Taketani, Yuji; Kang, Jing X; Kozuma, Shiro; Arai, Hiroyuki; Arita, Makoto; Osuga, Yutaka; Fujii, Tomoyuki

    2013-01-01

    Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have anti-inflammatory effects. Preterm birth is an important problem in modern obstetrics and one of the main causes is an inflammation. We here showed that abundance of omega-3 fatty acids reduced the incidence of preterm birth induced by LPS with fat-1 mice, capable of converting omega-6 to omega-3 fatty acids. We also indicated that the gene expression of IL-6 and IL-1β in uteruses and the number of cervical infiltrating macrophages were reduced in fat-1 mice. The analyses of lipid metabolomics showed the high level of 18-hydroxyeicosapentaenoate in fat-1 mice, which was derived from EPA and was metabolized to anti-inflammatory product named resolvin E3 (RvE3). We finally showed that the administration of RvE3 to LPS-exposed pregnant wild type mice lowered the incidence of preterm birth. Our data suggest that RvE3 could be a potential new therapeutic for the prevention of preterm birth. PMID:24177907

  15. Transcriptional and antioxidative responses to endogenous polyunsaturated fatty acid accumulation in yeast.

    PubMed

    Andrisic, Luka; Collinson, Emma J; Tehlivets, Oksana; Perak, Eleonora; Zarkovic, Tomislav; Dawes, Ian W; Zarkovic, Neven; Cipak Gasparovic, Ana

    2015-01-01

    Pathophysiology of polyunsaturated fatty acids (PUFAs) is associated with aberrant lipid and oxygen metabolism. In particular, under oxidative stress, PUFAs are prone to autocatalytic degradation via peroxidation, leading to formation of reactive aldehydes with numerous potentially harmful effects. However, the pathological and compensatory mechanisms induced by lipid peroxidation are very complex and not sufficiently understood. In our study, we have used yeast capable of endogenous PUFA synthesis in order to understand the effects triggered by PUFA accumulation on cellular physiology of a eukaryotic organism. The mechanisms induced by PUFA accumulation in S. cerevisiae expressing Hevea brasiliensis Δ12-fatty acid desaturase include down-regulation of components of electron transport chain in mitochondria as well as up-regulation of pentose-phosphate pathway and fatty acid β-oxidation at the transcriptional level. Interestingly, while no changes were observed at the transcriptional level, activities of two important enzymatic antioxidants, catalase and glutathione-S-transferase, were altered in response to PUFA accumulation. Increased intracellular glutathione levels further suggest an endogenous oxidative stress and activation of antioxidative defense mechanisms under conditions of PUFA accumulation. Finally, our data suggest that PUFA in cell membrane causes metabolic changes which in turn lead to adaptation to endogenous oxidative stress. PMID:25280400

  16. Chemotherapeutic Properties of n-3 Polyunsaturated Fatty Acids - Old Concepts and New Insights

    PubMed Central

    Kim, Wooki; McMurray, David N.; Chapkin, Robert S.

    2009-01-01

    Over the past several decades, data from both experimental animal studies and human clinical trials have shown that dietary n-3 polyunsaturated fatty acids (PUFA) exhibit anti-inflammatory bioactive properties, compared to n-6 PUFA. Collectively, these studies have identified multiple mechanisms by which n-3 PUFA affect immune cell responses. In this review, we discuss the putative targets of anti-inflammatory n-3 PUFA, specifically, cytokine production, antagonism of n-6 PUFA metabolism, binding to nuclear receptors as ligands, and the alteration of signaling protein acylation. In addition, we investigate the effect of n-3 PUFA on the coalescence of lipid rafts, specialized signaling platforms in the plasma membrane. PMID:19823600

  17. 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

  18. 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

  19. Red blood cell polyunsaturated fatty acids measured in red blood cells and schizophrenia: a meta-analysis.

    PubMed

    Hoen, Wendela P; Lijmer, Jeroen G; Duran, Marinus; Wanders, Ronald J A; van Beveren, Nico J M; de Haan, Lieuwe

    2013-05-15

    Alterations of polyunsaturated fatty acids (PUFA) in schizophrenia have been reported, but there is substantial variation in the findings. We performed a systematic review and meta-analysis for docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), linoleic acid (LA), and arachidonic acid (AA). We identified 18 studies which compared PUFA in the erythrocyte cell membrane between patients with schizophrenia and controls. A total of 642 patients (169 were antipsychotic-naïve) and 574 controls participated in these studies. We found suggestive evidence that the levels of DPA (C22:5n3) and DHA (C22:6n3) are decreased both in patients currently being treated with antipsychotic medication and antipsychotic-naïve patients. Our findings furthermore suggest that the levels of LA (C18:2n6) are decreased in the medicated subgroup, but not in the antipsychotic-naive group. Finally, we found decreased levels of AA (C20:4n6), most convincingly in antipsychotic-naive patients. Taken together, there is substantial evidence that decreased levels of DPA (C22:5n3), DHA (C22:6n3), and AA (C20:4n6) are associated with the schizophrenia syndrome, apart from a possible influence of antipsychotic medication. Given the large heterogeneity in results, these conclusions should be interpreted cautiously. PMID:23068078

  20. Kinetics of tumour necrosis factor and prostaglandin production by murine resident peritoneal macrophages as affected by dietary n-3 polyunsaturated fatty acids.

    PubMed Central

    Hardard'ottir, I; Whelan, J; Kinsella, J E

    1992-01-01

    Cell-associated and secreted tumour necrosis factor (TNF), prostaglandin (PG) E2, and 6-keto PGF1 alpha were monitored at various times following in vitro stimulation of resident peritoneal macrophages with lipopolysaccharide (LPS). Macrophages were obtained from mice maintained on diets containing 1.5 wt% n-3 polyunsaturated fatty acids (PUFA)+ 1.5 wt% n-6 fatty acids; 1.5 wt% n-6 fatty acids; or 3 wt% n-6 fatty acids, for 4 weeks. Cell-associated TNF increased transiently in the resident peritoneal macrophages from mice consuming all diets and decreased after TNF secretion had reached maximum and plateaued. Macrophages from mice consuming the n-3 PUFA contained more cell-associated TNF and secreted more TNF than macrophages from mice consuming diets containing n-6 fatty acids only, at all time-points studied. Macrophages from mice consuming the n-3 PUFA showed an earlier increase in cell-associated and secreted TNF compared with macrophages from mice consuming n-6 fatty acids only. Kinetics of maximum TNF production was not affected by the diets and dietary n-3 PUFA did not cause a prolonged increase in TNF secretion. Macrophages from mice consuming the n-3 PUFA produced less PG than macrophages from mice consuming the n-6 fatty acids only. PG secretion increased following appearance of cell-associated TNF but when PG had accumulated in the medium there was no further increase in TNF production. PMID:1398747

  1. 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

  2. The role of n-3 polyunsaturated fatty acids in the prevention and treatment of breast cancer.

    PubMed

    Liu, Jiajie; Ma, David W L

    2014-11-01

    Breast cancer (BC) is the most common cancer among women worldwide. Dietary fatty acids, especially n-3 polyunsaturated fatty acids (PUFA), are believed to play a role in reducing BC risk. Evidence has shown that fish consumption or intake of long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for inhibiting mammary carcinogenesis. The evidence regarding α-linolenic acid (ALA), however, remains equivocal. It is essential to clarify the relation between ALA and cancer since ALA is the principal source of n-3 PUFA in the Western diet and the conversion of ALA to EPA and DHA is not efficient in humans. In addition, the specific anticancer roles of individual n-3 PUFA, alone, have not yet been identified. Therefore, the present review evaluates ALA, EPA and DHA consumed individually as well as in n-3 PUFA mixtures. Also, their role in the prevention of BC and potential anticancer mechanisms of action are examined. Overall, this review suggests that each n-3 PUFA has promising anticancer effects and warrants further research. PMID:25412153

  3. Metabolism of omega-6 polyunsaturated fatty acids in women with dysmenorrhea.

    PubMed

    Wu, Chao-Chih; Huang, Mei-Yu; Kapoor, Rakesh; Chen, Chih-Hung; Huang, Yung-Sheng

    2008-01-01

    Menstrual pain (dysmenorrhea) is one of the main complaints in clinics for women. The pain is often accompanied by other symptoms such as headache, nausea, constipation or diarrhea, urinary frequency, and vomiting which often leave the patients incapacitated for work or school for a few days. Dietary supplementation with polyunsaturated fatty acids (PUFA) has been shown to alleviate the menstrual pain. The purpose of the present study was to compare the effect of dietary supplementation with PUFA (sunflower seed oil, borage oil and fish oil concentrate) for three months on RBC membrane fatty acid composition in healthy and dysmenorrheica young women. Conversion of linoleic acid, via gamma-linolenic acid, to dihomo-gamma-linolenic acid (a precursor of anti-inflammatory prostaglandin E1) in dysmenorrheic subjects as compared to the controls was slower whereas the level of arachidonic acid (a precursor of pro-inflammatory PGE2) was not affected by the supplementation. Since there are no known side-effects associated with supplementation of these nutrients, management of dysmenorrhea through nutrition modulation should be an acceptable alternative to drug treatments. PMID:18296341

  4. Novel Simplified and Rapid Method for Screening and Isolation of Polyunsaturated Fatty Acids Producing Marine Bacteria

    PubMed Central

    Tilay, Ashwini; Annapure, Uday

    2012-01-01

    Bacterial production of polyunsaturated fatty acids (PUFAs) is a potential biotechnological approach for production of valuable nutraceuticals. Reliable method for screening of number of strains within short period of time is great need. Here, we report a novel simplified method for screening and isolation of PUFA-producing bacteria by direct visualization using the H2O2-plate assay. The oxidative stability of PUFAs in growing bacteria towards added H2O2 is a distinguishing characteristic between the PUFAs producers (no zone of inhibition) and non-PUFAs producers (zone of inhibition) by direct visualization. The confirmation of assay results was performed by injecting fatty acid methyl esters (FAMEs) produced by selected marine bacteria to Gas Chromatography-Mass Spectrometry (GCMS). To date, this assay is the most effective, inexpensive, and specific method for bacteria producing PUFAs and shows drastically reduction in the number of samples thus saves the time, effort, and cost of screening and isolating strains of bacterial PUFAs producers. PMID:22934188

  5. A mechanism underlying the effects of polyunsaturated fatty acids on breast cancer.

    PubMed

    Zhang, Hao; Zhou, Lei; Shi, Wei; Song, Ning; Yu, Karu; Gu, Yuchun

    2012-09-01

    Breast cancer is the most frequent cancer in women. Evidence suggests that the polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) affect breast cancer proliferation, differentiation and prognosis. However, the mechanism still remains unclear. In this study, the expression of transient receptor potential canonical (TRPC)3 was detected throughout the cell cytoplasm and at the cell surface of MCF-7 cells. Ca(2+) entry was induced in these cells via activated TRPC3 by either the diacylglycerol analogue (OAG) or by intracellular Ca(2+) store depletion. TRPC-mediated Ca(2+) entry was inhibited by PUFAs including arachidonic acid (AA) and linolenic acid (LA) but not saturated fatty acids. Overexpression of the PUFA degradation enzyme, cyclooxygenase 2 (COX2), enhanced capacitative Ca(2+) entry. In addition, inhibition of COX2 reduced [Ca(2+)](i). Nevertheless, inhibition of TRPC reduced the cell cycle S phase and cell migration, implicating a functional role for TRP-mediated Ca(2+) entry in cell proliferation and invasion. Exogenous PUFA as well as a TRPC3 antagonist consistently attenuated breast cancer cell proliferation and migration, suggesting a mechanism in which PUFA restrains the breast cancer partly via its inhibition of TRPC channels. Additionally, our results also suggest that TRPC3 appears as a new mediator of breast cancer cell migration/invasion and represents a potential target for a new class of anticancer agent. PMID:22692672

  6. Polyunsaturated Fatty Acid Regulation of Adipocyte FADS1 and FADS2 Expression and Function

    PubMed Central

    Ralston, Jessica C.; Matravadia, Sarthak; Gaudio, Nicholas; Holloway, Graham P.; Mutch, David M.

    2016-01-01

    Objective Polyunsaturated fatty acids (PUFAs) regulate fatty acid desaturase (FADS1, FADS2) expression in the liver; however, it is unknown whether PUFAs regulate FADS in adipocytes. This is important to study considering reports that link altered desaturase activity with adipose tissue PUFA profiles, body weight, and whole-body glucose homeostasis. Therefore, the present study aimed to determine the direct effects of PUFAs on FADS expression in differentiated 3T3-L1 adipocytes. Methods Differentiated 3T3-L1 adipocytes were treated with either α-linolenic (ALA), linoleic (LA), eicosapentaenoic (EPA), or arachidonic acid (AA). Gene expression, protein abundance, and cellular PUFA content were analyzed by real-time RT-PCR, Western blotting, and gas chromatography, respectively. Results Fads1 and Fads2 gene expression was reduced by EPA and AA, but not ALA or LA. Reductions in gene expression were reflected in FADS2 protein levels, but not FADS1. Treating cells with ALA and LA led to significant increases in the cellular content of downstream PUFAs. Neither ALA nor EPA changed docosahexaenoic acid content. Conclusions Differentiated 3T3-L1 adipocytes have a functional FADS pathway that can be regulated by PUFA. Therefore, this common adipocyte model is suitable to study dietary regulation of the FADS pathway. PMID:25755223

  7. The Role of n-3 Polyunsaturated Fatty Acids in the Prevention and Treatment of Breast Cancer

    PubMed Central

    Liu, Jiajie; Ma, David W. L.

    2014-01-01

    Breast cancer (BC) is the most common cancer among women worldwide. Dietary fatty acids, especially n-3 polyunsaturated fatty acids (PUFA), are believed to play a role in reducing BC risk. Evidence has shown that fish consumption or intake of long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for inhibiting mammary carcinogenesis. The evidence regarding α-linolenic acid (ALA), however, remains equivocal. It is essential to clarify the relation between ALA and cancer since ALA is the principal source of n-3 PUFA in the Western diet and the conversion of ALA to EPA and DHA is not efficient in humans. In addition, the specific anticancer roles of individual n-3 PUFA, alone, have not yet been identified. Therefore, the present review evaluates ALA, EPA and DHA consumed individually as well as in n-3 PUFA mixtures. Also, their role in the prevention of BC and potential anticancer mechanisms of action are examined. Overall, this review suggests that each n-3 PUFA has promising anticancer effects and warrants further research. PMID:25412153

  8. 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. PMID:16047026

  9. Alternative route for the biosynthesis of polyunsaturated fatty acids in K562 cells.

    PubMed Central

    Naval, J; Martínez-Lorenzo, M J; Marzo, I; Desportes, P; Piñeiro, A

    1993-01-01

    K562 human leukaemia cells lack a significant delta 6-desaturase activity. However, they synthesize long-chain polyunsaturated fatty acids (PUFA) from linoleic (C18:2(9,12)) and linolenic (C18:3(9,12,15)) acids, by reactions involving a C2 chain elongation followed by a delta 5-desaturation step and, to some extent, a further elongation. The main products formed were separated by argentation t.l.c. and identified by g.l.c. as the uncommon fatty acids C20:3(5,11,14) and C20:4(5,11,14,17) respectively. These acids were also produced when cells were supplemented with C20:2(11,14) or C20:3(11,14,17) respectively. The presence of a delta 5-desaturase was further confirmed by using its corresponding normal substrates, C20:3(8,11,14) and C20:4(8,11,14,17), which led to C20:4(5,8,11,14) and C20:5(5,8,11,14,17) respectively. On the other hand, a high delta 9-desaturase activity, but no significant delta 4-desaturase activity, were detected in K562 cells. These results indicate the existence of an alternative pathway, involving delta 5-desaturase, which is the only route for PUFA biosynthesis in K562 cells. This pathway may be relevant for the biosynthesis of PUFA in cells lacking delta 6-desaturase activity. PMID:8489510

  10. Prevention of cardiovascular diseases and highly concentrated n-3 polyunsaturated fatty acids (PUFAs).

    PubMed

    Weber, Heinz S; Selimi, Dzevair; Huber, Gustav

    2006-12-01

    30 years ago the observation of a lower incidence of cardiovascular diseases in Inuits (Eskimos) was related to the higher fish consumption when compared to the residual Danish population. Clinical studies confirmed this finding. It was explained by the higher content of polyunsaturated fatty acids (PUFA) in fish, especially of omega-3 PUFAs. Experimental studies in cell cultures and also in animals with and without infarction models verified the anti-arrhythmic effect of omega-3 PUFAs among other possible contributing factors when compared to other fatty acids. In clinical studies a significant reduction (ca. 40%) of sudden cardiac deaths (SCD) could be found in patients after an acute myocardial infarction, if they were treated with at least 1 g omega-3 PUFAs daily, either by consumption of fish twice weekly or of a highly purified preparation omega-3 PUFAs in capsules. These findings led to recommendations of the American Heart Association and the European Society of Cardiology to a higher fish consumption and/or the daily intake of 1 g omega-3 PUFAs for primary and especially for secondary prevention of cardiovascular diseases. The much fewer side-effects, and the standardised dosage on one hand and the negative effect of the sometimes higher mercury content of fish make the intake of omega-3 PUFAs as capsules the better choice. PMID:17575803

  11. Cholestane as a digestibility marker in the absorption of polyunsaturated fatty acid ethyl esters in Atlantic salmon.

    PubMed

    Sigurgisladottir, S; Lall, S P; Parrish, C C; Ackman, R G

    1992-06-01

    Salmonid fish require long-chain n-3 fatty acids in their diet. The digestibility of different chemical forms of fish oil fatty acids, fed as triacylglycerols, free fatty acids or ethyl esters, was examined in 300 g farmed Atlantic salmon (Salmo salar) using cholestane as an indicator of fat absorption in lieu of the chromium oxide (Cr2O3) which is commonly used as a marker in digestibility studies. It was established that the two digestibility markers gave similar results. Conveniently, cholestane does not require a separate analysis if fatty acids are to be determined by appropriate gas-liquid chromatography. The long-chain polyunsaturated fatty acids were particularly well absorbed, the apparent digestibility being 90-98% when feeding triacylglycerols or free fatty acids. However, the digestibility of monounsaturated fatty acids (75-94%) was lower, and lower still for saturated fatty acids (50-80%). Ethyl esters of fatty acids were significantly less well absorbed (P less than 0.05) than were the corresponding fatty acids in free acid or triacylglycerol form. Irrespective of dietary fat type, only free fatty acids were identified in feces, indicating total hydrolysis of triacylglycerols and ethyl esters. PMID:1630276

  12. Metabolic engineering of the omega-3 long chain polyunsaturated fatty acid biosynthetic pathway into transgenic plants.

    PubMed

    Ruiz-López, Noemi; Sayanova, Olga; Napier, Johnathan A; Haslam, Richard P

    2012-04-01

    Omega-3 (ω-3) very long chain polyunsaturated fatty acids (VLC-PUFAs) such as eicosapentaenoic acid (EPA; 20:5 Δ5,8,11,14,17) and docosahexaenoic acid (DHA; 22:6 Δ4,7,10,13,16,19) have been shown to have significant roles in human health. Currently the primary dietary source of these fatty acids are marine fish; however, the increasing demand for fish and fish oil (in particular the expansion of the aquaculture industry) is placing enormous pressure on diminishing marine stocks. Such overfishing and concerns related to pollution in the marine environment have directed research towards the development of a viable alternative sustainable source of VLC-PUFAs. As a result, the last decade has seen many genes encoding the primary VLC-PUFA biosynthetic activities identified and characterized. This has allowed the reconstitution of the VLC-PUFA biosynthetic pathway in oilseed crops, producing transgenic plants engineered to accumulate ω-3 VLC-PUFAs at levels approaching those found in native marine organisms. Moreover, as a result of these engineering activities, knowledge of the fundamental processes surrounding acyl exchange and lipid remodelling has progressed. The application of new technologies, for example lipidomics and next-generation sequencing, is providing a better understanding of seed oil biosynthesis and opportunities for increasing the production of unusual fatty acids. Certainly, it is now possible to modify the composition of plant oils successfully, and, in this review, the most recent developments in this field and the challenges of producing VLC-PUFAs in the seed oil of higher plants will be described. PMID:22291131

  13. Dietary long-chain polyunsaturated fatty acids upregulate expression of FADS3 transcripts.

    PubMed

    Reardon, Holly T; Hsieh, Andrea T; Park, Woo Jung; Kothapalli, Kumar S D; Anthony, Joshua C; Nathanielsz, Peter W; Brenna, J Thomas

    2013-01-01

    The fatty acid desaturase (FADS) gene family at 11q12-13.1 includes FADS1 and FADS2, both known to mediate biosynthesis of omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA). FADS3 is a putative desaturase due to its sequence similarity with FADS1 and FADS2, but its function is unknown. We have previously described 7 FADS3 alternative transcripts (AT) and 1 FADS2 AT conserved across multiple species. This study examined the effect of dietary LCPUFA levels on liver FADS gene expression in vivo and in vitro, evaluated by qRT-PCR. Fourteen baboon neonates were randomized to three diet groups for their first 12 weeks of life, C: Control, no LCPUFA, L: 0.33% docosahexaenoic acid (DHA)/0.67% arachidonic acid (ARA) (w/w); and L3: 1.00% DHA/0.67% ARA (w/w). Liver FADS1 and both FADS2 transcripts were downregulated by at least 50% in the L3 group compared to controls. In contrast, FADS3 AT were upregulated (L3 > C), with four transcripts significantly upregulated by 40% or more. However, there was no evidence for a shift in liver fatty acids to coincide with increased FADS3 expression. Significant upregulation of FADS3 AT was also observed in human liver-derived HepG2 cells after DHA or ARA treatment. The PPARγ antagonist GW9662 prevented FADS3 upregulation, while downregulation of FADS1 and FADS2 was unaffected. Thus, FADS3 AT were directly upregulated by LCPUFA by a PPARγ-dependent mechanism unrelated to regulation of other desaturases. This opposing pattern and mechanism of regulation suggests a dissimilar function for FADS3 AT compared to other FADS gene products. PMID:22398025

  14. The Effects of Dietary Changes in the Ratio of Omega-3 to Omega-6 Polyunsaturated Fatty Acids on Lung Carcinogenesis in A/J Mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyunsaturated fatty acid metabolites are known to be involved in inflammation, and fatty acid precursors and metabolites may also exert genomic control over the expression of genes involved in proliferation and differentiation. Some researchers suggest that a higher ratio of omega-3/omega-6 fatty ...

  15. Effect of ω-3 polyunsaturated fatty acids on the growth of IEC-6 cells injured by heavy metals

    PubMed Central

    ZHANG, FENG; YU, HAINING; NI, XIAOFENG; ZHU, JING; WANG, SHANSHAN; SHEN, SHENGRONG

    2016-01-01

    Environmental pollution is a current area of focus worldwide, particularly heavy metal pollution. Feasible prevention or therapeutic strategies are required. Exploration of the correlation between ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and intestinal epithelial cells injured by heavy metals may be of significance for intestinal health. In the present study, the effects of ω-3 PUFAs on the rat intestinal crypt cell line (IEC-6) injured by heavy metals and its mechanisms were determined according to the evaluation of cell viability and expression levels of reactive oxygen species (ROS), epidermal growth factor (EGF) and interleukin-6 (IL-6). The results demonstrated that ω-3 PUFAs can improve the viability of IEC-6 cells injured by heavy metals and the expression level of ROS was correlated with oxidative damage; the increased expression level of inflammatory factors is associated with cell apoptosis. In the present study, ω-3 PUFAs significantly decreased the expression levels of ROS, EGF and IL-6. This indicates that the protective action of ω-3 PUFAs was associated with a decrease of oxidative damage and pro-inflammatory cytokine expression against the damage of heavy metals. PMID:27123260

  16. Citrus Pulp as a Dietary Source of Antioxidants for Lactating Holstein Cows Fed Highly Polyunsaturated Fatty Acid Diets

    PubMed Central

    Santos, G. T.; Lima, L. S.; Schogor, A. L. B.; Romero, J. V.; De Marchi, F. E.; Grande, P. A.; Santos, N. W.; Santos, F. S.; Kazama, R.

    2014-01-01

    The effects of feeding pelleted citrus pulp (PCP) as a natural antioxidant source on the performance and milk quality of dairy cows fed highly polyunsaturated fatty acid (FA) diets were evaluated. Four lactating Holstein cows were assigned to a 4×4 Latin-square. Treatments, on a dry matter (DM) basis, were i) control diet; ii) 3% soybean oil; iii) 3% soybean oil and 9% PCP and; iv) 3% soybean oil and 18% PCP. When cows fed on citrus pulp, the DM intake tended to decrease. The total tract apparent digestibility of DM and ether extract decreased when cows fed on the control diet compared to other diets. Cows fed PCP had higher polyphenols and flavonoids content and higher total ferric reducing antioxidant power (FRAP) in milk compared to those fed no pelleted citrus pulp. Cows fed 18% PCP showed higher monounsaturated FA and lower saturated FA in milk fat compared with cows fed the other diets. The lowest n-6 FA proportion was in milk fat from cows fed control. The present study suggests that pelleted citrus pulp added to 9% to 18% DM increases total polyphenols and flavonoids concentration, and the FRAP in milk. PMID:25083104

  17. Transcriptomic and metabolomic signatures of an n-3 polyunsaturated fatty acids supplementation in a normolipidemic/normocholesterolemic Caucasian population.

    PubMed

    Rudkowska, Iwona; Paradis, Ann-Marie; Thifault, Elisabeth; Julien, Pierre; Tchernof, André; Couture, Patrick; Lemieux, Simone; Barbier, Olivier; Vohl, Marie-Claude

    2013-01-01

    OMIC technologies, including transcriptomics and metabolomics, may provide powerful tools for identifying the effects of nutrients on molecular functions and metabolic pathways. The objective was to investigate molecular and metabolic changes following n-3 polyunsaturated fatty acid (PUFA) supplementation in healthy subjects via traditional biomarkers as well as transcriptome and metabolome analyses. Thirteen men and 17 women followed a 2-week run-in period based on Canada's Food Guide and then underwent 6-week supplementation with n-3 PUFA (3 g/day). Traditional biochemical markers such as plasma lipids, inflammatory markers, glycemic parameters and erythrocyte fatty acid concentrations were measured. Changes in gene expression of peripheral blood mononuclear cells were assessed by microarrays, and metabolome profiles were assessed by mass spectrometry assay kit. After supplementation, plasma triglycerides decreased and erythrocyte n-3 PUFA concentrations increased to a similar extent in both genders. Further, plasma high-density lipoprotein cholesterol concentrations and fasting glucose levels increased in women after n-3 PUFA supplementation. N-3 PUFA supplementation changed the expression of 610 genes in men, whereas the expression of 250 genes was altered in women. Pathway analyses indicate changes in gene expression of the nuclear receptor peroxisome proliferator-activated receptor-alpha, nuclear transcription-factor kappaB, oxidative stress and activation of the oxidative stress response mediated by nuclear factor (erythroid-derived 2)-like 2. After n-3 PUFA supplementation, metabolomics profiles demonstrate an increase in acylcarnitines, hexose and leucine in men only and a decrease in saturation of glycerophosphatidylcholine and lysophosphatidylcholine concentrations in all subjects. Overall, traditional and novel biomarkers suggest that n-3 PUFA supplementation exerts cardioprotective effects. PMID:22748805

  18. 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.

  19. Differential effect of saturated and polyunsaturated fatty acids on hepatic glucose metabolism in humans.

    PubMed

    Clore, John N; Stillman, Julie S; Li, Jing; O'Keefe, Stephen J D; Levy, James R

    2004-08-01

    Prolonged infusions of lipid and heparin that achieve high physiological free fatty acid (FFA) concentrations inhibit hepatic (and peripheral) insulin sensitivity in humans. These infusions are composed largely of polyunsaturated fatty acids (PUFA; linoleic and linolenic). It is not known whether fatty acid composition per se affects hepatic glucose metabolism in humans. To address this issue, we examined the impact of enteral infusions of either palm oil (48% palmitic, 35% oleic, and 8% linoleic acids) or safflower oil (6% palmitic, 12% oleic, 74% linoleic acids) in 14 obese nondiabetic subjects. (2)H(2)O was administered to determine the contribution of gluconeogenesis to endogenous glucose production (EGP), and a primed continuous infusion of [6,6-(2)H]glucose was administered to assess glucose appearance. As a result of the lipid infusions, plasma FFA concentrations increased significantly in both the palm oil (507.5 +/- 47.4 to 939.3 +/- 61.3 micromol/l, P < 0.01) and safflower oil (588.2.0 +/- 43.0 to 857.8 +/- 68.7 micromol/l, P < 0.01) groups after 4 h. EGP was similar at baseline (12.4 +/- 1.8 vs. 11.2 +/- 1.0 micromol x kg FFM(-1) x min(-1)). During a somatostatin-insulin clamp, the glucose infusion rate was significantly lower (AUC glucose infusion rate 195.8 +/- 50.7 vs. 377.8 +/- 38.0 micromol/kg FFM, P < 0.01), and rates of EGP were significantly higher (10.7 +/- 1.4 vs. 6.5 +/- 1.5 micromol x kg FFM(-1) x min(-1), P < 0.01) after palm oil compared with safflower oil, respectively. Baseline rates of gluconeogenesis and glycogenolysis were also similar. However, after lipid infusion, rates of glycogenolysis were suppressed by safflower oil but not by palm oil. Thus these studies demonstrate, for the first time in humans, a differential effect of saturated fatty acids and PUFA on hepatic glucose metabolism. PMID:15082421

  20. Formation of Small Gas Phase Carbonyls from Heterogeneous Oxidation of Polyunsaturated Fatty Acids (PUFA)

    NASA Astrophysics Data System (ADS)

    Zhou, S.; Zhao, R.; Lee, A.; Gao, S.; Abbatt, J.

    2011-12-01

    Fatty acids (FAs) are emitted into the atmosphere from gas and diesel powered vehicles, cooking, plants, and marine biota. Field measurements have suggested that FAs, including polyunsaturated fatty acids (PUFA), could make up an important contribution to the organic fraction of atmospheric aerosols. Due to the existence of carbon-carbon double bonds in their molecules, PUFA are believed to be highly reactive towards atmospheric oxidants such as OH and NO3 radicals and ozone, which will contribute to aerosol hygroscopicity and cloud condensation nuclei activity. Previous work from our group has shown that small carbonyls formed from the heterogeneous reaction of linoleic acid (LA) thin films with gas-phase O3. It is known that the formation of small carbonyls in the atmosphere is not only relevant to the atmospheric budget of volatile organic compounds but also to secondary organic aerosol formation. In the present study, using an online proton transfer reaction mass spectrometry (PTR-MS) and off-line gas chromatography-mass spectrometry (GC-MS) we again investigated carbonyl formation from the same reaction system, i.e. the heterogeneous ozonolysis of LA film. In addition to the previously reported carbonyls, malondialdehyde (MDA), a source of reactive oxygen species that is mutagenic, has been identified as a product for the first time. Small dicarbonyls, e.g. glyoxal, are expected to be formed from the further oxidation of MDA. In this presentation, the gas-phase chemistry of MDA with OH radicals using a newly built Teflon chamber in our group will also be presented.

  1. Screening of marine bacterial producers of polyunsaturated fatty acids and optimisation of production.

    PubMed

    Abd El Razak, Ahmed; Ward, Alan C; Glassey, Jarka

    2014-02-01

    Water samples from three different environments including Mid Atlantic Ridge, Red Sea and Mediterranean Sea were screened in order to isolate new polyunsaturated fatty acids (PUFAs) bacterial producers especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Two hundred and fifty-one isolates were screened for PUFA production and among them the highest number of producers was isolated from the Mid-Atlantic Ridge followed by the Red Sea while no producers were found in the Mediterranean Sea samples. The screening strategy included a simple colourimetric method followed by a confirmation via GC/MS. Among the tested producers, an isolate named 66 was found to be a potentially high PUFA producer producing relatively high levels of EPA in particular. A Plackett-Burman statistical design of experiments was applied to screen a wide number of media components identifying glycerol and whey as components of a production medium. The potential low-cost production medium was optimised by applying a response surface methodology to obtain the highest productivity converting industrial by-products into value-added products. The maximum achieved productivity of EPA was 20 mg/g, 45 mg/l, representing 11% of the total fatty acids, which is approximately five times more than the amount produced prior to optimisation. The production medium composition was 10.79 g/l whey and 6.87 g/l glycerol. To our knowledge, this is the first investigation of potential bacteria PUFA producers from Mediterranean and Red Seas providing an evaluation of a colourimetric screening method as means of rapid screening of a large number of isolates. PMID:24292901

  2. Mediterranean diet and cardioprotection: the role of nitrite, polyunsaturated fatty acids and polyphenols

    PubMed Central

    Nadtochiy, Sergiy M.; Redman, Emily K.

    2010-01-01

    The continually increasing rate of myocardial infarction (MI) in the Western world at least partly can be explained by a poor diet lacking in green vegetables, fruits, and fish, and enriched in food that contains saturated fat. In contrast, a number of epidemiological studies provide strong evidence highlighting the cardioprotective benefits of the Mediterranean diet enriched in green vegetables, fruits, fish and grape wine. Regular consumption of these products leads to an accumulation of nitrate/nitrite/NO•, polyunsaturated fatty acids (PUFA), and polyphenolic compounds, such as resveratrol, in the human body. Studies have confirmed that these constituents are bioactive exogenous mediators, which induce strong protection against MI. The aim of this review is to provide a critical, in-depth analysis of the cardioprotective pathways mediated by nitrite/NO•, PUFA, and phenolic compounds of grape wines discovered in the recent years, including cross-talk between different mechanisms and compounds. Overall, these findings may facilitate the design and synthesis of novel therapeutic tools for the treatment of MI. PMID:21454053

  3. Perioperative ω-3 Polyunsaturated Fatty Acid Nutritional Support in Gastrointestinal Cancer Surgical Patients: A Systematic Evaluation.

    PubMed

    Ma, Ying-Jie; Liu, Lian; Xiao, Jing; Cao, Bang-Wei

    2016-01-01

    This study was a systematic evaluation of the beneficial effects of n-3 polyunsaturated fatty acid (PUFA) in abdominal cancer surgical patients. A literature search of the databases PubMed, Medline, Cochrane, and EMBASE was conducted for studies published up to November 2014 in English language journals. Randomized controlled trials (RCTs) examining the effects of n-3 PUFA intake relative to conventional nutrition in surgical patients were included. The main outcomes were the duration of systemic inflammatory response syndrome (SIRS), length of hospital stay (LOS), serum C-reactive protein (CRP) levels, and postoperative complications. We identified 15 RCTs among 158 relevant trials. The results indicated the associations between n-3 PUFA intake and reduced LOS [mean differences (MDs), -2.47 d; 95% confidence intervals (CIs), -3.25 to -1.69], duration of SIRS (MD, -0.57 d; 95% CI, -0.92 to -0.22), and serum CRP levels (MD, -3.97 mg/l; 95% CI, -7.88 to -0.07) compared with consumption of conventional nutrition, as well as reduced incidence of postoperative infectious complications (risk ratio, 0.66; 95% CI, 0.49-0.87). This systematic evaluation suggests that n-3 PUFA significantly reduces the postoperative infectious complication rate, and shortens hospitalization and SIRS duration, particularly in malnourished gastrointestinal cancer patients. PMID:27115734

  4. A 5-month open study with long-chain polyunsaturated fatty acids in dyslexia.

    PubMed

    Lindmark, Lars; Clough, Peter

    2007-12-01

    This open pilot study investigated effects of a docosahexaenoic acid (DHA)-rich supplement on learning ability in a group of 20 dyslexic children in Sweden. Children formally diagnosed as dyslexic took eight capsules per day of a long-chain polyunsaturated fatty acid (LC-PUFA) supplement containing high-DHA fish oil and evening primrose oil. Subjective assessments by the children and their parents were completed at baseline and 6, 12, and 20 weeks after supplementation. Quantitative evaluation by word-chain test was completed before and after 4 months of supplementation to measure word decoding (speed of reading) and letter decoding (motoric-perceptual speed). Subjective parent and child assessments showed increasing numbers of positive responders over time in reading speed, general schoolwork, and overall perceived benefit. Significant improvements were observed in reading speed and motor-perceptual velocity. Thirteen of 17 children had a significant improvement on the word-chain test (P < .04). Reading speed improved by 60% from 1.76 +/- 0.29 before the study to 2.82 +/- 0.36 after supplementation (P < .01 by Wilcoxon sign test). Motoric-perceptual velocity improved by 23% from a stanine value of 3.76 +/- 0.42 to 4.65 +/- 0.66 after supplementation (P < .05 by Wilcoxon sign test). Thus LC-PUFA supplementation for 5 months provides positive and clear beneficial effect on variables usually impaired by dyslexia. PMID:18158838

  5. Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall

    PubMed Central

    Zanetti, Michela; Grillo, Andrea; Losurdo, Pasquale; Panizon, Emiliano; Mearelli, Filippo; Cattin, Luigi; Barazzoni, Rocco; Carretta, Renzo

    2015-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFA) consumption is associated with reduced cardiovascular disease risk. Increasing evidence demonstrating a beneficial effect of n-3 PUFA on arterial wall properties is progressively emerging. We reviewed the recent available evidence for the cardiovascular effects of n-3 PUFA focusing on structural and functional properties of the vascular wall. In experimental studies and clinical trials n-3 PUFA have shown the ability to improve arterial hemodynamics by reducing arterial stiffness, thus explaining some of its cardioprotective properties. Recent studies suggest beneficial effects of n-3 PUFA on endothelial activation, which are likely to improve vascular function. Several molecular, cellular, and physiological pathways influenced by n-3 PUFA can affect arterial wall properties and therefore interfere with the atherosclerotic process. Although the relative weight of different physiological and molecular mechanisms and the dose-response on arterial wall properties have yet to be determined, n-3 PUFA have the potential to beneficially impact arterial wall remodeling and cardiovascular outcomes by targeting arterial wall stiffening and endothelial dysfunction. PMID:26301252

  6. Interactions between alpha-tocopherol, polyunsaturated fatty acids, and lipoxygenases during embryogenesis

    PubMed Central

    Lebold, Katie M; Traber, Maret G

    2013-01-01

    α-Tocopherol is a lipid-soluble antioxidant that is specifically required for reproduction and embryogenesis. However, since its discovery, α-tocopherol’s specific biologic functions, other than as an antioxidant, and the mechanism(s) mediating its requirement for embryogenesis, remain unknown. As an antioxidant, α-tocopherol protects polyunsaturated fatty acids (PUFAs) from lipid peroxidation. α-Tocopherol is likely required during embryonic development to protect PUFAs that are crucial to development, specifically arachidonic (ARA) and docosahexaenoic (DHA) acids. Additionally, ARA and DHA are metabolized to bioactive lipid mediators via lipoxygenase enzymes and α-tocopherol may directly protect, or it may mediate the production and/or actions of these lipid mediators. In this review, we discuss how α-tocopherol 1) prevents the nonspecific, radical-mediated peroxidation of PUFAs, 2) functions within a greater antioxidant network to modulate the production and/or function of lipid mediators derived from 12- and 12/15-lipoxygenase and 3) modulates 5-lipoxygenase activity. The application and implication of such interactions with be discussed in the context α-tocopherol requirements during embryogenesis. PMID:23920314

  7. Intake of Polyunsaturated Fatty Acids and Distal Large Bowel Cancer Risk in Whites and African Americans

    PubMed Central

    Kim, Sangmi; Sandler, Dale P.; Galanko, Joseph; Martin, Christopher; Sandler, Robert S.

    2010-01-01

    Long-chain ω-3 polyunsaturated fatty acids (PUFAs) may have antineoplastic properties in the colon. The authors examined the association between intakes of different PUFAs and distal large bowel cancer in a population-based case-control study of 1,503 whites (716 cases; 787 controls) and 369 African Americans (213 cases; 156 controls) in North Carolina (2001–2006). Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals for distal large bowel cancer risk in relation to quartiles of PUFA intake. Increased consumption of long-chain ω-3 PUFAs was associated with reduced risk of distal large bowel cancer in whites (multivariable odds ratios = 0.88 (95% confidence interval (CI): 0.63, 1.22), 0.69 (95% CI: 0.49, 0.98), and 0.49 (95% CI: 0.34, 0.71) for second, third, and highest vs. lowest quartile) (Ptrend < 0.01). Intake of individual eicosapentaenoic acids and docosahexaenoic acids was inversely related to distal large bowel cancer risk, whereas the ratio of ω-6 to long-chain ω-3 PUFAs was associated with increased risk of distal large bowel cancer in whites, but not among African Americans (Pinteraction < 0.05). Study results support the hypothesis that long-chain ω-3 PUFAs have beneficial effects in colorectal carcinogenesis. Whether or not the possible benefit of long-chain ω-3 PUFAs varies by race warrants further evaluation. PMID:20392864

  8. Omega-3 polyunsaturated fatty acids and cancer: lessons learned from clinical trials.

    PubMed

    Nabavi, Seyed Fazel; Bilotto, Stefania; Russo, Gian Luigi; Orhan, Ilkay Erdogan; Habtemariam, Solomon; Daglia, Maria; Devi, Kasi Pandima; Loizzo, Monica Rosa; Tundis, Rosa; Nabavi, Seyed Mohammad

    2015-09-01

    Over the past decades, extensive studies have addressed the therapeutic effects of omega-3 polyunsaturated fatty acids (omega-3 FAs) against different human diseases such as cardiovascular and neurodegenerative diseases, cancer, etc. A growing body of scientific research shows the pharmacokinetic information and safety of these natural occurring substances. Moreover, during recent years, a plethora of studies has demonstrated that omega-3 FAs possess therapeutic role against certain types of cancer. It is also known that omega-3 FAs can improve efficacy and tolerability of chemotherapy. Previous reports showed that suppression of nuclear factor-κB, activation of AMPK/SIRT1, modulation of cyclooxygenase (COX) activity, and up-regulation of novel anti-inflammatory lipid mediators such as protectins, maresins, and resolvins, are the main mechanisms of antineoplastic effect of omega-3 FAs. In this review, we have collected the available clinical data on the therapeutic role of omega-3 FAs against breast cancer, colorectal cancer, leukemia, gastric cancer, pancreatic cancer, esophageal cancer, prostate cancer, lung cancer, head and neck cancer, as well as cancer cachexia. We also discussed the chemistry, dietary source, and bioavailability of omega-3 FAs, and the potential molecular mechanisms of anticancer and adverse effects. PMID:26227583

  9. Levels of polyunsaturated fatty acids correlate with growth rate in plant cell cultures

    PubMed Central

    Meï, Coline; Michaud, Morgane; Cussac, Mathilde; Albrieux, Catherine; Gros, Valérie; Maréchal, Eric; Block, Maryse A.; Jouhet, Juliette; Rébeillé, Fabrice

    2015-01-01

    In higher plants, fatty acids (FAs) with 18 carbons (18C) represent about 70% of total FAs, the most abundant species being 18:2 and 18:3. These two polyunsaturated FAs (PUFAs) represent about 55% of total FAs in Arabidopsis cell suspension cultures, whereas 18:1 represents about 10%. The level of PUFAs may vary, depending on ill-defined factors. Here, we compared various sets of plant cell cultures and noticed a correlation between the growth rate of a cell population and the level of unsaturation of 18C FAs. These observations suggest that the final level of PUFAs might depend in part on the rate of cell division, and that FAD2 and FAD3 desaturases, which are respectively responsible for the formation of 18:2 and 18:3 on phospholipids, have limiting activities in fast-growing cultures. In plant cell culture, phosphate (Pi) deprivation is known to impair cell division and to trigger lipid remodeling. We observed that Pi starvation had no effect on the expression of FAD genes, and that the level of PUFAs in this situation was also correlated with the growth rate. Thus, the level of PUFAs appears as a hallmark in determining cell maturity and aging. PMID:26469123

  10. Upstream Treatment of Atrial Fibrillation with n-3 Polyunsaturated Fatty Acids: Myth or Reality?

    PubMed Central

    Orso, Francesco; Fabbri, Gianna; Maggioni, Aldo Pietro

    2015-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia in adults and is associated with an increased risk of fatal and non-fatal events. Antiarrhythmic drugs provide limited protection against AF recurrence and have a poor safety profile. Several mechanisms have been proven to be involved in AF, e.g. inflammation, oxidative stress, fibrosis and ischaemia. Prevention of AF with interventions that target these mechanisms has emerged as a result of experimental studies suggesting the use of upstream therapies. Long chain n-3 polyunsaturated fatty acids (n-3 PUFA) have multiple effects on cardiac electrophysiology, and epidemiological studies on fish oil suggest a possible use of n-3 PUFA in AF prevention. Several randomised clinical trials have been designed to evaluate the efficacy of n-3 PUFA in preventing AF. In this review, we report the conflicting results of these trials in two different clinical settings: recurrence in patients with history of AF and development of post-operative AF in patient undergoing cardiac surgery. PMID:26835119

  11. Maternal Malnutrition in the Etiopathogenesis of Psychiatric Diseases: Role of Polyunsaturated Fatty Acids.

    PubMed

    Morgese, Maria Grazia; Trabace, Luigia

    2016-01-01

    Evidence from human studies indicates that maternal metabolic state and malnutrition dramatically influence the risk for developing psychiatric complications in later adulthood. In this regard, the central role of polyunsaturated fatty acids (PUFAs), and particularly n-3 PUFAs, is emerging considering that epidemiological evidences have established a negative correlation between n-3 PUFA consumption and development of mood disorders. These findings were supported by clinical studies indicating that low content of n-3 PUFAs in diet is linked to an increased susceptibility to psychiatric disorders. PUFAs regulate membrane fluidity and exert their central action by modulating synaptogenesis and neurotrophic factor expression, neurogenesis, and neurotransmission. Moreover, they are precursors of molecules implicated in modulating immune and inflammatory processes in the brain. Importantly, their tissue concentrations are closely related to diet intake, especially to maternal consumption during embryonal life, considering that their synthesis from essential precursors has been shown to be inefficient in mammals. The scope of this review is to highlight the possible mechanisms of PUFA functions in the brain during pre- and post-natal period and to evaluate their role in the pathogenesis of psychiatric diseases. PMID:27472366

  12. Upstream Treatment of Atrial Fibrillation with n-3 Polyunsaturated Fatty Acids: Myth or Reality?

    PubMed

    Orso, Francesco; Fabbri, Gianna; Maggioni, Aldo Pietro

    2015-12-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia in adults and is associated with an increased risk of fatal and non-fatal events. Antiarrhythmic drugs provide limited protection against AF recurrence and have a poor safety profile. Several mechanisms have been proven to be involved in AF, e.g. inflammation, oxidative stress, fibrosis and ischaemia. Prevention of AF with interventions that target these mechanisms has emerged as a result of experimental studies suggesting the use of upstream therapies. Long chain n-3 polyunsaturated fatty acids (n-3 PUFA) have multiple effects on cardiac electrophysiology, and epidemiological studies on fish oil suggest a possible use of n-3 PUFA in AF prevention. Several randomised clinical trials have been designed to evaluate the efficacy of n-3 PUFA in preventing AF. In this review, we report the conflicting results of these trials in two different clinical settings: recurrence in patients with history of AF and development of post-operative AF in patient undergoing cardiac surgery. PMID:26835119

  13. Biopolymer nanoparticles designed for polyunsaturated fatty acid vehiculization: Protein-polysaccharide ratio study.

    PubMed

    Perez, Adrián A; Sponton, Osvaldo E; Andermatten, Romina B; Rubiolo, Amelia C; Santiago, Liliana G

    2015-12-01

    Information about the design of biopolymer nanoparticles (BNPs) for polyunsaturated fatty acid (PUFA) vehiculization is provided. Linoleic acid (LA) was used as a model PUFA. The binding ability of LA to β-lactoglobulin (BLG) was applied for obtaining BLG-LA complexes. BLG-LA complex formation was monitored by fluorimetry and it was observed that a moderate heat treatment (60 °C, 10 min) enhanced BLG-LA complexation. Obtaining BNPs involved the electrostatic deposition of high methoxyl pectin (HMP) onto the BLG-LA complex surface. The phase behavior of biopolymer systems was discussed at different Prot:HMP ratio (RProt:HMP, wt.%) levels (1:1-6:1). Absorbance at 600 nm, particle size, and ζ potential were analyzed at pH 4.0. At 1:1-2:1 RProt:HMP, BNPs showed appreciable turbidity, a nanometric diameter (337-364 nm), and a negative ζ potential. Finally, intrinsic and extrinsic fluorimetry was used for examining the HMP protective role at the LA binding site. At 2:1 RProt:HMP, HMP cover could promote significant LA protection in BNPs. PMID:26041229

  14. N-3 Polyunsaturated Fatty Acids and Inflammation in Obesity: Local Effect and Systemic Benefit

    PubMed Central

    Wang, Yue; Huang, Feiruo

    2015-01-01

    Overwhelming consensus emerges among countless evidences that obesity is characterized by a chronic low-grade inflammation in the adipose tissue (AT), which subsequently develops into a systemic inflammatory state contributing to obesity-associated diseases. N-3 Polyunsaturated fatty acids (n-3 PUFA), known as important modulators participating in inflammatory process, turn out to be an effective mitigating strategy dealing with local and systemic inflammation observed in obesity. Some of the effects of n-3 PUFA are brought about by regulation of gene expression through interacting with nuclear receptors and transcription factors; other effects are elicited by modulation of the amount and type of mediator derived from PUFAs. The metabolic effects of n-3 PUFA mainly result from their interactions with several organ systems, not limited to AT. Notably, the attenuation of inflammation in hard-hit AT, in turn, contributes to reducing circulating concentrations of proinflammatory cytokines and detrimental metabolic derivatives, which is beneficial for the function of other involved organs. The present review highlights a bridging mechanism between n-3 PUFA-mediated inflammation relief in AT and systemic benefits. PMID:26339623

  15. Polyunsaturated fatty acids, cognition and literacy in children with ADHD with and without learning difficulties.

    PubMed

    Milte, Catherine M; Sinn, Natalie; Buckley, Jonathan D; Coates, Alison M; Young, Ross M; Howe, Peter Rc

    2011-12-01

    Suboptimal omega-3 polyunsaturated fatty acid (n-3 PUFA) levels may contribute to attention deficit hyperactivity disorder (ADHD) and related developmental problems. Associations between n-3 and omega-6 (n-6) PUFA levels in red blood cells (erythrocytes) and learning and behaviour were investigated in 75 children aged 7-12 with ADHD. Children provided blood samples and underwent cognitive assessments. Parents completed questionnaires and Conners' Rating Scales. Controlling for covariates, higher n-3 PUFA predicted lower anxiety/shyness (β = -.27), higher docosahexaenoic acid (DHA) better word reading (β = .22), and higher n-6 PUFA poorer reading (β = -.34), vocabulary (β = .-.26), spelling (β = -.30) and attention (β = -.30). Thirty-six per cent of the sample with learning difficulties had lower DHA than those without (M = 3.26 ± 0.54 vs M = 3.68 ± 0.76, p = .02). This study is the first to compare erythrocyte PUFAs (a measure of PUFA status) in children who have ADHD with and without learning difficulties, and supports emerging indications that the former may be more likely responders to n-3 PUFAs. PMID:21828168

  16. Polyunsaturated fatty acids inhibit Kv1.4 by interacting with positively charged extracellular pore residues.

    PubMed

    Farag, N E; Jeong, D; Claydon, T; Warwicker, J; Boyett, M R

    2016-08-01

    Polyunsaturated fatty acids (PUFAs) modulate voltage-gated K(+) channel inactivation by an unknown site and mechanism. The effects of ω-6 and ω-3 PUFAs were investigated on the heterologously expressed Kv1.4 channel. PUFAs inhibited wild-type Kv1.4 during repetitive pulsing as a result of slowing of recovery from inactivation. In a mutant Kv1.4 channel lacking N-type inactivation, PUFAs reversibly enhanced C-type inactivation (Kd, 15-43 μM). C-type inactivation was affected by extracellular H(+) and K(+) as well as PUFAs and there was an interaction among the three: the effect of PUFAs was reversed during acidosis and abolished on raising K(+) Replacement of two positively charged residues in the extracellular pore (H508 and K532) abolished the effects of the PUFAs (and extracellular H(+) and K(+)) on C-type inactivation but had no effect on the lipoelectric modulation of voltage sensor activation, suggesting two separable interaction sites/mechanisms of action of PUFAs. Charge calculations suggest that the acidic head group of the PUFAs raises the pKa of H508 and this reduces the K(+) occupancy of the selectivity filter, stabilizing the C-type inactivated state. PMID:27281482

  17. ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy.

    PubMed

    O'Rourke, Eyleen J; Kuballa, Petric; Xavier, Ramnik; Ruvkun, Gary

    2013-02-15

    Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing C. elegans culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs. PMID:23392608

  18. Dietary supply with polyunsaturated fatty acids and resulting maternal effects influence host – parasite interactions

    PubMed Central

    2013-01-01

    Background Interactions between hosts and parasites can be substantially modulated by host nutrition. Polyunsaturated fatty acids (PUFAs) are essential dietary nutrients; they are indispensable as structural components of cell membranes and as precursors for eicosanoids, signalling molecules which act on reproduction and immunity. Here, we explored the potential of dietary PUFAs to affect the course of parasitic infections using a well-established invertebrate host – parasite system, the freshwater herbivore Daphnia magna and its bacterial parasite Pasteuria ramosa. Results Using natural food sources differing in their PUFA composition and by experimentally modifying the availability of dietary arachidonic acid (ARA) and eicosapentaenoic acid (EPA) we examined PUFA-mediated effects resulting from direct consumption as well as maternal effects on offspring of treated mothers. We found that both host and parasite were affected by food quality. Feeding on C20 PUFA-containing food sources resulted in higher offspring production of hosts and these effects were conveyed to a great extent to the next generation. While feeding on a diet containing high PUFA concentrations significantly reduced the likelihood of becoming infected, the infection success in the next generation increased whenever the maternal diet contained PUFAs. We suggest that this opposing effect was caused by a trade-off between reproduction and immunity in the second generation. Conclusions Considering the direct and maternal effects of dietary PUFAs on host and parasite we propose that host – parasite interactions and thus disease dynamics under natural conditions are subject to the availability of dietary PUFAs. PMID:24175981

  19. The effects of antioxidants on the content of polyunsaturated fatty acids in the hen's egg.

    PubMed

    Kassab, A; Abrams, J T; Sainsbury, D W

    1979-01-01

    In experiments to see whether, in the possible interests of human health, the polyunsaturated fatty acid (PUFA) content of the chicken's egg can be increased by nutritional means, three strains of hen, light, medium, and heavy, each at the peak of lay, were first fed a basal, commercial, low-fat diet. The hens were then transferred to one of the following diets: basal + safflower oil (SO); basal + SO + butylated hydroxytoluene; or basal + SO + dl-a-toco-pheryl acetate. The diets were designated "Blank", "BHT", and "Vitamin E", respectively, the second and third containing the added antioxidants. The eggs produced were weighed, and their yolks weighed and analysed for lipid components. Additional of SO (7.5%) to the basal diet led to the PUFA content of the yolk lipids rising by 15.4% (linoleic acid, 14.1%), the magnitude of the increases being unaffected by the antioxidants. Diet "BHT" produced larger eggs and yolks than the other diets, but the proportion of yolk was the same on the three types of feed. The total cholesterol content of egg yolks was significantly affected neither by diet, nor by strain or age of hen. The implications of these results are discussed. PMID:468476

  20. Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders

    PubMed Central

    Su, Kuan-Pin; Matsuoka, Yutaka; Pae, Chi-Un

    2015-01-01

    Psychiatric disorders in general, and major depression and anxiety disorders in particular, account for a large burden of disability, morbidity and premature mortality worldwide. Omega-3 polyunsaturated fatty acids (PUFAs) have a range of neurobiological activities in modulation of neurotransmitters, anti-inflammation, anti-oxidation and neuroplasticity, which could contribute to psychotropic effects. Here we reviewed recent research on the benefits of omega-3 PUFA supplements in prevention against major depression, bipolar disorders, interferon-α-induced depression patients with chronic hepatitis C viral infection, and posttraumatic stress disorder. The biological mechanisms underlying omega-3 PUFAs’ psychotropic effects are proposed and reviewed. Nutrition is a modifiable environmental factor that might be important in prevention medicine, which have been applied for many years in the secondary prevention of heart disease with omega-3 PUFAs. This review extends the notion that nutrition in psychiatry is a modifiable environmental factor and calls for more researches on prospective clinical studies to justify the preventive application of omega-3 PUFAs in daily practice. PMID:26243838

  1. Omega-3 polyunsaturated fatty acids in Alzheimer's disease: key questions and partial answers.

    PubMed

    Calon, F

    2011-08-01

    The current rise in the prevalence of Alzheimer's disease (AD) is unfortunately not matched by new treatment options. In the last 10 years, epidemiological, preclinical and clinical data have enlightened the possible preventive action of omega-3 polyunsaturated fatty acids (n-3 PUFA) in AD and other diseases. While the contribution of recent studies to our general knowledge is priceless, many important new questions have been raised. In the present review, we aim at addressing some of these timely interrogations. First, the transport of n-3 PUFA across the blood-brain barrier is underscored based on preclinical data. Second, the relative contribution of two neuroactive n-3 PUFA found in fish oil, docosahexaenoic acid (DHA; 22:6 n-3) and eicosapentaenoic acid (EPA, 20:5 n-3), remains unclear and is reviewed. Third, clinical trials on neurodegenerative diseases consistently remind us that treating early is critical, and this is likely to be the case with n-3 PUFA in AD as well. Fourth, we draw attention to the possibility that the current knowledge translation approach to make health recommendations might have to be adapted to non-patentable endogenous compounds like n-3 PUFA. We propose that answers to these critical questions will be instrumental toward a rational use of n-3 PUFA in AD. PMID:21605051

  2. 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

  3. Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer

    PubMed Central

    Moro, Kazuki; Nagahashi, Masayuki; Ramanathan, Rajesh; Takabe, Kazuaki; Wakai, Toshifumi

    2016-01-01

    Inflammation is a central process in several disorders and contributes to cancer progression. Inflammation involves a complex cascade of pro-inflammatory and anti-inflammatory signaling events with protein and lipid mediators. Recent advances in lipid detection have revealed the importance of lipid mediators in inflammation. Omega three polyunsaturated fatty acids (ω-3 PUFA) are found naturally in fish oil and have been extensively studied in multiple inflammatory diseases with improved outcomes. Resolvins are thought to be the active metabolites of ω-3 PUFA, and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, micro and macro vascular response to injury, and inhibition of microglia-activated inflammation in neurodegenerative disorders. In addition to inflammatory diseases, ω-3 PUFA and resolvins appear to modulate cancer progression. ω-3 PUFA intake has been associated with reduced inflammation in colorectal cancer, and favorable phenotype in breast cancer. Resolvins offer promising therapeutic potential as they may modulate inflammation with minimal side-effects, in contrast to currently available anti-inflammatory medications. This review describes the roles of ω-3 PUFA and resolvins in the inflammatory cascade, various inflammatory diseases, and specific cancers. Additionally, it will discuss the clinical therapeutic potential of resolvins as targets in inflammatory diseases and cancers. PMID:27458590

  4. 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. PMID:26324193

  5. Regulation of mevalonate synthesis in rat mammary glands by dietary n-3 and n-6 polyunsaturated fatty acids.

    PubMed

    El-Sohemy, A; Archer, M C

    1997-09-01

    It is well established that dietary n-6 polyunsaturated fatty acids (PU-FAs) enhance rat mammary tumor development whereas n-3 PUFAs inhibit it, yet the mechanisms are unclear. The objective of this study was to investigate a mechanism by which n-3 and n-6 PUFAs could modulate mammary carcinogenesis. Female Sprague Dawley rats were fed diets containing either menhaden (n-3) or safflower oil (n-6) in a 7% fat diet for 1 week. In comparison to the n-6 diet, the n-3 diet significantly reduced the activity and levels of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase in mammary glands, thereby suppressing the formation of mevalonate. In addition to being essential for cholesterol biosynthesis, mevalonate is also required for DNA synthesis and may be involved in malignant transformation. Serum cholesterol was lower in the n-3 group than in the n-6 group (1.91 +/- 0.18 versus 2.61 +/- 0.37 mM; P < 0.01). Extrahepatic tissues meet most of their cholesterol requirements from circulating cholesterol, and the internalized cholesterol down-regulates HMG-CoA reductase. Thus, the concomitant decrease in serum cholesterol and mammary gland HMG-CoA reductase levels suggests that changes in circulating cholesterol levels do not solely determine the activity of extrahepatic reductase. We conclude that the mevalonate pathway may be a mechanism through which different types of dietary fat modulate breast cancer development. PMID:9288773

  6. [Differences in percent composition of long chain polyunsaturated fatty acids in maternal-fetal erythrocytes in term and preterm infants].

    PubMed

    Araya Araya, J; Rojas García, M; Fernández Fraile, P; Mateluna Acevedo, A

    1998-09-01

    The content and distribution of long-chain polyunsaturated fatty acids (LCP) of maternal-fetal erythrocytes phospholipids was investigated. Blood samples from healthy pregnant women were taken from maternal veins and umbilical cord at spontaneous delivery time. Two groups were segregated and compared in terms of fetuses gestational age: preterm delivery (32-34 weeks) and term delivery (40 weeks). The results showed that in erythrocytes of term newborn the content of LCP omega 6 and omega 3; particularly 20:4w6 (ARA) and 22:6w3 (DHA), were found to be statistically higher than their respective mother. However, in preterm newborns, all LCP from phospholipids erythrocytes were found to be statistically lower than in their mother. Comparing the content of ARA and DHA between the newborn groups, it observed that only DHA was decreased in preterm group. Women who delivered premature babies showed a blood ratio ARA/DHA higher than those who delivered term-babies. From this study and considering previous information it can be suggested that a high content of ARA and ARA/DHA ratio in maternal and fetal erythrocytes may considered an early risk signal of preterm delivery. PMID:9951532

  7. Ketogenic Diet, but Not Polyunsaturated Fatty Acid Diet, Reduces Spontaneous Seizures in Juvenile Rats with Kainic Acid-induced Epilepsy

    PubMed Central

    Dustin, Simone M.; Stafstrom, Carl E.

    2016-01-01

    Background and Purpose: The high-fat, low-carbohydrate ketogenic diet (KD) is effective in many cases of drug-resistant epilepsy, particularly in children. In the classic KD, fats consist primarily of long-chain saturated triglycerides. Polyunsaturated fatty acids (PUFAs), especially the n-3 type, decrease neuronal excitability and provide neuroprotection; pilot human studies have raised the possibility of using PUFAs to control seizures in patients. Methods: To determine the relative roles of the KD and PUFAs in an animal model, we induced epilepsy in juvenile rats (P29–35) using intraperitoneal kainic acid (KA). KA caused status epilepticus in all rats. Two days after KA, rats were randomized to one of 4 dietary groups: Control diet; PUFA diet; KD; or KD plus PUFA. All diets were administered isocalorically at 90% of the rat recommended daily calorie requirement. Spontaneous recurrent seizures (SRS) were assessed for 3 months after diet randomization. Results: Rats receiving the KD or KD-PUFA diet had significantly fewer SRS than those receiving the Control diet or PUFA diet. The PUFA diet did not reduce SRS compared to the Control diet. Conclusions: In the KA epilepsy model, the KD protects against SRS occurrence but dietary enhancement with PUFA does not afford additional protection against spontaneous seizures. PMID:27390673

  8. CONSUMPTION OF A HIGH N-3 POLYUNSATURATED FATTY ACID DIET DURING GRADUAL MILD PHYSIOLOGICAL STRESS IN RATS

    PubMed Central

    Appleton, KM; Grippo, AJ; Beltz, TG; Johnson, AK

    2015-01-01

    SUMMARY n-3 polyunsaturated fatty acids (n-3PUFAs) may be beneficial for anxiety and depression under stressful conditions. Studies however, typically utilise physical or sudden physiological stress, while gradual physiological stress is also relevant to human conditions. Using deoxycorticosterone acetate (DOCA) administration to induce gradual physiological stress, this study investigated the impact of n-3PUFAs under gradual physiological stress in rats. Animals (aged 2 months) (N=8–12/group) received daily injections of DOCA or vehicle and were concurrently fed a high n-3PUFA or control diet for eight weeks. Behavioural measures were taken throughout. Behavioural tests and physiological measures were conducted after six and eight weeks respectively. DOCA administration decreased plasma renin, plasma proteins and relative adrenal weight, and increased water intake, relative kidney weight, and anxiety in the open field. These findings demonstrate disruptions to the rennin-angiotensin-aldosterone system, a result of mild physiological stress, that also impact on anxiety behaviours. No effects of n-3PUFAs were found. PMID:25534694

  9. Changes in lipid peroxidation and antioxidant enzyme activities by triiodothyronine (T3) and polyunsaturated fatty acids (PUFA) in rat liver.

    PubMed

    Varghese, S; Lakshmy, P S; Oommen, O V

    2001-11-01

    Thyroid hormones play an important role in the control of metabolism of vertebrates. This investigation was carried out to examine the effects of triiodothyronine (T3) and polyunsaturated fatty acids (PUFA) on lipid peroxidation in rat liver. Male Wistar strain of rats treated with 6-propylthiouracil (6-PTU) showed no significant change in lipid peroxidation as evident from the generation of malondialdehyde and conjugated dienes. However, in PUFA fed animals as well as 6-PTU + PUFA + T3 treated groups, increased peroxidation products were found. Superoxide dismutase (SOD) activity was low in 6-PTU, 6-PTU + PUFA, PUFA, 6-PTU + PUFA + T3 treated animals while glutathione peroxidase (GPx) activity was high in these groups. Catalase activity was low in all treated groups except PUFA alone fed animals. Glutathione reductase (GR) activity was decreased by 6-PTU treatment and increased in PTU + PUFA fed rats. Cellular glutathione level was high in PUFA and low in PTU-treated groups. From these results it can be concluded that both T3 and PUFA have profound influence on lipid peroxidation and antioxidant enzyme activities in rat liver. PMID:11794465

  10. Consumption of a high n-3 polyunsaturated fatty acid diet during gradual mild physiological stress in rats.

    PubMed

    Appleton, K M; Grippo, A J; Beltz, T G; Johnson, A K

    2015-04-01

    n-3 Polyunsaturated fatty acids (n-3PUFAs) may be beneficial for anxiety and depression under stressful conditions. Studies however, typically utilise physical or sudden physiological stress, while gradual physiological stress is also relevant to human conditions. Using deoxycorticosterone acetate (DOCA) administration to induce gradual physiological stress, this study investigated the impact of n-3PUFAs under gradual physiological stress in rats. Animals (aged 2 months) (N=8-12/group) received daily injections of DOCA or vehicle and were concurrently fed a high n-3PUFA or control diet for eight weeks. Behavioural measures were taken throughout. Behavioural tests and physiological measures were conducted after six and eight weeks respectively. DOCA administration decreased plasma renin, plasma proteins and relative adrenal weight, and increased water intake, relative kidney weight, and anxiety in the open field. These findings demonstrate disruptions to the renin-angiotensin-aldosterone system, a result of mild physiological stress, that also impact on anxiety behaviours. No effects of n-3PUFAs were found. PMID:25534694

  11. Polyunsaturated Fatty Acid (PUFA) Status in Pregnant Women: Associations with Sleep Quality, Inflammation, and Length of Gestation

    PubMed Central

    Christian, Lisa M.; Blair, Lisa M.; Porter, Kyle; Lower, Mary; Cole, Rachel M.; Belury, Martha A.

    2016-01-01

    Mechanistic pathways linking maternal polyunsaturated fatty acid (PUFA) status with gestational length are poorly delineated. This study examined whether inflammation and sleep quality serve as mediators, focusing on the antiinflammatory ω-3 docosahexaenoic acid (DHA; 22:6n3) and proinflammatory ω-6 arachidonic acid (AA; 20:4n6). Pregnant women (n = 135) provided a blood sample and completed the Pittsburgh Sleep Quality Index (PSQI) at 20–27 weeks gestation. Red blood cell (RBC) fatty acid levels were determined by gas chromatography and serum inflammatory markers [interleukin (IL)-6, IL-8, tumor necrosis factor-α, IL-1β, and C-reactive protein] by electrochemiluminescence using high sensitivity kits. Both higher serum IL-8 (95% CI = 0.10,3.84) and poor sleep (95% CI = 0.03,0.28) served as significant mediators linking lower DHA:AA ratios with shorter gestation. Further, a serial mediation model moving from the DHA:AA ratio → sleep → IL-8 → length of gestation was statistically significant (95% CI = 0.02, 0.79). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. No interactions with race were observed in relation to length of gestation as a continuous variable. However, a significant interaction between race and the DHA:AA ratio in predicting preterm birth was observed (p = 0.049); among African Americans only, odds of preterm birth decreased as DHA:AA increased (p = 0.048). These data support a role for both inflammatory pathways and sleep quality in linking less optimal RBC PUFA status with shorter gestation in African American and European American women and suggest that African-Americans have greater risk for preterm birth in the context of a low DHA:AA ratio. PMID:26859301

  12. 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. PMID:27070119

  13. Polyunsaturated Fatty Acid (PUFA) Status in Pregnant Women: Associations with Sleep Quality, Inflammation, and Length of Gestation.

    PubMed

    Christian, Lisa M; Blair, Lisa M; Porter, Kyle; Lower, Mary; Cole, Rachel M; Belury, Martha A

    2016-01-01

    Mechanistic pathways linking maternal polyunsaturated fatty acid (PUFA) status with gestational length are poorly delineated. This study examined whether inflammation and sleep quality serve as mediators, focusing on the antiinflammatory ω-3 docosahexaenoic acid (DHA; 22:6n3) and proinflammatory ω-6 arachidonic acid (AA; 20:4n6). Pregnant women (n = 135) provided a blood sample and completed the Pittsburgh Sleep Quality Index (PSQI) at 20-27 weeks gestation. Red blood cell (RBC) fatty acid levels were determined by gas chromatography and serum inflammatory markers [interleukin (IL)-6, IL-8, tumor necrosis factor-α, IL-1β, and C-reactive protein] by electrochemiluminescence using high sensitivity kits. Both higher serum IL-8 (95% CI = 0.10,3.84) and poor sleep (95% CI = 0.03,0.28) served as significant mediators linking lower DHA:AA ratios with shorter gestation. Further, a serial mediation model moving from the DHA:AA ratio → sleep → IL-8 → length of gestation was statistically significant (95% CI = 0.02, 0.79). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. No interactions with race were observed in relation to length of gestation as a continuous variable. However, a significant interaction between race and the DHA:AA ratio in predicting preterm birth was observed (p = 0.049); among African Americans only, odds of preterm birth decreased as DHA:AA increased (p = 0.048). These data support a role for both inflammatory pathways and sleep quality in linking less optimal RBC PUFA status with shorter gestation in African American and European American women and suggest that African-Americans have greater risk for preterm birth in the context of a low DHA:AA ratio. PMID:26859301

  14. Effects of n-3 Polyunsaturated Fatty Acids (ω-3) Supplementation on Some Cardiovascular Risk Factors with a Ketogenic Mediterranean Diet

    PubMed Central

    Paoli, Antonio; Moro, Tatiana; Bosco, Gerardo; Bianco, Antonino; Grimaldi, Keith A.; Camporesi, Enrico; Mangar, Devanand

    2015-01-01

    Background: the ketogenic diet (KD) has become a widely used nutritional approach for weight loss. Some of the KD’s positive effects on metabolism and cardiovascular risk factors are similar to those seen after n-3 polyunsaturated fatty acids (ω-3) supplementation. We hypothesized that a ketogenic Mediterranean diet with phytoextracts combined with ω-3 supplementation may have increased positive effects on cardiovascular risk factors and inflammation. Methods: We analyzed 34 male overweight subjects; aged between 25 and 65 years who were overall healthy apart from overweight. The subjects followed a ketogenic diet protocol for four weeks; with (KDO3) or without (KD) ω-3 supplementation. Results: All subjects experienced a significant loss of body weight and body fat and there was no significant differences between treatment (body weight: KD—4.7 kg, KDO3—4.03 kg, body fat KD—5.41 kg, KDO3—5.86 kg). There were also significant decreases in total cholesterol, LDL-c, and glucose levels. Triglycerides and insulin levels decreased more in KDO3 vs. KD subjects, with a significant difference. All the investigated inflammatory cytokines (IL-1β, IL-6, TNF-α) decreased significantly in KDO3 subjects whilst only TNF-α showed a significant decrease in KD subjects over the 12 month study period. No significant changes were observed in anti-inflammatory cytokines (IL-10 and IL-1Ra), creatinine, urea and uric acid. Adiponectin increased significantly only in the KDO3 group. Conclusions: ω-3 supplementation improved the positive effects of a ketogenic Mediterranean diet with phytoextracts on some cardiovascular/metabolic risk factors and inflammatory state. PMID:25689563

  15. Role of Omega-3 Polyunsaturated Fatty Acids in the Production of Prostaglandin E2 and Nitric Oxide during Experimental Murine Paracoccidioidomycosis

    PubMed Central

    Sargi, S. C.; Dalalio, M. M. O.; Moraes, A. G.; Visentainer, J. E. L.; Morais, D. R.; Visentainer, J. V.

    2013-01-01

    There has recently been increased interest in the potential health effects of omega-3 polyunsaturated fatty acids on the immune system. Paracoccidioidomycosis is the most important endemic mycosis in Latin America. Macrophages have a fundamental role and act as first line of organism defense. The purpose of this study was to analyze the effect of n-3 fatty acids on the production of PGE2 and NO by mice infected with Pb18 and fed a diet enriched with LNA for 8 weeks. To study the effect of omega-3 fatty acids on macrophage activity during experimental paracoccidioidomycosis, mice were infected with Pb18 and fed a diet supplemented with LNA. PGE2 in the serum of animals was analyzed and NO in the supernatants of macrophages cultured and challenged in vitro with Pb18 was measured. Omega-3 fatty acids seemed to decrease the production of PGE2 in vivo in the infected group fed an LNA-supplemented diet during the 4th and 8th weeks of the experiment. At the same time, we observed an increase in synthesis of NO by peritoneal macrophages in this group. Omega-3 fatty acids thus appear to have an immunomodulatory effect in paracoccidioidomycosis. PMID:24455741

  16. 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. PMID:27344166

  17. Modulation of fear memory by dietary polyunsaturated fatty acids via cannabinoid receptors.

    PubMed

    Yamada, Daisuke; Takeo, Jiro; Koppensteiner, Peter; Wada, Keiji; Sekiguchi, Masayuki

    2014-07-01

    Although the underlying mechanism remains unknown, several studies have suggested benefits of n-3 long-chain polyunsaturated fatty acid (PUFA) for patients with anxiety disorders. Elevated fear is thought to contribute to the pathogenesis of particular anxiety disorders. The aim of the present study was to evaluate whether the dietary n-3 to n-6 PUFA (3:6) ratio influences fear memory. For this purpose, the effects of various dietary 3:6 ratios on fear memory were examined in mice using contextual fear conditioning, and the effects of these diets on central synaptic transmission were examined to elucidate the mechanism of action of PUFA. We found that fear memory correlated negatively with dietary, serum, and brain 3:6 ratios in mice. The low fear memory in mice fed a high 3:6 ratio diet was increased by the cannabinoid CB1 receptor antagonist rimonabant, reaching a level seen in mice fed a low 3:6 ratio diet. The agonist sensitivity of CB1 receptor was enhanced in the basolateral nucleus of the amygdala (BLA) of mice fed a high 3:6 ratio diet, compared with that of mice fed a low 3:6 ratio diet. Similar enhancement was induced by pharmacological expulsion of cholesterol in the neuronal membrane of brain slices from mice fed a low 3:6 ratio diet. CB1 receptor-mediated short-term synaptic plasticity was facilitated in pyramidal neurons of the BLA in mice fed a high 3:6 ratio diet. These results suggest that the ratio of n-3 to n-6 PUFA is a factor regulating fear memory via cannabinoid CB1 receptors. PMID:24518289

  18. Lack of Dietary Polyunsaturated Fatty Acids Causes Synapse Dysfunction in the Drosophila Visual System

    PubMed Central

    Ziegler, Anna B.; Ménagé, Cindy; Grégoire, Stéphane; Garcia, Thibault; Ferveur, Jean-François; Bretillon, Lionel; Grosjean, Yael

    2015-01-01

    Polyunsaturated fatty acids (PUFAs) are essential nutrients for animals and necessary for the normal functioning of the nervous system. A lack of PUFAs can result from the consumption of a deficient diet or genetic factors, which impact PUFA uptake and metabolism. Both can cause synaptic dysfunction, which is associated with numerous disorders. However, there is a knowledge gap linking these neuronal dysfunctions and their underlying molecular mechanisms. Because of its genetic manipulability and its easy, fast, and cheap breeding, Drosophila melanogaster has emerged as an excellent model organism for genetic screens, helping to identify the genetic bases of such events. As a first step towards the understanding of PUFA implications in Drosophila synaptic physiology we designed a breeding medium containing only very low amounts of PUFAs. We then used the fly’s visual system, a well-established model for studying signal transmission and neurological disorders, to measure the effects of a PUFA deficiency on synaptic function. Using both visual performance and eye electrophysiology, we found that PUFA deficiency strongly affected synaptic transmission in the fly’s visual system. These defects were rescued by diets containing omega-3 or omega-6 PUFAs alone or in combination. In summary, manipulating PUFA contents in the fly’s diet was powerful to investigate the role of these nutrients on the fly´s visual synaptic function. This study aims at showing how the first visual synapse of Drosophila can serve as a simple model to study the effects of PUFAs on synapse function. A similar approach could be further used to screen for genetic factors underlying the molecular mechanisms of synaptic dysfunctions associated with altered PUFA levels. PMID:26308084

  19. Antibacterial activity of long-chain polyunsaturated fatty acids against Propionibacterium acnes and Staphylococcus aureus.

    PubMed

    Desbois, Andrew P; Lawlor, Keelan C

    2013-11-01

    New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32-1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15-30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. PMID:24232668

  20. Antibacterial Activity of Long-Chain Polyunsaturated Fatty Acids against Propionibacterium acnes and Staphylococcus aureus

    PubMed Central

    Desbois, Andrew P.; Lawlor, Keelan C.

    2013-01-01

    New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32–1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15–30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. PMID:24232668

  1. Inhibition of endometrial cancer by n-3 polyunsaturated fatty acids in preclinical models.

    PubMed

    Zheng, Hang; Tang, Hongjun; Liu, Miao; He, Minhong; Lai, Pinglin; Dong, Heling; Lin, Jun; Jia, Chunhong; Zhong, Mei; Dai, Yifan; Bai, Xiaochun; Wang, Liping

    2014-08-01

    Although preclinical and epidemiologic studies have shown the importance of n-3 polyunsaturated fatty acids (PUFA) in the prevention of hormone-responsive cancers such as breast cancer, evidence of the association between n-3 PUFAs and endometrial cancer risk is limited and no previous study has examined the effect of n-3 PUFAs on endometrial cancer in cellular and animal models. In this study, we demonstrated that docosahexenoic acid (DHA) dose- and time-dependently inhibited endometrial cancer cell proliferation, colony formation, and migration and promoted apoptosis. Dietary n-3 PUFAs efficiently prevented endometrial cancer cell growth in xenograft models. Moreover, ectopic expression of fat-1, a desaturase, catalyzed the conversion of n-6 to n-3 PUFAs and produced n-3 PUFAs endogenously, also suppressed endometrial tumor cell growth and migration, and potentiated apoptosis in endometrial cancer cell lines. Interestingly, implanted endometrial cancer cells were unable to grow in fat-1 transgenic SCID mice. Further study revealed that mTOR signaling, which plays an essential role in cell proliferation and endometrial tumorigenesis, is a target of n-3 PUFAs. Exogenous or endogenous n-3 PUFAs efficiently suppressed both mTOR complex 1 (mTORC1) and mTORC2 in vitro and in vivo. Moreover, both dietary n-3 PUFAs and transgenic expression of fat-1 in mice effectively repressed mTORC1/2 signaling and endometrial growth elicited by unopposed estrogen. Taken together, our findings provide comprehensive preclinical evidences that n-3 PUFAs efficiently prevent endometrial cancer and establish mTORC1/2 as a target of n-3 PUFAs. PMID:24866178

  2. Selective transfer of polyunsaturated fatty acids from phytoplankton to planktivorous fish in large boreal lakes.

    PubMed

    Strandberg, Ursula; Hiltunen, Minna; Jelkänen, Elli; Taipale, Sami J; Kainz, Martin J; Brett, Michael T; Kankaala, Paula

    2015-12-01

    Lake size influences various hydrological parameters, such as water retention time, circulation patterns and thermal stratification that can consequently affect the plankton community composition, benthic-pelagic coupling and the function of aquatic food webs. Although the socio-economical (particularly commercial fisheries) and ecological importance of large lakes has been widely acknowledged, little is known about the availability and trophic transfer of polyunsaturated fatty (PUFA) in large lakes. The objective of this study was to investigate trophic trajectories of PUFA in the pelagic food web (seston, zooplankton, and planktivorous fish) of six large boreal lakes in the Finnish Lake District. Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and α-linolenic acid (ALA) were the most abundant PUFA in pelagic organisms, particularly in the zooplanktivorous fish. Our results show that PUFA from the n-3 family (PUFAn-3), often associated with marine food webs, are also abundant in large lakes. The proportion of DHA increased from ~4±3% in seston to ~32±6% in vendace (Coregonus albula) and smelt (Osmerus eperlanus), whereas ALA showed the opposite trophic transfer pattern with the highest values observed in seston (~11±2%) and the lowest in the opossum shrimp (Mysis relicta) and fish (~2±1%). The dominance of diatoms and cryptophytes at the base of the food web in the study lakes accounted for the high amount of PUFAn-3 in the planktonic consumers. Furthermore, the abundance of copepods in the large lakes explains the effective transfer of DHA to planktivorous fish. The plankton community composition in these lakes supports a fishery resource (vendace) that is very high nutritional quality (in terms of EPA and DHA contents) to humans. PMID:26282609

  3. 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. PMID:27041644

  4. Omega-3 polyunsaturated fatty acid supplementation in the prevention of cardiovascular disease

    PubMed Central

    Walz, Courtney P.; Barry, Arden R.; Koshman, Sheri L.

    2016-01-01

    Introduction: Omega-3 polyunsaturated fatty acids (PUFAs) have purported protective cardiovascular (CV) effects. We sought to assess the evidence available for the use of omega-3 PUFAs for the prevention of cardiovascular disease (CVD). Methods: A systematic literature search was conducted using MEDLINE and EMBASE from 1999 to 2015. Placebo-controlled, randomized controlled trials (RCTs) that enrolled over 1000 patients with follow-up greater than 1 year and meta-analyses of RCTs were included. Results: Eight RCTs and 2 meta-analyses were included. In patients with preexisting CVD, only 1 of 5 included RCTs demonstrated a reduction in CV events with omega-3 PUFAs; however, the effect size was minimal, and the study was limited by an open-label design and lack of placebo control. Two meta-analyses concluded omega-3 PUFAs do not reduce CV events in addition to standard, evidence-based therapy in patients after myocardial infarction. Of the 3 predominantly primary prevention RCTs, only 1 demonstrated a minor reduction in major coronary events; however, it was also an open-label study. Furthermore, the safety of omega-3 PUFAs should be considered. While data from RCTs have not demonstrated serious safety concerns, omega-3 PUFAs can increase the risk of bleeding and may interact with other medications that affect hemostasis, such as antiplatelet agents and warfarin. Discussion and Conclusion: There is currently a lack of evidence to support the routine use of omega-3 PUFAs in the primary and secondary prevention of CVD. Pharmacists are ideally situated to engage patients in the discussion of the lack of benefit and possible risk of omega-3 PUFA supplements. PMID:27212967

  5. Omega-3 polyunsaturated fatty acids and cognition in a college-aged population.

    PubMed

    Karr, Justin E; Grindstaff, Tyler R; Alexander, Joel E

    2012-06-01

    The cognitive influences of omega-3 polyunsaturated fatty acids (n-3 PUFA) remain unclear throughout the life span. Dietary n-3 PUFA appear cognitively beneficial prenatally and neuroprotective at later age; however, researchers using supplementation designs have reported disparate findings across age groups. Few studies have examined the cognitive impact of n-3 PUFA during young adulthood. This study assessed the cognitive effects of fish oil supplementation at college age, hypothesizing benefits on affect, executive control, inhibition, and verbal learning and memory. College-aged participants were assigned to active (n = 20, 5 men; age = 19.9, sage = 1.8) or placebo (n = 21, 7 men; age = 20.4, sage = 1.6) treatments, receiving fish oil (480 mg DHA/720 mg EPA) or coconut oil, respectively. Both groups completed four weeks of supplementation. At baseline and posttreatment, the researchers administered the Rey Auditory Verbal Learning Test (RAVLT; Lezak, 1995), Stroop Color and Word Test (SCWT; Golden & Freshwater, 2002), Trail Making Test (TMT; Corrigan & Hinkeldey, 1987; Gaudino, Geisler, & Squires, 1995; Lezak, 1995), and Positive and Negative Affect Schedule (PANAS; Watson, Clark, & Tellegen, 1988). Repeated-measures ANOVAs indicated no benefits of fish oil on the SCWT, RAVLT Stages 1 to 5, or PANAS. An interaction occurred between condition and time of measurement (i.e., baseline and posttreatment) on RAVLT Stages 6 and 7, and placebo significantly improved TMT performance over fish oil. The benefits of n-3 PUFA on RAVLT performance derived more from depreciated placebo performance than improved performance due to fish oil. The placebo gain on TMT performance likely derived from a learning effect. Together, these results present limited cognitive benefits of n-3 PUFA at college age; however, the treatment may have been subtherapeutic, with a larger sample needed to generalize these results. PMID:22250656

  6. Lack of Dietary Polyunsaturated Fatty Acids Causes Synapse Dysfunction in the Drosophila Visual System.

    PubMed

    Ziegler, Anna B; Ménagé, Cindy; Grégoire, Stéphane; Garcia, Thibault; Ferveur, Jean-François; Bretillon, Lionel; Grosjean, Yael

    2015-01-01

    Polyunsaturated fatty acids (PUFAs) are essential nutrients for animals and necessary for the normal functioning of the nervous system. A lack of PUFAs can result from the consumption of a deficient diet or genetic factors, which impact PUFA uptake and metabolism. Both can cause synaptic dysfunction, which is associated with numerous disorders. However, there is a knowledge gap linking these neuronal dysfunctions and their underlying molecular mechanisms. Because of its genetic manipulability and its easy, fast, and cheap breeding, Drosophila melanogaster has emerged as an excellent model organism for genetic screens, helping to identify the genetic bases of such events. As a first step towards the understanding of PUFA implications in Drosophila synaptic physiology we designed a breeding medium containing only very low amounts of PUFAs. We then used the fly's visual system, a well-established model for studying signal transmission and neurological disorders, to measure the effects of a PUFA deficiency on synaptic function. Using both visual performance and eye electrophysiology, we found that PUFA deficiency strongly affected synaptic transmission in the fly's visual system. These defects were rescued by diets containing omega-3 or omega-6 PUFAs alone or in combination. In summary, manipulating PUFA contents in the fly's diet was powerful to investigate the role of these nutrients on the fly´s visual synaptic function. This study aims at showing how the first visual synapse of Drosophila can serve as a simple model to study the effects of PUFAs on synapse function. A similar approach could be further used to screen for genetic factors underlying the molecular mechanisms of synaptic dysfunctions associated with altered PUFA levels. PMID:26308084

  7. Metabolites derived from omega-3 polyunsaturated fatty acids are important for cardioprotection.

    PubMed

    Gilbert, Kim; Malick, Mandy; Madingou, Ness; Touchette, Charles; Bourque-Riel, Valérie; Tomaro, Leandro; Rousseau, Guy

    2015-12-15

    Although controversial, some data suggest that omega-3 polyunsaturated fatty acids (PUFA) are beneficial to cardiovascular diseases, and could reduce infarct size. In parallel, we have reported that the administration of Resolvin D1 (RvD1), a metabolite of docosahexaenoic acid, an omega-3 PUFA, can reduce infarct size. The present study was designed to determine if the inhibition of two important enzymes involved in the formation of RvD1 from omega-3 PUFA could reduce the cardioprotective effect of omega-3 PUFA. Sprague-Dawley rats were fed with a diet rich in omega-3 PUFA during 10 days before myocardial infarction (MI). Two days before MI, rats received a daily dose of Meloxicam, an inhibitor of cyclooxygenase-2, PD146176, an inhibitor of 15-lipoxygenase, both inhibitors or vehicle. MI was induced by the occlusion of the left coronary artery for 40min followed by reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion while caspase-3, -8 and Akt activities were assessed at 30min of reperfusion. Rats receiving inhibitors, alone or in combination, showed a larger infarct size than those receiving omega-3 PUFA alone. Caspase-3 and -8 activities are higher in ischemic areas with inhibitors while Akt activity is diminished in groups treated with inhibitors. Moreover, the study showed that RvD1 restores cardioprotection when added to the inhibitors. Results from this study indicate that the inhibition of the metabolism of Omega-3 PUFA attenuate their cardioprotective properties. Then, resolvins seem to be an important mediator in the cardioprotection conferred by omega-3 PUFA in our experimental model of MI. PMID:26550951

  8. Dietary n-3 polyunsaturated fatty acids modify fatty acid composition in hepatic and abdominal adipose tissue of sucrose-induced obese rats.

    PubMed

    Alexander-Aguilera, Alfonso; Berruezo, Silvia; Hernández-Diaz, Guillermo; Angulo, Ofelia; Oliart-Ros, Rosamaria

    2011-12-01

    The fatty acid profile of hepatocytes and adipocytes is determined by the composition of the dietary lipids. It remains unclear which fatty acid components contribute to the development or reduction of insulin resistance. The present work examined the fatty acid composition of both tissues in sucrose-induced obese rats receiving fish oil to determine whether the effect of dietary (n-3) polyunsaturated fatty acids (PUFAs) on the reversion of metabolic syndrome in these rats is associated to changes in the fatty acid composition of hepatocyte and adipocyte membrane lipids. Animals with metabolic syndrome were divided into a corn-canola oil diet group and a fish oil diet group, and tissues fatty acids composition were analyzed after 6 weeks of dietary treatment. Fatty acid profiles of the total membrane lipids were modified by the fatty acid composition of the diets fed to rats. N-3 PUFAs levels in animals receiving the fish oil diet plus sucrose in drinking water were significantly higher than in animals under corn-canola oil diets. It is concluded that in sucrose-induced obese rats, consumption of dietary fish oil had beneficial effects on the metabolic syndrome and that such effects would be conditioned by the changes in the n-3 PUFAs composition in hepatic and adipose tissues because they alter membrane properties and modify the type of substrates available for the production of active lipid metabolites acting on insulin resistance and obesity. PMID:21695545

  9. Metabolic engineering of Phaeodactylum tricornutum for the enhanced accumulation of omega-3 long chain polyunsaturated fatty acids☆

    PubMed Central

    Hamilton, Mary L.; Haslam, Richard P.; Napier, Johnathan A.; Sayanova, Olga

    2014-01-01

    We have engineered the diatom Phaeodactylum tricornutum to accumulate the high value omega-3 long chain polyunsaturated fatty acid docosahexaenoic acid (DHA). This was achieved by the generation of transgenic strains in which the Δ5-elongase from the picoalga Ostreococcus tauri was expressed to augment the endogenous fatty acid biosynthetic pathway. Expression of the heterologous elongase resulted in an eight-fold increase in docosahexaenoic acid content, representing a marked and valuable change in the fatty acid profile of this microalga. Importantly, DHA was shown to accumulate in triacylglycerols, with several novel triacylglycerol species being detected in the transgenic strains. In a second iteration, co-expression of an acyl-CoA-dependent Δ6-desaturase with the Δ5-elongase further increased DHA levels. Together, this demonstrates for the first time the potential of using iterative metabolic engineering to optimise omega-3 content in algae. PMID:24333273

  10. A Prospective Study of Dietary Polyunsaturated Fatty Acids and Colorectal Cancer Risk in Chinese women

    PubMed Central

    Murff, Harvey J; Shu, Xiao-Ou; Li, Honglan; Dai, Qi; Kallianpur, Asha; Yang, Gong; Cai, Hui; Wen, Wanqing; Gao, Yu-Tang; Zheng, Wei

    2009-01-01

    In animal models of colon cancer, n-3 polyunsaturated fatty acids (PUFA) have anti-neoplastic properties while n-6 PUFAs may promote carcinogenesis. Prior epidemiological studies have been inconsistent regarding the association of PUFAs and colorectal cancer. We prospectively evaluated the association between PUFA intake and colorectal cancer in a cohort of 73242 Chinese women who were interviewed in person at the baseline survey for the Shanghai Women’s Health Study. Dietary fatty acid consumption was derived using data collected from two food frequency questionnaires administered at baseline and 2 to 3 years later. The dietary total n-6 to n-3 PUFA ratio was strongly associated with colorectal cancer risk. Compared to women in the lowest quintile group, elevated relative risks were observed for the second (RR = 1.52, 95% CI 1.00–2.32); third (RR = 2.20, 1.41–3.45); fourth (RR= 1.65, 0.99–2.75); and fifth (RR= 1.95, 1.07–3.54) quintile groups. Arachidonic acid was associated with colorectal cancer risk with elevated relative risks of 1.20Q2-Q1 (0.87–1.64), 1.44 Q3-Q1 (1.05–1.98), 1.61 Q4-Q1 (1.17–2.23), and 1.39 Q5-Q1 (0.97–1.99) (Ptrend = 0.03) with increasing dietary quintile. In a subset of 150 cancer cases and 150 controls, we found a statistically significant trend between an increasing n-6 to n-3 PUFA ratio and increasing production of prostaglandin E2 as measured by urinary PGE2 metabolites (P = 0.03). These results suggest that dietary PUFA and the ratio of n-6 to n-3 PUFA intake may be positively associated with colorectal cancer risk, and this association may be mediated in part through PGE2 production. PMID:19661088

  11. Milk Yield, Composition, and Fatty Acid Profile in Dairy Cows Fed a High-concentrate Diet Blended with Oil Mixtures Rich in Polyunsaturated Fatty Acids.

    PubMed

    Thanh, Lam Phuoc; Suksombat, Wisitiporn

    2015-06-01

    To evaluate the effects of feeding linseed oil or/and sunflower oil mixed with fish oil on milk yield, milk composition and fatty acid (FA) profiles of dairy cows fed a high-concentrate diet, 24 crossbred primiparous lactating dairy cows in early lactation were assigned to a completely randomized design experiment. All cows were fed a high-concentrate basal diet and 0.38 kg dry matter (DM) molasses per day. Treatments were composed of a basal diet without oil supplement (Control), or diets of (DM basis) 3% linseed and fish oils (1:1, w/w, LSO-FO), or 3% sunflower and fish oils (1:1, w/w, SFO-FO), or 3% mixture (1:1:1, w/w) of linseed, sunflower, and fish oils (MIX-O). The animals fed SFO-FO had a 13.12% decrease in total dry matter intake compared with the control diet (p<0.05). No significant change was detected for milk yield; however, the animals fed the diet supplemented with SFO-FO showed a depressed milk fat yield and concentration by 35.42% and 27.20%, respectively, compared to those fed the control diet (p<0.05). Milk c9, t11-conjugated linoleic acid (CLA) proportion increased by 198.11% in the LSO-FO group relative to the control group (p<0.01). Milk C18:3n-3 (ALA) proportion was enhanced by 227.27% supplementing with LSO-FO relative to the control group (p<0.01). The proportions of milk docosahexaenoic acid (DHA) were significantly increased (p<0.01) in the cows fed LSO-FO (0.38%) and MIX-O (0.23%) compared to the control group (0.01%). Dietary inclusion of LSO-FO mainly increased milk c9, t11-CLA, ALA, DHA, and n-3 polyunsaturated fatty acids (PUFA), whereas feeding MIX-O improved preformed FA and unsaturated fatty acids (UFA). While the lowest n-6/n-3 ratio was found in the LSO-FO, the decreased atherogenecity index (AI) and thrombogenicity index (TI) seemed to be more extent in the MIX-O. Therefore, to maximize milk c9, t11-CLA, ALA, DHA, and n-3 PUFA and to minimize milk n-6/n-3 ratio, AI and TI, an ideal supplement would appear to be either LSO-FO or

  12. Milk Yield, Composition, and Fatty Acid Profile in Dairy Cows Fed a High-concentrate Diet Blended with Oil Mixtures Rich in Polyunsaturated Fatty Acids

    PubMed Central

    Thanh, Lam Phuoc; Suksombat, Wisitiporn

    2015-01-01

    To evaluate the effects of feeding linseed oil or/and sunflower oil mixed with fish oil on milk yield, milk composition and fatty acid (FA) profiles of dairy cows fed a high-concentrate diet, 24 crossbred primiparous lactating dairy cows in early lactation were assigned to a completely randomized design experiment. All cows were fed a high-concentrate basal diet and 0.38 kg dry matter (DM) molasses per day. Treatments were composed of a basal diet without oil supplement (Control), or diets of (DM basis) 3% linseed and fish oils (1:1, w/w, LSO-FO), or 3% sunflower and fish oils (1:1, w/w, SFO-FO), or 3% mixture (1:1:1, w/w) of linseed, sunflower, and fish oils (MIX-O). The animals fed SFO-FO had a 13.12% decrease in total dry matter intake compared with the control diet (p<0.05). No significant change was detected for milk yield; however, the animals fed the diet supplemented with SFO-FO showed a depressed milk fat yield and concentration by 35.42% and 27.20%, respectively, compared to those fed the control diet (p<0.05). Milk c9, t11-conjugated linoleic acid (CLA) proportion increased by 198.11% in the LSO-FO group relative to the control group (p<0.01). Milk C18:3n-3 (ALA) proportion was enhanced by 227.27% supplementing with LSO-FO relative to the control group (p<0.01). The proportions of milk docosahexaenoic acid (DHA) were significantly increased (p<0.01) in the cows fed LSO-FO (0.38%) and MIX-O (0.23%) compared to the control group (0.01%). Dietary inclusion of LSO-FO mainly increased milk c9, t11-CLA, ALA, DHA, and n-3 polyunsaturated fatty acids (PUFA), whereas feeding MIX-O improved preformed FA and unsaturated fatty acids (UFA). While the lowest n-6/n-3 ratio was found in the LSO-FO, the decreased atherogenecity index (AI) and thrombogenicity index (TI) seemed to be more extent in the MIX-O. Therefore, to maximize milk c9, t11-CLA, ALA, DHA, and n-3 PUFA and to minimize milk n-6/n-3 ratio, AI and TI, an ideal supplement would appear to be either LSO-FO or

  13. Effect of omega-3 polyunsaturated fatty acid treatment over mechanical allodynia and depressive-like behavior associated with experimental diabetes.

    PubMed

    Redivo, Daiany D B; Schreiber, Anne K; Adami, Eliana R; Ribeiro, Deidiane E; Joca, Samia R L; Zanoveli, Janaína M; Cunha, Joice M

    2016-02-01

    Neuropathic pain and depression are very common comorbidities in diabetic patients. As the pathophysiological mechanisms are very complex and multifactorial, current treatments are only symptomatic and often worsen the glucose control. Thus, the search for more effective treatments are extremely urgent. In this way, we aimed to investigate the effect of chronic treatment with fish oil (FO), a source of omega-3 polyunsaturated fatty acid, over the mechanical allodynia and in depressive-like behaviors in streptozotocin-diabetic rats. It was observed that the diabetic (DBT) animals, when compared to normoglycemic (NGL) animals, developed a significant mechanical allodynia since the second week after diabetes induction, peaking at fourth week which is completely prevented by FO treatment (0.5, 1 or 3g/kg). Moreover, DBT animals showed an increase of immobility frequency and a decrease of swimming and climbing frequencies in modified forced swimming test (MFST) since the second week after diabetes injection, lasting up at the 4th week. FO treatment (only at a dose of 3g/kg) significantly decreased the immobility frequency and increased the swimming frequency, but did not induce significant changes in the climbing frequency in DBT rats. Moreover, it was observed that DBT animals had significantly lower levels of BDNF in both hippocampus and pre frontal cortex when compared to NGL rats, which is completely prevented by FO treatment. In conclusion, our study demonstrates that FO treatment was able to prevent the mechanical allodynia and the depressive-like behaviors in DBT rats, which seems to be related to its capacity of BDNF level restoration. PMID:26546881

  14. Hormonal and metabolic effects of polyunsaturated fatty acid (omega-3) on polycystic ovary syndrome induced rats under diet

    PubMed Central

    Ouladsahebmadarek, Elaheh; Khaki, Arash; Khanahmadi, Sharareh; Ahmadi Ashtiani, Hamidreza; Paknejad, Pooya; Ayubi, Mohammad Reza

    2014-01-01

    Objective(s): PCOS (polycystic ovary syndrome) produces symptoms in approximately 5% to 10% of women of reproductive age (12–45 years old). It is thought to be one of the leading causes of female subfertility. This study aimed to confirm the role of nutrition containing omega-3 (polyunsaturated fatty acid) on control of experimental PCO induced by estradiol-valerat in rats. Materials and Methods: Wistar female rats (n=40) were allocated into control (n=10) and test groups (n= 30), test group was subdivided into 3 groups: G1, received omega-3 (240 mg/kg/orally/daily); G2 and G3 groups were induced PCO by single injection of estradiol-valerate (16 mg/kg/IM). Group 3 received omega-3 (240 mg/kg/orally/daily) and low carbohydrate feeding for 60 subsequent days; on sixtieth day 5 ml blood samples and ovarian tissues of all rats in the group were removed and prepared for biochemical and hormonal analysis. Results: Catalase, GPX (Glutathione peroxidase), SOD (Superoxide dismutase) in groups that received omega-3 showed higher levels, but MDA (malondialdehyde) level was significantly decreased (P<0.05) in comparison with other experimental groups. Ovarian weights in both experimental and control groups were similar (P<0.05). Level of serum FSH (follicle stimulating hormone) was decreased, but level of testosterone was significantly increased (P<0.05) in PCO group in comparison with control and omega-3 groups. Conclusion: Results revealed that administration of omega-3 plus lower carbohydrate food significantly controlled   PCO syndrome and balanced FSH and testosterone. PMID:24711896

  15. Growth Inhibitory Effect of Polyunsaturated Fatty Acids (PUFAs) on Colon Cancer Cells via Their Growth Inhibitory Metabolites and Fatty Acid Composition Changes

    PubMed Central

    Zhang, Chengcheng; Yu, Haining; Ni, Xiaofeng; Shen, Shengrong; Das, Undurti N.

    2015-01-01

    Background Colorectal cancer is common. Polyunsaturated fatty acids (PUFAs) exert growth-inhibitory and pro-apoptotic effects on colon cancer cells. Metabolites of PUFAs such as prostaglandins (PGs), leukotrienes (LTs) and lipoxins (LXs) play a significant role in colon cancer. Methods Human colon cancer LoVo and RKO cells were cultured with different concentration of PUFAs and 5-fluorouracil (5-FU) in vitro. Cell morphological changes, fatty acid composition, formation of PGE2, LTB4 and LXA4 and expression of COX-2, ALOX5, PGD synthase (PGDS), microsomal prostaglandin E synthase (mPGES) were assessed in LoVo and RKO cells when supplemented with PUFAs and 5-FU. Results PUFAs and 5-FU inhibited growth of LoVo and RKO cells to the same extent at the doses used and produced significant alterations in their shape. As expected, higher concentrations of supplemented PUFAs were noted in the cells compared to control. LA, GLA, AA, ALA and EPA supplementation to LoVo cells suppressed production of PGE2, LTB4,and ALOX5, mPGES expression, but enhanced that of LXA4; whereas DHA enhanced PGE2 and LXA4 synthesis but decreased LTB4 formation and COX-2, ALOX5, mPGES expression. In contrast, 5-FU enhanced formation of PGE2, LTB4 and mPGES expression, but suppressed LXA4 synthesis and COX-2 expression. PGE2, LTB4 synthesis and ALOX5 expression was suppressed by LA, GLA, ALA and DHA; whereas AA, EPA and 5-FU enhanced PGE2 but paradoxically AA decreased and EPA and 5-FU enhanced LTB4 synthesis in RKO cells. All the PUFAs tested enhanced, while 5-FU decreased LXA4 formation in RKO cells; whereas GLA, AA, and 5-FU augmented while LA, ALA, EPA and DHA enhanced COX-2 expression in RKO cells. Conclusions Tumoricidal action of PUFAs on colorectal LoVo and RKO cancer cells in vitro was associated with increased formation of LXA4, decreased synthesis of PGE2 and LTB4 and suppressed expression of COX-2, ALOX5, mPGES, whereas 5-FU produced contrasting actions on these indices. PMID:25886460

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2016-01-01

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

  18. 18-carbon polyunsaturated fatty acids ameliorate palmitate-induced inflammation and insulin resistance in mouse C2C12 myotubes.

    PubMed

    Chen, Pei-Yin; Wang, John; Lin, Yi-Chin; Li, Chien-Chun; Tsai, Chia-Wen; Liu, Te-Chung; Chen, Haw-Wen; Huang, Chin-Shiu; Lii, Chong-Kuei; Liu, Kai-Li

    2015-05-01

    Skeletal muscle is a major site of insulin action. Intramuscular lipid accumulation results in inflammation, which has a strong correlation with skeletal muscle insulin resistance (IR). The aim of this study was to explore the effects of linoleic acid, alpha-linolenic acid, and gamma-linolenic acid (GLA), 18-carbon polyunsaturated fatty acids (PUFAs), on palmitic acid (PA)-induced inflammatory responses and IR in C2C12 myotubes. Our data demonstrated that these three test 18-carbon PUFAs can inhibit PA-induced interleukin-6 and tumor necrosis factor-α messenger RNA (mRNA) expression and IR as evidenced by increases in phosphorylated AKT and the 160-kD AKT substrate, mRNA and plasma membrane protein expression of glucose transporter 4, and glucose uptake. Moreover, the 18-carbon PUFAs blocked the effects of PA on activation of mitogen-activated protein kinases (MAPKs), protein kinase C-θ (PKC-θ), AMP-activated protein kinase (AMPK) and nuclear factor-κB (NF-κB). Of note, supplementation with GLA-rich borage oil decreased proinflammatory cytokine production and hindered the activation of MAPKs, PKC-θ and NF-κB in the skeletal muscles of diabetic mice. The 18-carbon PUFAs did not reverse PA-induced inflammation or IR in C2C12 myotubes transfected with a constitutively active mutant IκB kinase-β plasmid, which suggests the importance of the inhibition of NF-κB activation by the 18-carbon PUFAs. Moreover, blockade of AMPK activation by short hairpin RNA annulled the inhibitory effects of the 18-carbon PUFAs on PA-induced IR but not inflammation. Our findings suggest that the 18-carbon PUFAs may be useful in the management of PA-induced inflammation and IR in myotubes. PMID:25687616

  19. N-3 polyunsaturated fatty acids inhibit IFN-γ-induced IL-18 binding protein production by prostate cancer cells.

    PubMed

    Wang, Xiaofeng; Breeze, Andrew; Kulka, Marianna

    2015-02-01

    Prostate cancer cells can produce IL-18 binding protein (IL-18BP) in response to interferon-γ (IFN-γ), which may function to neutralize IL-18, an anti-tumor factor formerly known as IFN-γ inducing factor. The consumption of n-3 polyunsaturated fatty acids (PUFAs) has been associated with a lower risk of certain types of cancer including prostate cancer, although the precise mechanisms of this effect are poorly understood. We hypothesized that n-3 PUFAs could modify IL-18BP production by prostate cancer cells by altering IFN-γ receptor-mediated signal transduction. Here, we demonstrate that n-3 PUFA treatment significantly reduced IFN-γ-induced IL-18BP production by DU-145 and PC-3 prostate cancer cells by inhibiting IL-18BP mRNA expression and was associated with a reduction in IFN-γ receptor expression. Furthermore, IFN-γ-induced phosphorylation of Janus kinase 1 (JAK1), signal transducers and activators of transcription 1 (STAT1), extracellular signal-regulated kinases 1/2 (ERK1/2), and P38 were suppressed by n-3 PUFA treatment. By contrast, n-6 PUFA had no effect on IFN-γ receptor expression, but decreased IFN-γ-induced IL-18BP production and IFN-γ stimulation of JAK1, STAT1, ERK1/2, and JNK phosphorylation. These data indicate that both n-3 and n-6 PUFAs may be beneficial in prostate cancer by altering IFN-γ signaling, thus inhibiting IL-18BP production and thereby rendering prostate cancer cells more sensitive to IL-18-mediated immune responses. PMID:25351720

  20. Effects of Polyunsaturated Fatty Acid Treatment on Postdischarge Outcomes After Acute Myocardial Infarction.

    PubMed

    Greene, Stephen J; Temporelli, Pier Luigi; Campia, Umberto; Vaduganathan, Muthiah; Degli Esposti, Luca; Buda, Stefano; Veronesi, Chiara; Butler, Javed; Nodari, Savina

    2016-02-01

    Clinical trials studying the efficacy of n-3 polyunsaturated fatty acids (PUFA) in reducing adverse events after acute myocardial infarction (AMI) have yielded conflicting results, and data regarding the influence of n-3 PUFA treatment after AMI in routine clinical practice are scarce. We conducted a retrospective observational cohort study including patients from 5 Italian Local Health Units who were discharged from the hospital with a primary diagnosis of AMI from January 1, 2010, to December 31, 2011. Using unique patient identifiers, patients were linked across governmental hospital discharge, medication prescription, and mortality databases and followed for 12-months post-index discharge. Patient characteristics and risk of all-cause mortality and repeat AMI were compared by n-3 PUFA prescription after discharge (for outcome analyses, defined as ≥ 2 prescriptions) at a presumed dose of 1 g/day. Overall, 11,269 patients met inclusion criteria, of which 2,425 patients (21.5%) were prescribed n-3 PUFA during follow-up. Patients treated with n-3 PUFA tended to be younger, men, and carry a diagnosis of diabetes and were more likely to be receiving guideline-recommended post-AMI medical therapy, including β blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, statins, and antiplatelet therapy (all p <0.001). After adjusting for patient characteristics and concurrent therapies, n-3 PUFA treatment was associated with reduced all-cause mortality (hazard ratio 0.76, 95% CI 0.59 to 0.97) and recurrent AMI (hazard ratio 0.65, 95% CI 0.49 to 0.87) through 12-month follow-up. In conclusion, in this large, contemporary, observational study of "real-world" Italian patients hospitalized for AMI, the use of n-3 PUFA was independently associated with a robust reduction in all-cause mortality and recurrent AMI. These data support further randomized controlled trials with n-3 PUFA therapy in the post-AMI setting. PMID:26708689

  1. Aberrant serum polyunsaturated fatty acids profile is relevant with acute coronary syndrome.

    PubMed

    Sakamoto, Atsushi; Saotome, Masao; Hosoya, Natsuko; Kageyama, Shigetaka; Yoshizaki, Toru; Takeuchi, Ryosuke; Murata, Koichiro; Nawada, Ryuzo; Onodera, Tomoya; Takizawa, Akinori; Satoh, Hiroshi; Hayashi, Hideharu

    2016-08-01

    Although a robust relationship between aberrant serum polyunsaturated fatty acids (PUFAs) profile and coronary artery disease (CAD) has been reported, the details concerning the association between aberrant PUFAs profile and clinical feature of CAD are not fully discovered. Therefore, we investigated the relationship between serum PUFAs and clinical profiles in CAD patients. We classified 595 consecutive CAD patients, who underwent coronary angiography into 3 groups according to the clinical profiles of CAD (group A: early phase ACS, n = 96; group B: stable CAD with previous history of ACS, n = 259; group C: stable CAD without previous history of ACS, n = 240) and measured serum n-3 [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and n-6 [arachidonic acid (AA)] PUFAs. Serum EPA, DHA, and EPA/AA ratio were significantly low in the order of group A < B < C [EPA; 48.1 (34.1-60.3) μg/ml, 61.7 (41.2-94.5) μg/ml, and 74.4 (52.7-104.9) μg/ml, DHA; 113.1 (92.8-135.1) μg/ml, 125.8 (100.4-167.2) μg/ml, and 140.1 (114.7-177.0) μg/ml, EPA/AA ratio; 0.31 (0.22-0.45), 0.39 (0.26-0.62), and 0.44 (0.31-0.69), medians with interquartile range, p < 0.01]. Multiple regression analysis revealed that EPA (p = 0.009) and EPA/AA ratio (p = 0.023), but not DHA and DHA/AA ratio, were negatively associated with clinical profiles of ACS in CAD patients. Significant correlation was not observed between PUFAs profile and severity of coronary stenosis. Low serum EPA and EPA/AA ratio correlates with clinical profiles of ACS in patients with CAD, regardless of the extent and severity of coronary artery stenosis. PMID:26233644

  2. Impact of saturated, polyunsaturated and monounsaturated fatty acid-rich micelles on lipoprotein synthesis and secretion in Caco-2 cells.

    PubMed

    Jackson, Kim G; Bateman, Paul A; Yaqoob, Parveen; Williams, Christine M

    2009-12-01

    Meal fatty acids have been shown to modulate the size and composition of triacylglycerol (TAG)-rich lipoproteins influencing the magnitude and duration of the postprandial plasma TAG response. As a result there is considerable interest in the origin of these meal fatty-acid induced differences in particle composition. Caco-2 cells were incubated over 4 days with fatty acid mixtures resembling the composition of saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acid (PUFA)-rich meals fed in a previous postprandial study to determine their impact on lipoprotein synthesis and secretion. The MUFA- and PUFA-rich mixtures supported greater intracellular TAG, but not cholesterol accumulation compared with the SFA-rich mixture (P < 0.001). The MUFA-rich mixture promoted significantly greater TAG and cholesterol secretion than the other mixtures and significantly more apolipoprotein B-100 secretion than the PUFA-rich mixture (P < 0.05). Electron microscopy revealed the SFA-rich mixture had led to unfavourable effects on cellular morphology, compared with the unsaturated fatty acid-rich mixtures. Our findings suggest the MUFA-rich mixture, may support the formation of a greater number of TAG-rich lipoproteins, which is consistent with indirect observations from our human study. Our electron micrographs are suggestive that some endocytotic uptake of MUFA-rich taurocholate micelles may promote greater lipoprotein synthesis and secretion in Caco-2 cells. PMID:19898980

  3. A novel oriented immobilized lipase on magnetic nanoparticles in reverse micelles system and its application in the enrichment of polyunsaturated fatty acids.

    PubMed

    Liu, Tao; Zhao, Yuandi; Wang, Xiaofeng; Li, Xiang; Yan, Yunjun

    2013-03-01

    A novel oriented immobilized lipase was derived from Yarrowia lipolytica lipase LIP2 covalently immobilized on functionalized Fe3O4 magnetic nanoparticles (MNPs) in reverse micelles system (RMS). The activity recovery reached 382% compared with 29% in aqueous phase, and further ran up to 1425% under optimum conditions. (3-Aminopropyl) triethoxysilane (APTES) coated Fe3O4 nanoparticles were characterized by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). A significant alteration in the secondary structure of the lipase in RMS with a 15.5% increase of α-helix content and a 12.5% decrease of β-sheet content was detected by circular dichroism (CD). The immobilized lipase was employed to enrich polyunsaturated fatty acids in fish oil, a 90% increase of DHA content was obtained after 12h, and after 20 cycles of successive usage, it still remained over 80% of relative hydrolysis degree, which shows a good recyclability. PMID:23395761

  4. Identification and Functional Characterization of Genes Encoding Omega-3 Polyunsaturated Fatty Acid Biosynthetic Activities from Unicellular Microalgae

    PubMed Central

    Vaezi, Royah; Napier, Johnathan A.; Sayanova, Olga

    2013-01-01

    In order to identify novel genes encoding enzymes involved in the biosynthesis of nutritionally important omega-3 long chain polyunsaturated fatty acids, a database search was carried out in the genomes of the unicellular photoautotrophic green alga Ostreococcus RCC809 and cold-water diatom Fragilariopsis cylindrus. The search led to the identification of two putative “front-end” desaturases (Δ6 and Δ4) from Ostreococcus RCC809 and one Δ6-elongase from F. cylindrus. Heterologous expression of putative open reading frames (ORFs) in yeast revealed that the encoded enzyme activities efficiently convert their respective substrates: 54.1% conversion of α-linolenic acid for Δ6-desaturase, 15.1% conversion of 22:5n-3 for Δ4-desaturase and 38.1% conversion of γ-linolenic acid for Δ6-elongase. The Δ6-desaturase from Ostreococcus RCC809 displays a very strong substrate preference resulting in the predominant synthesis of stearidonic acid (C18:4Δ6,9,12,15). These data confirm the functional characterization of omega-3 long chain polyunsaturated fatty acid biosynthetic genes from these two species which have until now not been investigated for such activities. The identification of these new genes will also serve to expand the repertoire of activities available for metabolically engineering the omega-3 trait in heterologous hosts as well as providing better insights into the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in marine microalgae. PMID:24351909

  5. Identification and functional characterization of genes encoding omega-3 polyunsaturated fatty acid biosynthetic activities from unicellular microalgae.

    PubMed

    Vaezi, Royah; Napier, Johnathan A; Sayanova, Olga

    2013-12-01

    In order to identify novel genes encoding enzymes involved in the biosynthesis of nutritionally important omega-3 long chain polyunsaturated fatty acids, a database search was carried out in the genomes of the unicellular photoautotrophic green alga Ostreococcus RCC809 and cold-water diatom Fragilariopsis cylindrus. The search led to the identification of two putative "front-end" desaturases (Δ6 and Δ4) from Ostreococcus RCC809 and one Δ6-elongase from F. cylindrus. Heterologous expression of putative open reading frames (ORFs) in yeast revealed that the encoded enzyme activities efficiently convert their respective substrates: 54.1% conversion of α-linolenic acid for Δ6-desaturase, 15.1% conversion of 22:5n-3 for Δ4-desaturase and 38.1% conversion of γ-linolenic acid for Δ6-elongase. The Δ6-desaturase from Ostreococcus RCC809 displays a very strong substrate preference resulting in the predominant synthesis of stearidonic acid (C18:4Δ6,9,12,15). These data confirm the functional characterization of omega-3 long chain polyunsaturated fatty acid biosynthetic genes from these two species which have until now not been investigated for such activities. The identification of these new genes will also serve to expand the repertoire of activities available for metabolically engineering the omega-3 trait in heterologous hosts as well as providing better insights into the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in marine microalgae. PMID:24351909

  6. n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice

    PubMed Central

    Cutuli, Debora; De Bartolo, Paola; Caporali, Paola; Laricchiuta, Daniela; Foti, Francesca; Ronci, Maurizio; Rossi, Claudia; Neri, Cristina; Spalletta, Gianfranco; Caltagirone, Carlo; Farioli-Vecchioli, Stefano; Petrosini, Laura

    2014-01-01

    As major components of neuronal membranes, omega-3 polyunsaturated acids (n-3 PUFA) exhibit a wide range of regulatory functions, modulating from synaptic plasticity to neuroinflammation, from oxidative stress to neuroprotection. Recent human and animal studies indicated the n-3 PUFA neuroprotective properties in aging, with a clear negative correlation between n-3 PUFA levels and hippocampal deficits. The present multidimensional study was aimed at associating cognition, hippocampal neurogenesis, volume, neurodegeneration and metabolic correlates to verify n-3 PUFA neuroprotective effects in aging. To this aim 19 month-old mice were given n-3 PUFA mixture, or olive oil or no dietary supplement for 8 weeks during which hippocampal-dependent mnesic functions were tested. At the end of behavioral testing morphological and metabolic correlates were analyzed. n-3 PUFA supplemented aged mice exhibited better object recognition memory, spatial and localizatory memory, and aversive response retention, without modifications in anxiety levels in comparison to controls. These improved hippocampal cognitive functions occurred in the context of an enhanced cellular plasticity and a reduced neurodegeneration. In fact, n-3 PUFA supplementation increased hippocampal neurogenesis and dendritic arborization of newborn neurons, volume, neuronal density and microglial cell number, while it decreased apoptosis, astrocytosis and lipofuscin accumulation in the hippocampus. The increased levels of some metabolic correlates (blood Acetyl-L-Carnitine and brain n-3 PUFA concentrations) found in n-3 PUFA supplemented mice also pointed toward an effective neuroprotection. On the basis of the present results n-3 PUFA supplementation appears to be a useful tool in health promotion and cognitive decline prevention during aging. PMID:25202271

  7. Effects of Polyunsaturated Fatty Acids in Growth Medium on Lipid Composition and on Physicochemical Surface Properties of Lactobacilli

    PubMed Central

    Kankaanpää, P.; Yang, B.; Kallio, H.; Isolauri, E.; Salminen, S.

    2004-01-01

    Most probiotic lactobacilli adhere to intestinal surfaces, a phenomenon influenced by free polyunsaturated fatty acids (PUFA). The present study investigated whether free linoleic acid, γ-linolenic acid, arachidonic acid, α-linolenic acid, or docosahexaenoic acid in the growth medium alters the fatty acid composition of lactobacilli and their physical characteristics. The most abundant bacterial fatty acids identified were oleic, vaccenic, and dihydrosterculic acids. PUFA, especially conjugated linoleic acid (CLA) isomers and γ-linolenic, eicosapentaenoic, docosahexaenoic, and α-linolenic acids, also were identified in lactobacilli. When lactobacilli were cultured in MRS broth supplemented with various free PUFA, the incorporation of a given PUFA into bacterial fatty acids was clearly observed. Moreover, PUFA supplementation also resulted in PUFA-dependent changes in the proportions of other fatty acids; major interconversions were seen in octadecanoic acids (18:1), their methylenated derivatives (19:cyc), and CLA. Intermittent changes in eicosapentaenoic acid proportions also were noted. These results were paralleled by minor changes in the hydrophilic or hydrophobic characteristics of lactobacilli, suggesting that PUFA interfere with microbial adhesion to intestinal surfaces through other mechanisms. In conclusion, we have demonstrated that free PUFA in the growth medium induce changes in bacterial fatty acids in relation to the regulation of the degree of fatty acid unsaturation, cyclization, and proportions of CLA and PUFA containing 20 to 22 carbons. The potential role of lactobacilli as regulators of PUFA absorption may represent another means by which probiotics could redirect the delicate balance of inflammatory mediators derived from PUFA within the inflamed intestine. PMID:14711634

  8. Immune response, productivity and quality of milk from grazing goats as affected by dietary polyunsaturated fatty acid supplementation.

    PubMed

    Caroprese, Mariangela; Ciliberti, Maria Giovana; Santillo, Antonella; Marino, Rosaria; Sevi, Agostino; Albenzio, Marzia

    2016-04-01

    This study was undertaken to assess how diet supplemented with fish oil and linseed improve the immune profile, the production performance, and milk quality of grazing goats by a diet supplementation of fish oil or linseed. Twenty-four Garganica grazing goats were divided into three groups named control (CON), fish oil (FO) and linseed (LIN) according to the fat supplement received in their diet. In vivo immune responses were evaluated by monitoring cell-mediated and humoral immune responses in order to verify the effects of polyunsaturated fatty acids supplementation on goats' health status. Goat milk samples were analysed weekly to determine milk chemical composition, fatty acid profile, and somatic cell count. Diet based on linseed supplementation (LIN) significantly increased milk yield by 30%, milk fat yield by 67%, protein yield by 34%, and casein yield by 41% as compared with CON. Fat content increased by 30% in LIN milk as compared with CON milk, and by 12% as compared with FO milk. Linseed modified milk fatty acid profile; LIN milk showed lower SFA and higher PUFA than FO milk. The modified fatty acid composition of LIN milk resulted in lower AI and TI indexes than FO and CON milk. Linseed and fish oil administration can reduce humoral immunity of goats, but has no effect in their cellular immunity. Dietary linseed supplementation in grazing dairy goat supports feeding programs to improve milk composition and quality, and a modulation of their immune responses. PMID:27033938

  9. Genomic Analysis of Genes Involved in the Biosynthesis of Very Long Chain Polyunsaturated Fatty Acids in Thraustochytrium sp. 26185.

    PubMed

    Zhao, Xianming; Dauenpen, Meesapyodsuk; Qu, Cunmin; Qiu, Xiao

    2016-09-01

    Thraustochytrium sp. 26185 is a marine protist that can produce a large amount of docosahexaenoic acid (DHA, 22:6n-3), an ω3 very long chain polyunsaturated fatty acid (VLCPUFA) of nutritional importance. However, the mechanism of how this fatty acid is synthesized and assembled into the storage lipid triacylglycerol is unclear. Here we report sequencing of the whole genome and genomic analysis of genes involved in the biosynthesis and assembly of the fatty acids in this species. Genome sequencing produced a total of 2,418,734,139 bp clean sequences with about 62 fold genome coverage. Annotation of the genome sequences revealed 10,797 coding genes. Among them, 10,216 genes could be assigned into 25 KOG classes where 451 genes were specifically assigned to the group of lipid transport and metabolism. Detailed analysis of these genes revealed co-existence of both aerobic pathway and anaerobic pathways for the biosynthesis of DHA in this species. However, in the aerobic pathway, a key gene encoding stearate Δ9 desaturase introducing the first double bond to long chain saturated fatty acid 18:0 was missing from the genome. Genomic survey of genes involved in the acyl trafficking among glycerolipids showed that, unlike plants, this protist did not possess phosphatidylcholine:diacylglycerol cholinephosphotransferase, an important enzyme in bridging two types of glycerolipids, diacylglycerols (DAG) and phosphatidylcholines (PtdCho). These results shed new insight on the biosynthesis and assembly of VLCPUFA in the Thraustochytrium. PMID:27514858

  10. Diets containing long-chain n-3 polyunsaturated fatty acids affect behaviour differently during development than ageing in mice.

    PubMed

    Carrié, I; Guesnet, P; Bourre, J M; Francès, H

    2000-04-01

    The effect of a standard diet providing essential fatty acids enriched in fish oil or palm oil was studied in young, mature and old mice. Two groups of pregnant and lactating OF1 mice were fed on diets with or without high levels of long-chain n-3 polyunsaturated fatty acids. Offspring were maintained on these diets after weaning. The litter size did not differ. The weight increased more quickly in fish-oil-fed mice than palm-oil-fed mice. The fish-oil diet induced a significant increase in exploratory activity in young mice which was not found in mature and old mice. The level of locomotor activity was significantly higher in young, no different in mature, and lower in old fish-oil-fed mice than in controls. Habituation, the simpler form of learning, occurred to the same extent in the two diet groups. For the place learning protocol of the Morris water maze there was no difference between the two diet groups; however, in the probe trial, the mature fish-oil-fed mice remembered the situation well compared with the control mice. In the active avoidance test, on the first day of acquisition the young fish-oil-fed mice made more avoidances than control mice, whereas in contrast, mature and old-fish-fed mice made less avoidances than control mice. These results suggest a positive effect on arousal and learning ability of a diet enriched in long chain n-3 polyunsaturated fatty acids in young mice and a detrimental effect in old mice. PMID:10858702