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Sample records for chain polyunsaturated fatty

  1. 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

  2. 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...

  3. 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

  4. Long-chain polyunsaturated fatty acid sources and evaluation of their nutritional and functional properties

    PubMed Central

    Abedi, Elahe; Sahari, Mohammad Ali

    2014-01-01

    Recent studies have clearly shown the importance of polyunsaturated fatty acids (as essential fatty acids) and their nutritional value for human health. In this review, various sources, nutritional properties, and metabolism routes of long-chain polyunsaturated fatty acids (LC-PUFA) are introduced. Since the conversion efficiency of linoleic acid (LA) to arachidonic acid (AA) and also α-linolenic acid (ALA) to docosahexaenoic acid (DHA) and eicosatetraenoic acid (EPA) is low in humans, looking for the numerous sources of AA, EPA and EPA fatty acids. The sources include aquatic (fish, crustaceans, and mollusks), animal sources (meat, egg, and milk), plant sources including 20 plants, most of which were weeds having a good amount of LC-PUFA, fruits, herbs, and seeds; cyanobacteria; and microorganisms (bacteria, fungi, microalgae, and diatoms). PMID:25473503

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  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. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  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. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

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

    PubMed

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

    2016-04-01

    Long-chain polyunsaturated fatty acids (LC-PUFA) are major components of complex lipid molecules and are also involved in numerous critical biological processes. Studies conducted mainly in vertebrates have demonstrated that LC-PUFA can be biosynthesized through the concerted action of two sets of enzymes, namely fatty acyl desaturases (Fads) and elongation of very long-chain fatty acid (Elovl) proteins. While LC-PUFA research is a thriving field, mainly focused on human health, an integrated view regarding the evolution of LC-PUFA biosynthetic genetic machinery in chordates is yet to be produced. Particularly important is to understand whether lineage specific life history trajectories, as well as major biological transitions, or particular genomic processes such as genome duplications have impacted the evolution of LC-PUFA biosynthetic pathways. Here we review the gene repertoire of Fads and Elovl in chordate genomes and the diversity of substrate specificities acquired during evolution. We take advantage of the magnitude of genomic and functional data to show that combination duplication processes and functional plasticity have generated a wide diversity of physiological capacities in extant lineages. A clear evolutionary framework is provided, which will be instrumental for the full clarification of functional capacities between the various vertebrate groups. PMID:26769304

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  13. BMI Affects the Relationship between Long Chain N-3 Polyunsaturated Fatty Acid Intake and Stroke Risk: a Meta-Analysis.

    PubMed

    Cheng, Pengfei; Huang, Wen; Bai, Shunjie; Wu, Yu; Yu, Jia; Zhu, Xiaofeng; Qi, Zhiguo; Shao, Weihua; Xie, Peng

    2015-01-01

    We performed a meta-analysis to clarify the relationship between long chain n-3 polyunsaturated fatty acid (PUFA) intake and stroke risk. Relevant studies were identified by searching online databases through May 2015. Log relative risks (RRs) of the highest versus the lowest for cohort studies were weighed by the inverse variance method to obtain pooled RRs. Fourteen prospective cohort studies including 514,483 individuals and 9,065 strokes were included. The pooled RR of overall stroke risk for long chain n-3 PUFA intake was 0.87 [95% confidence interval (CI), 0.79-0.95]. Stratification analysis showed that higher long chain n-3 PUFAs intake was associated with reduced fatal stroke risk (RR = 0.84; 95% CI, 0.73-0.97), reduced stroke risk for BMI < 24 (RR = 0.86; 95% CI, 0.75-0.98) and reduced stroke risk for females (RR = 0.81; 95% CI, 0.71-0.92), but was not associated with stroke risk for either BMI ≥ 24 or men. This meta-analysis reveals that higher long chain n-3 PUFA intake is inversely associated with risk of stroke morbidity and mortality with BMI and sex as key factors influencing this risk. Individuals should be encouraged to manage their body weight while increasing their intake of long chain n-3 PUFAs. PMID:26369699

  14. BMI Affects the Relationship between Long Chain N-3 Polyunsaturated Fatty Acid Intake and Stroke Risk: a Meta-Analysis

    PubMed Central

    Cheng, Pengfei; Huang, Wen; Bai, Shunjie; Wu, Yu; Yu, Jia; Zhu, Xiaofeng; Qi, Zhiguo; Shao, Weihua; Xie, Peng

    2015-01-01

    We performed a meta-analysis to clarify the relationship between long chain n-3 polyunsaturated fatty acid (PUFA) intake and stroke risk. Relevant studies were identified by searching online databases through May 2015. Log relative risks (RRs) of the highest versus the lowest for cohort studies were weighed by the inverse variance method to obtain pooled RRs. Fourteen prospective cohort studies including 514,483 individuals and 9,065 strokes were included. The pooled RR of overall stroke risk for long chain n-3 PUFA intake was 0.87 [95% confidence interval (CI), 0.79–0.95]. Stratification analysis showed that higher long chain n-3 PUFAs intake was associated with reduced fatal stroke risk (RR = 0.84; 95% CI, 0.73–0.97), reduced stroke risk for BMI < 24 (RR = 0.86; 95% CI, 0.75–0.98) and reduced stroke risk for females (RR = 0.81; 95% CI, 0.71–0.92), but was not associated with stroke risk for either BMI ≥ 24 or men. This meta-analysis reveals that higher long chain n-3 PUFA intake is inversely associated with risk of stroke morbidity and mortality with BMI and sex as key factors influencing this risk. Individuals should be encouraged to manage their body weight while increasing their intake of long chain n-3 PUFAs. PMID:26369699

  15. Altered development and function of the placental regions in preeclampsia and its association with long-chain polyunsaturated fatty acids.

    PubMed

    Rani, Alka; Wadhwani, Nisha; Chavan-Gautam, Preeti; Joshi, Sadhana

    2016-09-01

    The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from the mother to the fetus. Nutrients taken up by the placenta are required for its own growth and development and to optimize fetal growth. Hence, placental function is an important determinant of pregnancy outcome. Among various nutrients, fatty acids, especially long-chain polyunsaturated fatty acids (LCPUFAs), including omega 3 and omega 6 fatty acids, are essential for placental development from the time of implantation. Studies have associated these LCPUFAs with placental development through their roles in regulating oxidative stress, angiogenesis, and inflammation, which may in turn influence their transfer to the fetus. The placenta has a heterogeneous morphology with variable regional vasculature, oxidative stress, and LCPUFA levels in healthy pregnancies depending upon the location within the placenta. However, these regional structural and functional parameters are found to be disturbed in pathological conditions, such as preeclampsia (PE), thereby affecting pregnancy outcome. Hence, the alterations in LCPUFA metabolism and transport in different regions of the PE placenta as compared with normal placenta could potentially be contributing to the pathological features of PE. The regional variations in development and function of the placenta and its possible association with placental LCPUFA metabolism and transport in normal and PE pregnancies are discussed in this review. WIREs Dev Biol 2016, 5:582-597. doi: 10.1002/wdev.238 For further resources related to this article, please visit the WIREs website. PMID:27239793

  16. Identification of a Long-Chain Polyunsaturated Fatty Acid Acyl-Coenzyme A Synthetase from the Diatom Thalassiosira pseudonana1

    PubMed Central

    Tonon, Thierry; Qing, Renwei; Harvey, David; Li, Yi; Larson, Tony Robert; Graham, Ian Alexander

    2005-01-01

    The draft genome of the diatom Thalassiosira pseudonana was searched for DNA sequences showing homology with long-chain acyl-coenzyme A synthetases (LACSs), since the corresponding enzyme may play a key role in the accumulation of health-beneficial polyunsaturated fatty acids (PUFAs) in triacylglycerol. Among the candidate genes identified, an open reading frame named TplacsA was found to be full length and constitutively expressed during cell cultivation. The predicted amino acid sequence of the corresponding protein, TpLACSA, exhibited typical features of acyl-coenzyme A (acyl-CoA) synthetases involved in the activation of long-chain fatty acids. Feeding experiments carried out in yeast (Saccharomyces cerevisiae) transformed with the algal gene showed that TpLACSA was able to activate a number of PUFAs, including eicosapentaenoic acid and docosahexaenoic acid (DHA). Determination of acyl-CoA synthetase activities by direct measurement of acyl-CoAs produced in the presence of different PUFA substrates showed that TpLACSA was most active toward DHA. Heterologous expression also revealed that TplacsA transformants were able to incorporate more DHA in triacylglycerols than the control yeast. PMID:15821149

  17. 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

  18. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-03-01

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

  2. 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

  3. Intakes of long-chain n-3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis

    PubMed Central

    He, Ka; Liu, Kiang; Daviglus, Martha L.; Mayer-Davis, Elisabeth; Jenny, Nancy Swords; Jiang, Rui; Ouyang, Pamela; Steffen, Lyn M.; Siscovick, David; Wu, Colin; Barr, R. Graham; Tsai, Michael; Burke, Gregory L.

    2014-01-01

    Background Data on the relations of different types of fish meals and long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) with measures of atherosclerosis are sparse. Objective We examined intakes of long-chain n-3 PUFAs and fish in relation to clinical measures of subclinical atherosclerosis. Design A cross-sectional study was conducted in 5,488 multiethnic adults aged 45–84 years and free of clinical cardiovascular disease. Diet was assessed using self-administered food frequency questionnaires. Subclinical atherosclerosis was determined by common carotid intima-media thickness (cCIMT, >80th percentile), internal CIMT (iCIMT, >80th percentile), coronary artery calcium score (CAC, >0) or ankle-brachial index (ABI, <0.90), respectively. Results After adjustment for potential confounders, intakes of long-chain n-3 PUFAs and non-fried (broiled, steamed, baked or raw) fish were inversely related to subclinical atherosclerosis determined by cCIMT but not iCIMT, CAC or ABI. The multivariable odds ratio comparing the highest to the lowest quartile of dietary exposures in relation to subclinical atherosclerosis determined by cCIMT was 0.69 (95% CI: 0.55, 0.86; p for trend<0.01) for n-3 PUFA intake, 0.80 (95% CI: 0.64, 1.01; p=0.054) for non-fried fish and 0.90 (95% CI: 0.73, 1.10; p=0.33) for fried fish consumption. Conclusions This study indicates that dietary intake of long-chain n-3 PUFAs or non-fried fish is associated with lower prevalence of subclinical atherosclerosis classified by cCIMT although significant changes in iCIMT, CAC and ABI were not observed. Our findings also suggest that the association of fish and atherosclerosis may vary depending on the type of fish meal consumed and the measures of atherosclerosis. PMID:18842801

  4. [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

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

    PubMed Central

    Hadders-Algra, Mijna

    2010-01-01

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

  6. Coexpression of multiple genes reconstitutes two pathways of very long-chain polyunsaturated fatty acid biosynthesis in Pichia pastoris.

    PubMed

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

    2014-09-01

    The introduction of novel traits to cells often requires the stable coexpression of multiple genes within the same cell. Herein, we report that C22 very long-chain polyunsaturated fatty acids (VLC-PUFAs) were synthesized from C18 precursors by reactions catalyzed by delta 6-desaturase, an ELOVL5 involved in VLC-PUFA elongation, and delta 5-desaturase. The coexpression of McD6DES, AsELOVL5, and PtD5DES encoding the corresponding enzymes, produced docosatetraenoic acid (C22:4 n-6) and docosapentaenoic acid (C22:5 n-3), as well as arachidonic acid (C20:4 n-6) and eicosapentaenoic acid (C20:5 n-3) in the methylotrophic yeast Pichia pastoris. The expression of each gene increased within 24 h, with high transcript levels after induction with 0.5 or 1 % methanol. High levels of the newly expressed VLC-PUFAs occurred after 144 h. This expression system exemplifies the recent progress and future possibilities of the metabolic engineering of VLC-PUFAs in oilseed crops. PMID:24863294

  7. Identification and quantification of triacylglycerols containing n-3 long-chain polyunsaturated fatty acids in bovine milk.

    PubMed

    Liu, Zhiqian; Moate, Peter; Ezerniks, Vilnis; Cocks, Benjamin G; Rochfort, Simone

    2015-12-01

    The n-3 long-chain polyunsaturated fatty acids (LC-PUFA) are low-abundance components in milk fat, but have great potential in promoting human health. A comprehensive survey on triacylglycerol (TAG) molecular species in milk that contain at least one type of n-3 LC-PUFA, namely eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, was conducted in this work using HPLC-linear trap quadrupole-Orbitrap and HPLC-triple quadrupole mass spectrometry techniques. A total of 51 TAG species that contain n-3 LC-PUFA have been identified in bovine milk and their structures assigned. The TAG species containing docosahexaenoic acid were found in much smaller number and at much lower abundance compared with the other 2 types of TAG. An HPLC-triple quadrupole mass spectrometry-based method was developed, which provides relative quantification of all these TAG species in a run of 36 min. Application of this method to the quantification of n-3 LC-PUFA-incorporated TAG in 32 individual animal milk samples allowed us to determine variation between animals, identify strong metabolic relationships between TAG species, and reveal negative effect of a grape marc supplement on the accumulation of eicosapentaenoic acid in milk. PMID:26476942

  8. Long chain polyunsaturated fatty acids alter oxytocin signaling and receptor density in cultured pregnant human myometrial smooth muscle cells.

    PubMed

    Kim, Paul Y; Zhong, Miao; Kim, Yoon-Sun; Sanborn, Barbara M; Allen, Kenneth G D

    2012-01-01

    Epidemiological studies and interventional clinical trials indicate that consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) such as docosahexaenoic acid (DHA) lengthen gestational duration. Although the mechanisms are not well understood, prostaglandins (PG) of the 2-series are known to play a role in the initiation and progress of labor. In animal studies, modest DHA provision has been shown to reduce placental and uterine PGE(2) and PGF(2α), matrix metalloproteinase (MMP)-2 and MMP-9 expression, and placental collagenase activity. However, modulation of PG biosynthesis may not account for all the effects of LC n-3 PUFAs in labor. We investigated one potential PG-independent mechanism of LC PUFA action using cultured pregnant human myometrial smooth muscle cells. Our goal was to characterize the effect of LC PUFA treatment on oxytocin signaling, a potent uterotonic hormone involved in labor. The addition of 10 µM-100 µM DHA or arachidonic acid (AA) to the culture media for 48 h resulted in dose dependent enrichment of these fatty acids in membrane lipid. DHA and AA significantly inhibited phosphatidylinositol turnover and [Ca(2+)](i) mobilization with oxytocin stimulation compared to bovine serum albumin control and equimolar oleic acid. DHA and AA significantly reduced oxytocin receptor membrane concentration without altering binding affinity or rate of receptor internalization. These findings demonstrate a role for LC n-3 PUFAs in regulation of oxytocin signaling and provide new insight into additional mechanisms pertaining to reports of dietary fish and fish oil consumption prolonging gestation. PMID:22848573

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

    PubMed

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

    2016-08-01

    Both the spotted scat Scatophagus argus and rabbitfish Siganus canaliculatus belong to the few cultured herbivorous marine teleost, however, their fatty acyl desaturase (Fad) system involved in long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis is different. The S. argus has a △6 Fad, while the rabbitfish has △4 and △6/△5 Fads, which were the first report in vertebrate and marine teleost, respectively. In order to compare the characteristics of elongases of very long-chain fatty acids (Elovl) between them, two Elovl cDNAs were cloned from S. argus in the present study. One has 885bp of open read fragment (ORF) encoding a protein with 294 amino acid (aa) showing Elovl5 activity functionally characterized by heterologous expression in yeast, which was primarily active for the elongation of C18 and C20 PUFAs. The other has 915bp of ORF coding for a 305 aa protein showing Elovl4 activity, which was more efficient in the elongation of C20 and C22 PUFAs. Tissue distribution analyses by RT-PCR showed that elovl5 was highly expressed in the liver compared to other tissues determined, whereas elovl4 transcripts were only detected in the eye. The expression of elovl5 and elovl4 were significantly affected by dietary fatty acid composition, with highest expression of mRNA in the liver and eye of fish fed a diet with an 18:3n-3/18:2n-6 ratio of 1.7:1. These results indicated that the S. argus has a similar Elovl system in the LC-PUFA biosynthetic pathway to that of rabbitfish although their Fad system was different, suggesting that the diversification of fish LC-PUFA biosynthesis specificities is more associated with its Fad system. These new insights expand our knowledge and understanding of the molecular basis and regulation of LC-PUFA biosynthesis in fish. PMID:27050407

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

    PubMed

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

    2015-12-15

    We assessed the presence of fatty acid (FA)-sensing mechanisms in hypothalamus of Senegalese sole (Solea senegalensis) and investigated their sensitivity to FA chain length and/or level of unsaturation. Stearate (SA, saturated FA), oleate (OA, monounsaturated FA of the same chain length), α-linolenate [ALA, a n-3 polyunsaturated fatty acid (PUFA) of the same chain length], and eicosapentanoate (EPA, a n-3 PUFA of a larger chain length) were injected intraperitoneally. Parameters related to FA sensing and neuropeptide expression in the hypothalamus were assessed after 3 h and changes in accumulated food intake after 4, 24, and 48 h. Three FA sensing systems characterized in rainbow trout were also found in Senegalese sole and were activated by OA in a way similar to that previously characterized in rainbow trout and mammals. These hypothalamic FA sensing systems were also activated by ALA, differing from mammals, where n-3 PUFAs do not seem to activate FA sensors. This might suggest additional roles and highlights the importance of n-3 PUFA in fish diets, especially in marine species. The activation of FA sensing seems to be partially dependent on acyl chain length and degree of saturation, as no major changes were observed after treating fish with SA or EPA. The activation of FA sensing systems by OA and ALA, but not SA or EPA, is further reflected in the expression of hypothalamic neuropeptides involved in the control of food intake. Both OA and ALA enhanced anorexigenic capacity compatible with the activation of FA sensing systems. PMID:26468264

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

    PubMed Central

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

    2015-01-01

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

  12. Influence of an n-3 long-chain polyunsaturated fatty acid-enriched diet on experimentally induced synovitis in horses.

    PubMed

    Ross-Jones, T N; McIlwraith, C W; Kisiday, J D; Hess, T M; Hansen, D K; Black, J

    2016-06-01

    Dietary n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation has previously been shown to modify joint-related inflammation in several species, although information in the horse is lacking. We investigated whether dietary supplementation with n-3 LCPUFA would modify experimentally induced synovitis in horses. Twelve, skeletally mature, non-pregnant mares were randomly assigned to either a control diet (CONT) or an n-3 long-chain fatty acid-enriched treatment diet (N3FA) containing 40 g/day of n-3 LCPUFA for 91 days. Blood samples taken on days 0, 30, 60 and 90, and synovial fluid collected on days 0 and 90 were processed for lipid composition. On day 91, joint inflammation was stimulated using an intra-articular (IA) injection of 100 ng of recombinant equine IL-1beta (reIL-1β). Synovial fluid samples taken at post-injection hours (PIH) 0, 4, 8 and 24 were analysed for prostaglandin E2 (PGE2 ), matrix metalloproteinase (MMP) activity and routine cytology. Synovium and articular cartilage samples collected at PIH 8 were analysed for gene expression of MMP 1 and MMP 13, interleukin-1beta (IL-1β), cyclooxygenase 2 (COX-2), tumour necrosis factor-alpha and the aggrecanases, a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5. A 90-day feeding period of n-3 LCPUFA increased serum phospholipid and synovial fluid lipid compositions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared to CONT horses. The reIL-1β injection caused an inflammatory response; however, there was no effect of dietary treatment on synovial fluid PGE2 content and MMP activity. Synovial tissue collected from N3FA horses exhibited lower expression of ADAMTS-4 compared to CONT horses. Despite the presence of EPA and DHA in the synovial fluid of N3FA horses, dietary n-3 LCPUFA supplementation did not modify synovial fluid biomarkers compared to CONT horses; however, the lower ADAMTS-4 mRNA expression in N3FA synovium warrants further

  13. Feeding infant piglets formula with long-chain polyunsaturated fatty acids as triacylglycerols or phospholipids influences the distribution of these fatty acids in plasma lipoprotein fractions.

    PubMed

    Amate, L; Gil, A; Ramírez, M

    2001-04-01

    Several sources of long-chain polyunsaturated fatty acids (LCP) are currently available for infant formula supplementation. These oils differ in their fatty acid composition, the chemical form of the fatty acid esters [triacylglycerols (TG) or phospholipids (PL)] and presence of other lipid components. These differences may affect LCP absorption, distribution and metabolic fate after ingestion. The purpose of the present study was to evaluate the influence of different chemical forms of dietary LCP on the composition of plasma, plasma lipoproteins, liver and jejunum in infant piglets. Thirty pigs (5 d old) were bottle-fed different diets for 4 wk: a control diet (C), a diet containing LCP as TG from tuna and fungal oils (TF-TG) or a diet containing LCP as PL from egg yolk (E-PL). We measured lipid and fatty acid composition of plasma and lipoproteins, as well as lipid composition of liver and intestinal mucosa. The arachidonic and docosahexaenoic acids in HDL-PL were significantly higher in piglets fed the E-PL diet than in those fed the TF-TG diet. Opposite results were found in the LDL-PL diet. No significant differences were found between groups in TG or cholesterol concentrations of plasma or lipoproteins. Arachidonic acid in plasma PL and cholesteryl esters was significantly higher in the E-PL group than in the TF-TG group. The chemical form in which LCP esters are present in different dietary sources influences their distribution in plasma lipoproteins. This may be important for infant nutrition and suggests that not all LCP sources may be biologically equivalent. PMID:11285334

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

    PubMed Central

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

    2012-01-01

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

  15. Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study

    PubMed Central

    Strain, J.J.; Davidson, Philip W.; Bonham, Maxine P.; Duffy, Emeir M.; Stokes-Riner, Abbie; Thurston, Sally W.; Wallace, Julie M.W.; Robson, Paula J.; Shamlaye, Conrad F.; Georger, Lesley A.; Sloane-Reeves, Jean; Cernichiari, Elsa; Canfield, Richard L.; Cox, Christopher; Huang, Li Shan; Janciuras, Joanne; Myers, Gary J.; Clarkson, Thomas W.

    2008-01-01

    Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies. PMID:18590765

  16. 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

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

    PubMed Central

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

    2015-01-01

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

  18. The role of Δ6-desaturase acyl-carrier specificity in the efficient synthesis of long-chain polyunsaturated fatty acids in transgenic plants.

    PubMed

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

    2012-02-01

    The role of acyl-CoA-dependent Δ6-desaturation in the heterologous synthesis of omega-3 long-chain polyunsaturated fatty acids was systematically evaluated in transgenic yeast and Arabidopsis thaliana. The acyl-CoA Δ6-desaturase from the picoalga Ostreococcus tauri and orthologous activities from mouse (Mus musculus) and salmon (Salmo salar) were shown to generate substantial levels of Δ6-desaturated acyl-CoAs, in contrast to the phospholipid-dependent Δ6-desaturases from higher plants that failed to modify this metabolic pool. Transgenic plants expressing the acyl-CoA Δ6-desaturases from either O. tauri or salmon, in conjunction with the two additional activities required for the synthesis of C20 polyunsaturated fatty acids, contained higher levels of eicosapentaenoic acid compared with plants expressing the borage phospholipid-dependent Δ6-desaturase. The use of acyl-CoA-dependent Δ6-desaturases almost completely abolished the accumulation of unwanted biosynthetic intermediates such as γ-linolenic acid in total seed lipids. Expression of acyl-CoA Δ6-desaturases resulted in increased distribution of long-chain polyunsaturated fatty acids in the polar lipids of transgenic plants, reflecting the larger substrate pool available for acylation by enzymes of the Kennedy pathway. Expression of the O. tauriΔ6-desaturase in transgenic Camelina sativa plants also resulted in the accumulation of high levels of Δ6-desaturated fatty acids. This study provides evidence for the efficacy of using acyl-CoA-dependent Δ6-desaturases in the efficient metabolic engineering of transgenic plants with high value traits such as the synthesis of omega-3 LC-PUFAs. PMID:21902798

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

    PubMed Central

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

    2016-01-01

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

  20. Long-chain polyunsaturated fatty acid supplementation had no effect on body weight but reduced energy intake in overweight and obese women.

    PubMed

    Harden, Charlotte J; Dible, Victoria A; Russell, Jean M; Garaiova, Iveta; Plummer, Sue F; Barker, Margo E; Corfe, Bernard M

    2014-01-01

    Longer-chain polyunsaturated fatty acids may have greater appetite-suppressing effects than shorter-chain, monosaturated, and saturated fatty acids. Because fish oils are predominantly composed of n-3 long-chain polyunsaturated fatty acid and may assist in the treatment of obesity comorbidities, their effect on body weight and body mass index is of interest. We hypothesized that daily supplementation with docosahexaenoic acid (DHA)-rich oil would reduce energy intake and body weight in overweight and obese women compared with supplementation with oleic acid (OA) rich oil. A double-blinded, randomized, parallel intervention was conducted. Body mass index (in kilograms per meter squared), body weight (in kilograms), body fat (in percent), and lean tissue (in kilograms) were measured at baseline and 12 weeks after intervention with DHA or OA. Diet diaries were also completed at these time points for estimation of energy and macronutrient intake. Subjects reported significantly lower energy (P = .020), carbohydrate (g) (P = .037), and fat (g) (P = .045) intake after DHA compared with OA. Body mass or composition was not affected by treatment, although a fall in body weight in the DHA group approached statistical significance (P = .089). Daily ingestion of DHA over a 12-week period may reduce energy intake in overweight and obese females, but longer-term and adequately powered studies using subjects of both sexes are needed. Other factors that should be considered include the following: the choice of control, the body mass index category of subjects, and ways of improving the compliancy and accuracy of dietary assessment. PMID:24418242

  1. Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop.

    PubMed

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

    2014-01-01

    Omega-3 (also called n-3) long-chain polyunsaturated fatty acids (≥C20; LC-PUFAs) are of considerable interest, based on clear evidence of dietary health benefits and the concurrent decline of global sources (fish oils). Generating alternative transgenic plant sources of omega-3 LC-PUFAs, i.e. eicosapentaenoic acid (20:5 n-3, EPA) and docosahexaenoic acid (22:6 n-3, DHA) has previously proved problematic. Here we describe a set of heterologous genes capable of efficiently directing synthesis of these fatty acids in the seed oil of the crop Camelina sativa, while simultaneously avoiding accumulation of undesirable intermediate fatty acids. We describe two iterations: RRes_EPA in which seeds contain EPA levels of up to 31% (mean 24%), and RRes_DHA, in which seeds accumulate up to 12% EPA and 14% DHA (mean 11% EPA and 8% DHA). These omega-3 LC-PUFA levels are equivalent to those in fish oils, and represent a sustainable, terrestrial source of these fatty acids. We also describe the distribution of these non-native fatty acids within C. sativa seed lipids, and consider these data in the context of our current understanding of acyl exchange during seed oil synthesis. PMID:24308505

  2. Perturbation and age-related changes in the fatty acid pattern of soleus muscle phospholipids and triglycerides in rats depleted in long-chain polyunsaturated omega3 fatty acids.

    PubMed

    Malaisse, Willy J; Portois, Laurence; Sener, Abdullah; Carpentier, Yvon A

    2007-12-01

    Altered D-glucose metabolism prevails in the soleus muscle of rats depleted in long-chain polyunsaturated omega3 fatty acids (omega3). In these animals, the prior intravenous injection of an omega3-rich medium-chain triglyceride:fish oil emulsion (omega3-FO rats), as compared to that of an omega3-poor medium-chain triglyceride:olive oil emulsion (omega3-OO rats), may either correct or aggravate selected metabolic variables. This study deals with the fatty acid pattern of soleus phospholipids and triglycerides in control animals versus omega3-depleted rats not injected with any lipid emulsion (omega3-NI rats) and in omega3-OO versus omega3-FO rats. In each group of omega3-depleted rats, age-related changes were also monitored. The omega3-depleted rats displayed low long-chain polyunsaturated omega3 fatty acid content, facilitated metabolism of long-chain polyunsaturated omega6 fatty acids, and increased Delta9-desaturase activity. Both the age-related changes in lipid variables and those attributable to the prior intravenous injection of the omega3-rich lipid emulsion consisted either in a move towards normalization or in the opposite direction, i.e. towards aggravation of the defect found in the omega3-depleted rats. Emphasis is placed, therefore, on the unusual situation found in the soleus muscle of omega3-depleted rats, in which both lipid and metabolic variables may be either favourably or adversely affected by the same environmental factor(s). PMID:17982700

  3. 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

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

    PubMed Central

    2011-01-01

    Background Increasing land restrictions and a reduced livestock-to-human ratio during the 20th century led the Maasai to lead a more sedentary, market-orientated lifestyle. Although plant-derived food nowadays contributes substantially to their diet, dairy products being high in saturated fatty acids (SFA) and low in polyunsaturated fatty acids (PUFA) still are an important energy source. Since reliable data regarding the Maasai diet date back to the 1980s, the study objective was to document current diet practices in a Kenyan Maasai community and to investigate the fatty acid distribution in diet and red blood cells. Methods A cross-sectional study was conducted among 26 Maasai (20 women, 6 men) from Loodokilani, Kajiado District, Kenya. Food intake was described by the subjects via 24-h recall, and both food and blood samples were analysed. Results Two main foods - milk and ugali - constituted the Maasai diet in this region. A total of 0.9 L of milk and 0.6 kg of ugali were consumed per person and day to yield an energy intake of 7.6 MJ/d per person. A major proportion of ingested food contributing 58.3% to the total dietary energy (en%) was plant-derived, followed by dairy products representing 41.1 en%. Fat consumed (30.5 en%) was high in SFA (63.8%) and low in PUFA (9.2%). Long-chain n-3 PUFA (EPA, DPA and DHA) made up only 0.15% of the ingested fatty acids, but 5.9% of red blood cell fatty acids. Conclusion The study indicates the Maasai diet is rich in SFA and low in PUFA. Nevertheless, red blood cells are composed of comparable proportions of long-chain n-3 PUFA to populations consuming higher amounts of this fatty acid group. PMID:21854590

  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. 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 ...

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2002-03-27

    The oxidative stability of long-chain polyunsaturated fatty acid (PUFA) and docosahexaenoic acid (DHA)-containing fish and algae oils varies widely according to their fatty acid composition, the physical and colloidal states of the lipids, the contents of tocopherols and other antioxidants, and the presence and activity of transition metals. Fish and algal oils were initially much more stable to oxidation in bulk systems than in the corresponding oil-in-water emulsions. The oxidative stability of emulsions cannot, therefore, be predicted on the basis of stability data obtained with bulk long-chain PUFA-containing fish oils and DHA-containing algal oils. The relatively high oxidative stability of an algal oil containing 42% DHA was completely lost after chromatographic purification to remove tocopherols and other antioxidants. Therefore, this evidence does not support the claim that DHA-rich oils from algae are unusually stable to oxidation. Addition of ethylenediaminetetraacetic acid (EDTA) prevented oxidation of both fish and algal oil emulsions without added iron and at low iron:EDTA molar concentrations. EDTA, however, promoted the oxidation of the corresponding emulsions that contained high iron:EDTA ratios. Therefore, to be effective as a metal chelator, EDTA must be added at molar concentrations higher than that of iron to inhibit oxidation of foods containing long-chain PUFA from either fish or algae and fortified with iron. PMID:11902962

  10. Omega-3 Long Chain Polyunsaturated Fatty Acids for Treatment of Parenteral Nutrition–Associated Liver Disease: A Review of the Literature

    PubMed Central

    Tillman, Emma M; Helms, Richard A

    2011-01-01

    Parenteral nutrition–associated liver disease (PNALD) is a complex disease that is diagnosed by clinical presentation, biochemical markers of liver injury, concurrent use of parenteral nutrition (PN), and negative workup for other causes of liver disease. For the past 30 years, clinicians have had few effective treatments for PNALD and when disease progressed to liver cirrhosis it was historically associated with poor outcomes. Within the past 5 years there has been some encouraging evidence for the potential benefits of fish oils, rich in omega-3 long-chain polyunsaturated fatty acids (ω3PUFA), in reversing liver injury associated with PN. This article reviews the current literature relating to ω3PUFA and PNALD. PMID:22477822

  11. Identification and characterization of a novel C20-elongase gene from the marine microalgae, Pavlova viridis, and its use for the reconstitution of two pathways of long-chain polyunsatured fatty acids biosynthesis in Saccharomyces cerevisiae.

    PubMed

    Shi, Tonglei; Yu, Aiqun; Li, Ming; Zhang, Meng; Xing, Laijun; Li, Mingchun

    2013-08-01

    The marine microalga, Pavlova viridis, contains long-chain polyunsatured fatty acids including eicosapentaenoic acid (EPA, 20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3). A full-length cDNA sequence, pvelo5, was isolated from P. viridis. From sequence alignment, the gene was homologous to fatty acyl elongases from other organisms. Heterologous expression of pvelo5 in Saccharomyces cerevisiae confirmed that it encoded a specific C20-elongase within the n-3 and n-6 pathways. Elongation activity was confined exclusively to EPA and arachidonic acid (20:4n-6). GC analysis indicated that pvelo5 could co-express with other genes for biosynthesis to reconstitute the Δ8 and Δ6 pathways. Real-time PCR results and fatty acid analysis demonstrated that long-chain polyunsatured fatty acids production by the Δ8 pathway might be more effective than that by the Δ6 pathway. PMID:23546943

  12. 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...

  13. Direct supplementation of diet is the most efficient way of enriching broiler meat with n-3 long-chain polyunsaturated fatty acids.

    PubMed

    Ribeiro, T; Lordelo, M M; Alves, S P; Bessa, R J B; Costa, P; Lemos, J P C; Ferreira, L M A; Fontes, C M G A; Prates, J A M

    2013-01-01

    1. Concentrations of beneficial omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) in poultry meat can be improved by increasing the concentration of n-3 PUFA in poultry diets. 2. A decrease in flavour quality is, however, usually associated with the dietary supplementation with n-3 PUFA, which is due to the susceptibility of PUFA to oxidation. 3. This experiment was conducted to study the effects of introducing two different n-3 fatty acid sources (extruded linseed and DHA Gold™, a proprietary algal product rich in docosahexaenoic acid), either separately or together, on broiler productive performance, and meat quality, oxidative stability, sensory traits and LC-PUFA profile. 4. Birds given the algal product displayed better productive performances than animals from other groups. 5. The data revealed an improvement in the fatty acid nutritional value of meat from birds receiving the algal product and an inefficient conversion of α-linolenic acid (LNA) into LC-PUFA. 6. Metabolisation of LNA in vivo is not sufficient to improve meat quality in n-3 LC-PUFA and direct supplementation of the diet with n-3 LC-PUFA is a better alternative to modulate an increase in beneficial fatty acids of broiler meat. 7. The overall acceptability of meat was negatively affected by the dietary supplementation with 7.4% of DHA, in contrast to the supplementation with 3.7% of DHA, which showed to be efficient in improving LC-PUFA meat content without affecting its sensory properties. PMID:24397512

  14. Does maternal long chain polyunsaturated fatty acid status in pregnancy influence the bone health of children? The Southampton Women’s Survey

    PubMed Central

    Harvey, Nicholas; Dhanwal, Dinesh; Robinson, Siân; Kim, Miranda; Inskip, Hazel; Godfrey, Keith; Dennison, Elaine; Calder, Philip; Cooper, Cyrus

    2013-01-01

    Purpose Maternal diet in pregnancy has been linked to childhood bone mass, but the mechanisms and nutrients involved are uncertain. Long-chain polyunsaturated fatty acids (LCPUFAs) have been shown to affect bone metabolism, but the relationship between maternal fatty acid status and bone mass in the offspring remains unknown. Methods We evaluated the association between maternal LCPUFA status in late pregnancy (34 weeks gestation) and bone density in their children at age four years, within 727 mother-child pairs taking part in the Southampton Women’s Survey. Results Concentrations of the n-3 LCPUFA component of maternal plasma phosphatidylcholine were positively associated with a number of bone mineral measures at the age of 4 years; these associations persisted after adjustment for maternal body build, walking speed and infant feeding. Relationships were most evident for eicosapentaenoic acid (r=0.09, p=0.02 for whole body areal bone mineral density [aBMD] and r=0.1, p=0.008 for lumbar spine aBMD) and for docosapentaenoic acid (r=0.09, p=0.02 for whole body aBMD and r=0.12, p=0.002 for lumbar spine aBMD). Conclusions These findings suggest that variation in early exposure to n-3 and n-6 LCPUFA may have potential consequences for bone development and that the effects appear to persist into early childhood. PMID:22159749

  15. 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.

  16. The impact of dietary long-chain polyunsaturated fatty acids on bone and cartilage in gilts and sows.

    PubMed

    O'Connor-Robison, C I; Spencer, J D; Orth, M W

    2014-10-01

    Dietary long-chain PFO including arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are precursors for several inflammatory mediators. The objective of this study was to characterize the effects of dietary PFO supplementation on bone, cartilage, and synovial fluid in 2 ages of pigs. Sows and gilts were fed either control corn/soybean meal based diets or the control diet supplemented with PFO from Gromega (PFO; JBS United, Sheridan, IN). Sows were fed their diets for 24.5 mo and slaughtered at 43 mo while gilts were fed their diets from weaning until slaughter at 111 kg. Cartilage was harvested from both humeroulnar joints of 14 sows (7/treatment) and 16 gilts (8/treatment) within 30 h of slaughter for fatty acid analysis and explant cultures. Synovial fluid was collected from the carpal joints of each pig postmortem. The right fused radius/ulna was collected for computed tomography (CT) analysis. Cortical width and density were determined and trabecular density was measured at the distal radius. Cartilage explants were allocated to 24-well culture plates with 2 discs per well and cultured over 72 h at 37°C in serum-free Dulbecco's modified Eagle's medium: nutrient mixture F-12 (Ham) medium. Six wells/pig were treated with 10 ng/mL of recombinant porcine interleukin-1 (rpIL-1). At 24, 48, and 72 h of culture, media were removed and reserved for analysis of proteoglycans, nitric oxide (NO), and PGE2 concentrations. The CT scans of the radius/ulna from gilts revealed no differences for cortical width and bone density. Sows fed PFO had greater cortical width of the proximal ulna (P < 0.05) and decreased cortical width of the distal radius (P < 0.05). Sows fed PFO had increased DHA (P < 0.01) and a decrease in the omega-6 to omega-3 ratio (P < 0.05) in cartilage. Gilts fed PFO had increased DHA (P < 0.01), C22:1 (P < 0.01), and docosapentaenoic acid (P < 0.01) and a tendency for increased EPA (P = 0.093) concentrations in cartilage

  17. Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection

    PubMed Central

    2010-01-01

    Background There are currently no accurate serum markers for detecting early risk of colorectal cancer (CRC). We therefore developed a non-targeted metabolomics technology to analyse the serum of pre-treatment CRC patients in order to discover putative metabolic markers associated with CRC. Using tandem-mass spectrometry (MS/MS) high throughput MS technology we evaluated the utility of selected markers and this technology for discriminating between CRC and healthy subjects. Methods Biomarker discovery was performed using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Comprehensive metabolic profiles of CRC patients and controls from three independent populations from different continents (USA and Japan; total n = 222) were obtained and the best inter-study biomarkers determined. The structural characterization of these and related markers was performed using liquid chromatography (LC) MS/MS and nuclear magnetic resonance technologies. Clinical utility evaluations were performed using a targeted high-throughput triple-quadrupole multiple reaction monitoring (TQ-MRM) method for three biomarkers in two further independent populations from the USA and Japan (total n = 220). Results Comprehensive metabolomic analyses revealed significantly reduced levels of 28-36 carbon-containing hydroxylated polyunsaturated ultra long-chain fatty-acids in all three independent cohorts of CRC patient samples relative to controls. Structure elucidation studies on the C28 molecules revealed two families harbouring specifically two or three hydroxyl substitutions and varying degrees of unsaturation. The TQ-MRM method successfully validated the FTICR-MS results in two further independent studies. In total, biomarkers in five independent populations across two continental regions were evaluated (three populations by FTICR-MS and two by TQ-MRM). The resultant receiver-operator characteristic curve AUCs ranged from 0.85 to 0.98 (average = 0.91 ± 0.04). Conclusions A

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

    PubMed

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

    2015-03-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation. PMID:25445491

  19. Long-Chain Omega-3 Polyunsaturated Fatty Acids Have Developmental Effects on the Crop Pest, the Cabbage White Butterfly Pieris rapae.

    PubMed

    Hixson, Stefanie M; Shukla, Kruti; Campbell, Lesley G; Hallett, Rebecca H; Smith, Sandy M; Packer, Laurence; Arts, Michael T

    2016-01-01

    Nutritional enhancement of crops using genetic engineering can potentially affect herbivorous pests. Recently, oilseed crops have been genetically engineered to produce the long-chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at levels similar to that found in fish oil; to provide a more sustainable source of these compounds than is currently available from wild fish capture. We examined some of the growth and development impacts of adding EPA and DHA to an artificial diet of Pieris rapae, a common pest of Brassicaceae plants. We replaced 1% canola oil with EPA: DHA (11:7 ratio) in larval diets, and examined morphological traits and growth of larvae and ensuing adults across 5 dietary treatments. Diets containing increasing amounts of EPA and DHA did not affect developmental phenology, larval or pupal weight, food consumption, nor larval mortality. However, the addition of EPA and DHA in larval diets resulted in progressively heavier adults (F 4, 108 = 6.78; p = 0.011), with smaller wings (p < 0.05) and a higher frequency of wing deformities (R = 0.988; p = 0.001). We conclude that the presence of EPA and DHA in diets of larval P. rapae may alter adult mass and wing morphology; therefore, further research on the environmental impacts of EPA and DHA production on terrestrial biota is advisable. PMID:27011315

  20. The metabolic syndrome of fructose-fed rats: effects of long-chain polyunsaturated ω3 and ω6 fatty acids. VII. Oxidative stress.

    PubMed

    Mellouk, Zoheir; Sener, Abdullah; Ait Yahia, Dalila; Malaisse, Willy J

    2012-12-01

    In the present study, the plasma concentration, and liver, heart, kidney, soleus muscle and visceral adipose tissue content of thiobarbituric acid reactive substrates (TBARS), carbonyl radicals, hydroperoxides and nitric oxide were measured in control rats exposed for 8 weeks to a diet containing 64% (w/w) starch and 5% sunflower oil and in animals fed a diet containing 64% D-fructose and 5% sunflower oil or 3.4% sunflower oil mixed with 1.6% safflower or salmon oil. Coherent measurements of the plasma concentrations or tissue contents of these metabolites revealed increases in TBARS, carbonyl radical and hydroperoxide levels and a decrease in nitric oxide levels in the 5% sunflower oil-fed rats. In the fructose-fed rats, the partial substitution of sunflower oil by either safflower or salmon oil minimized the changes. These findings provide further evidence in support of the favorable effects of the dietary supply of long-chain polyunsaturated ω6 and ω3 fatty acids upon the metabolic disturbances prevailing in the fructose-induced metabolic syndrome. PMID:23007226

  1. Long-Chain Omega-3 Polyunsaturated Fatty Acids Have Developmental Effects on the Crop Pest, the Cabbage White Butterfly Pieris rapae

    PubMed Central

    Hixson, Stefanie M.; Shukla, Kruti; Campbell, Lesley G.; Hallett, Rebecca H.; Smith, Sandy M.; Packer, Laurence; Arts, Michael T.

    2016-01-01

    Nutritional enhancement of crops using genetic engineering can potentially affect herbivorous pests. Recently, oilseed crops have been genetically engineered to produce the long-chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at levels similar to that found in fish oil; to provide a more sustainable source of these compounds than is currently available from wild fish capture. We examined some of the growth and development impacts of adding EPA and DHA to an artificial diet of Pieris rapae, a common pest of Brassicaceae plants. We replaced 1% canola oil with EPA: DHA (11:7 ratio) in larval diets, and examined morphological traits and growth of larvae and ensuing adults across 5 dietary treatments. Diets containing increasing amounts of EPA and DHA did not affect developmental phenology, larval or pupal weight, food consumption, nor larval mortality. However, the addition of EPA and DHA in larval diets resulted in progressively heavier adults (F 4, 108 = 6.78; p = 0.011), with smaller wings (p < 0.05) and a higher frequency of wing deformities (R = 0.988; p = 0.001). We conclude that the presence of EPA and DHA in diets of larval P. rapae may alter adult mass and wing morphology; therefore, further research on the environmental impacts of EPA and DHA production on terrestrial biota is advisable. PMID:27011315

  2. The role of long chain omega-3 polyunsaturated fatty acids in reducing lipid peroxidation among elderly patients with mild cognitive impairment: a case-control study.

    PubMed

    Lee, Lai Kuan; Shahar, Suzana; Rajab, NorFadilah; Yusoff, Noor Aini Mohd; Jamal, Rahman A; Then, Sue Mian

    2013-05-01

    The present work explores the effect of dietary omega-3 polyunsaturated fatty acids (PUFAs) intake on lipid peroxidation among mild cognitive impairment (MCI) patients. The plasma lipid hydroperoxide (LPO) levels in 67 MCI patients were compared to those of 134 healthy elderly controls. Omega-3 PUFA intake was assessed using an interviewer-administered food frequency questionnaire. Apolipoprotein E genotyping was performed using polymerase chain reaction and restriction enzyme digestion. The association between various confounders and lipid peroxidation was evaluated using regression analysis. The influence of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake on LPO level was investigated. The results revealed that LPO levels were significantly higher in the MCI group than in the control group. Inverse correlations were found between DHA and EPA intake and LPO level among the MCI group. LPO levels decreased significantly with increasing DHA and EPA intake. In summary, the findings revealed that DHA and EPA can play a role in alleviating oxidative stress and reducing the risk of neurodegenerative diseases. PMID:22898566

  3. Long chain polyunsaturated fatty acid supplementation in infancy increases length- and weight-for-age but not BMI to 6 years when controlling for effects of maternal smoking.

    PubMed

    Currie, L M; Tolley, E A; Thodosoff, J M; Kerling, E H; Sullivan, D K; Colombo, J; Carlson, S E

    2015-07-01

    Long chain polyunsaturated fatty acids (LCPUFA) are added to infant formula but their effect on long-term growth of children is under studied. We evaluated the effects of feeding LCPUFA-supplemented formula (n = 54) compared to control formula (n = 15) throughout infancy on growth from birth-6 years. Growth was described using separate models developed with the MIXED procedure of SAS(®) that included maternal smoking history and gender. Compared to children fed control formula, children who consumed LCPUFA supplemented formula had higher length-/stature-/and weight-for-age percentiles but not body mass index (BMI) percentile from birth to 6 years. Maternal smoking predicted lower stature (2-6 years), higher weight-for-length (birth-18 months) and BMI percentile (2-6 years) independent of LCPUFA effects. Gender interacted with the effect of LCPUFA on stature, and the relationship between smoking and BMI, with a larger effect for boys. Energy intake did not explain growth differences. A relatively small control sample is a limitation. PMID:25936840

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

    PubMed

    Janssen, Carola I F; Kiliaan, Amanda J

    2014-01-01

    Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are important components of neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid also affect cardiovascular health and inflammation. In neural development, LCPUFA deficiency can lead to severe disorders like schizophrenia and attention deficit hyperactivity disorder. Perinatal LCPUFA supplementation demonstrated beneficial effects in neural development in humans and rodents resulting in improved cognition and sensorimotor integration. In normal aging, the effect of LCPUFA on prevention of cognitive impairment will be discussed. LCPUFA are important for neuronal membrane integrity and function, and also contribute in prevention of brain hypoperfusion. Cerebral perfusion can be compromised as result of obesity, cerebrovascular disease, hypertension, or diabetes mellitus type 2. Last, we will focus on the role of LCPUFA in most common neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. These disorders are characterized by impaired cognition and connectivity and both clinical and animal supplementation studies have shown the potential of LCPUFA to decrease neurodegeneration and inflammation. This review shows that LCPUFA are essential throughout life. PMID:24334113

  5. 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

  6. 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

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

    PubMed

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

    2016-03-01

    The natural food for Atlantic salmon (Salmo salar) in freshwater has relatively lower levels of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA) than found in prey for post-smolt salmon in seawater. Land-locked salmon such as the Gullspång population feed exclusively on freshwater type lipids during its entire life cycle, a successful adaptation derived from divergent evolution. Studying land-locked populations may provide insights into the molecular and genetic control mechanisms that determine and regulate n-3 LC-PUFA biosynthesis and retention in Atlantic salmon. A two factorial study was performed comparing land-locked and farmed salmon parr fed diets formulated with fish or rapeseed oil for 8 weeks. The land-locked parr had higher capacity to synthesise n-3 LC-PUFA as indicated by higher expression and activity of desaturase and elongase enzymes. The data suggested that the land-locked salmon had reduced sensitivity to dietary fatty acid composition and that dietary docosahexaenoic acid (DHA) did not appear to suppress expression of LC-PUFA biosynthetic genes or activity of the biosynthesis pathway, probably an evolutionary adaptation to a natural diet lower in DHA. Increased biosynthetic activity did not translate to enhanced n-3 LC-PUFA contents in the flesh and diet was the only factor affecting this parameter. Additionally, high lipogenic and glycolytic potentials were found in land-locked salmon, together with decreased lipolysis which in turn could indicate increased use of carbohydrates as an energy source and a sparing of lipid. PMID:26732752

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

    PubMed

    Brenna, J Thomas

    2016-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. N-3 long-chain polyunsaturated fatty acids and risk of all-cause mortality among general populations: a meta-analysis

    PubMed Central

    Chen, Guo-Chong; Yang, Jing; Eggersdorfer, Manfred; Zhang, Weiguo; Qin, Li-Qiang

    2016-01-01

    Prospective observational studies have shown inconsistent associations of dietary or circulating n-3 long-chain polyunsaturated fatty acids (LCPUFA) with risk of all-cause mortality. A meta-analysis was performed to evaluate the associations. Potentially eligible studies were identified by searching PubMed and EMBASE databases. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the random-effects model. Eleven prospective studies involving 371 965 participants from general populations and 31 185 death events were included. The summary RR of all-cause mortality for high-versus-low n-3 LCPUFA intake was 0.91 (95% CI: 0.84–0.98). The summary RR for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake was 0.83 (95% CI: 0.75–0.92) and 0.81 (95% CI: 0.74–0.95), respectively. In the dose-response analysis, each 0.3 g/d increment in n-3 LCPUFA intake was associated with 6% lower risk of all-cause mortality (RR = 0.94, 95% CI: 0.89–0.99); and each 1% increment in the proportions of circulating EPA and DHA in total fatty acids in blood was associated with 20% (RR = 0.80, 95% CI: 0.65–0.98) and 21% (RR = 0.79, 95% CI: 0.63–0.99) decreased risk of all-cause mortality, respectively. Moderate to high heterogeneity was observed across our anlayses. Our findings suggest that both dietary and circulating LCPUFA are inversely associated with all-cause mortality. PMID:27306836

  11. N-3 long-chain polyunsaturated fatty acids and risk of all-cause mortality among general populations: a meta-analysis.

    PubMed

    Chen, Guo-Chong; Yang, Jing; Eggersdorfer, Manfred; Zhang, Weiguo; Qin, Li-Qiang

    2016-01-01

    Prospective observational studies have shown inconsistent associations of dietary or circulating n-3 long-chain polyunsaturated fatty acids (LCPUFA) with risk of all-cause mortality. A meta-analysis was performed to evaluate the associations. Potentially eligible studies were identified by searching PubMed and EMBASE databases. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the random-effects model. Eleven prospective studies involving 371 965 participants from general populations and 31 185 death events were included. The summary RR of all-cause mortality for high-versus-low n-3 LCPUFA intake was 0.91 (95% CI: 0.84-0.98). The summary RR for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake was 0.83 (95% CI: 0.75-0.92) and 0.81 (95% CI: 0.74-0.95), respectively. In the dose-response analysis, each 0.3 g/d increment in n-3 LCPUFA intake was associated with 6% lower risk of all-cause mortality (RR = 0.94, 95% CI: 0.89-0.99); and each 1% increment in the proportions of circulating EPA and DHA in total fatty acids in blood was associated with 20% (RR = 0.80, 95% CI: 0.65-0.98) and 21% (RR = 0.79, 95% CI: 0.63-0.99) decreased risk of all-cause mortality, respectively. Moderate to high heterogeneity was observed across our anlayses. Our findings suggest that both dietary and circulating LCPUFA are inversely associated with all-cause mortality. PMID:27306836

  12. Restoration of fillet n-3 long-chain polyunsaturated fatty acid is improved by a modified fish oil finishing diet strategy for atlantic salmon (Salmo salar L.) smolts fed palm fatty acid distillate.

    PubMed

    Codabaccus, Mohamed B; Bridle, Andrew R; Nichols, Peter D; Carter, Chris G

    2012-01-11

    Reducing the lipid content in fish prior to feeding a fish oil finishing diet (FOFD) has the potential to improve n-3 long-chain (≥ C(20)) polyunsaturated fatty acid (LC-PUFA) restoration. This study had two main objectives: (1) determine whether feeding Atlantic salmon smolt a 75% palm fatty acid distillate diet (75PFAD) improves the apparent digestibility (AD) of saturated fatty acids (SFA) and (2) examine whether a food deprivation period after growth on 75PFAD leads to higher n-3 LC-PUFA restoration in the fillet when applying a FOFD. The AD of SFA was higher for 75PFAD compared to that of a fish oil (FO) diet. The relative level (as % total fatty acids (FA)) of n-3 LC-PUFA was higher in unfed fish compared to that in continuously fed fish after 21 and 28 day FOFD periods, respectively. Our results suggest that a food deprivation period prior to feeding a FOFD improves the efficiency of n-3 LC-PUFA restoration in the fillet of Atlantic salmon smolt. PMID:22128889

  13. The antidepressant role of dietary long-chain polyunsaturated n-3 fatty acids in two phases in the developing brain.

    PubMed

    Ferraz, Anete Curte; Kiss, Agata; Araújo, Renata Lins Fuentes; Salles, Hélidy Maria Rossi; Naliwaiko, Katya; Pamplona, Juliana; Matheussi, Francesca

    2008-03-01

    In this work we investigated the effect from fish oil (FO) supplementation, rich in n-3 fatty acids, on an antidepressant effect on adult rats in Phase A (supplementation during pregnancy and lactation) and phase B (supplementation during post-weaning until adulthood). During Phase A, female rats, used as matrix to obtain male rats, were divided in three groups: FO (daily supplemented), CF (coconut fat daily supplemented) and control (not supplemented). Our results showed that adult rats whose mothers were supplemented with FO during Phase A and rats supplemented during phase B demonstrated a significantly decreased immobility time when compared to control and CF groups. There was no difference in neither motor activity nor anxiety behavior in the three groups excluding false positive results. Our results suggest that n-3 fatty acids supplementation during Phases A and B had a beneficial effect on preventing the development of depression-like behavior in adult rats. PMID:18378130

  14. Long-chain polyunsaturated fatty acids upregulate LDL receptor protein expression in fibroblasts and HepG2 cells.

    PubMed

    Yu-Poth, Shaomei; Yin, Dezhong; Kris-Etherton, Penny M; Zhao, Guixiang; Etherton, Terry D

    2005-11-01

    The objective of this study was to investigate the effect of individual PUFAs on LDL receptor (LDLr) expression in human fibroblasts and HepG2 cells, and to evaluate whether acyl CoA:cholesterol acyltransferase (ACAT) and sterol regulatory element-binding protein 1 (SREBP-1) were involved in the regulation of LDLr expression by fatty acids. When fibroblasts and HepG2 cells were cultured with serum-free defined medium for 48 h, there was a 3- to 5-fold (P < 0.05) increase in LDLr protein and mRNA levels. Incubation of fibroblasts and HepG2 cells in serum-free medium supplemented with 25-hydroxycholesterol (25OH-cholesterol, 5 mg/L) for 24 h decreased LDLr protein and mRNA levels by 50-90% (P < 0.05). Arachidonic acid [AA, 20:4(n-6)], EPA [20:5(n-3)], and DHA [22:6(n-3)] antagonized the depression of LDLr gene expression by 25OH-cholesterol and increased LDLr protein abundance 1- to 3-fold (P < 0.05), but had no significant effects on LDLr mRNA levels. Oleic (18:1), linoleic (18:2), and alpha-linolenic acids [18:3(n-3)] did not significantly affect LDLr expression. ACAT inhibitor (58-035, 1 mg/L) attenuated the regulatory effect of AA on LDLr protein abundance by approximately 40% (P < 0.05), but did not modify the regulatory effects of other unsaturated fatty acids in HepG2 cells. The present results suggest that AA, EPA, and DHA increase LDLr protein levels, and that ACAT plays a role in modulating the effects of AA on LDLr protein levels. Furthermore, the effects of the fatty acids appeared to be independent of any change in SREBP-1 protein. PMID:16251608

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. Cytochrome P450 2C8 ω3-Long-Chain Polyunsaturated Fatty Acid Metabolites Increase Mouse Retinal Pathologic Neovascularization—Brief Report

    PubMed Central

    Shao, Zhuo; Fu, Zhongjie; Stahl, Andreas; Joyal, Jean-Sébastien; Hatton, Colman; Juan, Aimee; Hurst, Christian; Evans, Lucy; Cui, Zhenghao; Pei, Dorothy; Gong, Yan; Xu, Dan; Tian, Katherine; Bogardus, Hannah; Edin, Matthew L.; Lih, Fred; Sapieha, Przemyslaw; Chen, Jing; Panigrahy, Dipak; Hellstrom, Ann; Zeldin, Darryl C.; Smith, Lois E.H.

    2014-01-01

    Objective Regulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary ω3-long-chain polyunsaturated fatty acids (ω3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on neovascularization is unknown. Approach and Results The mouse model of oxygen-induced retinopathy was used to investigate retinal neovascularization. We found that CYP2C (localized in wild-type monocytes/macrophages) is upregulated in oxygen-induced retinopathy, whereas sEH is suppressed, resulting in an increased retinal epoxide:diol ratio. With a ω3LCPUFA-enriched diet, retinal neovascularization increases in Tie2-driven human-CYP2C8–overexpressing mice (Tie2-CYP2C8-Tg), associated with increased plasma 19,20-epoxydocosapentaenoic acid and retinal epoxide:diol ratio. 19,20-Epoxydocosapentaenoic acids and the epoxide:diol ratio are decreased with overexpression of sEH (Tie2-sEH-Tg). Overexpression of CYP2C8 or sEH in mice does not change normal retinal vascular development compared with their wild-type littermate controls. The proangiogenic role in retina of CYP2C8 with both ω3LCPUFA and ω6LCPUFA and antiangiogenic role of sEH in ω3LCPUFA metabolism were corroborated in aortic ring assays. Conclusions Our results suggest that CYP2C ω3LCPUFA metabolites promote retinal pathological angiogenesis. CYP2C8 is part of a novel lipid metabolic pathway influencing retinal neovascularization. PMID:24458713

  18. Long chain n-3 polyunsaturated fatty acids increase the efficacy of docetaxel in mammary cancer cells by downregulating Akt and PKCε/δ-induced ERK pathways.

    PubMed

    Chauvin, Lucie; Goupille, Caroline; Blanc, Charly; Pinault, Michelle; Domingo, Isabelle; Guimaraes, Cyrille; Bougnoux, Philippe; Chevalier, Stephan; Mahéo, Karine

    2016-04-01

    Taxanes can induce drug resistance by increasing signaling pathways such as PI3K/Akt and ERK, which promote survival and cell growth in human cancer cells. We have previously shown that long chain n-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA, 22:6n-3) decrease resistance of experimental mammary tumors to anticancer drugs. Our objective was to determine whether DHA could increase tumor sensitivity to docetaxel by down-regulating these survival pathways. In docetaxel-treated MDA-MB-231 cells, phosphorylated-ERK1/2 levels were increased by 60% in membrane and nuclear compartments, compared to untreated cells. Our data showed that ERK1/2 activation depended on PKC activation since: i) enzastaurin (a pan-PKC inhibitor) blocked docetaxel-induced ERK1/2 phosphorylation ii) docetaxel increased PKC activity by 30% and phosphatidic acid level by 1.6-fold iii) inhibition of PKCε and PKCδ by siRNA resulted in reduced phosphorylated ERK1/2 levels. In DHA-supplemented cells, docetaxel was unable to increase PKCε and δ levels in membrane and nuclear fractions, resulting in diminished ERK1/2 phosphorylation and increased docetaxel efficacy. Reduced membrane level of PKCε and PKCδ was associated with significant incorporation of DHA in all phospholipids, including phosphatidylcholine which is a major source of phosphatidic acid. Additionally, examination of the Akt pathway showed that DHA could repress docetaxel-induced Ser473Akt phosphorylation. In rat mammary tumors, dietary DHA supplementation during docetaxel chemotherapy repressed ERK and Akt survival pathways and in turn strongly improved taxane efficacy. The P-ERK level was negatively correlated with tumor regression. These findings are of potential clinical importance in treating chemotherapy-refractory cancer. PMID:26821209

  19. The Effects of n-3 Long-Chain Polyunsaturated Fatty Acid Supplementation on Biomarkers of Kidney Injury in Adults With Diabetes

    PubMed Central

    Miller, Edgar R.; Juraschek, Stephen P.; Anderson, Cheryl A.; Guallar, Eliseo; Henoch-Ryugo, Karen; Charleston, Jeanne; Turban, Sharon; Bennett, Michael R.; Appel, Lawrence J.

    2013-01-01

    OBJECTIVE Long-chain n-3 polyunsaturated fatty acid (n-3 PUFA) supplements may have renoprotective effects in patients with diabetes, but previous trials have been inconsistent. We performed a randomized controlled trial of n-3 PUFA supplementation on urine albumin excretion and markers of kidney injury in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a randomized, placebo-controlled, two-period crossover trial to test the effects of 4 g/day of n-3 PUFA supplementation on markers of glomerular filtration and kidney injury in adults with adult-onset diabetes and greater than or equal to trace amounts of proteinuria. Each period lasted 6 weeks and was separated by a 2-week washout. The main outcome was urine albumin excretion and, secondarily, markers of kidney injury (kidney injury molecule-1, N-acetyl β-d-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and liver fatty acid–binding protein [LFABP]), serum markers of kidney function (cystatin C, β2-microglobulin, and creatinine), and estimated glomerular filtration rate (eGFR). RESULTS Of the 31 participants, 29 finished both periods. A total of 55% were male, and 61% were African American; mean age was 67 years. At baseline, mean BMI was 31.6 kg/m2, median eGFR was 76.9 mL/min/1.73 m2, and median 24-h urine albumin excretion was 161 mg/day. Compared with placebo, n-3 PUFA had nonsignificant effects on urine albumin excretion (−7.2%; 95% CI −20.6 to 8.5; P = 0.35) and significant effects on urine NGAL excretion (−16% [−29.1 to −0.5%]; P = 0.04). There was no effect on serum markers of kidney function or eGFR. In subgroup analyses, there were significant decreases in 24-h urinary excretion of albumin, NGAL, LFABP, and NAG among participants taking medications that block the renin-angiotensin-aldosterone system (RAAS). CONCLUSIONS These results suggest a potential effect of n-3 PUFA supplementation on markers of kidney injury in patients with diabetes and

  20. The effects of n-3 long-chain polyunsaturated fatty acid supplementation on biomarkers of kidney injury in adults with diabetes: results of the GO-FISH trial.

    PubMed

    Miller, Edgar R; Juraschek, Stephen P; Anderson, Cheryl A; Guallar, Eliseo; Henoch-Ryugo, Karen; Charleston, Jeanne; Turban, Sharon; Bennett, Michael R; Appel, Lawrence J

    2013-06-01

    OBJECTIVE Long-chain n-3 polyunsaturated fatty acid (n-3 PUFA) supplements may have renoprotective effects in patients with diabetes, but previous trials have been inconsistent. We performed a randomized controlled trial of n-3 PUFA supplementation on urine albumin excretion and markers of kidney injury in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a randomized, placebo-controlled, two-period crossover trial to test the effects of 4 g/day of n-3 PUFA supplementation on markers of glomerular filtration and kidney injury in adults with adult-onset diabetes and greater than or equal to trace amounts of proteinuria. Each period lasted 6 weeks and was separated by a 2-week washout. The main outcome was urine albumin excretion and, secondarily, markers of kidney injury (kidney injury molecule-1, N-acetyl β-d-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and liver fatty acid-binding protein [LFABP]), serum markers of kidney function (cystatin C, β2-microglobulin, and creatinine), and estimated glomerular filtration rate (eGFR). RESULTS Of the 31 participants, 29 finished both periods. A total of 55% were male, and 61% were African American; mean age was 67 years. At baseline, mean BMI was 31.6 kg/m(2), median eGFR was 76.9 mL/min/1.73 m(2), and median 24-h urine albumin excretion was 161 mg/day. Compared with placebo, n-3 PUFA had nonsignificant effects on urine albumin excretion (-7.2%; 95% CI -20.6 to 8.5; P = 0.35) and significant effects on urine NGAL excretion (-16% [-29.1 to -0.5%]; P = 0.04). There was no effect on serum markers of kidney function or eGFR. In subgroup analyses, there were significant decreases in 24-h urinary excretion of albumin, NGAL, LFABP, and NAG among participants taking medications that block the renin-angiotensin-aldosterone system (RAAS). CONCLUSIONS These results suggest a potential effect of n-3 PUFA supplementation on markers of kidney injury in patients with diabetes and early

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

    PubMed Central

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

    2016-01-01

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

  2. Differential effect of maternal diet supplementation with α-Linolenic adcid or n-3 long-chain polyunsaturated fatty acids on glial cell phosphatidylethanolamine and phosphatidylserine fatty acid profile in neonate rat brains

    PubMed Central

    2010-01-01

    Background Dietary long-chain polyunsaturated fatty acids (LC-PUFA) are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the neonates. Methods Sprague-Dawley rats were fed during the whole gestation and lactation period with a diet containing either docosahexaenoic acid (DHA, 0.55%) and eicosapentaenoic acid (EPA, 0.75% of total fatty acids) or α-linolenic acid (ALA, 2.90%). At two weeks of age, gastric content and brain glial cell PE and PS of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA) profile. Data were analyzed by bivariate and multivariate statistics. Results In the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric content (+65%, P < 0.0001) and brain glial cell PE (+18%, P = 0.0001) and PS (+15%, P = 0.0009) were significantly increased compared to the ALA group. The filtered correlation analysis (P < 0.05) underlined that levels of dihomo-γ-linolenic acid (DGLA), DHA and n-3 docosapentaenoic acid (DPA) were negatively correlated with arachidonic acid (ARA) and n-6 DPA in PE of brain glial cells. No significant correlation between n-3 and n-6 LC-PUFA were found in the PS dataset. DMA level in PE was negatively correlated with n-6 DPA. DMA were found to occur in brain glial cell PS fraction; in this class DMA level was correlated negatively with DHA and positively with ARA. Conclusion The present study confirms that early supplementation of maternal diet with n-3 fatty acids supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE and PS in the neonate than ALA. Negative correlation between n-6 DPA, a conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that potentially be considered as a marker of tissue

  3. 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

  4. 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

  5. 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

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

    PubMed

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

    2015-03-01

    The endogenous production of long-chain polyunsaturated fatty acids (LC-PUFA) in carnivorous teleost species inhabiting freshwater environments is poorly understood. Although a predatory lifestyle could potentially supply sufficient LC-PUFA to satisfy the requirements of these species, the nutrient-poor characteristics of the freshwater food web could impede this advantage. In this study, we report the cloning and functional characterisation of an elongase enzyme in the LC-PUFA biosynthesis pathway from striped snakehead (Channa striata), which is a strict freshwater piscivore that shows high deposition of LC-PUFA in its flesh. We also functionally characterised a previously isolated fatty acyl desaturase cDNA from this species. Results showed that the striped snakehead desaturase is capable of Δ4 and Δ5 desaturation activities, while the elongase showed the characteristics of Elovl5 elongases. Collectively, these findings reveal that striped snakehead exhibits the genetic resources to synthesise docosahexaenoic acid (DHA; 22:6n-3) from eicosapentaenoic acid (EPA; 20:5n-3). Both genes are expressed at considerable levels in the brain and the liver. In liver, both genes were up-regulated by dietary C18 PUFA, although this increase did not correspond to a significant rise in the deposition of muscle LC-PUFA. Brain tissue of fish fed with plant oil diets showed higher expression of fads2 gene compared to fish fed with fish oil-based diet, which could ensure DHA levels remain constant under limited dietary DHA intake. This suggests the importance of DHA production from EPA via the ∆4 desaturation step in order to maintain an optimal reserve of DHA in the neuronal tissues of carnivores. PMID:25542509

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

    PubMed

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

    2016-08-01

    Despite the potential of vegetable oils as aquafeed ingredients, a major drawback associated with their utilization is the inferior level of beneficial n-3 long-chain polyunsaturated fatty acids (LC-PUFA). Echium oil (EO), which is rich in stearidonic acid (SDA, 18:4n-3), could potentially improve the deposition of n-3 LC-PUFA as the biosynthesis of LC-PUFA is enhanced through bypassing the rate-limiting ∆6 desaturation step. We report for the first time an attempt to investigate whether the presence of a desaturase (Fads2) capable of ∆4 desaturation activities and an elongase (Elovl5) will leverage the provision of dietary SDA to produce a higher rate of LC-PUFA bioconversion. Experimental diets were designed containing fish oil (FO), EO or linseed oil (LO) (100FO, 100EO, 100LO), and diets which comprised equal mixtures of the designated oils (50EOFO and 50EOLO) were evaluated in a 12-week feeding trial involving striped snakeheads (Channa striata). There was no significant difference in growth and feed conversion efficiency. The hepatic fatty acid composition and higher expression of fads2 and elovl5 genes in fish fed EO-based diets indicate the utilization of dietary SDA for LC-PUFA biosynthesis. Collectively, this resulted in a higher deposition of muscle eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) compared to LO-based diets. Dietary EO improved the ratio of n-3 LC-PUFA to n-6 LC-PUFA in fish muscle, which is desirable for human populations with excessive consumption of n-6 PUFA. This study validates the contribution of SDA in improving the content of n-3 LC-PUFA and the ratio of EPA to arachidonic acid (ARA, 20:4n-6) in a freshwater carnivorous species. PMID:26842427

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

    PubMed

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

    2013-09-01

    Long-chain n-3 PUFA (LCPUFA) and palmitate (16:0) positioning in the triacylglycerol (TAG) of infant formula may affect calcium-uptake which could affect bone health. We investigated if a human milk fat substitute (HMFS) with a modified TAG structure holding 16:0 predominantly in the sn-2-position compared with a control (CONT) and if increasing n-3LCPUFA intake giving fish oil (FO) compared with sunflower oil (SO) would affect bone parameters in piglets in two sets of controlled 14d-interventions (n=12/group). We assessed this by dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography and mechanical strength. Bone mineral content (BMC) was higher in the FO compared to the SO-group (p=0.03). Despite similar weight gain in HMFS- and CONT-groups, body fat accumulation was higher with HMFS (p<0.001), and BMC, bone area (BA) and cortical BA in femur were lower (p=0.002, p=0.005, and p=0.02, respectively), indicating importance of both n-3LCPUFA and 16:0 TAG-positioning in infant formulas. PMID:23867727

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

    PubMed Central

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

    2016-01-01

    Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long-term use can cause neurobiological side-effects associated with depression. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), the essential fatty acids found in fish oil, possess neuroprotecitve and antidepressant activities. Thus, the aim of this study was to explore the potential protective effects of ω-3 PUFAs against DOX-induced behavioral changes and neurotoxicity. ω-3 PUFAs were given daily by gavage (1.5 g/kg) over three weeks starting seven days before DOX administration (2.5 mg/kg). Open-field test (OFT) and forced swimming test (FST) were conducted to assess exploratory activity and despair behavior, respectively. Our data showed that ω-3 PUFAs supplementation significantly mitigated the behavioral changes induced by DOX. ω-3 PUFAs pretreatment also alleviated the DOX-induced neural apoptosis. Meanwhile, ω-3 PUFAs treatment ameliorated DOX-induced oxidative stress in the prefrontal cortex and hippocampus. Additionally, gene expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and the protein levels of NF-κB and iNOS were significantly increased in brain tissues of DOX-treated group, whereas ω-3 PUFAs supplementation significantly attenuated DOX-induced neuroinflammation. In conclusion, ω-3 PUFAs can effectively protect against DOX-induced depressive-like behaviors, and the mechanisms underlying the neuroprotective effect are potentially associated with its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. PMID:27120616

  10. 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...

  11. 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

  12. 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

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

    PubMed

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

    2010-06-01

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

  14. 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

  15. Conversion of linoleic acid and alpha-linolenic acid to long-chain polyunsaturated fatty acids (LCPUFAs), with a focus on pregnancy, lactation and the first 2 years of life.

    PubMed

    Gibson, Robert A; Muhlhausler, Bev; Makrides, Maria

    2011-04-01

    Over the past two decades, there has been a marked shift in the fatty acid composition of the diets of industrialized nations towards increased intake of the n-6 fatty acid linoleic acid (LA, 18:2n-6), largely as a result of the replacement of saturated fats with plant-based polyunsaturated fatty acid (PUFA). While health agencies internationally continue to advocate for high n-6 PUFA intake combined with increased intakes of preformed n-3 long-chain PUFAs (LCPUFA) docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) to reduce the incidence of cardiovascular disease (CVD), there are questions as to whether this is the best approach. LA competes with alpha-linolenic acid (18:3n-3) for endogenous conversion to the LC derivatives EPA and DHA, and LA also inhibits incorporation of DHA and EPA into tissues. Thus, high-LA levels in the diet generally result in low n-3 LCPUFA status. Pregnancy and infancy are developmental periods during which the fatty acid supply is particularly critical. The importance of an adequate supply of n-3 LCPUFA for ensuring optimal development of infant brain and visual systems is well established, and there is now evidence that the supply of n-3 LCPUFA also influences a range of growth, metabolic and immune outcomes in childhood. This review will re-evaluate the health benefits of modern Western diets and pose the question of whether the introduction of similar diets to nations with emerging economies is the most prudent public health strategy for improving health in these populations. PMID:21366864

  16. 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

  17. 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.

  18. 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...

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

    PubMed Central

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

    2015-01-01

    The present case-control study explored the interaction between marine-derived n-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs) and uric acid (UA) on glucose metabolism and risk of type 2 diabetes mellitus (T2DM). Two hundred and eleven healthy subjects in control group and 268 T2DM subjects in case group were included. Plasma phospholipid (PL) fatty acids and biochemical parameters were detected by standard methods. Plasma PL C22:6n-3 was significantly lower in case group than in control group, and was negatively correlated with fasting glucose (r = −0.177, p < 0.001). Higher plasma PL C22:6n-3 was associated with lower risk of T2DM, and the OR was 0.32 (95% confidence interval (CI), 0.12 to 0.80; p = 0.016) for per unit increase of C22:6n-3. UA was significantly lower in case group than in control group. UA was positively correlated with fasting glucose in healthy subjects, but this correlation became negative in T2DM subjects. A significant interaction was observed between C22:6n-3 and UA on fasting glucose (p for interaction = 0.005): the lowering effect of C22:6n-3 was only significant in subjects with a lower level of UA. In conclusion, C22:6n-3 interacts with UA to modulate glucose metabolism. PMID:26343686

  20. Modifications of proteins by polyunsaturated fatty acid peroxidation products

    NASA Astrophysics Data System (ADS)

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

    2000-01-01

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

  1. 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

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

    PubMed

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

    2014-04-01

    This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake. PMID:24456663

  3. Long chain fatty acids and dietary fats in fetal nutrition

    PubMed Central

    Cetin, Irene; Alvino, Gioia; Cardellicchio, Manuela

    2009-01-01

    Long chain polyunsaturated fatty acids are essential nutrients for a healthy diet. The different kinds consumed by the mother during gestation and lactation may influence pregnancy, fetal and also neonatal outcome. The amount of fatty acids transferred from mother to fetus depends not only on maternal metabolism but also on placental function, i.e. by the uptake, metabolism and then transfer of fatty acids to the fetus. The third trimester of gestation is characterized by an increase of long chain polyunsaturated fatty acids in the fetal circulation, in particular docosahexaenoic acid, especially to support brain growth and visual development. These mechanisms may be altered in pathological conditions, such as intrauterine growth restriction and diabetes, when maternal and fetal plasma levels of long chain polyunsaturated fatty acids undergo significant changes. The aim of this review is to describe the maternal and placental factors involved in determining fetal fatty acid availability and metabolism, focusing on the specific role of long chain polyunsaturated fatty acids in normal and pathological pregnancies. PMID:19528253

  4. The Association of Prenatal Exposure to Perfluorinated Chemicals with Maternal Essential and Long-Chain Polyunsaturated Fatty Acids during Pregnancy and the Birth Weight of Their Offspring: The Hokkaido Study

    PubMed Central

    Nakajima, Tamie; Goudarzi, Houman; Kobayashi, Sachiko; Sasaki, Seiko; Okada, Emiko; Miyashita, Chihiro; Itoh, Sachiko; Araki, Atsuko; Ikeno, Tamiko; Iwasaki, Yusuke; Nakazawa, Hiroyuki

    2015-01-01

    long-chain polyunsaturated fatty acids during pregnancy and the birth weight of their offspring: the Hokkaido Study. Environ Health Perspect 123:1038–1045; http://dx.doi.org/10.1289/ehp.1408834 PMID:25840032

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

    PubMed Central

    Meyer, Barbara J.

    2016-01-01

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

  6. Continuous gradient temperature Raman spectroscopy of the long chain polyunsaturated fatty acids docosapentaenoic (DPA, 22:5n-6) and docosahexaenoic (DHA; 22:6n-3) from -100 to 20° C

    NASA Astrophysics Data System (ADS)

    Broadhurst, C. Leigh; Schmidt, Walter F.; Kim, Moon S.; Nguyen, Julie K.; Qin, Jianwei; Chao, Kuanglin; Bauchan, Gary L.; Shelton, Daniel R.

    2016-05-01

    The structural, cognitive and visual development of the human brain and retina strictly require long-chain polyunsaturated fatty acids (LC-PUFA). Excluding water, the mammalian brain is about 60% lipid. One of the great unanswered questions with respect to biological science in general is the absolute necessity of the LC-PUFA docosahexaenoic acid (DHA; 22:6n-3) in these fast signal processing tissues. A lipid of the same chain length with just one less diene group, docosapentaenoic acid (DPA; 22:5n-6) is fairly abundant in terrestrial food chains yet cannot substitute for DHA. Gradient Temperature Raman spectroscopy (GTRS) applies the temperature gradients utilized in differential scanning calorimetry to Raman spectroscopy, providing a straightforward technique to identify molecular rearrangements that occur near and at phase transitions. Herein we apply GTRS to DPA, and DHA from -100 to 20°C. 20 Mb three-dimensional data arrays with 1°C increments and first/second derivatives allows complete assignment of solid, liquid and transition state vibrational modes, including low intensity/frequency vibrations that cannot be readily analyzed with conventional Raman. DPA and DHA show significant spectral changes with premelting (-33 and -60°C, respectively) and melting (-27 and -44°C, respectively). The CH2-(HC=CH)-CH2 moieties are not identical in the second half of the DHA and DPA structures. The DHA molecule contains major CH2 twisting (1265 cm-1) with no noticeable CH2 bending, consistent with a flat helical structure with small pitch. Further modeling of neuronal membrane phospholipids must take into account this structure for DHA, which would be configured parallel to the hydrophilic head group line.

  7. Association Between Serum Long-Chain n-3 and n-6 Polyunsaturated Fatty Acid Profiles and Glomerular Filtration Rate Assessed by Serum Creatinine and Cystatin C Levels in Japanese Community-Dwellers

    PubMed Central

    Higashiyama, Aya; Kubota, Yoshimi; Marumo, Mikio; Konishi, Masami; Yamashita, Yoshiko; Nishimura, Kunihiro; Fukuda, Yoshihiro; Okamura, Tomonori; Wakabayashi, Ichiro

    2015-01-01

    Background Plasma concentration of n-3 polyunsaturated fatty acids (PUFAs) has been reported to be associated with renal function in Western populations. However, few studies have investigated the association between serum long-chain n-3 and n-6 PUFA profiles and renal function in a Japanese population with high marine-derived long-chain n-3 PUFA intake. Methods A cross-sectional study was performed in 549 Japanese rural community-dwellers aged 40 to 64 years. In adjusted analysis of covariance, we assessed the relationship between estimated glomerular filtration rate (eGFR) and tertiles of serum long-chain n-3 and n-6 PUFA profiles ([eicosapentaenoic acid {EPA} + docosahexaenoic acid {DHA}]:arachidonic acid [AA]). GFR was estimated by Japanese specific equations using serum creatinine and cystatin C (eGFRcre and eGFRcys). Using multivariate-adjusted linear regression models, we also assessed the relationships between eGFRs and several n-3 and n-6 PUFAs, which have been suggested to be associated with renal function. Results In all participants, higher dietary fish intake as assessed by a semi-quantitative questionnaire was associated with higher serum value of (EPA+DHA):AA. Participants in the higher (EPA+DHA):AA tertiles had non-significantly higher eGFRcre and significantly higher eGFRcys (P = 0.016). In addition, eGFRcys in T2+T3 of (EPA+DHA):AA was significantly higher than that in T1 (adjusted mean eGFRcys, T1: 87 ml/min/1.73 m2, T2+T3: 91 ml/min/1.73 m2; P < 0.01). Among the PUFAs, only (EPA+DHA) was significantly associated with eGFRcys. Conclusions Serum (EPA+DHA):AA, which reflects an individual’s fish intake, might be associated with eGFRcys in Japanese community-dwellers. PMID:25728619

  8. 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

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

    PubMed

    Bowzer, J; Jackson, C; Trushenski, J

    2016-03-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. 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

  12. 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

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

    PubMed

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

    2012-12-01

    The present study deals with the possible effects of dietary ω3 and ω6 fatty acids upon the metabolic syndrome found in rats exposed for 8 weeks to a diet containing 64% (w/w) D-fructose instead of starch. Fructose-fed rats were found to display a modest increase in plasma albumin and protein concentration and more pronounced increases in plasma urea, creatinine, phospholipids, triglycerides and cholesterol concentrations, glycated hemoglobin concentration and liver contents of cholesterol, triglycerides and phospholipids. The plasma concentrations of HDL-cholesterol, calcium and iron were decreased, however, in the fructose-fed rats. In general, the partial substitution of sunflower oil by either safflower oil or salmon oil opposed the metabolic perturbations otherwise associated with the fructose-induced metabolic syndrome in the fructose-fed rats, with salmon oil demonstrating particular efficacy. Consideration is given to the possible biological determinants of these perturbations and their attenuation in rats exposed to safflower or salmon oil. PMID:23007116

  14. Opposing Effects of Omega-3 and Omega-6 Long Chain Polyunsaturated Fatty Acids on the Expression of Lipogenic Genes in Omental and Retroperitoneal Adipose Depots in the Rat

    PubMed Central

    Muhlhausler, B. S.; Cook-Johnson, R.; James, M.; Miljkovic, D.; Duthoit, E.; Gibson, R.

    2010-01-01

    This study aimed to determine the effect of varying dietary intake of the major n-3 PUFA in human diets, α-linolenic acid (ALA; 18 : 3n-3), on expression of lipogenic genes in adipose tissue. Rats were fed diets containing from 0.095%en to 6.3%en ALA and a constant n-6 PUFA level for 3 weeks. Samples from distinct adipose depots (omental and retroperitoneal) were collected and mRNA expression of the pro-lipogenic transcription factors Sterol-Retinoid-Element-Binding-Protein1c (SREBP1c) and Peroxisome Proliferator Activated Receptor-γ (PPARγ), lipogenic enzymes Sterol-coenzyme Desaturase1 (SCD-1), Fatty Acid Synthase (FAS), lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (G3PDH) and adipokines leptin and adiponectin determined by qRT-PCR. Increasing dietary ALA content resulted in altered expression of SREBP1c, FAS and G3PDH mRNA in both adipose depots. SREBP1c mRNA expression was related directly to n-6 PUFA concentrations (omental, r2 = .71; P < .001; Retroperitoneal, r2 = .20; P < .002), and inversely to n-3 PUFA concentrations (omental, r2 = .59; P < .001; Retroperitoneal, r2 = .19; P < .005) independent of diet. The relationship between total n-6 PUFA and SREBP1c mRNA expression persisted when the effects of n-3 PUFA were controlled for. Altering red blood cell concentrations of n-3 PUFA is thus associated with altered expression of lipogenic genes in a depot-specific manner and this effect is modulated by prevailing n-6 PUFA concentrations. PMID:20814437

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

    PubMed

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

    2009-09-01

    The present study was designed to evaluate the independent and interactive effects of a once-a-day yoghurt drink providing 2 g plant sterols/d and capsules providing 2 g fish oil n-3 long-chain (LC) PUFA/d on plasma lipids, apolipoproteins and LDL particle size. Following a 2-week run-in period, 200 mildly hypercholesterolaemic Indian adults aged 35-55 years were randomised into one of four groups of a 2 x 2 factorial, double-blind controlled trial. The 4-week treatments consisted of (1) control yoghurt drink and control capsules, (2) control yoghurt drink and fish oil capsules, (3) plant sterol-enriched yoghurt drink and control capsules, or (4) plant sterol-enriched yoghurt drink and fish oil capsules. Blood was drawn before and after the 4-week intervention. Changes in health status, lifestyle and dietary habits, and daily compliance were recorded. The main effects of plant sterols were a 4.5 % reduction in LDL-cholesterol and a 15 % reduction in TAG without a significant change in HDL-cholesterol. Overall, fish oil n-3 LC-PUFA did not significantly affect cholesterol concentrations but reduced TAG by 15 % and increased HDL-cholesterol by 5.4 %. The combination significantly lowered TAG by 15 % v. control. No significant interaction between plant sterols and n-3 LC-PUFA was observed on plasma cholesterol concentrations. In conclusion, once-a-day intake of 2 g plant sterols/d in a yoghurt drink, 2 g fish oil n-3 LC-PUFA/d in capsules, and their combination had beneficial effects on the lipid profile of mildly hypercholesterolaemic Indian adults. The potent hypotriacylglycerolaemic effect of plant sterols observed in the present study and this population warrants additional investigation. PMID:19296875

  16. 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

  17. 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

  18. [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

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

    PubMed

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

    2013-11-27

    Omega-3 polyunsaturated fatty acids (n-3 PUFA) enriched eggs have a growing market share in the egg industry. This study examined the stability of n-3 PUFA enriched eggs fortified with antioxidants (vitamin E or organic Selenium [Sel-Plex] or both) following cooking and storage. The total fat content was not affected by cooking or simulated retail storage conditions, whereas, n-3 fatty acids were reduced. The content of n-3 fatty acids in boiled eggs was higher than in fried eggs. Lipid oxidation was significantly affected by the different cooking methods. Fried eggs contained higher levels of malondialdehyde (MDA, 2.02 μg/kg) and cholesterol oxidation products (COPs, 13.58 μg/g) compared to boiled (1.44 and 10.15 μg/kg) and raw eggs (0.95 and 9.03 μg/kg, respectively, for MDA and COPs). Supplementation of antioxidants reduced the formation of MDA by 40% and COPs by 12% in fried eggs. Although the content of MDA was significantly increased after 28 days of storage, COPs were not affected by storage. Our study indicated that the n-3 PUFA in enriched eggs was relatively stable during storage and home cooking in the presence of antioxidants. PMID:24164329

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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 ...

  10. 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

  11. [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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  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. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. 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

  3. 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

  4. 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),…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. 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

  7. 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

  8. 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

  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. 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

  11. 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

  12. 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

  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. 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 ...

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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...

  20. 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

  1. 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 ...

  2. 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-...

  3. 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…

  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. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Identification of novel n-4 series polyunsaturated fatty acids in a deep-sea clam, Calyptogena phaseoliformis.

    PubMed

    Saito, Hiroaki

    2007-09-01

    Novel fatty acids originated from the cold-seep clam Calyptogena phaseoliformis, collected from hydrothermal vents in the Japan Trench at a depth of 6354-6367 m, were determined by using gas chromatography-mass spectrometry analysis of the 4,4-dimethyloxazoline derivatives. The major fatty acids present in the C. phaseoliformis lipids belong to the n-4 family non-methylene interrupted polyunsaturated fatty acids (NMI-PUFA): 20:3n-4,7,15, 20:4n-1,4,7,15, and 21:3n-4,7,16, with significant levels of 20:2n-7,15 and 21:2n-7,16 as non-methylene interrupted n-7 dienes. Compared with the lipids of shallow-water clam Mactra chinensis, which contains photosynthetic n-3 PUFA, such as docosahexaenoic acid and icosapentaenoic acid, C. phaseoliformis might have an intrinsic mechanism in vivo so as to maintain the fluidity of the high-melting fatty acids in the membrane lipids by exogenous n-4 family PUFA adaptation as substitutes. Such special kinds of fatty acids are assimilated by the symbiotic chemosynthetic bacteria, which use geothermal energy and minerals from the cold-seep vents. Its unique fatty acid composition corresponding to the novel n-4 family NMI-PUFA markedly differs from those of the reported lipid compositions of other marine animals, which depend on the marine grazing food chain originating from phytoplankton. Thus, the present findings confirm a perfect and closed novel food chain in the cold-seep bivalve and in its symbionts, which is independent from the photosynthetic food chain. PMID:17604037

  14. 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

  15. 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

  16. 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

  17. 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...

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. DNA methylation perturbations in genes involved in polyunsaturated Fatty Acid biosynthesis associated with depression and suicide risk.

    PubMed

    Haghighi, Fatemeh; Galfalvy, Hanga; Chen, Sean; Huang, Yung-Yu; Cooper, Thomas B; Burke, Ainsley K; Oquendo, Maria A; Mann, J John; Sublette, M Elizabeth

    2015-01-01

    Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention. PMID:25972837

  7. DNA Methylation Perturbations in Genes Involved in Polyunsaturated Fatty Acid Biosynthesis Associated with Depression and Suicide Risk

    PubMed Central

    Haghighi, Fatemeh; Galfalvy, Hanga; Chen, Sean; Huang, Yung-yu; Cooper, Thomas B.; Burke, Ainsley K.; Oquendo, Maria A.; Mann, J. John; Sublette, M. Elizabeth

    2015-01-01

    Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention. PMID:25972837

  8. [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

  9. The effects of dietary lipid and strain difference on polyunsaturated fatty acid composition and conversion in anadromous and landlocked salmon (Salmo salar L.) parr.

    PubMed

    Rollin, Xavier; Peng, Jinglan; Pham, Diep; Ackman, Robert G; Larondelle, Yvan

    2003-02-01

    Five experimental diets containing different proportions of olive, sunflower and linseed oils were used in a 55-day feeding trial on both anadromous and landlocked parr of Atlantic salmon (Salmo salar) of the same age, in order to study the effects of diet and strain on growth and fatty acid composition and absolute gains in fish whole body triacylglycerols (TAG) and phospholipids (PL). Growth rate was higher in landlocked than in anadromous parr, but not between the different diets. By contrast, the effect of diet on whole body fatty acid composition was much more pronounced than that of strain difference. The fatty acids deposition results establish significant (P<0.05) positive correlations and linear relationships between the percentage of several fatty acids (18:1n-9, 18:2n-6, 18:3n-3) in dietary lipids and their absolute gains in whole body TAG and PL of both stocks. They also indicate the selective deposition of 18:1n-9 compared with linoleic acid (LLA) and linolenic acid (LNA). Finally, the results suggest the occurrence of the conversion of LLA and LNA to long-chain polyunsaturated fatty acids, its stimulation by increased substrate availability, a significantly higher n-3 and n-6 polyunsaturated fatty acids conversion capacity in landlocked than in anadromous parr and a strong genetic influence on docosahexaenoic acid content in salmon parr PL. PMID:12568812

  10. Phospholipids that contain polyunsaturated fatty acids enhance neuronal cell mechanics and touch sensation

    PubMed Central

    Vásquez, Valeria; Krieg, Michael; Lockhead, Dean; Goodman, Miriam B.

    2014-01-01

    Summary Mechano-electrical transduction (MeT) channels embedded in neuronal cell membranes are essential for touch and proprioception. Little is understood about the interplay between native MeT channels and membrane phospholipids, in part because few techniques are available for altering plasma membrane composition in vivo. Here, we leverage genetic dissection, chemical complementation, and optogenetics to establish that arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, enhances touch sensation and mechanoelectrical transduction activity while incorporated into membrane phospholipids in C. elegans touch receptor neurons (TRNs). Because dynamic force spectroscopy reveals that AA modulates the mechanical properties of TRN plasma membranes, we propose that this PUFA is needed for MeT channel activity. These findings establish that polyunsaturated phospholipids are crucial determinants of both the biochemistry and mechanics of mechanoreceptor neurons and reinforce the idea that sensory mechanotransduction in animals relies on a cellular machine composed of both proteins and membrane lipids. PMID:24388754

  11. Biochemical and genetic engineering of diatoms for polyunsaturated fatty acid biosynthesis.

    PubMed

    Li, Hong-Ye; Lu, Yang; Zheng, Jian-Wei; Yang, Wei-Dong; Liu, Jie-Sheng

    2014-01-01

    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

  12. Biochemical and Genetic Engineering of Diatoms for Polyunsaturated Fatty Acid Biosynthesis

    PubMed Central

    Li, Hong-Ye; Lu, Yang; Zheng, Jian-Wei; Yang, Wei-Dong; Liu, Jie-Sheng

    2014-01-01

    The role of diatoms as a source of bioactive compounds has been recently explored. Diatom cells store a high amount of fatty acids, especially certain polyunsaturated fatty acids (PUFAs). However, many aspects of diatom metabolism and the production of PUFAs remain unclear. This review describes a number of technical strategies, such as modulation of environmental factors (temperature, light, chemical composition of culture medium) and culture methods, to influence the content of PUFAs in diatoms. Genetic engineering, a newly emerging field, also plays an important role in controlling the synthesis of fatty acids in marine microalgae. Several key points in the biosynthetic pathway of PUFAs in diatoms as well as recent progresses are also a critical part and are summarized here. PMID:24402175

  13. 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

  14. Omega-3 Polyunsaturated Fatty Acids Intake to Regulate Helicobacter pylori-Associated Gastric Diseases as Nonantimicrobial Dietary Approach.

    PubMed

    Park, Jong-Min; Jeong, Migyeong; Kim, Eun-Hee; Han, Young-Min; Kwon, Sung Hun; Hahm, Ki-Baik

    2015-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs), commonly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been acknowledged as essential long-chain fatty acids imposing either optimal health promotion or the rescuing from chronic inflammatory diseases such as atherosclerosis, fatty liver, and various inflammatory gastrointestinal diseases. Recent studies dealing with EPA and DHA have sparked highest interests because detailed molecular mechanisms had been documented with the identification of its receptor, G protein coupled receptor, and GPR120. In this review article, we have described clear evidences showing that n-3 PUFAs could reduce various Helicobacter pylori- (H. pylori-) associated gastric diseases and extended to play even cancer preventive outcomes including H. pylori-associated gastric cancer by influencing multiple targets, including proliferation, survival, angiogenesis, inflammation, and metastasis. Since our previous studies strongly concluded that nonantimicrobial dietary approach for reducing inflammation, for instance, application of phytoceuticals, probiotics, natural products including Korean red ginseng, and walnut plentiful of n-3 PUFAs, might be prerequisite step for preventing H. pylori-associated gastric cancer as well as facilitating the rejuvenation of precancerous atrophic gastritis, these beneficial lipids can restore or modify inflammation-associated lipid distortion and correction of altered lipid rafts to send right signaling to maintain healthy stomach even after chronic H. pylori infection. PMID:26339635

  15. Omega-3 Polyunsaturated Fatty Acids Intake to Regulate Helicobacter pylori-Associated Gastric Diseases as Nonantimicrobial Dietary Approach

    PubMed Central

    Park, Jong-Min; Jeong, Migyeong; Kim, Eun-Hee; Han, Young-Min; Kwon, Sung Hun; Hahm, Ki-Baik

    2015-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs), commonly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been acknowledged as essential long-chain fatty acids imposing either optimal health promotion or the rescuing from chronic inflammatory diseases such as atherosclerosis, fatty liver, and various inflammatory gastrointestinal diseases. Recent studies dealing with EPA and DHA have sparked highest interests because detailed molecular mechanisms had been documented with the identification of its receptor, G protein coupled receptor, and GPR120. In this review article, we have described clear evidences showing that n-3 PUFAs could reduce various Helicobacter pylori- (H. pylori-) associated gastric diseases and extended to play even cancer preventive outcomes including H. pylori-associated gastric cancer by influencing multiple targets, including proliferation, survival, angiogenesis, inflammation, and metastasis. Since our previous studies strongly concluded that nonantimicrobial dietary approach for reducing inflammation, for instance, application of phytoceuticals, probiotics, natural products including Korean red ginseng, and walnut plentiful of n-3 PUFAs, might be prerequisite step for preventing H. pylori-associated gastric cancer as well as facilitating the rejuvenation of precancerous atrophic gastritis, these beneficial lipids can restore or modify inflammation-associated lipid distortion and correction of altered lipid rafts to send right signaling to maintain healthy stomach even after chronic H. pylori infection. PMID:26339635

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

    PubMed Central

    2011-01-01

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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. Biosynthetic production of universally (13)C-labelled polyunsaturated fatty acids as reference materials for natural health product research.

    PubMed

    Le, Phuong Mai; Fraser, Catherine; Gardner, Graeme; Liang, Wei-Wan; Kralovec, Jaroslav A; Cunnane, Stephen C; Windust, Anthony J

    2007-09-01

    Long-chain polyunsaturated fatty acids (LCPUFA) including eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) have become important natural health products with numerous proven benefits related to brain function and cardiovascular health. Not only are omega-3 fatty acids available in a plethora of dietary supplements, but they are also increasingly being incorporated as triglycerides into conventional foods, including bread, milk, yoghurt and confectionaries. Recently, transgenic oil seed crops and livestock have been developed that enhance omega-3 fatty acid content. This diverse array of matrices presents a difficult analytical challenge and is compounded further by samples generated through clinical research. Stable isotope (13)C-labelled LCPUFA standards offer many advantages as research tools because they may be distinguished from their naturally abundant counterparts by mass spectrometry and directly incorporated as internal standards into analytical procedures. Further, (13)C-labelled LCPUFAs are safe to use as metabolic tracers to study uptake and metabolism in humans. Currently, (13)C-labelled LCPUFAs are expensive, available in limited supply and not in triglyceride form. To resolve these issues, marine heterotrophic microorganisms are being isolated and screened for LCPUFA production with a view to the efficient biosynthetic production of U-(13)C-labelled fatty acids using U-(13)C glucose as a carbon source. Of 37 isolates obtained, most were thraustochytrids, and either DHA or omega-6 docosapentaenoic acid (22:5n-6) were produced as the major LCPUFA. The marine protist Hyalochlorella marina was identified as a novel source of EPA and omega-3 docosapentaenoic acid (22:5n-3). As proof of principle, gram-level production of (13)C-labelled DHA has been achieved with high chemical purity ( >99%) and high (13)C incorporation levels (>90%), as confirmed by NMR and MS analyses. Finally, U-(13)C-DHA was enzymatically re-esterified to

  5. 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

  6. 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

  7. 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

  8. 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

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

    PubMed Central

    Mihálik, Daniel; Klčová, Lenka; Ondreičková, Katarína; Hudcovicová, Martina; Gubišová, Marcela; Klempová, Tatiana; Čertík, Milan; Pauk, János; Kraic, Ján

    2015-01-01

    The artificial gene D6D encoding the enzyme ∆6desaturase was designed and synthesized using the sequence of the same gene from the fungus Thamnidium elegans. The original start codon was replaced by the signal sequence derived from the wheat gene for high-molecular-weight glutenin subunit and the codon usage was completely changed for optimal expression in wheat. Synthesized artificial D6D gene was delivered into plants of the spring wheat line CY-45 and the gene itself, as well as transcribed D6D mRNA were confirmed in plants of T0 and T1 generations. The desired product of the wheat genetic modification by artificial D6D gene was the γ-linolenic acid. Its presence was confirmed in mature grains of transgenic wheat plants in the amount 0.04%–0.32% (v/v) of the total amount of fatty acids. Both newly synthesized γ-linolenic acid and stearidonic acid have been detected also in leaves, stems, roots, awns, paleas, rachillas, and immature grains of the T1 generation as well as in immature and mature grains of the T2 generation. Contents of γ-linolenic acid and stearidonic acid varied in range 0%–1.40% (v/v) and 0%–1.53% (v/v) from the total amount of fatty acids, respectively. This approach has opened the pathway of desaturation of fatty acids and production of essential polyunsaturated fatty acids in wheat. PMID:26694368

  10. An alternate pathway to long-chain polyunsaturates: the FADS2 gene product Δ8-desaturates 20:2n-6 and 20:3n-3

    PubMed Central

    Park, Woo Jung; Kothapalli, Kumar S. D.; Lawrence, Peter; Tyburczy, Cynthia; Brenna, J. Thomas

    2009-01-01

    The mammalian Δ6-desaturase coded by fatty acid desaturase 2 (FADS2; HSA11q12-q13.1) catalyzes the first and rate-limiting step for the biosynthesis of long-chain polyunsaturated fatty acids. FADS2 is known to act on at least five substrates, and we hypothesized that the FADS2 gene product would have Δ8-desaturase activity. Saccharomyces cerevisiae transformed with a FADS2 construct from baboon neonate liver cDNA gained the function to desaturate 11,14-eicosadienoic acid (20:2n-6) and 11,14,17-eicosatrienoic acid (20:3n-3) to yield 20:3n-6 and 20:4n-3, respectively. Competition experiments indicate that Δ8-desaturation favors activity toward 20:3n-3 over 20:2n-6 by 3-fold. Similar experiments show that Δ6-desaturase activity is favored over Δ8-desaturase activity by 7-fold and 23-fold for n-6 (18:2n-6 vs 20:2n-6) and n-3 (18:3n-3 vs 20:3n-3), respectively. In mammals, 20:3n-6 is the immediate precursor of prostaglandin E1 and thromboxane B1. 20:3n-6 and 20:4n-3 are also immediate precursors of long-chain polyunsaturated fatty acids arachidonic acid and eicosapentaenoic acid, respectively. These findings provide unequivocal molecular evidence for a novel alternative biosynthetic route to long-chain polyunsaturated fatty acids in mammals from substrates previously considered to be dead-end products. PMID:19202133

  11. Circulating Omega‐3 Polyunsaturated Fatty Acids and Subclinical Brain Abnormalities on MRI in Older Adults: The Cardiovascular Health Study

    PubMed Central

    Virtanen, Jyrki K.; Siscovick, David S.; Lemaitre, Rozenn N.; Longstreth, William T.; Spiegelman, Donna; Rimm, Eric B.; King, Irena B.; Mozaffarian, Dariush

    2013-01-01

    Background Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega‐3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI. Methods and Results In the community‐based Cardiovascular Health Study, 3660 participants aged ≥65 underwent brain MRI in 1992–1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992–1993 and related to cross‐sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest long‐chain omega‐3 PUFA quartile. Higher long‐chain omega‐3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate‐chain omega‐3 PUFA alpha‐linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha‐linolenic acid intake. Conclusions Among older adults, higher phospholipid long‐chain omega‐3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long‐chain omega‐3 PUFAs, on brain health in later life. The role of plant‐derived alpha‐linolenic acid in brain health requires further investigation. PMID:24113325

  12. 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

  13. 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 ...

  14. 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

  15. 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

  16. Membrane lateral compressibility determined by NMR and x-ray diffraction: effect of acyl chain polyunsaturation.

    PubMed Central

    Koenig, B W; Strey, H H; Gawrisch, K

    1997-01-01

    The elastic area compressibility modulus, Ka, of lamellar liquid crystalline bilayers was determined by a new experimental approach using 2H-NMR order parameters of lipid hydrocarbon chains together with lamellar repeat spacings measured by x-ray diffraction. The combination of NMR and x-ray techniques yields accurate determination of lateral area per lipid molecule. Samples of saturated, monounsaturated, and polyunsaturated phospholipids were equilibrated with polyethylene glycol (PEG) 20,000 solutions in water at concentrations from 0 to 55 wt % PEG at 30 degrees C. This procedure is equivalent to applying 0 to 8 dyn/cm lateral pressure to the bilayers. The resulting reductions in area per lipid were measured with a resolution of +/-0.2 A2 and the fractional area decrease was proportional to applied lateral pressure. For 1,2-dimyristoyl(d54)-sn-glycero-3-phosphocholine, 1-stearoyl(d35)-2-oleoyl-sn-glycero-3-phosphocholine (SOPC-d35), and 1-stearoyl(d35)-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC-d35) cross-sectional areas per molecule in excess water of 59.5, 61.4, and 69.2 A2 and bilayer elastic area compressibility moduli of 141, 221, and 121 dyn/cm were determined, respectively. Combining NMR and x-ray results enables the determination of compressibility differences between saturated and unsaturated hydrocarbon chains. In mixed-chain SOPC-d35 both chains have similar compressibility moduli; however, in mixed-chain polyunsaturated SDPC-d35, the saturated stearic acid chain appears to be far less compressible than the polyunsaturated docosahexaenoic acid chain. Images FIGURE 3 FIGURE 5 PMID:9336191

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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}.

  2. 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

  3. [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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Serum n-3 polyunsaturated fatty acids and psychological distress in early pregnancy: Adjunct Study of Japan Environment and Children's Study.

    PubMed

    Hamazaki, K; Harauma, A; Otaka, Y; Moriguchi, T; Inadera, H

    2016-01-01

    N-3 polyunsaturated fatty acids (PUFAs), especially long-chain types such as docosahexaenoic acid, are important nutrients in pregnancy, but the relationship between n-3 PUFA levels and perinatal and postnatal depression remains controversial. This study examined the possible relationship between serum n-3 PUFA levels and psychological distress among expectant mothers in early pregnancy. Data and specimen samples were obtained in a birth cohort study started at Toyama Regional Center in July 2012 as an adjunct study of the Japan Environment and Children's Study. Blood samples were collected at 9-14 weeks' gestation (75% of samples) or after 15 weeks (25%). Subjects with a Kessler Psychological Distress Scale score (K6) ⩾ 9 were assigned to the psychological distress group (n=283). The control group (n=283) was matched for age, educational level and family income. Fatty acid composition was determined from serum samples by gas chromatography. Associations between fatty acid levels and incident psychological distress were evaluated by logistic regression. After adjusting for possible confounders, eicosapentaenoic acid showed an inverse association with risk of psychological distress, with an odds ratio of 0.47 (95% confidence interval: 0.30, 0.73) for the highest tertile. This inverse association remained even after applying a higher cutoff score (K6 ⩾ 13) indicating severe psychological distress (74 pairs). We believe this is the first study to reveal the associations between serum n-3 PUFAs and risk of psychological distress in early pregnancy. Further research is required to verify the causality of these associations. PMID:26882037

  10. 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