Polyunsaturated Fatty Acid Precursors Research Articles

N-3 Enrichment of Chicken Meat. 2. Use of Precursors of Long-Chain Polyunsaturated Fatty Acids: Linseed Oil

To assess the effect of supplying linseed oil (LO) in the diet on performance, fatty acid (FA) composition, and quality objective parameters of broiler meat, diets enriched with 0, 2, or 4% LO plus tallow (T) up to 8% added fat (T1, T2, and T3, respectively) were given to broiler chickens throughout a 38-d growth period. T3 birds were slaughtered at 24 or at 52 d of age to study the effect of feeding time on FA accumulation in tissue. Objective and subjective evaluations of meat quality were performed on samples from 38-d-old birds, and the FA profiles of thigh and liver samples were determined. Performance parameters showed little difference between treatments. The differences in carcass yield values or in the objective quality parameters of the meat between treatments were not significant. Increased levels of LO clearly decreased the saturated (SAT) and monounsaturated FA (MUFA) contents. LO increased the amount of polyunsaturated FA (PUFA), mainly because of the linolenic (LNA) and linoleic (LA) acid content in the T3 samples, but they hardly reflected the wide range given in the experimental diets. The n-3 long-chain (LC) PUFA content of T3 thighs was slightly higher than in T1 thighs. Unexpectedly, longer feeding time of LO diets did not result in peripheral tissue accumulation of n-3 LC-PUFA, although chickens could convert LNA to longer-chain metabolites in liver at 24 d of age.

Biochemistry and physiology of eicosanoid precursors in cell membranes

Excessive action of omega-6 eicosanoids formed from the body’s omega-6 essential fats occurs in many health disorders, and it can be diminished with dietary omega-3 fats. The current abundance of omega-6 (n-6) eicosanoidmediated disorders (e.g. thrombotic heart attack and stroke, cardiac arrhythmia, atherogenesis, arthritis, asthma, osteoporosis, tumour metastases, etc.) accompanies n-6 acid intakes that are more than ten times than the adequate level of 0·5% of energy. The n-3 and n-6 highly unsaturated fatty acids (HUFAs) are maintained in tissue phospholipids in a competitive, hyperbolic relationship to the dietary abundance of their 18-carbon polyunsaturated fatty acid (PUFA) precursors. In contrast, 18:2n-6 and 18:3n-3 acids are maintained in tissue triacylglycerols in a linear proportion to their dietary abundance expressed as percentage of daily caloric energy. The near absence of 20:3n-9 acid in plasma phospholipids in the U.S.A. population reflects very high intakes of polyunsaturated fats that compete with oleate for conversion to tissue HUFAs. The ethnic food combinations for Greenland, Japanese, Mediterranean, and American populations give proportions of omega-6 isomers in the body long-chain acids near 30%, 50% 60% and 80%, respectively. It is of interest that these values mimic clinical outcomes associated with cardiovascular mortalities ranging from 20 to 50 to 90 to 200 per 100 000, respectively. Therapeutic treatment to cut excessive omega-6 eicosanoid signalling has involved billions of dollars being spent to develop and market new pharmaceutical agents while a preventive nutrition approach to cut excessive omega-6 eicosanoid signalling has yet to be applied systematically in dietetics, clinical nutrition and public health. Voluntary choices of food combinations can produce proportions of omega-6 HUFAs and of omega-3 plus omega-6 HUFAs in the total body ranging from 30% to 90%, respectively. Adverse eects of excessive omega-6 eicosanoid signalling can be lowered by two interdependent dietary changes: first, reduce the daily intake of foods overly rich in the precursors of 20:4n-6 acid; and second, simultaneously increase the omega-3 PUFAs in the diet to competitively inhibit the conversion of LA into tissue omega-6 HUFAs. An inter active computer software application has been developed to combine the complex biomedical information on competitive interactions among essential fats and eicosanoids, and to interpret and display the finding in terms of multiple daily food choices understandable by the general public.

Plasma free fatty acid and lipoproteins as sources of polyunsaturated fatty acid for the brain.

Polyunsaturated fatty acids (PUFA), which comprise 25-30% of the fatty acids in the human brain, are necessary for normal brain development and function. PUFA cannot be synthesized de novo and must be supplied to the brain by the plasma. It is necessary to know the PUFA content and composition of the various plasma lipids and lipoproteins in order to understand how these fatty acids are taken up and metabolized by the brain. Human plasma free fatty acid (FFA) ordinarily contains about 15% linoleic acid (18:2n-6) and 1% arachidonic acid (AA) (20:4n-6). Plasma triglycerides, phospholipids, and cholesterol esters also are rich in linoleic acid, and the phospholipids and cholesterol esters contain about 10% AA. These findings suggest that the brain probably can obtain an adequate supply of n-6 PUFA from either the plasma FFA or lipoproteins. By contrast, the plasma ordinarily contains only one-tenth as much n-3 PUFA, and the amounts range from 1% alpha-linolenic acid (18:3n-3) in the plasma FFA to 2% docosahexaenoic acid (22:6n-3, DHA) in the plasma phospholipids. The main n-3 PUFA in the brain is DHA. Therefore, if the plasma FFA is the primary source of fatty acid for the brain, much of the DHA must be synthesized in the brain from n-3 PUFA precursors. Alternatively, if the brain requires large amounts of preformed DHA, the phospholipids contained in plasma lipoproteins are the most likely source.

Polyunsaturated fatty acid synthesis and release by brain-derived cells in vitro.

The brain is more highly enriched than most other tissues in long-chain polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA). In vitro studies of PUFA synthesis and release utilizing cell cultures of astrocytes, neurons, and cerebral microvascular endothelium have contributed significantly to our understanding of mechanisms potentially involved in the accretion of PUFA in brain. Both cerebral endothelium and astrocytes avidly elongate and desaturate precursors of the long-chain PUFAs when grown individually or in various co-culture combinations. The products, such as arachidonic acid (AA) and DHA, are released from the cells. In contrast, neurons appear unable to carry out fatty acid desaturation and thus are dependent upon preformed long-chain PUFA. Indeed, neurons co-cultured with astrocytes accumlate docosahexaenoate synthesized by the glial cells. Cerebral endothelial cultures are additionally capable of enriching the basolateral compartment (analogous to the brain extracellular space) with n-3 PUFA when grown in a membrane/chamber apparatus. The enrichment of this compartment with DHA is increased when cerebral endothelium is co-cultured with astrocytes. These data suggest that endothelial cells and astrocytes cooperate in the local synthesis and release of PUFA, collectively maintaining a brain environment enriched in long-chain PUFA.

Polyunsaturated fatty acids in human milk and their role in early infant development.

The lipid fraction of human milk represents the main source of energy for the newborn infant and supplies essential nutrients such as fat-soluble vitamins and polyunsaturated fatty acids (PUFA). The essential fatty acids linoleic and alpha-linolenic acids are precursors of long-chain polyunsaturated fatty acids (LC-PUFA), such as arachidonic (C20:4 n-6) and docosahexaenoic (C22:6 n-3) acids, present in human milk in considerable amounts. LC-PUFA are indispensable structural components of all cellular membranes, and they are incorporated in relatively large amounts during early growth of the brain and the retina. Moreover, some LC-PUFA are precursors of eicosanoids, molecules with potent biological activity that modulates various cellular and tissue processes. The supply of long-chain fatty acids has been associated with functional outcomes of the recipient infants such as visual acuity and development of cognitive functions during the first year of life. Here we discuss the PUFA composition of human milk, factors which determine and modulate milk PUFA content, and possible effects of milk LC-PUFA on infant growth and development.

Changes in mucosal fatty acid profile in inflammatory bowel disease and in experimental colitis: a common response to bowel inflammation

Background and aims: Plasma polyunsaturated fatty acid profile in patients with inflammatory bowel disease is abnormal. We aimed to assess the mucosal fatty acid pattern in patients with ulcerative colitis and Crohn's disease, and in rats with trinitrobenzene-sulfonic acid (TNB) induced colitis. Methods: Fatty acids were measured in colonic mucosa of patients with ulcerative colitis ( n = 30), Crohn's disease ( n = 21), and healthy controls ( n = 13). Likewise, they were assessed in the colonic mucosa of rats with TNB- and sham-colitis. Results: There was an increase of the end-products (C22:5n3, C22:6n3, C20:4n6, C22:5n6) and a decrease of the precursors (C18:3n3, C18:2n6) of both n3 and n6 polyunsaturated fatty acids in the mucosa of active ulcerative colitis and TNB-colitis. Also, high values of saturated (C16:0, C18:0) and low values of monounsaturated fatty acids (C18:1n9) were observed. Furthermore, the mucosa of active Crohn's disease showed substantial changes in saturated, monounsaturated and essential fatty acids, but not in polyunsaturated fatty acids. Mucosa of patients with inactive disease showed intermediate fatty acid values between the mucosa of active patients and healthy controls. Conclusions: Colonic inflammation causes a characteristic modification of the mucosal fatty acid profile which appears to be common to different aetiologies and seems to be related to the degree of inflammation.

Effects of dietary γ-linolenic acid-rich borage oil combined with marine fish oils on tissue phospholipid fatty acid composition and production of prostaglandins E and F of the 1-, 2- and 3-series in a marine fish deficient in Δ5 fatty acyl desaturase

The effects of γ-linolenic acid-rich borage oil (BO), in combination with different marine oils, namely an eicosapentaenoic acid (EPA) rich oil (MO) or a DHA-rich oil (TO), on tissue fatty acid composition and prostaglandin production were investigated in turbot, a species which lacks appreciable Δ5 fatty acyl desaturase activity. The juvenile turbot grew well on the experimental diets and there were no significant differences in final weights between dietary treatments. Irrespective of the marine oil component, both the BO-containing diets increased tissue phospholipid levels of 18:2 n-6 and 18:3 n-6, and their respective elongation products, 20:2 n-6 and 20:3 n-6, compared to fish fed a control diet containing a standard Northern hemisphere fish oil. Both the BO-containing diets increased the production of 1-series prostaglandins (PG), this being observed across all tissues investigated with PGF and especially PGE. The BO/MO diet also reduced 20:4 n-6 in tissue phospholipids without affecting 20:5 n-3, whereas the BO/TO combination decreased 20:5 n-3 but increased 20:4 n-6. The production of 2-series and 3-series PGs was also altered by the dietary treatments but the changes were less dependent upon the tissue levels of their respective precursor fatty acids, 20:4 n-6 and 20:5 n-3. The BO-containing diets had very significant effects on gross fatty acid compositions of the phospholipids including increased proportions of saturated fatty acids and n-6 polyunsaturated fatty acids (PUFA) and decreased proportions of monounsaturated fatty acids and n-3 PUFA. Overall, this study shows that eicosanoid production in turbot tissues can be influenced by dietary fatty acids, not only by changes in the absolute and relative levels of specific eicosanoid precursor PUFA in tissue phospholipids, but also by general effects on membrane composition, structure and function induced by gross fatty acid compositional changes.

Effects of Polyunsaturated Fatty Acids on Bile Acid-Induced Gastric Mucosal Injury

Arachidonic acid is a polyunsaturated fatty acid precursor to prostaglandin formation in the stomach. When applied topically to gastric mucosa it prevents injury from a variety of damaging agents, similar to the effects observed with exogenous prostaglandins. Alternatively, fatty acids could act as mild irritants and protect the gastric mucosa in an adaptive cytoprotective process. This study was undertaken to ascertain whether arachidonic acid attenuates gastric injury from bile acid by acting as a mild irritant to the gastric epithelium or by increasing biosynthesis of cytoprotective prostaglandins. Accordingly, adult anesthetized rat stomachs were pretreated for 30 min with either topical 1 mMarachidonic acid, docusahexaenoic acid or eicosatrienoic acid prior to injury with topical 5 mMacidified taurocholate. In a second set of experiments using a similar protocol, the role of prostaglandins was evaluated by giving indomethacin (5 mg/kg/sc) 30 min prior to fatty acid pretreatment. Mucosal injury was assessed by measuring net transmucosal ion fluxes, the appearance of DNA into the gastric lumen, and histology. Gastric luminal PGE2content was determined by radioimmunoassay. Pretreatment with topical arachidonic acid, but not docusahexaenoic acid or eicosatrienoic acid, significantly (P< 0.05) decreased bile acid induced net luminal ion fluxes, DNA accumulation and histologic injury scores, an effect negated by indomethacin. Further, pretreatment with arachidonic acid was associated with increased luminal PGE2content, an effect also abolished by indomethacin. Thus, arachidonic acid does not act as a mild irritant, but protects the gastric mucosa from bile acid injury through a mechanism involving increased bioavailability of substrate for prostaglandin formation.

Eicosanoids mediate nodulation responses to bacterial infections in larvae of the tenebrionid beetle, Zophobas atratus

Nodulation is the temporally and quantitatively predominant cellular defense response to bacterial infection in insects and other invertebrates. Inhibition of eicosanoid biosynthesis in larvae of the tenebrionid beetle, Zophobas atratus, immediately prior to intrahemocoelic injections with heat killed preparations of the bacterium, Serratia marcescens, strongly reduced the nodulation response. Separate treatments with specific inhibitors of phospholipase A 2, cyclooxygenase, and lipoxygenase reduced nodulation, supporting the view that nodule formation is a complex process involving both cyclooxygenase and lipoxygenase products. The inhibitory effects of the phospholipase A 2 inhibitor, dexamethasone, on nodulation were apparent 1 h after infection, and the effects increased, relative to controls, over 24 h. The dexamethasone effects were expressed in a dose-dependent manner, and they were reversed by treating bacteria injected insects with the eicosanoid-precursor polyunsaturated fatty acid, arachidonic acid (C20:4n-6). Treatments with the saturated fatty acid, 16:0, which is not an eicosanoid precursor, did not reverse the dexamethasone effects on nodulation. The insects contain low levels of three eicosanoid precursor polyunsaturated fatty acids in six different tissues, and fat body preparations are competent to produce both cyclooxygenase and lipoxygenase products. These findings strongly support the identification of nodulation as a specific insect cellular defense mechanism that is mediated by eicosanoids.

Effects of Low-Dose Aspirin Therapy on Plasma Levels of Polyunsaturated Fatty Acids: A Preliminary Investigation

Polyunsaturated fatty acids play an important yet poorly understood role in pregnancy complications. We are interested in the effects of aspirin therapy on the metabolism of these compounds. To determine the effects of low-dose aspirin on plasma levels of polyunsaturated fatty acid precursors, we assayed linoleic, linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acids using high-performance liquid chromatography. Seventeen pregnant women being treated with aspirin therapy (81 mg/day) were evaluated between 9 and 37 weeks' gestation. Blood was drawn before initiation of aspirin therapy and after 3 or 4 days, and again after 3 or 4 weeks of therapy. We found no significant change in the plasma levels of fatty acids during aspirin therapy at either 3 or 4 days or 3 or 4 weeks compared with baseline. In this group of women with preexisting disease, low-dose aspirin does not appear to change the plasma levels of polyunsaturated fatty acid precursors of eicosanoids. Data on pregnant women without hypertensive disorders is needed to help in understanding the role and physiology of these important compounds.

Biosynthesis and metabolism of 4‐hydroxynonenal in canine ceroid‐lipofuscinosis

Canine ceroid-lipofuscinosis (CCL) is a model of the juvenile type of Batten disease in human patients. Abnormalities have been reported previously in 4-hydroxynonenal (HNE) levels in English setters with CCL. The purpose of this study was to examine the sources of HNE in neutrophil membranes and plasma of CCL dogs. The fatty acid composition of neutrophil phospholipids, i.e., phosphatidyl ethanolamine and phosphatidyl serine, was determined by gas-liquid-chromatography (GLC) since some polyunsaturated fatty acids (PUFA) are precursors of HNE. The copper catalyzed peroxidation of low density lipoprotein (LDL) was examined to determine the susceptibility of LDL from CCL dogs to peroxidation. The results indicated that a number of PUFA precursors of HNE decreased in affected an carrier neutrophil phospholipids, indicating that this source of HNE may be disease specific. The Cu++ catalyzed formation of HNE from LDL demonstrated that carrier and normal LDL produced large amounts of HNE, while LDL from affected dogs required much higher concentrations of Cu++ for maximal HNE production. These results provide additional support for the role of HNE in the pathogenetic events in NCL and support the view that lipid peroxidation may be an important contributor to the complex pathogenesis of the NCL.

Biosynthesis of conjugated triene-containing fatty acids by a novel isomerase from the red marine alga Ptilota filicina.

The biosynthesis of conjugated triene-containing fatty acids by the red alga Ptilota filicina is catalyzed by a novel enzyme, polyenoic fatty acid isomerase. The enzyme has been highly purified and is described here for the first time. Matrix-assisted laser-induced desorption mass spectrometry was used to determine that the major protein in the purified enzyme is composed of similar or identical subunits of M(r) 58,119 Da. The native enzyme emerges with an apparent M(r) of 174,000 Da from a gel permeation chromatography column. While this enzyme catalyzes the formation of conjugated trienes from a variety of polyunsaturated fatty acid precursors [arachidonate ((5Z,8Z,11Z,14Z)- eicosatetraenoate) is converted to (5Z,7E,9E,14Z)-eicosatetraenoate; gamma-linolenate ((6Z,9Z,12Z)-octadecatrienoate) is converted to 6Z,8E,-10E-octadecatrienoate], this occurs most rapidly with eicosapentaenoate [(5Z,7E,9E,14Z,17Z)- eicosapentaenoate], which is likely the native substrate. Through a series of experiments utilizing gamma-linolenates stereospecifically labeled with deuterium, we have determined that the enzyme intramolecularly transfers the bis-allylic pro-S hydrogen from the C11 position to the C13 position. Furthermore, the bis-allylic pro-R hydrogen at C8 in gamma-linolenate is lost to the solvent. Using arachidonate as substrate, we demonstrated that the C11 olefinic position becomes protonated by a solvent-derived proton. There appears to be no requirement for molecular oxygen, and the transformation is catalyzed by this single enzyme.

Expression of an ovine growth hormone transgene in mice increases archidonic acid in cellular membranes

The degree of unsaturation of membrane lipids has been implicated in a number of physiological disorders, yet its regulation remains poorly understood, especially the regulation of the synthesis and distribution of arachidonic acid levels, the most abundant long chain polyunsaturated fatty acid in membranes. Transgenic mice expressing the ovine metallothionein 1a-ovine growth hormone (oMt1a-oGH) fusion gene exhibited significantly elevated levels of a number of long chain polyunsaturated fatty acids in serum, including arachidonic acid. In oMt1a-oGH transgenic mice the products of all three desaturation pathways are affected by the expression of the ovine growth hormone transgene. The essential precursors of membrane long chain polyunsaturated fatty acids, 18:2n-6 and 18:3n-3, were reduced in transgenics relative to controls, and their desaturation and elongation products, arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3), were elevated. As rare intermediate long chain polyunsaturated fatty acids such as eicosatrienoic acid (20:3n-9) were also significantly elevated, we conclude that these observations reflect increased activity of the delta-5 and delta-6 desaturase enzymes. In contrast, the products of the stearoyl CoA or delta-9 desaturase, were significantly reduced in oMt1a-oGH expressing transgenics relative to their levels in control mice.

Utilization of Uniformly Labeled 13C‐Polyunsaturated Fatty Acids in the Synthesis of Long‐Chain Fatty Acids and Cholesterol Accumulating in the Neonatal Rat Brain

Polyunsaturated fatty acids are needed for normal neonatal brain development, but the degree of conversion of the 18-carbon polyunsaturated fatty acid precursors consumed in the diet to their respective 20- and 22-carbon polyunsaturates accumulating in the brain is not well known. In the present study, in vivo 13C nuclear magnetic resonance spectroscopy was used to monitor noninvasively the brain uptake and metabolism of a mixture of uniformly 13C-enriched 16- and 18-carbon polyunsaturated fatty acid methyl esters injected intragastrically into neonatal rats. In vivo NMR spectra of the rat brain at postnatal days 10 and 17 had larger fatty acid signals than in uninjected controls, but changes in levels of individual fatty acids could not be distinguished. One day after injection of the U-13C-polyunsaturated fatty acid mixture, 13C enrichment (measured by isotope ratio mass spectrometry) was similar in brain phospholipids, free fatty acids, free cholesterol, and brain aqueous extract; 13C enrichment remained high in the phospholipids and cholesterol for 15 days. 13C enrichment was similar in the main fatty acids of the brain within 1 day of injection but 15 days later had declined in all except arachidonic acid while continuing to increase in docosahexaenoic acid. These changes in 13C enrichment in brain fatty acids paralleled the developmental changes in brain fatty acid composition. We conclude that, in the neonatal rat brain, dietary 16- and 18-carbon polyunsaturates are not only elongated and desaturated but are also utilized for de novo synthesis of long-chain saturated and monounsaturated fatty acids and cholesterol.

Fatty acid compositions of phospholipids and triacylglycerols from selected terrestrial arthropods

The fatty acid compositions of phospholipids and triacylglycerols from selected orthognath spider tissues, scorpion body segments, whole millipedes, and whole labidognath spiders were determined. The major components were C16 and C18 saturated and unsaturated fatty acids as well as C20 polyunsaturated fatty acids. The eicosanoid precursor polyunsaturated fatty acids 20:4n-6 and 20:5n-3 were present in substantial proportions of phospholipids in all tissues examined. The fatty acid profiles of these terrestrial arthropods differ markedly from corresponding profiles of terrestrial insects in that substantially greater proportions of C20 polyunsaturated fatty acids are present in the organisms in this study. This finding supports the idea that maintaining low proportions of C20 polyunsaturated fatty acids is a special condition of terrestrial insects.

Effect of fish oil on neutrophil chemiluminescence induced by different stimuli in patients with rheumatoid arthritis.

Lipid composition plays an important part in the structural and metabolic functions of cell membranes. In particular the production of inflammatory mediators such as prostaglandins and leukotrienes is dependent on polyunsaturated fatty acid precursors. Neutrophil leucocytes participate in inflammatory processes by their phagocytic and killing activities which can be monitored by measuring the photon emission (chemiluminescence). Chemiluminescence was measured in a luminol dependent system after stimulation by either particulate (zymosan) or soluble (phorbol myristate acetate) stimulus in a group of 10 patients with rheumatoid arthritis before and 21 and 45 days after treatment with a diet supplemented with eicosapentaenoic and docosahexaenoic acids. Ten patients with rheumatoid arthritis continuing their usual diet were used as control subjects. A progressive reduction of chemiluminescence stimulated by zymosan and phorbol myristate acetate was found in the patients treated with fish oil supplementation. This result correlated well with the reduction in erythrocyte sedimentation rate and an improvement of clinical parameters. The effects of fish oil derived lipids on neutrophil chemiluminescence are probably due to a change of the lipid composition of the cell membrane which is dependent on the esterification of eicosapentaenoic acid and docosahexaenoic acid in cellular membrane phospholipids. The modification of membrane lipid composition seems to interact in a non-specific way with the metabolic activation of neutrophils during phagocytosis.

Dietary Manipulation of Prostanoid Synthesis and Prevention of Pregnancy-Induced Hypertensive Disorders: A Review

Prostanoid synthesis can be influenced by dietary supplementation of essential polyunsaturated fatty acid (PUFA) precursors. Results of observational and experimental studies in nonpregnant humans suggest that a diet rich in marine fish or supplemented with eicosapentaenoic acid (EPA) or PUFAs in various plant oils may cause a shift in prostanoid synthesis resulting in increased vasodilatation and reduced platelet activity. Based on these observations dietary supplementation with various PUFAs, including EPA, has been investigated on a small scale as an approach to prevent adaptational disorders in pregnancy. As yet these studies have provided no evidence to recommend the clinical use of fish oil or evening primrose preparations to prevent or treat pregnancy-induced hypertensive disorders and fetal growth retardation.

Synthesis of Prostaglandins by Tissues of the Viviparous Lizard, Sceloporus jarrovi

Although prostaglandin synthesis in reptilian tissues has not been previously documented, studies have demonstrated that this class of hormones influences several aspects of reptilian reproductive biology. Gas chromatographic analysis for prostaglandin (PG) precursors in oviductal and hepatic tissues of the viviparous lizard Sceloporus jarrovi revealed that eicosatrienoic acid (monoenoic series precursor) and arachidonic acid (dienoic series precursor) were present. No eicosapentaenoic acid (trienoic series precusor) was detected in either tissue. Ovary, oviduct, liver, testis, and epididymis synthesized in vitro compounds which migrate with authentic series 2 (dienoic) PG standards on TLC. Furthermore, in vitro incubation of hepatic tissue produced significant amounts of PGF2 and PGE2 in the culture media. These data indicate that reptiles synthesize PG's as do other vertebrates. Prostaglandins (PG's) are potent local hormones or parahormones synthesized from polyunsaturated fatty acid precursors by tissues from mammals, birds, amphib- ians, fishes, and a number of invertebrate

The effect of dietary eicosapentaenoic acid on arachidonic acid incorporation and metabolism in rat leukocytes

Arachidonic Acid (AA) released from membrane phospholipids by phospholipase A 2 during cell activation is the major polyunsaturated fatty acid precursor in mammals for the cyclooxygenase and lipoxygenase pathways. Eicosaspentaenoic acid (EPA), a major polyunsaturated fatty acid in fish oils competes with AA for these enzymes. The resulting products from EPa are generally less potent than the corresponding AA metabolites which may explain the beneficial effects of this oil in reducing thrombotic and inflammatory responses. This study compares the incorporation of 14C-AA into leukocyte phospholipids and its release and metabolism by the cyclooxygenase and lipoxygenase pathways in rats fed a ‘Max EPA’ fish oil rich diet (EPA group) and a hydrogenated coconut/safflower oil control diet. More than 75% of radiolabel was incorporated into leukocytes with no difference seen between dietary groups. Upon stimulation with calcium ionophore, the EPA group released significantly more radiolabelled AA than the control group. The EPA diet showed a significant increase in the formation of 5-hydroxyeicosatetraenoic acid and 6-keto-prostaglandin F 1α but no difference was seen in leukotriene B 4 formation. The majority of radiolabel released was free AA, this being significantly higher in the EPA grou than in the control. The percentage of radiolabel remaining after stimulation in phosphatidylglycerol, phosphatidylethanolamine and neutral lipids was significantly less in EPA fed rats. As the release and metabolism of endogenous AA may not be the same as 14C-AA, these results do not necessarily indicate that the mass of AA available for eicosanoid biosynthesis has been altered by the EPA diet.

Evidence against a PGF4a prostaglandin structure in trout tissue—A correction

Analysis of the oxygenated products generated from docosahexaenoic acid by trout gill tissue and reinterpretation of the mass spectrum of the proposed novel protanoid indicate that the compounds identified as n-3 prostaglandins are trihydroxylated derivatives of the precursor polyunsaturated fatty acids.