8-11-14-eicosatrienoic-acid and docosapentaenoic-acid

Oxylipins, which are circulating bioactive lipids generated from polyunsaturated fatty acids (PUFAs) by cyclooxygenase, lipooxygenase and cytochrome P450 enzymes, have diverse effects on endothelial cells. Although studies of the effects of oxylipins on endothelial cell function are accumulating, a review that provides a comprehensive compilation of current knowledge and recent advances in the context of vascular homeostasis is lacking. This is the first compilation of the various in vitro, ex vivo and in vivo reports to examine the effects and potential mechanisms of action of oxylipins on endothelial cells. The aggregate data indicate docosahexaenoic acid-derived oxylipins consistently show beneficial effects related to key endothelial cell functions, whereas oxylipins derived from other PUFAs exhibit both positive and negative effects. Furthermore, information is lacking for certain oxylipin classes, such as those derived from α-linolenic acid, which suggests additional studies are required to achieve a full understanding of how oxylipins affect endothelial cells.

Topics: 8,11,14-Eicosatrienoic Acid; Arachidonic Acid; Diet; Eicosapentaenoic Acid; Endothelial Cells; Fatty Acids, Unsaturated; Humans; Linoleic Acid; Oxylipins

This study prospectively investigates associations between fatty acids assessed in plasma phospholipids (PPL) and diet, and breast cancer risk, including subgroups defined by hormone receptor status.. We performed a case-cohort analysis within the Melbourne Collaborative Cohort Study using a random sample of 2,021 women and 470 breast cancer cases. At baseline, fatty acids were assessed in PPL and estimated from diet using a 121-item food frequency questionnaire. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using Cox regression.. Breast cancer risk was positively associated with %PPL saturated fatty acids (SFA); HRQ5vsQ1 = 1.64 (95 % CI 1.17-2.30); p trend = 0.004. Positive associations were found for ER+ or PR+ tumors for %PPL SFA and palmitic acid and for ER-/PR- tumors for %PPL n-6 polyunsaturated fatty acid (PUFA), TFA, TFA 16:1, and TFA 18:1n-7 (all p homogeneity <0.05). Breast cancer risk was inversely associated with dietary docosapentaenoic acid (DPA); HRQ5vsQ1 = 0.57 (95 % CI 0.40-0.82); p trend = 0.001 [with similar inverse associations observed for dietary docosahexaenoic (DHA) and eicosapentaenoic acid (EPA)] and positively associated with dietary n-6:n-3 PUFA. Inverse associations for ER-/PR- tumors were found for dietary dihomo-γ-linolenic acid (DGLA) for older women (p homogeneity = 0.04).. Breast cancer risk was positively associated with %PPL SFA and the ratio of dietary n-6 to n-3 PUFA and inversely associated with dietary long-chain n-3 PUFA intake. Some associations between fatty acids and breast cancer varied by age and tumor phenotype defined by hormone receptor status. Increased intake of fish and other foods rich in long-chain n-3 PUFAs and reduced n-6 PUFA intake might reduce breast cancer risk.

Topics: 8,11,14-Eicosatrienoic Acid; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Animals; Breast Neoplasms; Case-Control Studies; Diet; Dietary Fats; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Fishes; Humans; Middle Aged; Phospholipids; Proportional Hazards Models; Prospective Studies; Receptors, Estrogen; Receptors, Progesterone; Risk

The objective of the present study was to assess the effect of elevating epoxygenated fatty acids on retinal vascular inflammation. To stimulate inflammation we utilized TNFα, a potent pro-inflammatory mediator that is elevated in the serum and vitreous of diabetic patients. In TNFα-stimulated primary human retinal microvascular endothelial cells, total levels of epoxyeicosatrienoic acids (EETs), but not epoxydocosapentaenoic acids (EDPs), were significantly decreased. Exogenous addition of 11,12-EET or 19,20-EDP when combined with 12-(3-adamantane-1-yl-ureido)-dodecanoic acid (AUDA), an inhibitor of epoxide hydrolysis, inhibited VCAM-1 and ICAM-1 expression and protein levels; conversely the diol product of 19,20-EDP hydrolysis, 19,20-DHDP, induced VCAM1 and ICAM1 expression. 11,12-EET and 19,20-EDP also inhibited leukocyte adherence to human retinal microvascular endothelial cell monolayers and leukostasis in an acute mouse model of retinal inflammation. Our results indicate that this inhibition may be mediated through an indirect effect on NFκB activation. This is the first study demonstrating a direct comparison of EET and EDP on vascular inflammatory endpoints, and we have confirmed a comparable efficacy from each isomer, suggesting a similar mechanism of action. Taken together, these data establish that epoxygenated fatty acid elevation will inhibit early pathology related to TNFα-induced inflammation in retinal vascular diseases.

Topics: 8,11,14-Eicosatrienoic Acid; Adamantane; Animals; Cells, Cultured; Disease Models, Animal; Down-Regulation; Endothelial Cells; Epoxy Compounds; Fatty Acids, Unsaturated; Humans; Intercellular Adhesion Molecule-1; Lauric Acids; Male; Mice; Retinal Vasculitis; Retinal Vessels; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders.. The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes.. Supplementation with several EO/BO combinations increased circulating 20-22 carbon (20-22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%.. This study shows that dietary supplementation with BO/EO alters 20-22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation.

Topics: 8,11,14-Eicosatrienoic Acid; Adolescent; Adult; alpha-Linolenic Acid; Asthma; Cells, Cultured; Dietary Supplements; Echium; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Inflammation; Leukocytes, Mononuclear; Leukotrienes; Male; Middle Aged; Plant Oils; Seeds

To assess the modifications of the main fatty acids (FA) in plasma and red blood cells during pregnancy.. A longitudinal study of 36 normal pregnant women was carried out with 3 cut-off points: first trimester, second trimester and third trimester. 14 FA in plasma and erythrocyte phospholipids were measured using capillary gas chromatography. Measurements were expressed in percentages and in absolute values.. In plasma there was a significant increase in the proportion of saturated FA and a decrease in the proportion of long chain polyunsaturated fatty acids (PUFA) both in the omega 6 (omega 6) and omega 3 (omega 3) series. On the other hand, in erythrocyte phospholipids there was a decrease in the proportion of eicosapentaenoic acid and an increase in that of docosahexaenoic acid. In the omega 6 series, dihomo-gamma-linolenic acid increased, whereas the omega 6 docosapentaenoic acid decreased.. There was a significant decrease in the proportion of omega 3 PUFA in plasma from the first to the third trimester. Thus, it is suggested that the omega 3 PUFA intake during pregnancy should be increased in the last trimester.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Eicosapentaenoic Acid; Erythrocytes; Fasting; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Gestational Age; Humans; Longitudinal Studies; Myristic Acid; Palmitic Acid; Phospholipids; Pregnancy

To test the null-hypothesis that no age difference in adipose tissue fatty acid composition exists independent of dietary fat intake.. A cross-sectional survey of coronary heart disease risk factors, the Scottish Heart Health Study, provided needle biopsy adipose tissue fatty acid data and food frequency-derived dietary data.. Twenty-two Scottish Districts between 1984 and 1986.. A total of 10,359 men and women aged 40-59 y were randomly recruited in sex and five-year age bands from GP lists. A sub-set of 2308 men and 2049 women (42%) provided satisfactory adipose tissue and dietary data.. Multiple regression analysis (adjusting for dietary fats, body mass index and smoking, with and without menopause status for women) of the relationship between individual fatty acids in adipose tissue and age, and between age and the ratio of linoleic acid (C18:2, n-6) to gamma-linolenic acid (C18:3, n-6) as an indicator of delta-6 desaturase activity.. Sex-consistent changes with age occurred for linoleate (adjusted regression slope +/- s.e. for men -0.299 +/- 0.1339 and for women -0.504 +/- 0.1731) and gamma-linolenate (adjusted regression slope +/- s.e. for men -0.141 +/- 0.0341 and for women -0.154 +/- 0.0469) both P < 0.0001. These changes gave rise to a significant increase (P < or = 0.005) in the C18:2, n-6 to C18:3, n-6 ratio with age). Dihomo-gamma-linolenic acid (C20:3, n-6) and docosahexa- plus docosapentaenoic acids (C22:5 + C22:6, n-3) also increased significantly with age (P < or = 0.01). For the latter, the adjusted regression slopes were far greater for women (0.596 +/- 0.0575) than men (0.131 +/- 0.0417).. The results show that ageing does influence adipose tissue fatty acid composition independent of diet. The sex differences may partially be due to inadequate adjustment for changes in sex hormone status in males with ageing. Using the current indicator, a decline in the rate limiting step of beta-6 desaturation appeared to occur with age, and was greater in women than in men. These results may indicate that an increase in dietary gamma-linolenic acid (C18:3, n-6) is necessary with age to offset the relative imbalance between PUFA levels which appears to occur. However, any direct health benefit regarding the common diseases of ageing from such a strategy still remain to be clarified.

Topics: 8,11,14-Eicosatrienoic Acid; Adipose Tissue; Adult; Aging; Cross-Sectional Studies; Diet; Docosahexaenoic Acids; Fatty Acids; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Linoleic Acid; Male; Menopause; Middle Aged; Random Allocation; Regression Analysis; Sex Characteristics

The fatty acid compositions of the major cerebral cortex phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine were measured in 16 term and one preterm 'cot death' infants fed exclusively either breast milk or one of two formulas. Docosahexaenoic acid (DHA; C22:6n-3) content in cerebral cortex phosphatidylethanolamine and phosphatidylserine of breast fed infants was greater than in both formula groups with significances varying between p < 0.1 and p < 0.001. Compensation for this deficiency in DHA in the formula fed infants was largely achieved by increased incorporation of docosapentaenoic acid (C22:5n-6) in the cerebral cortex of term infants and Mead (C20:3n-9) and dihomo Mead acids (C22:3n-9) in the preterm infant. As the phospholipids most affected are known to perform an important role in membrane function and are possibly integral to neurotransmission it is recommended that breast milk substitute infant formulas should contain n-3 and n-6 series polyunsaturated fatty acids in proportions similar to those of human milk.

Topics: 8,11,14-Eicosatrienoic Acid; Cerebral Cortex; Docosahexaenoic Acids; Fatty Acids; Fatty Acids, Unsaturated; Female; Humans; Infant; Infant Food; Infant, Newborn; Infant, Premature; Male; Milk, Human; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylserines; Phospholipids; Sudden Infant Death

We examined the effect of dietary alpha-linolenic acid (ALA) on the indices of lipid and coagulation status and on the fatty acid composition of serum and peripheral blood mononuclear cell (PBMNC) lipids in ten healthy men (age 21-37 yr) who consumed all their meals at the Western Human Nutrition Research Center for 126 d. There was a stabilization period of 14 d at the start when all 10 subjects consumed the basal diet (BD) containing 23.4 energy percent (en%) fat and two intervention periods of 56 d each. During the first intervention period, 5 subjects consumed the BD containing 23.4 en% fat, and 5 subjects consumed a diet providing 6.3% calories from alpha-linolenic acid [flaxseed oil (FSO) diet containing 28.8 en% fat]. Diets were crossed over between the two groups during the second intervention period. Feeding the FSO diet did not significantly alter serum triglycerides, cholesterol, high-density lipoproteins, low-density lipoproteins, apoprotein A-I and apoprotein B when compared to the corresponding values in the subjects fed the BD, nor was there any effect of the FSO diet on the bleeding time, prothrombin time and partial prothrombin time for these subjects. Feeding the ALA-containing diet did cause a significant increase in ALA concentration in serum (P < 0.001) and PBMNC lipids (P < 0.05). It also caused a significant increase (P < 0.05) in the eicosapentaenoic and docosapentaenoic acid contents of PBMNC lipids, and a decrease (P < 0.01) in linoleic and eicosatrienoic acid contents of serum lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 8,11,14-Eicosatrienoic Acid; Adult; alpha-Linolenic Acid; Bleeding Time; Blood Coagulation; Dietary Fats; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Unsaturated; Humans; Leukocytes, Mononuclear; Linoleic Acid; Linoleic Acids; Linolenic Acids; Lipids; Lipoproteins; Male; Prothrombin Time

Fatty acid analyses were performed on samples of liver from 325 human infants less than 1 yr old, 275 of whom had died of sudden infant death syndrome (SIDS), and 50 of other causes (non-SIDS). Data for fatty acid composition were analyzed in relation to cause of death, age of infant, liver biotin, liver metals, and other variables by a variety of statistical methods. There were significant differences in the levels of liver fatty acids between SIDS and non-SIDS infants in the age group 1 to 6 months, notably in that the fatty acids of the SIDS infants appeared to have lower levels of dihomo-gamma-linolenic acid, which is the precursor of the "1-series" prostaglandins. Statistically significant relationships were observed between various fatty acids, and there were also significant relationships involving docosapentaenoic acid and infant age, and docosahexaenoic acid and liver iron content.

Topics: 8,11,14-Eicosatrienoic Acid; Age Factors; Biotin; Docosahexaenoic Acids; Fatty Acids; Fatty Acids, Unsaturated; Humans; Infant; Infant, Newborn; Iron; Liver; Sudden Infant Death