The relative deacylation of different molecular species of endogenous phosphatidylethanolamine in rat liver microsomes by phospholipase activity.

The relative deacylation of the 1-palmitoyl and 1-stearoyl homologues of different molecular species of endogenous phosphatidylethanolamine in rat liver microsomes via phospholipase activity was studied. For this purpose, the various molecular species of microsomal phosphatidylethanolamine were labelled specifically in the 1-position by incubation of rat liver microsomes with [14C]palmitoyl-CoA or [14C]stearoyl-CoA plus 2-acyl-sn-glycero-3-phosphorylethanolamine containing 18:1, 18:2, 20:4, 22:6, etc. followed by resuspension of the microsomal pellet. The loss of radioactivity from the total 1-[14C]palmitoyl and 1-[14C]stearoyl homologues of phosphatidylethanolamine amounted to 31 and 29%, respectively, when these microsomal preparations were incubated for 1 h in 50 mM Tris-HCl buffer (pH 8.5) containing 10 mM Ca2+. Regardless of whether palmitate or stearate resided in the 1-position, the susceptibility of the phosphatidylethanolamines to deacylation was not influenced significantly by the nature of the unsaturated fatty acid in the 2-position, as judged by selectivity indices for the relative disappearance of radioactivity from the individual classes (monoenoic, dienoic, trienoic, tetraenoic, pentaenoic and hexaenoic). A moderate discrimination against 1-stearoyl 2-saturated species was indicated. The findings indicate that fatty acid selectivity in the microsomal deacylation of phosphatidylethanolamine cannot account for the unique fatty acid and molecular species composition of this phospholipid in rat liver.

The biosynthesis of phosphatidylserines by acylation of 1-acyl-sn-glycero-3-phosphoserine in rat liver.

The conversion of 1-[14C]acyl-sn-glycero-3-phosphoserine into molecular species of [14C]phosphatidylserine was studied using rat liver homogenate and microsomal preparations in the absence of added fatty acyl moieties. In liver homogenates, 81% of the newly-formed phosphatidylserines were tetraenoic (arachidonoyl) species while saturated, monoenoic, dienoic, trienoic, pentaenoic, and hexaenoic (docosahexaenoyl) species each represented 2-5% of the total. A similar pattern of molecular species was produced in liver microsomes. The selectivity of the microsomal acyl-CoA:1-acyl-sn-glycero-3-phosphoserine acyltransferase towards different acyl-CoA derivatives was also investigated. The relative suitability of the various acyl-CoA esters as substrates was found to be of the following order:20:4 = 18:2 greater than 18:1 greater than 16:0 = 18:0. These results with endogenous acyl donors suggest that the acylation of 1-acyl-sn-glycero-3-phosphoserine may partly account for the enrichment of liver phosphatidylserine in arachidonic acid but does not appear to be primarily responsible for the preponderance of docosahexaenoic acid in this phospholipid. The fatty acid specificity of the acyl-CoA: 1-acyl-sn-glycero-3-phosphoserine acyltransferase may contribute to the preferential formation of arachidonoyl phosphatidylserine.

The suitability of different acyl acceptors as substrates for the acyl-Coa : 2-acyl-sn-glycero-3-phosphorylcholine acyltransferase in rat liver microsomes.

The fatty acid selectivity of the acyl-CoA : 2-acyl-sn-glycero-3-phosphorylcholine acyltransferase towards different acyl acceptors was studied in rat liver microsomes. The individual molecular species of 2-acylglycerylphosphorylcholine tested as enzyme substrates contained either palmitate, stearate, oleate, linoleate, linolenate or arachidonate with an equimolar mixture of [14C]palmitoyl-CoA plus [3H]stearoyl-CoA serving as the acyl donor. At 2-acyl-sn-glycero-3-phosphorylcholine concentrations of 16 or 64 microM, the various acyl acceptors gave generally similar reactivities, although reaction velocities with the linoleoyl, linolenoyl or arachidonoyl species were moderately greater than those with 2-stearoyl-sn-glycero-3-phosphorylcholine. Regardless of the acyl acceptor tested, little preference towards either palmitoyl-CoA or stearoyl-CoA was indicated at 64 microM 2-acyl-sn-glycero-3-phosphorylcholine whereas a distinct preference for stearate over palmitate (by 1.9--2.6-fold) was exhibited when a lower concentration (16 microM) of the acceptor was employed. The results support the potential importance of the acyl-CoA : 2-acyl-sn-glycero-3-phosphorylcholine acyltransferase for the synthesis of 1-stearoyl 2-unsaturated species of phosphatidylcholine. However, it cannot independently account for the varying palmitate : stearate ratios in the 1-position of this phospholipid when different unsaturated fatty acids reside in the 2-position.

Eicosanoid-dependent and -independent formation of individual [14C]stearoyl-labelled lysophospholipids in collagen-stimulated human platelets.

Low level collagen activation of platelets is mediated via the release of arachidonic acid (AA) from membrane phospholipids and the formation of thromboxane A2 (TxA2). To assess the specific phospholipids undergoing deacylation via phospholipase A2 thereby providing source(s) of releasable AA, we have measured the individual lysophospholipid formations in platelets prelabelled with [14C]stearic acid and incubated with a low level (2 micrograms/ml) or a high level (10 micrograms/ml) of collagen in the absence or presence of BW755C, a dual inhibitor of cyclooxygenase and lipoxygenase activities. Collagen activation resulted in the generation of [14C]stearoyl-labelled lysophosphatidylinositol (lysoPI), lysophosphatidylcholine (lysoPC), lysophosphatidylethanolamine (lysoPE) and lysophosphatidylserine. BW755C significantly inhibited these collagen-induced changes, suggesting that much of the lysophospholipid, and therefore AA release, was eicosanoid-mediated. At the lower level of collagen, considerable generation of [14C]lysoPE was maintained even in the presence of BW755C, suggesting an eicosanoid-independent degradation of phosphatidyl-ethanolamine. The TxA2-dependent release of AA was also investigated in U-46619-stimulated platelets. This TxA2 mimetic induced considerable formation of the 14C-labelled lysophospholipids, including lysoPI and lysoPC, but not lysoPE. These results suggest that an eicosanoid-independent degradation of phosphatidylethanolamine via phospholipase A2 at lower collagen levels may provide a source of the initial AA for conversion to TxA2 and the subsequent deacylation of phosphatidylinositol, phosphatidylcholine, and also phosphatidylserine.

The molecular species composition of individual diacyl phospholipids in human platelets.

The molecular species composition of the individual diacyl phospholipids was determined in human platelets. The 1-acyl (16:0, 18:0, etc.) homologues of the various 2-acyl (16:0, 18:1, 18:2, 20:4, etc) species of the phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were assessed by the use of thin-layer and gas-liquid chromatography in combination with specific lipases for establishing the positional distribution of the fatty acyl chains and generating the diacylglycerol derivatives. A marked heterogeneity was found in the complement of individual molecular species associated with the different platelet phospholipids. The 1-16:0 2-18:1 species predominated in the phosphatidylcholine (21% of total) but contributed only 5%, 2%, and trace amounts to the ethanolamine, inositol, and serine phospholipids, respectively. The 1-stearoyl 2-arachidonoyl species was by far the most prevalent one in the diacyl phosphatidylethanolamine (47% of total) and phosphatidylinositol (71% of total) but represented only 10% of the phosphatidylcholine. The 1-18:0 2-18:1 (37%) plus 1-18:0 2-20:4 (41%) together contributed 78% to the total phosphatidylserine. Interestingly, the 1-stearoyl 2-arachidonyl phosphatidylinositol represented only 6 mol% of the total diacyl phospholipid in human platelets. Of the total mixed 1-acyl 2-20:4 species in human platelets, 31, 35, 17 and 17% was found in the phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol, respectively. These results indicate that the mechanisms involved in the release of arachidonate for prostaglandin and thromboxane synthesis would need to possess a profound degree of selectivity if any single molecular species of a given platelet phospholipid were the source of the released arachidonic acid.

The cleavage of plasmenylethanolamine by phospholipase A2 appears to be mediated by the low affinity binding site of the TxA2/PGH2 receptor in U46619-stimulated human platelets.

Two TxA2/PGH2 receptor binding sites linked to different effector systems have recently been identified. Since plasmenylethanolamine represents the major phospholipid reservoir of arachidonic acid (AA) in resting human platelets, we assessed the differential role of these binding sites on plasmenylethanolamine hydrolysis by phospholipase A2 activity upon platelet activation by determining the generation of the corresponding [3H]lysoplasmenylethanolamine. Ethanolamine-containing phospholipids in platelets were pre-labelled with [3H]ethanolamine prior to platelet stimulation with U46619 (1 microM), a TxA2 mimetic, in the presence or absence of S-145, an antagonist of the low affinity TxA2/PGH2 receptor. Labelled platelets were also treated with the TxA2/PGH2 receptor antagonist, GR32191B, prior to washing (which blocks the low affinity site of the receptor) and subsequent stimulation. The above conditions provided for blockage of platelet aggregation but not shape change with U46619. The rise in [3H]lysoplasmenylethanolamine accumulation (170% of unstimulated controls) with U46619 as the agonist was inhibited in platelets pre-treated with S-145 and in platelets washed from GR32191B. Similar findings were also obtained for [3H]lysophosphatidylethanolamine accumulation. The present results indicate that the TxA2-dependent activation of plasmenylethanolamine cleavage by phospholipase A2 in intact human platelets is predominantly linked to the low affinity site of the TxA2/PGH2 receptor and may be important for platelet aggregation but not shape change.

Altered phospholipid composition of plasma membranes from thrombin-stimulated human platelets.

The individual phospholipid concentrations, and their respective fatty acid distributions, in whole platelet lysates and plasma membranes derived from unstimulated and thrombin-stimulated intact human platelets were studied. This was of interest, since previous work had led to the suggestion that altered phospholipid concentrations in plasma membranes of intact stimulated cells may be of importance in mediating cellular responses. The concentrations (nmol/mg protein) of phosphatidylinositol in whole platelet lysates and plasma membranes derived from thrombin-activated platelets decreased by 37 and 45%, respectively, a compared to their corresponding controls. As well, concentrations of plasma membrane phosphatidylcholine and phosphatidylethanolamine in thrombin-stimulated platelets decreased by 20 and 9%, respectively, when compared with their control values. The amounts of phosphatidylserine and sphingomyelin in whole platelet lysates and plasma membranes were unchanged by exposure to thrombin. Fatty acid analyses revealed that thrombin stimulation of intact human platelets induced a decrease in the arachidonate content (from 37.7 to 33.1 wt.% of total fatty acid) of plasma membrane phosphatidylinositol. Similar shifts in the wt% of arachidonic acid in plasma membrane phosphatidylcholine were found. These results indicate that thrombin stimulation of intact human platelets produces a significant decrease in the mass of phosphatidylinositol in plasma membranes and raises the suggestion that the preferential depletion of the plasma membrane in arachidonoyl-containing phosphatidylinositol may be of importance in mediating cellular responses to external stimuli.

Synthesis of 1-palmitoyl and 1-stearoyl phosphatidylcholines from mixtures of acyl acceptors via acyl-CoA:1-acyl-sn-glycero-3-phosphorylcholine acyltransferase in liver microsomes.

The fatty acid selectivity of the acyl-CoA:1-acyl-sn-glycero-3-phosphorylcholine acyltransferase in rat liver microsomes was studied using a mixture of the [1-(3)H]palmitoyl plus [1-(14C)stearoyl molecular species of 1-acylglyceryl-phosphorylcholine. At a 1-acyl-sn-glycero-3-phosphorylcholine concentration of 0.16 mM, the enzyme exhibited a selectivity of 3.5-fold for the 1-palmitoyl over the 1-stearoyl species of the acyl acceptor and reaction velocities with linoleoyl- and arachidonoyl-CoA were 38--47% greater than with oleoyl-CoA. Lowering the acceptor concentration to 0.016 mM gave reaction rates with the polyenoic thiolesters which were 174--187% greater than with oleoyl-CoA and the 1-palmitoyl-sn-glycero-3-phosphorylcholine was preferred by 2.2, 1.6, and 1.6-fold with oleoyl-, linoleoyl- and arachidonoyl-CoA, respectively. The results support the potential importance of the fatty acid selectivities of the acyl-CoA:1-acyl-sn-glycero-3-phosphorylcholine acyltransferase towards both acyl acceptor and donor in regulating the phosphatidylcholine species formed by the reaction in vivo.

Effects of dietary n - 3 fatty acids on mass changes and [3H]glycerol incorporation in various glycerolipid classes of rat kidney in vivo.

The effects of dietary fish oil containing n - 3 polyunsaturated fatty acids on triacylglycerol synthesis and phospholipid metabolism (including the alkylacyl subclass of choline glycerophospholipids (CGP)) was studied in rat kidney in vivo. After a 3 week feeding period, the triacylglycerol content (in mumol/g kidney) was 47% lower in the fish oil group relative to animals given sunflower oil. This alteration was accompanied by a substantially lower amount of arachidonic acid (20:4(n - 6)) and higher level (mumol/g tissue) of eicosapentaenoic acid (20:5(n - 3)) plus docosahexaenoic acid (22:6(n - 3)) in the triacylglycerol, CGP, and ethanolamine glycerophospholipids (EGP) of the fish oil group. The labelling of triacylglycerol relative to phospholipid from [3H]glycerol following i.p. administration was 49% lower in the fish oil as compared to the sunflower oil group, indicating a suppression of renal triacylglycerol synthesis relative to phospholipid synthesis. Modest differences in the labelling of CGP and EGP were found. A moderate and significantly lower proportional labelling (by 35%) of the alkylacyl subclass of CGP was observed in the fish oil as compared to the sunflower oil animals. These findings may have relevance to eicosanoid and platelet activating factor (PAF) biosyntheses as well as renal function and pathophysiology.

Altered acyl chain compositions of alkylacyl, alkenylacyl, and diacyl subclasses of choline and ethanolamine glycerophospholipids in rat heart by dietary fish oil.

The effects of dietary fish oil containing n - 3 polyunsaturated fatty acids on the fatty acid compositions of the alkylacyl and alkenylacyl species of choline glycerophospholipids (CGP) and ethanolamine glycerophospholipids (EGP) were studied in rat heart and compared with the corresponding diacylglycerophospholipids. After a 7 week feeding period, all phospholipid classes from the fish oil group exhibited much higher levels of the n - 3 polyunsaturated fatty acids including eicosapentaenoic acid (20:5(n - 30)), docosapentaenoic acid (22:5(n - 3)) and docosahexaenoic acid (22:6(n - 3)), as well as lower levels of the n - 6 series (18:2, 20:4, 22:4 and 22:5), relative to animals given sunflower seed oil-enriched in 18:2(n - 6). However, the docosahexaenoic acid rather than eicosapentaenoic acid provided a much greater contribution to the n - 3 accumulation (fish oil group) in the ether-containing CGP, as indicated by the 20:5(n - 3)/22:6(n - 3) molar ratios of 0.32, 0.26 and 0.56 in the alkylacyl, alkenylacyl and diacyl classes, respectively. In addition to accumulating very high levels of docosahexaenoic acid (e.g., 47.2 mol% of fatty acids in alkenylacylglycerophosphoethanolamine of fish oil group), both ether-linked classes of EGP exhibited significantly higher levels of docosapentaenoic acid than the diacylglycerophosphoethanolamine (GPE) and all classes of CGP. These findings may bear relevance to possible beneficial effects of dietary fish oil on pathophysiological states (including myocardial ischemia) in cardiac tissue and their mediation via platelet-activating factor, 1-alkyl-2-acetylglycerophosphocholine (PAF) and arachidonic acid (20:4(n - 6))-derived eicosanoids.

Inhibition of phosphatidic acid production and lysophospholipid formation in collagen-stimulated human platelets by staurosporine, a protein kinase inhibitor.

To investigate a possible regulatory role of protein kinase C (PKC) on collagen-induced phospholipase activity, human platelets were prelabelled with either [3H] arachidonic acid or [14C]stearic acid and stimulated with collagen (2 micrograms/ml) in the presence or absence of the protein kinase inhibitor, staurosporine (1 microM). The collagen-induced release of [3H]arachidonic acid and formation of [14C]stearoyl-labelled lysophospholipids was inhibited by prior incubation with staurosporine, as was the formation of 3H-labelled thromboxane B2, thereby suggesting inhibition of the collagen-induced phospholipase A2 activity. The degradation of phosphatidylinositol (PI) and elevation of phosphatidic acid (PA) in platelets prelabelled with either radiotracer were also completely blocked by staurosporine pretreatment, indicating a suppression of collagen-stimulated phospholipase C activity. Suppressed phospholipase C activity may have been due to diminished thromboxane A2 formation since treatment with the dual cyclo-oxygenase/lipoxygenase inhibitor, BW755C, also resulted in an inhibition of the collagen-stimulated loss of 14C-labelled PI and rise in PA by 75-80%. Our results suggest that protein kinase, possible PKC, may be involved in the regulation of these phospholipases in collagen-stimulated human platelets.

Effect of garlic and fish-oil supplementation on serum lipid and lipoprotein concentrations in hypercholesterolemic men.

This study examined the effects of garlic and fish-oil supplementation (alone and in combination) on fasting serum lipids and lipoproteins in hypercholesterolemic subjects. After an initial run-in phase, 50 male subjects with moderate hypercholesterolemia were randomly assigned for 12 wk to one of four groups: 1) 900 mg garlic placebo/d + 12 g oil placebo/d; 2) 900 mg garlic/d + 12 g oil placebo/d; 3) 900 mg garlic placebo/d + 12 g fish oil/d, providing 3.6 g n-3 fatty acids/d; and 4) 900 mg garlic/d + 12 g fish oil/d. In the placebo group, mean serum total cholesterol, low-density-lipoprotein cholesterol (LDL-C), and triacylglycerols were not significantly changed in relation to baseline. Mean group total cholesterol concentrations were significantly lower with garlic+fish oil (-12.2%) and with garlic (-11.5%) after 12 wk but not with fish oil alone. Mean LDL-C concentrations were reduced with garlic+fish oil (-9.5%) and with garlic (-14.2%) but were raised with fish oil (+8.5%). Mean triacylglycerol concentrations were reduced with garlic+fish oil (-34.3%) and fish oil alone (-37.3%). The garlic groups (with and without fish oil) had significantly lower ratios of total cholesterol to high-density-lipoprotein cholesterol (HDL-C) and LDL-C to HDL-C. In summary, garlic supplementation significantly decreased both total cholesterol and LDL-C whereas fish-oil supplementation significantly decreased triacylglycerol concentrations and increased LDL-C concentrations in hypercholesterolemic men. The combination of garlic and fish oil reversed the moderate fish-oil-induced rise in LDL-C. Coadministration of garlic with fish oil was well-tolerated and had a beneficial effect on serum lipid and lipoprotein concentrations by providing a combined lowering of total cholesterol, LDL-C, and triacylglycerol concentrations as well as the ratios of total cholesterol to HDL-C and LDL-C to HDL-C.

Fatty acid-related functions.

The first recommendations for specific nutrient quantities that must be obtained to support health were made by the US Department of Agriculture before 1939. Hazel Stiebeling was the leader of this effort and the scientific background was published in the Yearbook of Agriculture. The recommendations clearly stated that food must be available to provide the nutrients to support health. The science of nutrition in the United States is engaged in the most thorough review and reexamination of the recommended dietary allowances in at least a generation of nutrition scientists. There is a new awareness of nutrition complexity and the likelihood of identification of new essential nutrients. This meeting was devoted to the search for functional endpoints to reach quantitative estimates of dietary substances needed to support a function. Included in that concept is determining a range of individual needs and identifying factors that alter these needs. We give the rationale for endpoints of fatty acid metabolism related to platelets and the risk of thrombosis, give the rationale for the recommendation for a new nutrient, and show the necessity for including nutrient interaction in the determination of needs for two nutrients.

Effect of vitamin E supplementation on serum and high-density lipoprotein-cholesterol in renal patients on maintenance hemodialysis.

A significant increase in high-density lipoprotein-cholesterol after the ingestion of short-term megadoses of vitamin E has been documented in the recent literature. No attempt has been made to examine the effect of vitamin E supplementation on the serum lipids in chronic renal patients undergoing maintenance hemodialysis. This patient group typically exhibits subnormal high-density lipoprotein-cholesterol levels which may be a factor responsible for their increased mortality rate from atherosclerosis. In the present study, seven male renal patients on dialysis were given 600 IU of vitamin E daily for 4 wk. The level of total, free, and esterified cholesterol and triglyceride in whole serum and high-density lipoprotein were measured pre- and postregimen. No significant change was noted in any of the parameters examined for the group as a whole. Our results suggest that short-term high-dose vitamin E ingestion is unlikely to benefit the majority of renal patients on maintenance hemodialysis in regards to their circulating levels of high-density lipoprotein-cholesterol.

alpha-Linolenic acid- and docosahexaenoic acid-enriched eggs from hens fed flaxseed: influence on blood lipids and platelet phospholipid fatty acids in humans.

This study was undertaken to examine the effects that consumption of eggs from hens fed diets containing flaxseed would have on plasma and platelet lipids of male volunteers. Feeding diets containing 0%, 10%, and 20% ground flaxseed to Leghorn pullets provided a marked progressive increase in n-3 fatty acid content as alpha-linolenic acid (alpha-LNA) (28, 261, and 527 mg/egg) and docosahexaenoic acid (DHA) (51, 81, and 87 mg/egg) but no alteration in the cholesterol concentration of the egg yolk. Twenty-eight male volunteers, divided into three groups, were fed four eggs per day for 2 wk according to a cyclic Latin-square design. No statistically significant changes were observed in total cholesterol, high-density-lipoprotein cholesterol, or plasma triglyceride concentrations. Significant increases in total n-3 fatty acids and in DHA content (which rose from 1.5 to 2.0% by wt or 33% overall), and a significant decrease in ratio of n-6 to n-3 fatty acids were found in platelet phospholipids of subjects consuming eggs from flaxseed-fed hens. Health and Welfare Canada in 1990 set recommended intakes for dietary n-3 fatty acids and for the ratio of n-6 to n-3 fatty acids, which are not being met currently by the overall population. Eggs modified by the inclusion of flaxseed in the laying hens' diet could provide an important nutritional source of n-3 fatty acid.

Effects of a fish-oil and vegetable-oil formula on aggregation and ethanolamine-containing lysophospholipid generation in activated human platelets and on leukotriene production in stimulated neutrophils.

The effects of consuming a liquid formula containing either fish oil enriched in omega-3 fatty acids or vegetable oil enriched in oleic acid was evaluated in 20 male subjects randomly allocated into two groups over a 42-d period. A decrease in collagen-induced aggregation by using washed platelet suspensions was found in both groups after nutritional supplementation. A considerable rise in omega-3 and a decrease in omega-6 fatty acids occurred in the platelet phospholipid with fish-oil consumption. The degree of eicosapentaenoic acid (EPA, 20:5n-3) enrichment (fish-oil group) was dramatically greater in the ether-containing plasmenylethanolamine (13.5 mol% of fatty acids; mol% of fatty acids = moles per 100 moles of total fatty acids) than in phosphatidylethanolamine (2.8 mol%) or phosphatidylcholine (2.9 mol%). Neither treatment significantly influenced the agonist-induced accumulation of lysoplasmenylethanolamine as derived via phospholipase A2 hydrolysis of plasmenylethanolamine. HPLC measurements of eicosanoid production in A23187-stimulated neutrophils revealed a considerable decrease in the formation of arachidonic acid-derived leukotriene B4 (LTB4), by 41%, and 5-HETE (5-hydroxyeicosatetraenoic acid), by 30%, in the fish-oil group along with the appearance of the corresponding EPA-derived products [LTB5 and 5-HEPE (5-hydroxyeicosapentaenoic acid)]. No such alterations in the formation of lipoxygenase products were found with the vegetable oil treatment.

Relations between n-3 fatty acid status and cardiovascular disease risk factors among Quebecers.

BACKGROUND: Epidemiologic evidence shows an inverse relation between fish consumption and death from ischemic heart disease. This beneficial effect is attributed to n-3 fatty acids. OBJECTIVES: The purpose of this study was to examine the association between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among Quebecers. DESIGN: The study population consisted of 1460 subjects aged 18-74 y who participated in the 1990 Quebec Heart Health and Nutrition Survey. Data were obtained through home interviews and clinic visits. RESULTS: Expressed as the percentage of total fatty acids in plasma phospholipids, the geometric means of EPA, DHA, and their combination were 0.47%, 1.19%, and 1.70%, respectively. Concentrations of n-3 fatty acids were positively associated with fish intake. We found positive associations between EPA and total cholesterol, LDL cholesterol, HDL cholesterol, plasma glucose, and systolic and diastolic blood pressure. We found positive associations between DHA and total cholesterol, the ratio of total to HDL cholesterol, triacylglycerols, systolic blood pressure, and plasma glucose and insulin. We also found positive associations between the ratio of EPA to arachidonic acid and total cholesterol, HDL cholesterol, and systolic blood pressure and a negative association with the ratio of total to HDL cholesterol. CONCLUSIONS: Our results indicate that concentrations of EPA and DHA in plasma phospholipids reflected Quebecer fish consumption. Results also show that EPA and the ratio of EPA to arachidonic acid can positively influence HDL-cholesterol concentrations.

n-3 Fatty acids and cardiovascular disease risk factors among the Inuit of Nunavik.

BACKGROUND: Inuit traditionally consume large amounts of marine foods rich in n-3 fatty acids. Evidence exists that n-3 fatty acids have beneficial effects on key risk factors for cardiovascular disease. OBJECTIVE: Our goal was to verify the relation between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among the Inuit of Nunavik, Canada. DESIGN: The study population consisted of 426 Inuit aged 18-74 y who participated in a 1992 health survey. Data were obtained through home interviews and clinical visits. Plasma samples were analyzed for phospholipid fatty acid composition. RESULTS: Expressed as the percentage of total fatty acids, geometric mean concentrations of EPA, DHA, and their combination in plasma phospholipids were 1.99%, 4.52%, and 6.83%, respectively. n-3 Fatty acids were positively associated with HDL-cholesterol concentrations and inversely associated with triacylglycerol concentrations and the ratio of total to HDL cholesterol. In contrast, concentrations of total cholesterol, LDL cholesterol, and plasma glucose increased as n-3 fatty acid concentrations increased. There were no significant associations between n-3 fatty acids and diastolic and systolic blood pressure and plasma insulin. CONCLUSIONS: Consumption of marine products, the main source of EPA and DHA, appears to beneficially affect some cardiovascular disease risk factors. The traditional Inuit diet, which is rich in n-3 fatty acids, is probably responsible for the low mortality rate from ischemic heart disease in this population.

Dietary canola oil: effect on the accumulation of eicosapentaenoic acid in the alkenylacyl fraction of human platelet ethanolamine phosphoglyceride.

Volunteers consumed a mixed-fat diet for 6 d (Pre-exp) and then either a canola-oil-based diet (CAN) containing linolenic acid (18:3n-3) or a sunflower-oil-based diet (SUN) rich in linoleic acid (18:2n-6) for 18 d, followed by the alternative diet in a crossover design. Platelet phospholipids were analyzed for changes in fatty acid composition. Eicosapentaenoic acid (EPA) (20:5n-3) was significantly higher in alkenylacyl ethanolamine phosphoglyceride (PPE) and in total phosphatidylcholine (PC) after CAN compared with SUN and Pre-exp. The 22:5n-3 was increased in PPE after CAN above concentrations found after both SUN and Pre-exp. Lower concentrations of 20:4n-6 and 22:4n-6 were observed with CAN in PC and lower concentrations of 22:4n-6 in PPE. These results indicate that the consumption of canola oil moderately increases EPA concentrations and alters the concentrations of other n-6 and n-3 fatty acids in human platelet phospholipids.

Effect of a fish-oil concentrate on serum lipids in postmenopausal women receiving and not receiving hormone replacement therapy in a placebo-controlled, double-blind trial.

BACKGROUND: n-3 Fatty acid supplementation lowered serum triacylglycerol concentrations in studies in which most of the subjects were male. The effects of n-3 fatty acid supplementation in postmenopausal women receiving and not receiving hormone replacement therapy (HRT) have received little attention. OBJECTIVE: We sought to determine the effects of a fish-oil-derived n-3 fatty acid concentrate on serum lipid and lipoprotein risk factors for cardiovascular disease in postmenopausal women receiving and not receiving HRT, with an emphasis on serum triacylglycerol concentrations and the ratio of triacylglycerol to HDL cholesterol. DESIGN: Postmenopausal women (n = 36) were grouped according to exogenous hormone use and were randomly allocated to receive 8 capsules/d of either placebo oil (control) or n-3 fatty acid-enriched oil (supplement). The supplement provided 2.4 g eicosapentaenoic acid (EPA) plus 1.6 g docosahexaenoic acid (DHA) daily. Serum lipids and the fatty acid composition of serum phospholipids were determined on days 0 and 28. RESULTS: Supplementation with n-3 fatty acids was associated with 26% lower serum triacylglycerol concentrations (P < 0.0001), a 28% lower overall ratio of serum triacylglycerol to HDL cholesterol (P < 0.01), and markedly greater EPA and DHA concentrations in serum phospholipids (P < 0.05). CONCLUSIONS: These results show that supplementation with a fish-oil-derived concentrate can favorably influence selected cardiovascular disease risk factors, particularly by achieving marked reductions in serum triacylglycerol concentrations and triacylglycerol:HDL cholesterol in postmenopausal women receiving and not receiving HRT. This approach could potentially reduce the risk of coronary heart disease by 27% in postmenopausal women.