Dietary (n-3) polyunsaturated fatty acids exert antihypertensive effects by modulating calcium signaling in T cells of rats

After 10 wk of feeding an experimental diet enriched with (n-3) polyunsaturated fatty acids (PUFA), i.e., eicosapentaenoic acid [EPA, 20:5(n-3)] and [DHA, 22:6(n-3)] (EPAX), blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats was reduced relative to rats fed an unsupplemented control diet. Concanavalin A-stimulated T-cell proliferation was diminished in both strains of rats fed the PUFA/EPAX diet. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. To determine whether there was a defect in calcium homeostasis in T cells during hypertension, we employed the following agents: caffeine, which recruits calcium from the cytosolic Ca(2+)-induced Ca(2+)-release pool; ionomycin, which at low concentrations opens calcium channels; and thapsigargin (TG), which mobilizes [Ca(2+)]i from the endoplasmic reticulum (ER) pool. Caffeine-induced increases in [Ca(2+)]i were not modified by the PUFA/EPAX diet. The ionomycin-induced increases in [Ca(2+)]i in T cells from SHR were greater than in those from WKY rats; consumption of the PUFA/EPAX diet did not modify Ca(2+) influx in cells of either strain. The TG-induced increases in [Ca(2+)]i in T cells from SHR were greater than those in cells from WKY rats. Interestingly, consumption of the experimental diet reduced TG-evoked increases in [Ca(2+)]i in T cells from SHR and increased those in T cells from WKY rats, indicating that the PUFA/EPAX diet could reverse the calcium mobilization from the ER pool in T cells. These results suggest that (n-3) PUFA exert antihypertensive effects and modulate T-cell calcium signaling during hypertension in rats.     

Changes in lipid metabolism and antioxidant defense status in spontaneously hypertensive rats and Wistar rats fed a diet enriched with fructose and saturated fatty acids

OBJECTIVE: Larger doses of fructose and saturated fat have been associated with oxidative stress and development of hypertension. The effects of modest amounts of fructose and saturated fatty acids on oxidative stress are unknown. METHODS: To increase knowledge on this question, 10-wk-old spontaneously hypertensive rats and Wistar rats were fed for 8 wk with a control diet or an experimental diet enriched with fructose (18%) and saturated fatty acids (11%; FS diet). The total antioxidant status of organs and red blood cells was assayed by monitoring the rate of free radical-induced red blood cell hemolysis. Sensitivity of very low-density lipoprotein and low-density lipoprotein (VLDL-LDL) to copper-induced lipid peroxidation was determined as the production of thiobarbituric acid-reactive substances. Antioxidant enzymes and vitamins were also measured to establish the oxidative stress effect. RESULTS: The FS diet did not affect blood pressure in either strain, but it increased plasma insulin concentrations only in Wistar rats without affecting those of glucose of either strain. The FS diet significantly enhanced plasma and VLDL-LDL triacylglycerol concentrations without affecting concentrations of VLDL-LDL thiobarbituric acid-reactive substances. The decreased content of arachidonic acid and total polyunsaturated fatty acids in VLDL-LDL by the FS diet may have prevented lipid peroxidation in this fraction. Moreover, FS consumption by both strains was accompanied by a significant increase in total antioxidant capacity of adipose tissue, muscle, heart, and liver. This may have resulted from increased tissue ascorbic acid levels and glutathione peroxidase and glutathione reductase activities in tissues. CONCLUSIONS: These findings clearly indicate that the FS diet did not alter blood pressure of spontaneously hypertensive rats and Wistar rats. The FS diet resulted in hypertriglyceridemia but increased the total antioxidant status, which may prevent lipid peroxidation in these rats.     

Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans.

Animal and human studies have shown that greatly increasing the amounts of flax seed oil [rich in the (n-3) polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALNA)] or fish oil [FO; rich in the long chain (n-3) PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease mitogen-stimulated lymphocyte proliferation. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA or FO on the proliferation of mitogen-stimulated human peripheral blood mononuclear cells (PBMC) and on the production of cytokines by those cells. The study was randomized, placebo-controlled, double-blinded and parallel. Healthy subjects ages 55-75 y consumed nine capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA or DHA or FO. Subjects in these groups consumed 2 g of ALNA or 770 mg of GLA or 680 mg of ARA or 720 mg of DHA or 1 g of EPA plus DHA (720 mg of EPA + 280 mg of DHA) daily from the capsules. Total fat intake from the capsules was 4 g/d. The fatty acid composition of PBMC phospholipids was significantly changed in the GLA, ARA, DHA and FO groups. Lymphocyte proliferation was not significantly affected by the placebo, ALNA, ARA or DHA treatments. GLA and FO caused a significant decrease (up to 65%) in lymphocyte proliferation. This decrease was partly reversed by 4 wk after stopping the supplementation. None of the treatments affected the production of interleukin-2 or interferon-gamma by PBMC and none of the treatments affected the number or proportion of T or B lymphocytes, helper or cytotoxic T lymphocytes or memory helper T lymphocytes in the circulation. We conclude that a moderate level GLA or EPA but not of other (n-6) or (n-3) PUFA can decrease lymphocyte proliferation but not production of interleukin-2 or interferon-gamma.     

Relationship between tissue lipid peroxidation and peroxidizability index after alpha-linolenic,eicosapentaenoic, or docosahexaenoic acid intake in rats

In a previous study, we found that the extent of dietary n-3 docosahexaenoic acid (DHA)-stimulated tissue lipid peroxidation was less than expected from the relative peroxidizability index of the total tissue lipids in rats with adequate vitamin E nutritional status. This suppression of lipid peroxidation was especially prominent in the liver. To elucidate whether this phenomenon was unique to DHA, we compared the peroxidation effects of n-3 alpha-linolenic acid (alpha-LN) and n-3 eicosapentaeonic acid (EPA) with those of DHA in rats. Either alpha-LN (8.6 % of total energy), EPA (8.2 %), or DHA (8.0 %) and one of two levels of dietary vitamin E (7.5 and 54 mg/kg diet) were fed to rats for 22 d. Levels of conjugated diene, chemiluminescence emission and thiobarbituric acid (TBA)-reactive substance in the liver, kidney, and testis were determined as indicators of lipid peroxidation. In rats fed the DHA diet deficient in vitamin E (7.5 mg/kg diet), TBA values in the liver, kidney, and testis correlated well with the tissues' relative peroxidizability indices. In rats fed the alpha-LN diet with an adequate level of vitamin E (54 mg/kg diet), a close association between relative peroxidizability indices and lipid peroxide levels was observed in all the tissues analysed. However, in rats fed either the EPA diet or the DHA diet with an adequate level of vitamin E, the extent of lipid peroxidation in each tissue was less than expected from the relative peroxidizability index. This suppression was particularly marked in the liver. We concluded that suppression of lipid peroxidation below the relative peroxidizability index was not unique to DHA, but was also seen with EPA, which has five double bonds, in rats with adequate vitamin E nutritional status, but not with alpha-LN, which has three double bonds.     

Vitamin E deficiency decreases long-chain PUFA in zebrafish (Danio rerio)

α-Tocopherol is a required, lipid-soluble antioxidant that protects PUFA. We hypothesized that α-tocopherol deficiency in zebrafish compromises PUFA status. Zebrafish were fed for 1 y either an α-tocopherol-sufficient (E+; 500 mg α-tocopherol/kg) or -deficient (E-; 1.1 mg α-tocopherol/kg) diet containing α-linolenic (ALA) and linoleic (LA) acids but without arachidonic acid (ARA), EPA, or DHA. Vitamin E deficiency in zebrafish decreased by ~20% (n-6) (P < 0.05) and (n-3) (P < 0.05) PUFA and increased the (n-6):(n-3) PUFA ratio (P < 0.05). In E- compared to E+ females, long chain-PUFA status was impaired, as assessed by a ~60% lower DHA:ALA ratio (P < 0.05) and a ~50% lower ARA:LA ratio (P < 0.05). fads2 (P < 0.05) and elovl2 (P < 0.05) mRNA expression was doubled in E- compared to E+ fish. Thus, inadequate vitamin E status led to a depletion of PUFA that may be a result of either or both increased lipid peroxidation and an impaired ability to synthesize sufficient PUFA, especially (n-3) PUFA.     

Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y

BACKGROUND: Animal studies showed that dietary flaxseed oil [rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid (ALA)], evening primrose oil [rich in the n-6 polyunsaturated fatty acid gamma-linolenic acid (GLA)], and fish oil [rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] can decrease natural killer (NK) cell activity. There have been no studies of the effect on NK cell activity of adding these oils to the diet of humans. OBJECTIVE: Our objective was to determine the effect of dietary supplementation with oil blends rich in ALA, GLA, arachidonic acid (AA), DHA, or EPA plus DHA (fish oil) on the NK cell activity of human peripheral blood mononuclear cells. DESIGN: A randomized, placebo-controlled, double-blind, parallel study was conducted. Healthy subjects aged 55-75 y consumed 9 capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil and oils rich in ALA, GLA, AA, DHA, or EPA plus DHA. Subjects in these groups consumed 2 g ALA, 770 mg GLA, 680 mg AA, 720 mg DHA, or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily, respectively. Total fat intake from the capsules was 4 g/d. RESULTS: The fatty acid composition of plasma phospholipids changed significantly in the GLA, AA, DHA, and fish oil groups. NK cell activity was not significantly affected by the placebo, ALA, GLA, AA, or DHA treatment. Fish oil caused a significant reduction (mean decline: 48%) in NK cell activity that was fully reversed by 4 wk after supplementation had ceased. CONCLUSION: A moderate amount of EPA but not of other n-6 or n-3 polyunsaturated fatty acids can decrease NK cell activity in healthy subjects.     

(n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary?

Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil. Whether individual long-chain (n-3) PUFA have shared or complementary effects is not well established. We reviewed evidence for dietary and endogenous sources and cardiovascular effects on biologic pathways, physiologic risk factors, and clinical endpoints of EPA [20:5(n-3)], docosapentaenoic acid [DPA, 22:5(n-3)], and DHA [22:6(n-3)]. DHA requires direct dietary consumption, with little synthesis from or retroconversion to DPA or EPA. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from EPA, and DPA can also undergo retroconversion back to EPA. In experimental and animal models, both EPA and DHA modulate several relevant biologic pathways, with evidence for some differential benefits. In humans, both fatty acids lower TG levels and, based on more limited studies, favorably affect cardiac diastolic filling, arterial compliance, and some metrics of inflammation and oxidative stress. All three (n-3) PUFA reduce ex vivo platelet aggregation and DHA also modestly increases LDL and HDL particle size; the clinical relevance of such findings is uncertain. Combined EPA+DHA or DPA+DHA levels are associated with lower risk of fatal cardiac events and DHA with lower risk of atrial fibrillation, suggesting direct or indirect benefits of DHA for cardiac arrhythmias (although not excluding similar benefits of EPA or DPA). Conversely, EPA and DPA, but not DHA, are associated with lower risk of nonfatal cardiovascular endpoints in some studies, and purified EPA reduced risk of nonfatal coronary syndromes in one large clinical trial. Overall, for many cardiovascular pathways and outcomes, identified studies of individual (n-3) PUFA were relatively limited, especially for DPA. Nonetheless, the present evidence suggests that EPA and DHA have both shared and complementary benefits. Based on current evidence, increasing consumption of either would be advantageous compared to little or no consumption. Focusing on their combined consumption remains most prudent given the potential for complementary effects and the existing more robust literature on cardiovascular benefits of their combined consumption as fish or fish oil for cardiovascular benefits.     

Dietary (n-3) fat and cholesterol alter tissue antioxidant enzymes and susceptibility to oxidation in SHR and WKY rats

Previously, 8% fish oil blend diets, compared to butter and soybean oil blend diets, reduced specific antioxidant enzyme activities and tissue susceptibility to in vitro oxidative stress in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. Moreover, high cholesterol (5.0 g/kg diet) diets protected against in vitro tissue lipid oxidation. In this study, we hypothesized that 160 g fat/kg diet as blends of (n-6) or (n-3) oils and cholesterol would alter antioxidant enzyme activities and thus increase tissue susceptibility to oxidation. The effects of diet blends of saturated (butter, B), (n-6) (soybean oil, SBO) or (n-3) (menhaden oil, MO) oils with cholesterol (0.5 or 5.0 g/kg) on systolic blood pressure (SBP), plasma lipids, antioxidant enzymes and susceptibility to oxidation were examined in SHR and WKY rats. SBP at 13 wk of age was greater (P < 0.001) in SHR than in WKY rats, but was not affected by diets. Plasma cholesterol and triacylglycerols were decreased (P < 0.001) by MO diets. Hepatic glutathione reductase activities were reduced (P < 0.001) in SBO-fed SHR and enhanced in SBO- and MO-fed WKY rats. Glutathione levels were reduced (P < 0.001) in RBC and enhanced (P < 0.001) in livers of MO-fed rats. Lipid oxidation was enhanced (P < 0.001) in red blood cells (RBC) from SBO groups, and hearts and livers of MO groups. High cholesterol diets reduced (P < or = 0.001) susceptibility to lipid peroxidation in RBC and liver of SHR and WKY rats. Greater amounts of dietary (n-3) fat enhance tissue susceptibility to oxidation, which can be modulated by increased dietary cholesterol in SHR and WKY rats.     

Dietary methods and biomarkers of omega 3 fatty acids: a systematic review

The aims of the present study were to review the validity of dietary methods used to measure the usual long chain (LC) omega-3 polyunsaturated fatty acid (n-3 PUFA) intake of a population and to assess the usefulness of different biomarkers of n-3 PUFA in healthy humans. Two systematic literature searches were conducted until May 2011 to update previous systematic reviews. The first literature search aimed to find studies validating the methodology used for measuring the dietary intake of n-3 PUFA. The second search aimed to find human intervention studies in which n-3 PUFA status changed after 2 weeks of n-3 PUFA supplementation. Sixteen studies were identified for inclusion in the first review. Correlation coefficients between fatty acids in subcutaneous fat or blood lipids and dietary intake of n-3 PUFA from different questionnaires were similar. Subcutaneous fat has been reported as the best reference method for some authors, and these studies showed moderate correlation coefficients with no dietary intake method being superior to any other. As for the evaluation of biomarkers of docosahexaenoic acid (DHA, 22 : 6 n-3) and eicosapentaenoic acid (EPA, 20 : 5n-3) status in response to supplementation, the new search reaffirmed and reinforced the evidence supporting that plasma phospholipid DHA, erythrocyte DHA, and platelet DHA were all effective and robust biomarkers of DHA status. Our findings only confirmed earlier studies and did not provide evidence for reaching new conclusions.     

Moderate fish-oil supplementation reverses low-platelet, long-chain n-3 polyunsaturated fatty acid status and reduces plasma triacylglycerol concentrations in British Indo-Asians

BACKGROUND: The mechanisms involved in the increased mortality from coronary artery disease in British Indo-Asians are not well understood. OBJECTIVES: This study aimed to investigate whether British Indo-Asian Sikhs have higher plasma triacylglycerol concentrations, lower platelet phospholipid levels, and lower dietary intakes of long-chain n-3 polyunsaturated fatty acids (PUFAs) than do age- and weight-matched Europeans and whether moderate dietary fish-oil intake can reverse these differences. DESIGN: A randomized, double-blind, placebo-controlled, parallel, fish-oil intervention study was performed. After a 2-wk run-in period, 44 Europeans and 40 Indo-Asian Sikhs were randomly assigned to receive either 4.0 g fish oil [1.5 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid (DHA)] or 4.0 g olive oil (control) daily for 12 wk. RESULTS: At baseline, the Indo-Asians had significantly higher plasma triacylglycerol, small dense LDL, apolipoprotein B, and dietary and platelet phospholipid n-6 PUFA values and significantly lower long-chain n-3 PUFAs (EPA and DHA) than did the Europeans. A significant decrease in plasma triacylglycerol, plasma apolipoprotein B-48, and platelet phospholipid arachidonic acid concentrations and a significant increase in plasma HDL concentrations and platelet phospholipid EPA and DHA levels were observed after fish-oil supplementation. No significant effect of ethnicity on the responses to fish-oil supplementation was observed. CONCLUSIONS: Moderate fish-oil supplementation contributes to a reversal of lipid abnormalities and low n-3 PUFA levels in Indo-Asians and should be considered as an important, yet simple, dietary manipulation to reduce CAD risk in Indo-Asians with an atherogenic lipoprotein phenotype.     

Fatty acid composition of serum lipid classes in mice following allergic sensitisation with or without dietary docosahexaenoic acid-enriched fish oil substitution

Dietary fatty acids have been shown to influence allergic sensitisation. Both n-3 and n-6 PUFA are involved in targeted mediation of inflammatory responses during allergic sensitisation and manifestation of atopic diseases. In the present experiments we investigated whether supplementation of DHA-enriched fish oil partly substituting dietary sunflower-seed oil, in comparison with sunflower-seed oil, supplemented to mice influences fatty acid composition of serum lipid classes. The effects of the two different diets were also investigated depending on allergic sensitisation. Supplementation of DHA and EPA in doses of 2 and 0.12 % (w/w) to non-sensitised and sensitised mice resulted in significantly increased percentile contributions of DHA to all lipid classes. In contrast, serum values of the n-6 PUFA arachidonic acid (AA) were significantly lower, both in non-sensitised and sensitised mice fed the DHA-enriched diet. The fatty acid composition of serum lipids also reflected allergic sensitisation: the EPA:AA ratio in TAG, cholesteryl esters and phospholipids in non-supplemented animals fell to 23, 29 and 29 % respectively of the original value after allergic sensitisation, whereas it decreased to 70, 80 and 76 % respectively only in the animals supplemented with DHA. In summary, allergic sensitisation alone decreased significantly the EPA:AA ratios in serum TAG, while concomitant supplementation of DHA-enriched fish oil ameliorated this decrease. We postulate from the present results that the amelioration of the severity of allergic sensitisation after DHA supplementation may be linked to altered ratios of the eicosanoid precursors EPA and AA as well as DHA needed for further metabolic activation to pro- or anti-inflammatory bioactive lipids.     

Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects

BACKGROUND: Dietary alpha-linolenic acid (ALA) can be converted to long-chain n-3 polyunsaturated fatty acids (PUFAs) in humans and may reproduce some of the beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease risk factors. OBJECTIVE: This study aimed to compare the effects of increased dietary intakes of ALA and EPA+DHA on a range of atherogenic risk factors. DESIGN: This was a placebo-controlled, parallel study involving 150 moderately hyperlipidemic subjects randomly assigned to 1 of 5 interventions: 0.8 or 1.7 g EPA+DHA/d, 4.5 or 9.5 g ALA/d, or an n-6 PUFA control for 6 mo. Fatty acids were incorporated into 25 g of fat spread and 3 capsules to be consumed daily. RESULTS: The change in fasting or postprandial lipid, glucose, or insulin concentrations or in blood pressure was not significantly different after any of the n-3 PUFA interventions compared with the n-6 PUFA control. The mean (+/- SEM) change in fasting triacylglycerols after the 1.7-g/d EPA+DHA intervention (-7.7 +/- 4.99%) was significantly (P < 0.05) different from the change after the 9.5-g/d ALA intervention (10.9 +/- 4.5%). The ex vivo susceptibility of LDL to oxidation was higher after the 1.7-g/d EPA+DHA intervention than after the control and ALA interventions (P < 0.05). There was no significant change in plasma alpha-tocopherol concentrations or in whole plasma antioxidant status in any of the groups. CONCLUSION: At estimated biologically equivalent intakes, dietary ALA and EPA+DHA have different physiologic effects.     

The Pattern of Fatty Acids Displaced by EPA and DHA Following 12 Months Supplementation Varies between Blood Cell and Plasma Fractions

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0–4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%–64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology.     

Adherence to a Mediterranean diet and plasma fatty acids: data from the Bordeaux sample of the Three-City study

Higher adherence to a Mediterranean diet (MeDi) and n-3 PUFA may both contribute to decreased dementia risk, but the association between MeDi adherence and lipid status is unclear. The aim of the present study was to analyse the relationship between plasma fatty acids and MeDi adherence in French elderly community dwellers. The study population (mean age 75·9 years) consisted of 1050 subjects from Bordeaux (France) included in the Three-City cohort. Adherence to the MeDi (scored as 0-9) was computed from a FFQ and 24?h recall. The proportion of each plasma fatty acid was determined. Cross-sectional analysis of the association between plasma fatty acids and MeDi adherence was performed by multi-linear regression. After adjusting for age, sex, energy intake, physical activity, smoking status, BMI, plasma TAG and apoE-?4 genotype, plasma palmitoleic acid was significantly inversely associated with MeDi adherence, whereas plasma DHA, the EPA+DHA index and total n-3 PUFA were positively associated with MeDi adherence. The n-6:n-3 PUFA, arachidonic acid (AA):EPA, AA:DHA and AA:(EPA+DHA) ratios were significantly inversely associated with MeDi adherence. Plasma EPA was positively associated with MeDi adherence only in apoE-?4 non-carriers. There was no association between MeDi adherence and SFA and total MUFA. The present results suggest that the protective effect of the MeDi on cognitive functions might be mediated by higher plasma DHA and lower n-6:n-3 PUFA ratios.     

Inhibition of tumour necrosis factor-alpha and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation

Increased dietary consumption of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (20 : 5n-3; EPA) and docosahexaenoic acid (22 : 6n-6; DHA) is associated with their incorporation into circulating phospholipid and increased production of lipid peroxide metabolites. The relationship between peripheral blood mononuclear cell (PBMC) function, n-3 PUFA intake and antioxidant co-supplementation is poorly defined. We therefore investigated tumour necrosis factor (TNF)-alpha and interleukin (IL) 6 production by PBMC and phospholipid fatty acid composition in plasma and erythrocytes of healthy male subjects (n 16) receiving supplemental intakes of 0.3, 1.0 and 2.0 g EPA+DHA/d, as consecutive 4-week courses. All subjects were randomised in a double-blind manner to receive a concurrent antioxidant supplement (200 microg Se, 3 mg Mn, 30 mg D-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 microg vitamin A (beta-carotene and retinol)) or placebo. There was a positive dose-dependent relationship between dietary n-3 PUFA intake and EPA and DHA incorporation into plasma phosphatidylcholine and erythrocyte phosphatidylethanolamine, with a tendency towards a plateau at higher levels of intake. Production of TNF-alpha and IL-6 by PBMC decreased with increasing n-3 PUFA intake but tended towards a 'U-shaped' dose response. Both responses appeared to be augmented by antioxidant co-supplementation at intermediate supplementary n-3 PUFA intakes. Thus, increased dietary n-3 PUFA consumption resulted in defined but contrasting patterns of modulation of phospholipid fatty acid composition and PBMC function, which were further influenced by antioxidant intake.     

High α-linolenic acid and fish oil ingestion promotes ovulation to the same extent in rats

Prostaglandins (PG) have a regulatory influence on ovulation. α-Linolenic acid (ALA) vs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differently influence PG biosynthesis. Whereas high EPA/DHA reduces PGE₂, enhancing ovulation, we hypothesized that ALA would not affect ovulation. Our objective was to determine the effect of low and high ALA intake vs EPA/DHA on ovarian phospholipids, ovulation, and PG synthesis in rats. Following 27 days on diet and ovulation induction, ovaries were isolated and analyzed in 22 pups per diet. Ovarian phospholipid (n-3) polyunsaturated fatty acid (PUFA) incorporation increased with EPA/DHA ingestion. With significant ovarian (n-3) PUFA or EPA (P < .05) enrichment in the high–n-3 PUFA diets, ova release increased. Although high ALA did not enrich total (n-3), it increased ova release and tissue EPA over low ALA or control. Dietary EPA/DHA more effectively reduced ovarian arachidonic acid levels than dietary ALA. Dietary ALA increased PGF and very high intake reduced PGE, whereas EPA/DHA did not alter PGE or PGF. Enhanced ova release with high (n-3) PUFA intake may be induced via multiple mechanisms including reduced ovarian arachidonic acid. Significant ovarian retention of EPA and DHA enhanced ovulation with unchanged total PGE and PGF. Lack of change in PGE may have resulted from reduced PGE₂ combined with increased PGE₃. When EPA alone was elevated, PGE was reduced, whereas PGF was increased. Results indicate that very high ALA intake enhances ovulation similar to very high EPA/DHA ingestion, an effect potentially mediated via similar patterns of PGF₂α and PGE₂ synthesis.     

Dietary flavonoids increase plasma very long-chain (n-3) fatty acids in rats

Flavonoids probably contribute to the health benefits associated with the consumption of fruit and vegetables. However, the mechanisms by which they exert their effects are not fully elucidated. PUFA of the (n-3) series also have health benefits. Epidemiological and clinical studies have suggested that wine flavonoids may interact with the metabolism of (n-3) PUFA and increase their blood and cell levels. The present studies in rats were designed to assess whether flavonoids actually increase plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main very long-chain (n-3) PUFA. Rats were fed a corn-derived anthocyanin (ACN)-rich (ACN-rich) or ACN-free diet with constant intakes of plant and marine (n-3) PUFA for 8 wk (Expt. 1). Plasma fatty acids were measured by GC. The ACN-rich diet contained ~0.24 ± 0.01 mg of ACN/g pellets. There were no significant differences between groups in the main saturated, monounsaturated, and (n-6) fatty acids. In contrast, plasma EPA and DHA were greater in the ACN-rich diet group than in the ACN-free diet group (P < 0.05). We obtained similar results in 2 subsequent experiments in which rats were administered palm oil (80 μL/d) and consumed the ACN-rich or ACN-free diet (Expt. 2) or were supplemented with fish oil (60 mg/d, providing 35 mg DHA and 12 mg EPA) and consumed the ACN-rich or ACN-free diet (Expt. 3). In both experiments, plasma EPA and DHA were significantly greater in the ACN-rich diet group. These studies demonstrate that the consumption of flavonoids increases plasma very long-chain (n-3) PUFA levels. These data confirm previous clinical and epidemiological studies and provide new insights into the health benefits of flavonoids.     

Long-chain (n-3) polyunsaturated fatty acids prevent metabolic and vascular disorders in fructose-fed rats

The crossover relationship between cardiometabolic risk, in terms of insulin resistance and vascular dysfunction, and the fatty acid (FA) profile of insulin-sensitive tissues as well as the dietary FA impact has almost never been explored in the same experiment. In this study, the intake of alpha-linolenic acid (ALA) alone and/or with its higher metabolites, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were evaluated in a nonobese, hypertriglyceridemic and insulin-resistant rat model, that exhibits the 2 main characteristics of metabolic syndrome. Wistar rats were fed either a cornstarch and (n-6) PUFA-based diet (C-N6) or a 66% fructose diet over a 10-wk period. Fructose-fed rats received a diet containing ALA alone (F-ALA group) or ALA plus EPA and DHA (F-LC3 group) or no (n-3) PUFA (F-N6 group). The 10-wk high-fructose diet (F-N6) induced an insulin-resistant state, as assessed by glucose and insulin tolerance tests. Insulin resistance was linked to a specific FA pattern in insulin-sensitive tissues, which probably involved modifications of Delta9, Delta6, and Delta5-desaturases. This pathological status was related to high cardiovascular risk as assessed by increases in systolic and diastolic blood pressures and particularly by the increase of pulse pressure, an index of vascular stiffness obtained from telemetry investigations. The (n-3) experimental diets prevented changes in the FA patterns in insulin-sensitive tissues, insulin resistance, and vascular dysfunction. This beneficial effect was large with an intake of long chain (n-3) PUFA (ALA+EPA+DHA) and to a lesser extent with dietary ALA alone.     

Beneficial effects of omega-3 fatty acids on the consequences of a fructose diet are not mediated by PPAR delta or PGC1 alpha

Purpose

To study, in high-fructose-fed rats, the effect of a dietary enrichment in omega-3 polyunsaturated fatty acids (n-3 PUFA) on the expression of genes involved in lipid metabolism and cardiovascular function.

Methods

Twenty-eight male “Wistar Han” rats received for 8 weeks, either a standard chow food or an isocaloric 67 % fructose diet enriched or not in alpha-linolenic acid (ALA) or in docosahexaenoic (DHA) and eicosapentaenoic acids (EPA) mix (DHA/EPA). After sacrifice, blood was withdrawn for biochemical analyses; heart, periepididymal adipose tissue and liver were collected and analyzed for the expression of 22 genes by real-time PCR.

Results

Fructose intake resulted in an increase in liver weight and triglyceride content, plasma triglyceride and cholesterol concentrations, although no difference in glucose and insulin. In the liver, lipogenesis was promoted as illustrated by an increase in stearoyl-CoA desaturase and fatty acid synthase (Fasn) together with a decrease in PPAR gamma, delta and PPAR gamma coactivator 1 alpha (PGC1 alpha) expression. In the heart, Fasn and PPAR delta expression were increased. The addition of ALA or DHA/EPA into the diet resulted in a protection against fructose effects except for the decreased expression of PPARs in the liver that was not counterbalanced by n-3 PUFA suggesting that n-3 PUFA and fructose act independently on the expression of PPARs and PGC1 alpha.

Conclusions

In liver, but not in heart, the fructose-enriched diet induces an early tissue-specific reduction in PPAR gamma and delta expression, which is insensitive to n-3 PUFA intake and dissociated from lipogenesis.