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.     

Docosahexaenoic acid and eicosapentaenoic acid affect ovarian prostaglandin levels differently in rats

Prostaglandins (PGs) play a key role in the regulation of ovulation. Typically, ingestion of the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) has been found to decrease, whereas arachidonic acid (ARA) increases PG biosynthesis in most systems. We hypothesized that DHA and EPA would decrease ovarian PGE₂, enhancing ovulation, with combined EPA and DHA having the greatest effect, whereas ARA would increase PGE₂, suppressing ovulation. Our objective was to determine how 0.3-g/100-g diet DHA and EPA alone or combined, or ARA would affect tissue composition, ovulation, and PG synthesis in rats. After 27 days on diet and ovulation induction, ovaries were isolated and analyzed from 22 pups per diet. Eicosapentaenoic acid alone reduced ovarian n-6 PUFA attributable to reduced ARA incorporation. Arachidonic acid ingestion reduced and EPA enhanced ovarian n-3 PUFA to levels above what was seen with DHA or DHA/EPA combinations. Docosahexaenoic acid alone increased total PGE 1.5-fold over control, whereas neither differed from the remaining treatments. Increased total PGE with DHA was attributable to elevated PGE₃ with PGE₂ unchanged by diet, and PGE₃ only increased with DHA ingestion alone. Total PGF differed from control with the highest DHA intake, alone or combined with EPA, or with ARA ingestion (P < .05). Increased PGF with DHA was attributable to increased PGF_3α. Experimental diets did not alter ovulation from control. Results indicate that DHA and EPA consumption at human achievable doses differently alters ovarian phospholipids and PGs associated with ovulation with potential for significant 3-series PG without significantly perturbing ovulation.     

Dietary intakes of α-linolenic and linoleic acids are inversely associated with serum C-reactive protein levels among Japanese men

Investigations suggest a protective role of n-3 polyunsaturated fatty acids (PUFA) but opposing roles of n-6 PUFA in inflammation, but the effects in vivo the human are not clear. We therefore tested the hypothesis that higher intakes of n-3 PUFA and n-6 PUFA are associated with lower levels of inflammation among a population consuming a diet high in PUFA. This study aimed to assess the association between PUFA intake and serum C-reactive protein (CRP) concentrations in a group of Japanese employees. The study subjects were 300 men and 211 women aged 21 to 67 years working in 2 municipal offices of Japan. We measured the serum high-sensitivity CRP concentrations by the latex agglutination nephelometry method and assessed dietary habits by a validated self-administered diet history questionnaire. We analyzed the data using multiple linear regression analysis with adjustment for potential confounding variables. Mean serum CRP concentrations tended to decrease as the intake of eicosapentaenoic acid, docosahexaenoic acid, or their combination increased in men and women, although none of these relationships was statistically significant. In men, there were statistically significant inverse relationships between dietary intake of n-3 or n-6 PUFA and serum CRP concentrations (P for trend = .03 and .008, respectively). Among specific PUFA, only α-linolenic acid and linoleic acid showed clear inverse relationships (P for trend = .001 and .003, respectively) in men. The results suggest that increased intake of not only α-linolenic acid (n-3 PUFA) but also linoleic acid (n-6 PUFA) has a beneficial effect on systemic inflammation in men.     

Dietary fat and selenium effects on ex vivo prostaglandin production in rat colon,kidney, and blood

The effects were determined of dietary fat and selenium (Se) levels on prostaglandin (PG) production in rat blood, kidney, and colon mucosa. For 30 weeks, male Wistar‐derived MRC rats were prefed diets containing low (6 g/367 kcal) or high (20 g/367 kcal) levels of fat with one of three Se supplements from sodium selenite: 0.0, 0.1, or 2.0 ppm Se. PG production was stopped by adding aspirin immediately following removal of the blood, kidney, and colon samples. Separate samples were allowed to incubate 10 or 60 minutes before blockage of PG production for determination of ex vivo PG production. Prostaglandin E₂ (PGE₂), thromboxane B₂, and 6‐keto‐prostaglandin F_1α (6‐keto‐PGF_1α) were measured by radioimmunoassay following separation on silicic acid columns. Basal levels of the three PGs were not influenced by diet. PGE₂ production in the colon was highest in the group fed the high‐fat diet that contained 2.0 ppm Se at 10 and 60 minutes, but PGE₂ production in the blood and kidney were not altered by diet. Thromboxane B₂ production in the rats’ blood was higher in those prefed high‐fat diets, but it was not influenced by dietary Se. Production of 6‐keto‐PGF_1α in the blood and thromboxane B₂ and 6‐keto‐PGF_1α production by the kidney and colonic mucosa were not influenced by either dietary fat or Se.     

Effects of Different Dietary Fatty Acids on the Fatty Acid Compositions and the Expression of Lipid Metabolic-Related Genes in Mammary Tumor Tissues of Rats

In this study, the effects of dietary fatty acids on the fatty acid compositions and lipid metabolic-related genes expression in N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinogenesis were evaluated. The 50-day-old female Sprague-Dawley rats were intervened by different dietary fats (15% wt/wt), including saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-6 polyunsaturated fatty acid (PUFA), n-3 PUFA, 1:1 n-6/n-3, 5:1 n-6/n-3, 10:1 n-6/n-3, and 1:2:1 S/M/P (1:1 n-6/n-3), alone or in combination with MNU. There was no mammary tumor occurrence in the control and MNU-treated n-3 PUFA groups after 18 wk. n-3 PUFA diet retarded the weight growth of rats. 1:1 n-6/n-3 diet significantly reduced the MNU-induced tumor incidence and tumor multiplicity compared with SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3 and 1:2:1 S/M/P diets (42.86% vs. 83.33%–92.31%, 0.79 vs. 2.62–2.85, P < 0.01). Additionally, 1:1 n-6/n-3 diet substantially increased cis-5,8,11,14,17-eicosapentaenoic acid and cis-4,7,10,13,16,19-docosahexaenoic acid levels, whereas it decreased C20:4 level and the mRNA expressions of fatty acid synthase, Cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) in mammary tissues (P < 0.05). These results suggest that 1:1 n-6/n-3 in the diet is effective in the prevention of mammary tumor development by increasing the n-3 PUFA content and reducing the expression of lipid metabolic-related genes.     

Dietary polyunsaturated fatty acids reduce retinal stress induced by an elevation of intraocular pressure in rats

N-6 and n-3 polyunsaturated fatty acids (PUFAs) have been shown to prevent tissue release of inflammatory molecules. We have shown that a combination of n-6 and n-3 PUFAs is more efficient than single supplementations on the long-term consequences of intraocular pressure elevation. We hypothesized that such an association is also more effective during early retinal stress by modifying retinal proinflammatory prostaglandin and cytokine productions. Rats were supplemented for 3 months with n-6 PUFAs, n-3 PUFAs, or both n-6 and n-3 PUFAs. After 3 months, a surgical elevation of intraocular pressure was induced. Retinal morphometry and glial cell activation were evaluated 24 hours after laser treatment. The retinal levels of prostaglandin E₁ (PGE₁) and prostaglandin E₂ (PGE₂) and the messenger RNA levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were measured. Retinal glial cell activation after laser treatment was partly prevented by dietary n-6, n-3, and n-6 and n-3 PUFAs. Retinal PGE₁ was unaffected by the laser treatment or by the diet. Dietary n-6 and/or n-3 PUFAs prevented the increase in PGE₂ levels observed in laser-treated retinas without affecting the induction of interleukin-1β, interleukin-6, and tumor necrosis factor-α messenger RNAs. This study shows that not only a combination of n-6 and n-3 PUFAs but also single supplementations can preserve the retina from early glial cell activation and PGE₂ release. The protective effect is not mediated by changes in cytokine expression but may be related to modifications in retinal prostaglandin metabolism.     

Dietary n-3 polyunsaturated fatty acids alter lipid composition and decrease prostaglandin synthesis in rat spleen

Three groups of rats were fed a semisynthetic diet containing 10% olive oil, 10% corn oil, or 10% menhaden oil for three weeks. Olive oil was used as a control and corn and menhaden oils as sources of n-6 and n-3 fatty acids, respectively. The spleen phospholipids were enriched with eicosapentaenoic (20:5 n-3) and docosahexaenoic acids (22:6 n-3) in rats on menhaden oil diets. The enrichment of these n-3 fatty acids was accompanied by a decrease in the arachidonic acid content (20:4 n-6) of spleen phospholipids. The syntheses of prostaglandin E₂ (PGE₂), 6-keto prostaglandin F_1α (6 keto PGF_1α) and thromboxane B₂ (TXB₂) from endogenous substrates in n-3 fatty acid enriched spleens were decreased by 50, 57 and 80% respectively. These studies indicate that dietary n-3 fatty acids can effectively displace arachidonic acid from phospholipids and decrease prostaglandin synthesis in rat spleen.     

Dietary conjugated α-linolenic acid did not improve glucose tolerance in a neonatal pig model

Purpose

There is an increased interest in the benefits of conjugated α-linolenic acid (CLNA) on obesity-related complications such as insulin resistance and diabetes. The aim of the study was to investigate whether a 1 % dietary supplementation of mono-CLNA isomers (c9-t11-c15-18:3 + c9-t13-c15-18:3) improved glucose and lipid metabolism in neonatal pigs.

Methods

Since mono-CLNA isomers combine one conjugated two-double-bond system with an n-3 polyunsaturated fatty acid (PUFA) structure, the experimental protocol was designed to isolate the dietary structural characteristics of the molecules by comparing a CLNA diet with three other dietary fats: (1) conjugated linoleic acid (c9-t11-18:2 + t10-c12-18:2; CLA), (2) non-conjugated n-3 PUFA, and (3) n-6 PUFA. Thirty-two piglets weaned at 3 weeks of age were distributed among the four dietary groups. Diets were isoenergetic and food intake was controlled by a gastric tube. After 2 weeks of supplementation, gastro-enteral (OGTT) and parenteral (IVGTT) glucose tolerance tests were conducted.

Results

Dietary supplementation with mono-CLNA did not modify body weight/fat or blood lipid profiles (p > 0.82 and p > 0.57, respectively) compared with other dietary groups. Plasma glucose, insulin, and C-peptide responses to OGTT and IVGTT in the CLNA group were not different from the three other dietary groups (p > 0.18 and p > 0.15, respectively). Compared to the non-conjugated n-3 PUFA diet, CLNA-fed animals had decreased liver composition in three n-3 fatty acids (18:3n-3; 20:3n-3; 22:5n-3; p < 0.001).

Conclusions

These results suggest that providing 1 % mono-CLNA is not effective in improving insulin sensitivity in neonatal pigs.     

CLA and n-3 PUFA differentially modulate clinical activity and colonic PPAR-responsive gene expression in a pig model of experimental IBD

BACKGROUND AND AIMS: Conjugated linoleic acid (CLA) and n-3 polyunsaturated fatty acids (PUFA) have been proposed as important pharmaco-nutrients for modulating mucosal immunity and therapeutic responses in patients with inflammatory bowel disease (IBD). We evaluated the ability of CLA and n-3 PUFA alone or in combination to modulate IBD in a pig model of dextran sodium sulfate (DSS)-induced colitis. METHODS: Sixty-four, 15-day-old pigs were used to evaluate the effect of CLA, n-3 PUFA and a 50:50 mixture of CLA and n-3 PUFA on growth, clinical activity and colonic PPAR-responsive gene expression. Diets were formulated to contain: 1.33% soybean oil (control); 1.33% CLA; 1.33% fish oil; or 1.33% of a 50:50 mixture of CLA and fish oil. Intestinal inflammation was induced by an intragastric challenge with DSS on day 42 of dietary supplementation. The colonic expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), PPAR gamma- and delta-responsive genes, keratinocyte growth factor (KGF) and tumor necrosis factor (TNF-alpha) were assayed by quantitative RT-PCR. RESULTS: The onset of IBD was delayed, colitis less severe and growth suppression attenuated in pigs fed CLA, which correlated with induction of colonic PPAR gamma and its responsive gene PPAR gamma-coactivator-1alpha (PGC1-alpha) and downregulation of TNF-alpha. However, dietary supplementation with n-3 PUFA alone or in combination with CLA resulted in an early onset of disease (i.e., day 2) and faster recovery on days 6 and 7, which correlated with a marked induction of the PPAR delta-responsive gene uncoupling protein 3 (UCP3). CLA and n-3 PUFA acted synergistically to upregulate colonic KGF expression in DSS-challenged pigs but n-3 PUFA blocked CLA-induced PPAR gamma activation. CONCLUSION: Dietary CLA-supplementation upregulated colonic PPAR gamma expression and contributed to delaying the onset of experimental IBD, whereas n-3 PUFA failed to protect from IBD, although it accelerated colonic regeneration and clinical remission by activating PPAR delta.     

不同n-3/n-6多不饱和脂肪酸构成比对大鼠脂代谢和食欲的影响

目的研究不同n-3/n-6配比脂肪酸对大鼠食欲影响及其与腺苷酸活化蛋白激酶(AMPK)基因表达的关系。方法58只SD大鼠适应性喂养7天后,尾静脉取血。根据血清总胆固醇(TC)水平随机分为6组:空白组(基础饲料),高脂组(高脂饲料),高脂1∶1组(高脂饲料+n-3/n-6=1∶1油),高脂1∶5组(高脂饲料+n-3/n-6=1∶5油),低脂1∶1组(脱脂基础饲料+n-3/n-6=1∶1油),低脂1∶5组(脱脂基础饲料+n-3/n-6=1∶5油),喂养45天,观察大鼠摄食与体重增长,并于实验第0、15、30和45天测定血清总胆固醇(TC)和甘油三酯(TG)含量。于45天处死动物,取下丘脑,用RT-PCR分别测下丘脑组织中NPY、AMPK-α2 mRNA表达。结果添加PUFA的四个组血清TC、TG、摄食量、体重及NPY、AMPK-α2mRNA表达均比高脂组大鼠明显降低(P<0.05)。结论PUFA改善血脂可能是通过影响AMPK表达,从而抑制下丘脑食欲相关基因表达,进而影响血脂代谢。     

Protective effect of dietary n-3 polyunsaturated fatty acids on myocardial resistance to ischemia-reperfusion injury in rats

Dietary n-3 polyunsaturated fatty acids (PUFA) reduce coronary heart disease (CHD) complications, such as chronic arrhythmia and sudden cardiac death. Improved myocardial resistance to ischemia-reperfusion injury results in smaller myocardial infarction, which is a major factor in the occurrence of CHD complications. We hypothesized that a specific dietary fatty acid profile (low in saturated and n-6 PUFA but high in plant and marine n-3 PUFA) may improve myocardial resistance to ischemia-reperfusion injury and reduce infarct size. To test this assumption, we used a well-defined rat model of myocardial infarction. Based on our results, in comparison to a diet that is high in either saturated or n-6 PUFA but poor in plant and marine n-3 PUFA, a diet that is low in saturated fats and n-6 PUFA but rich in plant and marine n-3 PUFA results in smaller myocardial infarct size (P < .01). The effects of the 3 diets were also examined by analyzing the fatty acid composition of plasma, erythrocyte cell membranes, and the phospholipids of myocardial mitochondria. The results show a great accumulation of n-3 PUFA and a parallel decrease in arachidonic acid, the main n-6 PUFA, in plasma, cell membranes, and cardiac mitochondria (P < .0001). We conclude that improved myocardial resistance to ischemia-reperfusion may be one of the critical factors explaining the protective effects of dietary n-3 PUFA against CHD complications in humans. In addition to increasing n-3 PUFA intake, an optimal dietary pattern aimed at reducing cardiovascular mortality should include a reduction of the intake of both saturated and n-6 PUFA.     

Dose-dependent effect of dietary conjugated linoleic acid on the growth of rat hepatoma dRLh-84 cells in vivo

In this study, the effect of varying doses of conjugated linoleic acid (CLA) on the growth of transplanted hepatoma dRLh-84 cells and the relationship between tumor growth and prostaglandin (PG) E2 production or cyclooxygenase (COX)-2 expression were examined. Donryu rats were fed an experimental diet containing 0, 0.1, 0.5, or 2 wt.% CLA for 3 wk, and then dRLh-84 cells were transplanted into the liver. Results show that dietary CLA (0.5 and 2 wt.%) significantly enhanced the growth of the transplanted hepatoma cells compared to the non-CLA diet group at 20 d after cell transplantation. Tumor weight at 10 d after transplantation was also significantly higher in the 2 wt.% CLA group than in non-CLA fed rats. Ten days after transplantation, the PGE2 level in the tumor tissue was shown to be depressed in a CLA dose-dependent manner. Cyclooxygenase-2 (COX-2) mRNA expression in the tumor also tended to be lower in the CLA group than in the non-CLA diet group 10 d after transplantation. Dietary CLA did not affect the tumor phospholipid arachidonic acid level, which is a substrate for PG synthesis. These results indicate that dietary CLA of at least 0.5 wt.% enhances the growth of transplanted dRLh-84 cells in vivo. It is believed that growth promotion of dRLh-84 cells in vivo by CLA cannot be clarified by the PG synthesis dependent mechanism.     

Lack of effect of dietary n-6:n-3 PUFA ratio on plasma lipids and markers of insulin responses in Indian Asians living in the UK

Summary Background Indian Asians living in Western Countries have an over 50 % increased risk of coronary heart disease (CHD) relative to their Caucasians counterparts. The atherogenic lipoprotein phenotype (ALP), which is more prevalent in this ethnic group, may in part explain the increased risk. A low dietary long chain n-3 fatty acid (LC n-3 PUFA) intake and a high dietary n-6 PUFA intake and n-6:n-3 PUFA ratio in Indian Asians have been proposed as contributors to the increased ALP incidence and CHD risk in this subgroup. Aim To examine the impact of dietary n-6:n-3 PUFA ratio on membrane fatty acid composition, blood lipid levels and markers of insulin sensitivity in Indian Asians living in the UK. Methods Twentynine males were assigned to either a moderate or high n-6:n-3 PUFA (9 or 16) diet for 6 weeks. Fasting blood samples were collected at baseline and 6 weeks for analysis of triglycerides, total-, LDL- and HDL-cholesterol, non-esterified fatty acids, glucose, insulin, markers of insulin sensitivity and C-reactive protein. Results Group mean saturated fatty acid, MUFA, n-6 PUFA and n-3 PUFA on the moderate and high n-6:n-3 PUFA diets were 26 g/d, 43 g/d, 15 g/d, 2 g/d and 25 g/d, 25 g/d, 28 g/d, 2 g/d respectively. A significantly lower total membrane n-3 PUFA and a trend towards lower EPA and DHA levels were observed following the high n-6:n-3 PUFA diet. However no significant effect of treatment on plasma lipids was evident. There was a trend towards a loss of insulin sensitivity on the high n-6:n- 3 PUFA diet, with the increase in fasting insulin (P = 0.04) and HOMA IR [(insulin x glucose)/ 22.5] (P = 0.02) reaching significance. Conclusion The results of the current study suggest that, within the context of a western diet, it is unlikely that dietary n-6:n-3 PUFA ratio has any major impact on the levels of LC n-3 PUFA in membrane phospholipids or have any major clinically relevant impact on insulin sensitivity and its associated dyslipidaemia. Source of support: This project was funded by the Food Standards Agency (FSA), UK.     

The effect of polyunsaturated fatty acids, including conjugated linoleic acid, on calcium absorption and bone metabolism and composition in young growing rats

The effect of polyunsaturated fatty acids (PUFA), in particular conjugated linoleic acid (CLA), on Ca and bone metabolism is unclear. In a 2x2 factorial design study, forty male 4-week-old rats were fed a control diet containing 70 g added fat (soyabean oil (SBO; n-6 PUFA-rich diet) or menhaden oil-safflower oil (MSO; n-3 PUFA-rich diet))/kg diet with 0 or 10 g CLA/kg for 8 weeks. Ex vivo prostaglandin E2 biosynthesis by bone organ culture was significantly higher (P<0.001) in rats consuming SBO compared with MSO, irrespective of CLA. Addition of the CLA treatment to either diet further lowered (P<0.05) ex vivo prostaglandin E2 production. Neither PUFA type nor CLA altered circulating or femoral mRNA levels of osteocalcin (a marker of bone formation) or insulin-like growth factor-I (a mediator of bone metabolism). While urinary pyridinium crosslinks levels (markers of bone resorption) were unaffected by CLA irrespective of PUFA type, they were significantly higher (P<0.05) in rats consuming SBO compared with MSO irrespective of CLA. Net fractional (%) and absolute (mg) Ca absorption were significantly (P<0.01 and P<0.05 respectively) higher in CLA-supplemented than unsupplemented animals fed on the n-3 PUFA-rich diet, whereas CLA had no effect in animals fed the n-6 PUFA-rich diet. There was no effect of CLA supplementation on bone mineral mass. In conclusion, CLA supplementation over 8 weeks appeared to enhance Ca absorption in young growing rats fed an n-3 PUFA-rich diet, but had no measurable effect on bone metabolism or bone mass over this time frame.     

Conjugated Linoleic Acid and Bone Biology

Osteoporosis, osteoarthritis and inflammatory joint disease afflict millions of people worldwide. Inflammatory cytokines inhibit chondrocyte proliferation and induce cartilage degradation for which part of the response is mediated by PGE₂. Excess production of PGE₂ is linked to osteoporosis and arthritis and is associated with bone and proteoglycan loss. PGE₂ also influences the IGF-I/IGFBP axis to facilitate bone and cartilage formation. Recent investigations with growing rats given butter fat and supplements of CLA demonstrated an increased rate of bone formation and reduced ex vivo bone PGE₂ production, respectively. Furthermore, the supplements of CLA isomers resulted in their enrichment in lipids of various bone compartments of animals. The effects of CLA on bone biology in rats (IGF action and cytokines) appear to be dependent on the level of n-6 and n-3 fatty acids in the diet; however, these studies generally showed that CLA decreased ex vivo bone PGE₂ production and in osteoblast-like cultures. Anti-inflammatory diets, including nutraceutical applications of CLA, may be beneficial in moderating cyclooygenase 2 (COX-2) activity or expression (influencing PGE₂ biosynthesis) and might help to reduce rheumatoid arthritis (secondary osteoporosis). This review summarizes findings of CLA on bone modeling in rats and effects on cellular functions of osteoblasts and chondrocytes. These experiments indicate that CLA isomers possess anti-inflammatory activity in bone by moderating prostanoid formation.     

Effects of dietary sodium intake on blood pressure and urinary excretion of prostaglandins in normotensive and hypertensive subjects

Blood pressure and the urinary excretion of prostaglandins (PG) E₂ and F_2α were evaluated in all female normotensive (NS), borderline hypertensive (BHS) and sustained essential hypertensive (EHS) subjects receiving diuretic treatment under normal and reduced dietary sodium intake. Plasma cholesterol, sodium, and potassium, and urinary sodium, potassium and creatinine were also assessed. As dietary sodium intake decreased, a decrease in blood pressure, an increase in urinary excretion of PGE₂ were observed in NS and BHS. Urinary PGF_2α excretion was increased in NS with dietary sodium restriction. There was no correlation between urinary sodium excretion and urinary excretion of PGE₂, PGF_2α or the ratio of PGE₂/PGF_2α. With normal sodium intake, urinary PGE₂ excretion was greater in NS as compared to BHS whereas with reduced dietary sodium intake, PGF_2α excretion was greater in NS than in EHS. Plasma cholesterol was decreased in NS and BHS during the sodium restriction period with the reduction occurring in very low density and low density lipoprotein fractions. The results of this study do not support a natriuretic role of renal PGE₂ but does support the hypothesis of decreased renal PGE₂ synthesis in hypertensive subjects.     

Dietary echium oil increases plasma and neutrophil long-chain (n-3) fatty acids and lowers serum triacylglycerols in hypertriglyceridemic humans

A wealth of evidence indicates that consumption of fish or dietary fish oils containing long-chain (n-3) PUFA such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with cardiovascular benefit, including a reduction in circulating triacylglycerol concentrations and reduced mortality from coronary heart disease. Shorter-chain dietary (n-3) PUFA such as alpha-linolenic acid from vegetable oils are inefficiently converted to EPA and DHA and do not possess the hypotriglyceridemic properties attributed to fish oils. The objective of this study was to investigate the effect of dietary Echium oil, a plant oil containing the 18-carbon (n-3) PUFA stearidonic acid, on tissue fatty acid content and serum triacylglycerol concentrations in hypertriglyceridemic humans. Asymptomatic subjects with mild-to-moderate hypertriglyceridemia were enrolled in an open-labeled study. Subjects underwent a 4-wk lead-in period and were then instructed to follow the National Cholesterol Education Program Step 1 diet. Subjects (n = 11) whose serum triacylglycerol concentrations remained between 3.4 and 5.1 mmol/L (300 and 450 mg/dL) were instructed to consume 15 g of Echium oil daily for 4 wk. During the treatment period, serum triacylglycerol concentrations decreased by 21%, or 0.87 +/- 0.26 mmol/L (mean +/- SD) compared with baseline (P < 0.05); 8 of 11 subjects had a decrease in serum triacylglycerols ranging from 13 to 52% with a decrease from baseline of 30%, or 1.26 +/- 0.41 mmol/L (mean +/- SD). There were no significant changes in any other clinical laboratory variables. Concentrations of long-chain (n-3) PUFA, including EPA, increased (P < 0.05) in plasma and neutrophils when subjects consumed Echium oil. In conclusion, dietary plant oils rich in stearidonic acid are metabolized to longer-chain, more unsaturated (n-3) PUFA. These oils appear to possess hypotriglyceridemic properties typically associated with fish oils.     

Dietary n-3 polyunsaturated fatty acids: rate and extent of modification of fatty acyl composition of lipid classes of mouse lung and kidney

The rate and extent of modification of fatty acid composition of mice lung and kidney by dietary menhaden oil (MO) was investigated. White mice were fed 2 wt% safflower oil and either 10 wt% MO or 10 wt% hydrogenated coconut oil (HCO) for 23 d. The stability of dietary MO-induced fatty acid modifications was assessed by replacing the MO diet of a group of mice after 23 d with the HCO diet for an additional 10 d. Mice were sacrificed on d 0, 1, 3, 5, 7, 14, 23 and 33. The n-3 polyunsaturated fatty acid (PUFA), 20:5n-3 and 22:6n-3 were rapidly incorporated into lung and kidney phosphoglyceride (PL) classes during the first 7 d of MO ingestion relative to the controls. After 1 wk of MO consumption, the rate of incorporation either plateaued at an elevated level or continued to increase at a much more gradual rate. A marked increase in the content of 22:5n-3 in lung and kidney was observed. A concomitant and rapid decrease was observed in the n-6 PUFA, 20:4n-6, 22:5n-6 and 18:2n-6. The minimum content of 20:4n-6 was reached between 1 and 2 wk, whereas the minimum levels of 18:2n-6 and 22:5n-6 occurred within 72 h. The n-6/n-3 PUFA ratio in lung and kidney and PL classes increased in mice fed HCO and decreased in mice fed dietary MO. When dietary MO was removed, the n-3 PUFA levels decreased with a concomitant increase in n-6 PUFA after 10 d of HCO consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increasing the dietary (n-3) to (n-6) polyunsaturated fatty acid ratio increases tumor necrosis factor production by murine resident peritoneal macrophages without an effect on elicited peritoneal macrophages.

Tumor necrosis factor (TNF), prostaglandin (PG) E2 and 6-keto-PGF1 alpha production by murine peritoneal macrophages was monitored following in vitro stimulation with lipopolysaccharide. Macrophages were obtained from mice fed diets containing increasing ratios of (n-3) to (n-6) fatty acids by addition of (n-3) polyunsaturated fatty acids (PUFA) to the (n-6) fatty acids in the diet, or by substituting (n-3) PUFA for the (n-6) fatty acids in the diet. Increasing the dietary (n-3) to (n-6) fatty acid ratio from 0 to 1 increased both cell-associated and secreted TNF production by resident peritoneal macrophages but did not affect TNF production by macrophages elicited with Complete Freund's Adjuvant (CFA). With increasing dietary (n-3): (n-6) ratio there was a decrease in the prostaglandin production by resident peritoneal macrophages, which may partly explain the increased TNF production. The CFA-elicited macrophages produced less prostaglandin than the resident macrophages, and the lower prostaglandin production may partly explain the lack of effect of dietary (n-3) PUFA on TNF production by CFA-elicited macrophages. Increasing the TNF production by resident macrophages with dietary (n-3) PUFA may be beneficial in enhancing antitumor actions and antipathogenicity; by not increasing the high TNF production of inflammatory macrophages, (n-3) PUFA may protect against undesirable systemic inflammatory effects of overproduction.     

Effects of alpha-linolenic acid vs. docosahexaenoic acid supply on the distribution of fatty acids among the rat cardiac subcellular membranes after a short- or long-term dietary exposure

Background

Previous work showed that the functional cardiac effect of dietary alpha-linolenic acid (ALA) in rats requires a long feeding period (6 months), although a docosahexaenoic (DHA) acid-supply affects cardiac adrenergic response after 2 months. However, the total cardiac membrane n-3 polyunsaturated fatty acid (PUFA) composition remained unchanged after 2 months. This delay could be due to a specific reorganization of the different subcellular membrane PUFA profiles. This study was designed to investigate the evolution between 2 and 6 months of diet duration of the fatty acid profile in sarcolemmal (SL), mitochondrial (MI), nuclear (NU) and sarcoplasmic reticulum (SR) membrane fractions.

Methods

Male Wistar rats were randomly assigned to 3 dietary groups (n = 10/diet/period), either n-3 PUFA-free diet (CTL), or ALA or DHA-rich diets. After 2 or 6 months, the subcellular cardiac membrane fractions were separated by differential centrifugations and sucrose gradients. Each membrane profile was analysed by gas chromatography (GC) after lipid extraction.

Results

As expected the n-3 PUFA-rich diets incorporated n-3 PUFA instead of n-6 PUFA in all the subcellular fractions, which also exhibited individual specificities. The diet duration increased SFA and decreased PUFA in SL, whereas NU remained constant. The SR and MI enriched in n-3 PUFA exhibited a decreased DHA level with ageing in the DHA and CTL groups. Conversely, the n-3 PUFA level remained unchanged in the ALA group, due to a significant increase in docosapentaenoic acid (DPA). N-3 PUFA rich diets lead to a better PUFA profile in all the fractions and significantly prevent the profile modifications induced by ageing.

Conclusion

With the ALA diet the n-3 PUFA content, particularly in SR and SL kept increasing between 2 and 6 months, which may partly account for the delay to achieve the modification of adrenergic response.