Lipid composition and prostaglandin synthesis in mouse lung microsomes: Alterations following the ingestion of menhaden oil

Three groups of male mice were fed a normal diet or a semisynthetic diet containing either 10% hydrogenated coconut oil (CO group) or 10% menhaden oil (MO group) for two wk. The synthetic diet altered the fatty acid composition of lung microsomal lipids. Mice ingesting menhaden oil contained greater amounts of eicosapentaenoic acid (20∶5 n−3), docosapentaenoic acid (22∶5 n−3) and docosahexaenoic acids (22∶6 n−3) and decreased amounts of n−6 fatty acids such as arachidonic and adrenic. Synthesis of prostaglandin E₂ and prostaglandin F_2α from exogenous arachidonic acid was significantly depressed in n−3 fatty acid-enriched lung microsomes. These studies indicated that dietary fish oil not only alters the fatty acid composition of lung microsomes but also lowers the capacity of lungs to synthesize prostaglandins from arachidonic acid.     

Influence of diet on (n−3) and (n−6) fatty acids in monkey erythrocytes

Cynomolgus monkeys were fed oils high in linoleic acid or with half of the linoleic acid replaced by either (n−3) linolenic acid or marine fatty acids. When the diet contained similar quantities of linoleic and (n−3) linolenic acid, erythrocyte fatty acids maintained a ratio of (n−6) to (n−3) fatty acids of approximately 2∶4. Fatty acids from menhaden oil enhanced the incorporation of eicosapentaenoic and docosahexaenoic acids into the monkey erythrocytes, the composition of which was not altered by additional α-tocopherol.     

Effect of low levels of dietary fish oil on fatty acid desaturation and tissue fatty acids in obese and lean rats

The effect of very low levels of dietary long-chain n−3 fatty acids on Δ6 desaturation of linoleic acid (18∶2n−6) and α-linolenic acid (18∶3n−3), and on Δ5 desaturation of dihomo-γ-linolenic acid (20∶3n−6), in liver microsomes and its influence on tissue fatty acids were examined in obese and lean Zucker rats and in Wistar rats. Animals fed for 12 wk a balanced diet containing ca. 200 mg of long-chain polyunsaturated n−3 fatty acids per 100 g of diet were compared to those fed the same amount of α-linoleic acid. Low amounts of long-chain n−3 fatty acids greatly inhibited Δ6 desaturation of 18∶2n−6 and Δ5 desaturation of 20∶3n−6, while Δ6 desaturation of 18∶3n−3 was not inhibited in Zucker rats and was even stimulated in Wistar rats. Inhibition of the biosynthesis of long-chain n−6 fatty acids was reflected in a decrease in arachidonic acid (20∶4n−6) content of serum lipids when fasting, and also in the phospholipid fatty acids of liver microsomes. On the contrary, heart and kidney phospholipids did not develop any decrease in 20∶4n−6 during fish oil ingestion. Docosahexaenoic acid (22∶6n−3), present in the dietary fish oil, was increased in serum lipids and in liver microsome, heart, and kidney phospholipids.     

The effects of a dietary oxidized oil on lipid metabolism in rats

This study was carried out to investigate the effects of a dietary oxidized oil on lipid metabolism in rats, particularly the desaturation of fatty acids. Two groups of rats were fed initially for a period of 35 d diets containing 10% of either fresh oil or thermally treated oil (150°C, 6d). The dietary fats used were markedly different for lipid peroxidation products (peroxide value: 94.5 vs. 3.1 meq O₂/kg; thiobarbituric acid-reactive substances: 230 vs. 7 μmol/kg) but were equalized for their fatty acid composition by using different mixtures of lard and safflower oil and for tocopherol concentrations by individual supplementation with dl-α-tocopherol acetate. In the second period which lasted 16 d, the same diets were supplemented with 10% linseed oil to study the effect of the oxidized oil on the desaturation of α-linolenic acid. During the whole period, all the rats were fed identical quantities of diet by a restrictive feeding system in order to avoid a reduced food intake in the rats fed the oxidized oil. Body weight gains and food conversion rates were only slightly lower in the rats fed the oxidized oil compared to the rats fed the fresh oil. Hence, the effects of lipid peroxidation products could be studied without a distortion by a marked reduced food intake and growth. To assess the rate of fatty acid desaturation, the fatty acid composition of liver and heart total lipids and phospholipids was determined and ratios between product and precursor of individual desaturation reactions were calculated. Rats fed the oxidized oil had reduced ratios of 20∶4n−6/18∶2n−6, 20∶5n−3/18∶3n−3, 20∶4n−6/20∶3n−6, and 22∶6n−3/22∶5n−3 in liver phospholipids and reduced ratios of 20∶4n−6/18∶2n−6, 22∶5n−3/18∶3n−3, and 22∶6n−3/18∶3n−3 in heart phospholipids. Those results suggest a reduced rate of desaturation of linoleic acid and α-linolenic acid by microsomal Δ4-, Δ5-, and Δ6-desaturases. Furthermore, liver total lipids of rats fed the oxidized oil exhibited a reduced ratio between total monounsaturated fatty acids and total saturated fatty acids, suggesting a reduced Δ9-desaturation. Besides those effects, the study observed a slightly increased liver weight, markedly reduced tocopherol concentrations in liver and plasma, reduced lipid concentrations in plasma, and an increased ratio between phospholipids and cholesterol in the liver. Thus, the study demonstrates that feeding an oxidized oil causes several alterations of lipid and fatty acid metabolism which might be of great physiologic relevance.     

Production of prostaglandins in homogenates of kidney medullae and cortices of spontaneously hypertensive rats fed menhaden oil

Menhaden oil (MO), whose polyunsaturated fatty acids consist mainly of (n−3) fatty acids, was fed to spontaneously hypertensive rats to determine the effect of (n−3) fatty acid on the in vitro production of prostaglandins produced from arachidonic acid (20∶4[n−6]). Capacity to form PGE₂ and PGF_2α was impaired in homogenates of kidney medullae and cortices from rats fed the MO diet compared to rats fed the control diet. The lower amounts of diene prostaglandins produced corresponded to the decrease in the amount of 20∶4 (n−6) in the tissue. Possibly changes produced in tissue lipids by dietary fatty acids affect prostaglandin production by reducing the availability of substrate in tissue lipids.     

Acyl group distributions in tissue lipids of rats fed evening primrose oil (λ-linolenic plus linoleic acid) or soybean oil (α-linolenic plus linoleic acid)

Three groups of rats were fed diets with either 10 weight percent (wt%) of evening primrose oil, safflower oil or soybean oil for 11 weeks. Diets contained 7.1 wt% linoleic acid +0.8 wt% γ-linolenic acid, 7.6 wt% linoleic acid, or 5.3 wt% linoleic acid +0.7 wt% α-linolenic acid, respectively. In liver mitochondria as well as in heart, dietary γ-linolenic acid did not affect the fatty acid profiles of phosphatidylcholnes (PC), phosphatidylethanolamines (PE) or cardiolipins (CL), whereas dietary α-linolenic acid caused an increased formation of (n−3) polyunsaturated fatty acids (PUFA). The liver Δ6− and Δ5-desaturase activities determined in vitro were not affected by the dietary fats. In brain PE, which are rich in C22− and C20-(n−3) PUFA, as well as in testes PC and PE, which are rich in (n−6) PUFA, no effects were found from a partial replacement of dietary linoleic acid with γ-linolenic acid or α-linolenic acid. In kidney PC, PE, phosphatidylinositol (PI) and CL, 20∶3(n−6) was moderately elevated to ca. 1% following intake of γ-linolenic acid, whereas partial replacement of linoleic acid with α-linolenic acid was followed by increased deposition of 22∶6(n−3) in PC and PE of testes and kidney. Thus, no general effect of evening primrose oil on the content of (n−6) PUFA in rat tissue phospholipids was observed, wheras a significant incorporation of γ-linolenic acid into liver and adipose tissue triglycerides was found.     

Effect of varying proportions of dietary menhaden and corn oil on experimental rat mammary tumor promotion

Dose-related effects of long-chain highly unsaturated n−3 fatty acids on the development ofN-nitrosomethylurea (NMU)-induced rat mammary tumors were assessed in female F344 rats. Four test groups (36 rats/group) were fed the following high-fat (HF) diets (23% fat, w/w): Group 1, 18% menhaden oil (MO) and 5% corn oil (CO); Group 2, 11% MO and 11.8% CO; Group 3,5% MO and 18% CO; Group 4, CO alone. A fifth group, serving as an internal control, was fed a low-fat diet containing 5% CO alone. Experimental diets were begun after initiation with NMU, and the experiment was terminated 31 wk later. Total tumor numbers in the five groups were 28, 16, 32, 26 and 11, respectively, indicating that the promotion phase of NMU-induced carcinogenesis was significantly suppressed only when equal parts of CO and MO (Group 2) were fed or when CO alone was fed at 5% (w/w). At high (Group 1) or low (Group 3) levels of MO, tumor numbers were indistinguishable from the HF CO group (Group 4). The same pattern was observed when assessed in terms of cumulative tumor incidence and multiplicity. However, when expressed in terms of final tumor incidence, dietary MO did not suppress tumor promotion in a statistically significant fashion at any concentration. Animals fed MO gained weight at the same rate as those fed CO, indicating that the presence of MO in the diet did not result in food avoidance behavior. Measurement of total serum cholesterol indicated an inverse trend with respect to the MO content of the diet. Analysis of serum fatty acid profiles indicated that the proportion of n−3 and n−6 polyun-saturated fatty acids (PUFA) in the serum reflected that of the diet. These results support the hypothesis that the relative proportions of dietary n−3/n−6 fatty acids play an important role in the suppression of experimental mammary tumorigenesis and suggest that changes in circulating cholesterol or n−3 PUFA levels, induced by dietary MO, are not directly related to tumor development. Presented in part at the 81st Annual Meeting of the American Association for Cancer Research, Washington, D.C., May 1990     

Accumulation of eicosapentaenoic acid in plasma phospholipids of subjects fed canola oil

The metabolism of α-linolenic acid from canola oil was studied in eight normolipidemic men. The 42-day study was divided into three periods: a 6-day pre-experimental and two 18-day experimental. Approximately 75% of the dietary fat (28% of total energy) was provided by a mixture of fats during the pre-experimental period and either canola oil (CO) or sunflower oil (SO) during the experimental periods. The CO and SO diets were fed in a cross-over design. The ratios of linoleic to linolenic acid were 2.6∶1 and 73.9∶1 in the CO and SO diets, respectively. Dietary fat source had an effect on plasma phospholipid fatty acids: 18∶1n−9, 18∶3n−3 and 20∶5n−3 were higher (p<0.05), and 18∶2n−6 was lower in the phosphatidylcholine fraction; 18∶1n−9 was higher and 20∶4n−6 lower in the phosphatidyl-ethanolamine fraction; and 18∶1n−9 and 20∶5n−3 were higher and 20∶4n−6 and 22∶6n−3 were lower in the alkenylacyl-ethanolamine phospholipid fraction on the CO diet as compared to the SO diet. Consumption of the canola oil diet resulted in higher n−3 fatty acid levels and lower n−6 fatty acid levels in plasma phospholipids than consumption of the sunflower oil diet.     

Dietary manipulation of long-chain polyunsaturated fatty acids in the retina and brain of guinea pigs

High levels of n−6 docosapentaenoic acid (22∶5n−6) have been reported in the retina of guinea pigs fed commercially-prepared grain-based rations (commercial diet). In rats and monkeys, high levels of 22∶5n−6 are an indicator of n−3 polyunsaturated fatty acid (PUFA) deficiency. We have examined the fatty acid composition of the retina and brain in guinea pigs fed a commercial diet or one of three semi-purified diets containing three different levels of n−3 PUFA. The diets comprised a diet deficient in n−3 PUFA (semi-purified diet containing safflower oil), two diets containing α-linolenic acid (standard commercial laboratory diet and semi-purified diet containing canola oil), and a diet containing α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA) (semi-purified diet containing canola oil, safflower oil, and fish oil). Two groups of guinea pigs were given the diets from day 1 to 4 wk or day 1 to 8 wk, when they were sacrificed and the retinal tissues were extracted and analyzed for PUFA content by gas-liquid chromatography. Fatty acid analyses of the retinal phospholipids of the four-week-old animals revealed that the group fed DHA (from the fish oil) had the highest level of DHA (32%), compared with values of 19 and 13% for the groups fed canola oil diet and commercial diet, respectively, and 2% for the group fed the diet deficient in n−3 PUFA. The levels of 22∶5n−6 in the retinal lipids were inversely related to the DHA values, being 0.6, 6.6, 11.4, and 20.6 for the fish oil, canola oil, commercial diet, and safflower oil diet groups, respectively. The long-chain PUFA profiles in the brain phospholipids of the four-week-old group were similar to those from the retina. The retinal PUFA values for the eight-week-old animals were similar to the four-week-old group. The safflower oil diet induced a greater deficit of DHA in retinal lipids than has been reported in rats and monkeys fed similar diets. The guinea pigs fed the commercial diet had retinal and brain PUFA patterns similar to that produced by n−3 PUFA-deficient diets in rats and monkeys. Guinea pigs fed the canola oil diet had significantly greater retinal DHA levels than those fed the commercial diet, but lower than those fed fish oil. The data suggest that the guinea pig has a reduced capacity for DHA synthesis from α-linolenic acid as compared with other mammals. Supplementation of guinea pig diets with fish oil produced high retinal and brain DHA levels and prevented the accumulation of 22∶5n−6.     

Effects of dietary fats on fatty acid composition and Δ5 desaturase in normal and diabetic rats

We have studied the effect of various diets on the phospholipid fatty acid composition andin vitro Δ5 desaturase activity of hepatic microsomes derived either from the normal or streptozotocin-induced diabetic rat. The diets studied were the standard rat chow diet and a basal fat-free diet supplemented either with 20 percent saturated fat, 20 percent unsaturated fat, or 20 percent menhaden oil. Phospholipid fatty acid composition analysis revealed that the normal rat fed the saturated fat or menhaden oil diet had significantly decreased arachidonate levels, consistent with decreased Δ5 desaturase activities and decreased 18∶2n−6 intake. On the contrary, the unsaturated fat diet decreased dihomo-γ-linolenate and increased arachidonate levels, without increased Δ5 desaturase activity. Streptozotocininduced diabetes resulted in decreased arachidonate and Δ5 desaturase activity. The unsaturated fat diet fed to the diabetic rat also failed to correct this decreased Δ5 desaturase activity. The unsaturated fatty acids in this diet also displaced a substantial amount of n−3 fatty acids in both normal and diabetic microsomes, due to the competition between these two fatty acid families for incorporation into the membrane phospholipids. Conversely, the menhaden oil diet fed to the normal and diabetic rats displaced n−6 fatty acids, reduced Δ5 desaturase activity, and enhanced 22∶6n−3 incorporation into diabetic microsomes.     

Fatty acyl desaturation in isolated hepatocytes from Atlantic salmon (Salmo salar): Stimulation by dietary borage oil containing γ-linolenic acid

The effects of different dietary oils on the fatty acid compositions of liver phospholipids and the desaturation and elongation of [1-¹⁴C]18∶3n−3 and [1-¹⁴C]18∶2n−6 were investigated in isolated hepatocytes from Atlantic salmon. Atlantic salmon smolts were fed diets containing either a standard fish oil (FO) as a control diet, a 1∶1 blend of Southern Hemisphere marine oil and tuna orbital oil (MO/TO), sunflower oil (SO), borage oil (BO), or oliver oil (OO) for 12 wk. The SO and BO diets significantly increased the percentages of 18:2n−6, 18:3n−6, 20:2n−6, 20:3n−6, and total n-6 polyunsaturated fatty acids (PUFA) in salmon liver lipids in comparison with the FO diet. The BO diet also increased the percentage of 20:4n−6. Both the SO and BO diets significantly reduced the percentages of all n−3 PUFA in comparison with the FO diet. The OO diet significantly increased the percentages of 18:1n−9, 18:2n−6, total monoenes, and total n−6 PUFA in liver lipids compared to the FO diet, and the percentages of all n−3 PUFA were significantly reduced. With [1-¹⁴C]18:3n−3, the recovery of radioactivity in the products of Δ6 desaturation was significantly greater in the hepatocytes from salmon fed SO, BO, and OO in comparison with the FO diet. The BO diet also increased the recovery of radioactivity in the products of Δ5 desaturation. Only the BO diet significantly affected the desaturation of [1-¹⁴C]18:2n−6, increasing recovery of radioactivity in both Δ6- and Δ5-desaturation products. In conclusion, dietary BO, enriched in γ-linolenic acid (18:3n−6), significantly increased the proportions of both 20:3n−6 and 20:4n−6 in salmon liver phospholipids and also significantly increased the desaturation of both 18:2n−6 and 18:3n−3 in salmon hepatocytes. The possible relationships between dietary fatty acid composition, tissue phospholipid fatty acid composition, and desaturation/elongation activities are discussed.     

Dietary menhaden, seal, and corn oils differentially affect lipid and Ex vivo eicosanoid and thiobarbituric acid-reactive substances generation in the guinea pig

This investigation was carried out to characterize the effects of specific dietary marine oils on tissue and plasma fatty acids and their capacity to generate metabolites (prostanoids, lipid peroxides). Young male guinea pigs were fed nonpurified diet (NP), or NP supplemented (10%, w/w) with menhaden fish oil (MO), harp seal oil (SLO), or corn oil (CO, control diet) for 23 to 28 d. Only the plasma showed significant n−3 polyunsaturated fatty acid (PUFA)-induced reductions in triacylglycerol (TAG) or total cholesterol concentration. Proportions of total n−3 PUFA in organs and plasma were elevated significantly in both MO and SLO dietary groups (relative to CO), and in all TAG fractions levels were significantly higher in MO-than SLO-fed animals. The two marine oil groups differed in their patterns of incorporation of eicosapentaenoic acid (EPA). In guinea pigs fed MO, the highest levels of EPA were in the plasma TAG, whereas in SLO-fed animals, maximal incorporation of EPA was in the heart polar lipids (PL). In both marine oil groups, the greatest increases in both docosahexaenoic acid (22∶6n−3, DHA) and docosapentaenoic acid (22∶5n−3, DPA) relative to the CO group, were in plasma TAG, although the highest proportions of DHA and DPA were in liver PL and heart TAG, respectively. In comparing the MO and SLO groups, the greatest difference in levels of DHA was in heart TAG (MO>SLO, P<0.005), and in levels of DPA was in heart PL (SLO>MO, P<0.0001). The only significant reduction in proportions of the major n−6 PUFA, arachidonic acid (AA), was in the heart PL of the SLO group (SLO>MO=CO, P<0.005). Marine oil feeding altered ex vivo generation of several prostanoid metabolites of AA, significantly decreasing thromboxane A₂ synthesis in homogenates of hearts and livers of guinea pigs fed MO and SLO, respectively (P<0.04 for both, relative to CO). Lipid peroxides were elevated to similar levels in MO- and SLO-fed animals in plasma, liver, and adipose tissue, but not in heart preparations. This study has shown that guinea pigs respond to dietary marine oils with increased organ and plasma n−3 PUFA, and changes in potential synthesis of metabolites. They also appear to respond to n−3 PUFA-enriched diets in a manner that is different from that of rats.     

Levels of polyunsaturated fatty acids in tissues from zinc-deficient rats fed a linseed oil diet

The effect of zinc deficiency on the levels of n−6 and n−3 polyunsaturated fatty acids (PUFA) in lipids from tissues of rats fed a diet containing linseed oil was investigated. Rats were fed either a control diet (25 mg Zn/kg) or a zinc-deficient diet (0.8 mg Zn/kg) for 10 d. To avoid energy and nutrient deficiency, 11.6 g of diet per day was administered by gastric tube. At the end of the experiment, rats fed the zinc-deficient diet had drastically reduced plasma zinc concentration and alkaline phosphatase activity consistent with severe zinc deficiency in these rats. Zinc-deficient rats had higher levels of n−3 PUFA, in particular eicosapentaenoic acid (EPA), and lower levels of n−6 PUFA, in particular linoleic acid, in liver and plasma phosphatidylcholine (PC) and in erythrocyte membrane total lipids than did control rats. By contrast, the levels of n−3 PUFA in PC from testes and heart, and in phosphatidylethanolamine (PE) from liver, testes and heart, were only slightly different between zinc-deficient and control rats. The study suggests that desaturation of α-linolenic acid is not inhibited by zinc deficiency, and that in zinc-deficient rats, n−3 PUFA preferentially incorporated into phospholipids at the expense of n−6 PUFA, especially EPA into PC. The study also shows that the effect of zinc deficiency on PUFA levels is different for PC and PE in rat tissues.     

Effects of diets enriched in n−6 or n−3 fatty acids on cholesterol metabolism in older rats chronically fed a cholesterol-enriched diet

Hypocholesterolemic effects in older animals after long-term feeding are unknown. Therefore, aged rats (24 wk of age) fed a conventional diet were shifted to diets containing 10% perilla oil [PEO; oleic acid+linoleic acid+α-linolenic acid; n−6/n−3, 0.3; polyunsaturated fatty acid/saturated fatty acid (P/S), 9.6], borage oil [oleic acid+linoleic acid+α-linolenic acid; n−6/n−3, 15.1; P/S, 5.3], evening primrose oil (FPO; linoleic acid+γ-linolenic acid; P/S, 10.5), mixed oil (MIO; oleic acid+linoleic acid+γ-linolenic acid+α-linolenic acid; n−6/n−3, 1.7; P/S, 6.7), or palm oil (PLO; palmitic acid+oleic acid+linoleic acid; n−6/n−3, 25.3; P/S, 0.2) with 0.5% cholesterol for 15 wk in this experiment. There were no significant differences in the food intake and body weight gain among the groups. The liver weight in the PEO (n−6/n−3, 0.3) group was significantly higher than those of other groups in aged rats. The serum total cholesterol and very low density lipoprotein (VLDL) +intermediate density lipoprotein (IDL)+low density lipoprotein (LDL)-cholesterol concentrations of the PLO (25.3) group were consistently higher than those in the other groups. The serum high density lipoprotein cholesterol concentrations of the PEO (0.3) and EPO groups were significantly lower than in the other groups at the end of the 15-wk feeding period. The liver cholesterol concentration of the PLO (25.3) group was significantly higher than those of other groups. There were no significant differences in the hepatic LDL receptor mRNA level among the groups. Hepatic apolipoprotein (apo) B mRNA levels were not affected by the experimental conditions. The fecal neutral steroid excretion of the PLO (25.3) group tended to be low compared to the other groups. The results of this study demonstrate that both n\t-6 fatty acid and n\t-3 fatty acids such as \gg-linolenic acid and \ga-linolenic acid inhibit the increase of serum total cholesterol and VLDL+IDL+LDL-cholesterol concentrations of aged rats in the presence of excess cholesterol in the diet compared with dietary saturated fatty acid.     

Lipid peroxidation during n−3 fatty acid and vitamin E supplementation in humans

The purpose of this study was to investigate in healthy humans the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake, alone or in combination with dL-α-tocopherol acetate (vitamin E) supplements on lipid peroxidation. Eightly men were randomly assigned in a double-blind fashion to take daily for 6 wk either menhaden oil (6.26 g, n−3 fatty acids) or olive oil supplements with either vitamin E (900 IU) or its placebo. Antioxidant vitamins, phospholipid composition, malondialdehyde (MDA), and lipid peroxides were measured in the plasma at baseline and week 6. At the same time, breath alkane output was measured. Plasma α-tocopherol concentration increased in those receiving vitamin E (P<0.0001). In those supplemented with n−3 fatty acids, EPA and DHA increased in plasma phospholipids (P<0.0001) and plasma MDA and lipid peroxides increased (P<0.001 and P<0.05, respectively). Breath alkane output did not change significantly and vitamin E intake did not prevent the increase in lipid peroxidation during menhaden oil supplementation. The results demonstrate that supplementing the diet with n−3 fatty acids resulted in an increase in lipid peroxidation, as measured by plasma MDA release and lipid peroxide products, which was not suppressed by vitamin E supplementation.     

Effect of diets rich in linoleic or α-linolenic acid on phospholipid fatty acid composition and eicosanoid production in atlantic salmon (Salmo salar)

Atlantic salmon post-smolts were fed diets rich in linoleic acid (sunflower oil, SO), α-linolenic acid (linseed oil, LO) or long-chain polyunsaturated fatty acids (fish oil, FO) for a period of 12 wk. In the liver phospholipids of fish fed SO, the levels of 18∶2n−6, 20∶2n−6, 20∶3n−6 and 20∶4n−6 were significantly elevated compared to both other treatment. In choline phospholipids (CPL), ethanolamine phospholipids (EPL) and phosphatidylserine (PS) the levels of 22∶4n−6 and 22∶5n−6 were significantly elevated in fish fed SO. In liver phospholipids from fish fed LO, 18∶2n−6, 20∶2n−6 and 20∶3n−6 were significantly elevated but 20∶4n−6, 22∶4n−6 and 22∶5n−6 were similar or significantly decreased compared to fish fed FO. Liver phospholipids from fish fed LO had increased 18∶3n−3 and 20∶4n−3 compared to both other treatments while EPL and phosphatidylinositol (PI) also had increased 20∶5n−3. In fish fed LO, 22∶6n−3 was significantly reduced in CPL, PS and PI compared to fish fed FO. Broadly similar changes occurred in gill phospholipids. Production of 12-lipoxygenase metabolites in isolated gill cells stimulated with the Ca²⁺-ionophore A23187 were significantly reduced in fish fed either SO or LO compared to those fed FO. However, the ratio 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE)/12-hydroxy-5,8,10,14,17-eicosapentaenoic acid (12-HEPE) was significantly elevated in stimulated gill cells from SO-fed fish. Although mean values of thromboxane B₂ (TXB₂) and prostaglandin E₂ (PGE₂) were increased in fish fed SO, they were not significantly different from those of the other two treatments.     

Black currant seed oil feeding and fatty acids in liver lipid classes of guinea pigs

Guinea pigs were fed one of three diets containing 10% black currant seed oil (a source of gamma-linolenic (18∶3 n−6) and stearidonic (18∶4 n−3) acids), walnut oil or lard for 40 days. The fatty acid composition of liver triglycerides, free fatty acids, cholesteryl esters, phosphatidylinositol, phosphatidylserine, cardiolipin, phosphatidylcholine and phosphatidylethanolamine were determined. Dietary n−3 fatty acids found esterified in liver lipids had been desaturated and elongated to longer chain analogues, notably docosapentaenoic acid (22∶5 n−3) and docosahexaenoic acid (22∶6 n−3). When the diet contained low amounts of n−6 fatty acids, proportionately more of the n−3 fatty acids were transformed. Significantly more eicosapentaenoic acid (EPA) (20∶5 n−3) was incorporated into triglycerides, cholesteryl esters, phosphatidylcholine and phosphatidylethanolamine of the black currant seed oil group compared with the walnut oil group. Feeding black currant seed oil resulted in significant increases of dihomogamma-linolenic acid (20∶3 n−6) in all liver lipid classes examined, whereas the levels of arachidonic acid (20∶4 n−6) remained relatively stable. The ratio dihomo-gamma-linolenic acid/arachidonic acid was significantly (2.5-fold in PI to 17-fold in cholesteryl esters) higher in all lipid classes from the black currant seed oil fed group.     

Eicosanoid synthesis in 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in Sprague-Dawley rats fed primrose oil,menhaden oil or corn oil diet

The comparative effects of high-fat diets (20%, w/w) on eicosanoid synthesis during mammary tumor promotion in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats were studied using diets containing 20% primrose oil (PO), 20% menhaden oil (MO) or 20% corn oil (CO). Sprague-Dawley rats fed the PO or MO diet had 21% or 24% fewer adenocarcinomas, respectively, than rats fed the CO diet. Histologically (i.e., mitotic figures, inflammatory cell infiltration and necrosis), the CO-fed rats exhibited the highest frequency of changes within tumors. Plasma fatty acid composition was significantly altered by diet, reflecting the composition of the oils which were being fed. Only the plasma of PO-fed rats contained detectable levels of gamma-linolenic acid (GLA). Arachidonic acid (AA) levels were significantly higher (p<0.05) in PO-fed than in CO- or MO-fed rats. MO-fed rats had significantly higher levels of plasma palmitic acid, while palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were detected only in MO-fed rats. As expected, linoleic acid (LA) and AA levels were lower (p<0.05) in the MO-fed rats than in PO- or CO-fed groups. The plasma of the CO-fed rats contained significantly higher levels of oleic acid. Eicosanoid synthesis in mammary carcinomas of rats fed the 20%-fat diets was 2–10 times higher than in mammary fat pads of control rats. The synthesis of PGE₁ and LTB₄ was significantly (p<0.05) higher in PO-fed rats than in CO-fed or MO-fed rats, although PGE values were significantly (p<0.05) higher in CO-fed rats than in Mo or PO groups. The synthesis of eicosanoids in both mammary fat pads and mammary carcinomas of MO-fed rats was lower (p<0.05) than in tissues of rats fed either CO or PO diets due to less AA precursor being fed and/or to competition between n−6 and n−3 fatty acids for cyclooxygenase and lipoxygenase. The ratios of monoenoic to dienoic eicosanoids in both mammary fat pads and mammary carcinomas were higher in the PO group than in the MO or CO groups. These results suggest that inclusion of GLA (PO feeding) or EPA and DHA (MO feeding) in the diet may decrease malignancy by altering eicosanoid profiles.     

Comparative study of the blood pressure effects of four different vegetable fats on young,spontaneously hypertensive rats

Following the suckling period, four groups of male four-week-old spontaneously hypertensive rats (SHR) were fed semisynthetic diets with 14% (by weight) of either sunflower seed oil [46% 18∶2(n−6); linoleic acid (LA)-rich], linseed oil [62.5% 18∶3(n−3)+12.9% 18∶2(n−6); α-linolenic acid (LNA)-rich], evening primrose oil [9.2% 18∶3(n−6)+71% 18∶2(n−6); γ-linolenic acid (LNA)-rich] or hydrogenated palm kernel fat [1.5% 18∶2(n−6); polyunsaturated fatty acid (PUFA)-deficient], respectively, up to an age of 18 wk. All diets enriched with PUFA provoked an attenuation of hypertension development. The effect was lowest in the LA-rich group and highest in the γ-LNA-rich group. Differences in fatty acid composition of renal phospholipids between groups reflect the fatty acids present in the respective dietary fats. Renomedullary production of PGF_2α was significantly reduced in α-LNA-rich and slightly diminished in γ-LNA-rich fed rats. Aortic formation of 6-keto-PGF_1α and TXB₂ was increased in animals fed the γ-LNA-rich diet. Thus, the attenuation of hypertension development cannot be explained only by changes in prostanoid formation. Other mechanisms possibly involved should be pursued.     

Dietary cod liver oil decreases arachidonic acid in rat gastric mucosa and increases stress-induced gastric erosions

The purpose of this study was to examine the influence of long-term feeding of dietary fat rich in either n−3 or n−6 fatty acids on the availability of arachidonic acid (20∶4n−6) in major phospholipids of gastric mucosa in rats. Three groups of male Wistar rats were fed either a standard diet, a cod liver oil-enriched diet (10% by weight), or a corn oil-enriched diet (10% by weight) for 8 mon. Dietary cod liver oil significantly reduced the level of 20∶4n−6 in phosphatidylcholine (PC) and in phosphatidylethanolamine (PE) of gastric mucosa. The loss of 20∶4n−6 was compensated for by eicosapentaenoic acid (20∶5n−3) in PC, whereas the decrease in 20∶4n−6 in PE corresponded to the increase in three n−3 fatty acids: 20∶5n−3, docosapentaenoic acid (22∶5n−3), and docosahexaenoic acid (22∶6n−3). The level of 20∶5n−3 was higher than the level of 22∶6n−3 both in PC and PE of mucosa in rats fed cod liver oil. Diets supplemented with corn oil increased the level of 18∶2n−6 but decreased the monoene fatty acids 16∶1 and 18∶1n−7 in PC but not in PE of gastric mucosa. The 20∶4n−6 levels of both PC and PE were markedly reduced by dietary cod liver oil, to about one-third of control levels. Similar changes were also observed in the stomach wall. Gastric erosions were observed in all rats exposed to restriction stress, but this form of stress induced twice the number of erosions in rats fed fish oil compared to control rats or rats fed corn oil. We conclude that a diet rich in fish oil altered the balance between n−6 and n−3 fatty acids in major gastric mucosal phospholipids, markedly reduced the availability of 20∶4n−6, and increased the incidence of gastric erosions induced by restriction or emotional stress.