Rats Fed Fish Oil Research Articles

Omega-3 fatty acids in colorectal cancer prevention.

Omega-3 fatty acids in colorectal cancer prevention.

Interaction of dietary fat types and sesamin on hepatic fatty acid oxidation in rats

The interaction of sesamin, one of the most abundant lignans in sesame seed, and types of dietary fats affecting hepatic fatty acid oxidation was examined in rats. Rats were fed purified experimental diets supplemented with 0% or 0.2% sesamin (1:1 mixture of sesamin and episesamin), and containing 8% of either palm, safflower or fish oil for 15 days. Among the groups fed sesamin-free diets, the activity of various fatty acid oxidation enzymes was higher in rats fed fish oil than in those fed palm and safflower oils. Dietary sesamin increased enzyme activities in all groups of rats given different fats. The extent of the increase depended on dietary fat type, and a diet containing sesamin and fish oil in combination appeared to increase many of these parameters synergistically. In particular, the peroxisomal palmitoyl-CoA oxidation rate and acyl-CoA oxidase activity levels were much higher in rats fed sesamin and fish oil in combination than in animals fed sesamin and palm or safflower oil in combination. Analyses of mRNA levels revealed that a diet containing sesamin and fish oil increased the gene expression of various peroxisomal fatty acid oxidation enzymes and PEX11α, a peroxisomal membrane protein, in a synergistic manner while it increased the gene expression of mitochondrial fatty acid oxidation enzymes and microsomal cytochrome P-450 IV A1 in an additive manner. It was concluded that a diet containing sesamin and fish oil in combination synergistically increased hepatic fatty acid oxidation primarily through up-regulation of the gene expression of peroxisomal fatty acid oxidation enzymes.

Protective effect of supplementation of fish oil with high n-3 polyunsaturated fatty acids against oxidative stress-induced DNA damage of rat liver in vivo.

The present study was undertaken to know the effect of supplementation of fish oil with high n-3 polyunsaturated fatty acids (PUFA) on oxidative stress-induced DNA damage of rat liver in vivo. Male Wistar rats were fed a diet containing fish oil or safflower oil with high n-6 PUFA at 50 g/kg of diet and an equal amount of vitamin E at 59 mg/kg of diet for 6 weeks. Livers of rats fed fish oil were rich in n-3 PUFA, whereas those of rats fed safflower oil were rich in n-6 PUFA. Ferric nitrilotriacetate was intraperitoneally injected to induce oxidative stress. The degree of lipid peroxidation of the liver was assessed by the levels of phospholipid hydroperoxides and thiobarbituric acid-reactive substances (TBARS), and the degree of oxidative DNA damage was assessed by comet type characterization in alkaline single-cell gel electrophoresis and 8-hydroxy-2'-deoxyguanosine levels. The levels of TBARS of the livers of the fish oil diet group increased to a greater extent than those of the safflower oil diet group, whereas the levels of the hydroperoxides of the livers of both diet groups increased to a similar extent. The vitamin E level of livers of the fish oil diet group was remarkably decreased. The degree of DNA damage of both diet groups was increased, but the increased level of the fish oil diet group was remarkably lower than that of the safflower oil diet group. The above results indicate that fish oil supplementation does not enhance but appears to protect against oxidative stress-induced DNA damage and suggest that lipid peroxidation does not enhance but lowers the DNA damage.

Dietary Fish Oil Increases Lipid Mobilization but Does Not Decrease Lipid Storage–Related Enzyme Activities in Adipose Tissue of Insulin-Resistant, Sucrose-Fed Rats

Fish oil feeding has been shown to limit visceral fat accumulation in insulin-resistant rats. Our goal was to determine whether this finding is due to increased fat mobilization or decreased lipid storage. Adipocytes were isolated from rats fed for 3 wk a diet containing 57.5 g/100 g sucrose and 14 g/100 g lipids as either fish oil (SF) or a mixture of standard oils (SC); there was also a reference group (R). Substituting fish oil for standard oils protected rats from visceral fat hypertrophy, hypertriglyceridemia and hyperglycemia. The stimulation of lipolysis was greater in adipocytes isolated from SF-fed rats than in those from SC-fed rats. Fatty acid synthase (FAS) activity was markedly lower in the liver but not in the adipose tissues of rats fed SF. Lipoprotein lipase (LPL) activity was 2.2-fold higher in the adipose tissues but not in the muscle in rats fed the SF diet than in those fed the SC diet. The decrease in visceral fat in rats fed fish oil could be attributed to decreased plasma triacylglycerol concentration and/or increased lipid mobilization rather than to reduced lipid storage.

IRP1 Activity and Expression Are Increased in the Liver and the Spleen of Rats Fed Fish Oil–Rich Diets and Are Related to Oxidative Stress

Many clinical studies have indicated that diets rich in fish oil (FO) reduce the risk of cardiovascular disease and have anti-inflammatory and antithrombotic properties. Although the therapeutic effects of FO have been well described, their impact on iron metabolism remains unclear. The aim of this work was to study the activity and expression of IRP1 in the liver and the spleen of rats fed FO-rich diets with 0 (FO-0) or 100 (FO-1) mg/kg of all-rac-alpha-tocopherol acetate. We also measured nonheme iron, alpha-tocopherol and retinol concentrations, and superoxide (SOD) and catalase activity in these organs. Rats fed FO were compared to rats fed a corn oil (CO)-rich diet with 100 mg/kg all-rac-alpha-tocopherol acetate. The activity and expression of IRP1 in both the liver and the spleen of rats fed FO diets were greater than in those fed the CO diet. FO-fed rats also had lower nonheme iron concentrations in these organs. Hepatic alpha-tocopherol and retinol concentrations and SOD activity were lower in FO-0-fed rats compared to those fed the CO diet. In the spleen, alpha-tocopherol and retinal concentrations were not altered but SOD activity was lower in FO-0- fed rats, whereas catalase activity was greater than in rats fed CO. The results indicate that there is an increase in oxidative stress in the liver and in the spleen of rats fed FO diets. These changes, together with the reduction of nonheme iron concentrations in both FO-0- and FO-1-fed rats, may explain the increase in activity and expression of IRP1. Therefore, the ingestion of FO-rich diets should be monitored under close supervision.

Fish Oil Feeding is Associated with an Increased Accumulation of Dietary Lipids in Enterocytes: Results from an in vivo Study in Rats

Background: Chronic fish oil consumption is associated with reduced postprandial lipaemia, but the mechanism behind this effect is not fully understood. We studied whether lipid absorption might be altered in rats fed fish oil. Methods: Male Wistar rats were fed fish oil enriched chow ( n r = r 6) or control oil enriched chow ( n r = r 6). After 4 weeks, 61 r mg 3 H-triolein was instilled into duodenal tied-off loops. Intestinal segments were removed after 15, 30, 45, 60 and 90 r min. Enterocytes were then isolated by calcium chelation and quantified by DNA determination. Non-absorbed 3 H-lipid and 3 H-lipid contents of enterocytes were determined by liquid scintillation counting. Two other groups of rats (2 r × r 6) fed the experimental diets were given an oral fat load and fasting and postprandial blood samples were taken. Results: The accumulation of 3 H-lipids in enterocytes was higher in rats fed fish oil than in controls (area under the 3 H-lipid time curve: 1041.3 versus 670.3 r nmol oleic acid r × r min/ 7 g DNA, P r < r 0.05). Separation of lipids showed that an accumulation of triglycerides and free fatty acids occurred in rats fed fish oil. The amount of non-absorbed 3 H-lipid tended to be higher in the fish oil fed rats ( P r > r 0.1). It was confirmed that the fish oil enriched chow caused lower postprandial lipaemia (34% reduction in serum triglyceride concentrations, P r < r 0.05). Conclusion: Attenuated postprandial lipaemia following fish oil feeding is explained, at least partly, by a transient lipid accumulation in enterocytes which may result in a delayed triglyceride efflux from the enterocytes into the circulation.

Effect of supplementation of n-3 polyunsaturated fatty acids on oxidative stress-induced DNA damage of rat hepatocytes.

The effect of supplementation of n-3 polyunsaturated fatty acids (PUFA) on oxidative stress-induced DNA damage of rat hepatocytes was examined. Male Wistar rats were fed a diet containing safflower oil (control n-6 PUFA diet) or fish oil (n-3 PUFA diet) in 50 g/kg of dried diet and an equal amount of vitamin E in 59 mg/kg of dried diet for 6 weeks. The liver of rats fed safflower oil was rich in n-6 PUFA, whereas that of rats fed fish oil was rich in n-3 PUFA. Isolated hepatocytes were treated in vitro with ADP/Fe (II) ion or hydrogen peroxide at 37 degrees C for 30 min to induce oxidative stress. The degree of lipid peroxidation was assessed by the levels of phospholipid hydroperoxides and thiobarbituric acid-reactive substances. The degree of oxidative DNA damage was assessed based on comet-type characterization in alkaline single-cell gel electrophoresis and 8-hydroxy-deoxyguanosine levels. In both ADP/Fe(II) ion and hydrogen peroxide oxidation, the degree of lipid peroxidation of hepatocytes increased in both diet groups, and the level of increase in the fish oil diet group was slightly higher than that in the safflower oil diet group. In ADP/Fe(II) ion oxidation, the degree of DNA damage increased in both diet groups, but there were no significant differences in the level of increase. In contrast, in hydrogen peroxide oxidation, the degree of DNA damage increased in both diet, and the increase in the fish oil diet group was significantly lower than that in the safflower oil diet group. It is unlikely that an n-3 PUFA-rich diet enhances oxidative stress-induced hepatocyte DNA damage as compared with the control n-6 PUFA-rich diet.

Dietary Polyunsaturated Fats Regulate Rat Liver Sterol Regulatory Element Binding Proteins-1 and -2 in Three Distinct Stages and by Different Mechanisms

Male Sprague-Dawley rats, trained to consume their daily energy needs in a single 3-h meal (0900-1200 h), were used to examine the hypothesis that polyunsaturated fatty acids (PUFA) lowered the nuclear content of sterol regulatory element binding protein (SREBP)-1 and/or -2 by suppressing the proteolytic release of mature SREBP from the membrane-anchored precursor pool. The nuclear concentrations of hepatic SREBP-1 and -2 were 50 and 42% lower (P < 0.05) in rats that consumed a single PUFA-supplemented meal (i.e., 10 g fish oil/100 g fat-free diet) than in rats fed the fat-free diet alone. This was paralleled by 63 and 52% reductions in the expression of the SREBP-1 and -2 target genes, fatty acid synthase and HMG-CoA synthase, respectively; but the marked increase in the amount of precursor SREBP-1 and -2 resulting from meal ingestion was unaffected. After the consumption of a second meal of fish oil, the nuclear level of mature SREBP-1 was only 16% of that in rats fed the fat-free diet, but the amount of nuclear SREBP-2 was not different from the level in rats fed the fat-free diet. Again, the sizes of the SREBP-1 and -2 precursor pools were not reduced. A decrease in the hepatic concentration of precursor SREBP-1 did not occur until rats had consumed 5 meals of fish oil. At this point, the nuclear content of SREBP-2 was actually twofold higher (P < 0.05) in rats fed fish oil or safflower oil, but the amount of precursor SREBP-2 was unaffected. These data indicate that PUFA suppress the in vivo proteolytic release of SREBP-1 and -2, but the effect on SREBP-2 is transitory, possibly reflecting the ability of PUFA to enhance cholesterol losses via bile acid synthesis.

Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content.

To examine the mechanism by which fish oil protects against fat-induced insulin resistance, we studied the effects of control, fish oil, and safflower oil diets on peroxisomal content, fatty acyl-CoA, diacylglycerol, and ceramide content in rat liver and muscle. We found that, in contrast to control and safflower oil-fed rats, fish oil feeding induced a 150% increase in the abundance of peroxisomal acyl-CoA oxidase and 3-ketoacyl-CoA thiolase in liver but lacked similar effects in muscle. This was paralleled by an almost twofold increase in hepatic peroxisome content (both P < 0.002 vs. control and safflower). These changes in the fish oil-fed rats were associated with a more than twofold lower hepatic triglyceride/diacylglycerol, as well as intramuscular triglyceride/fatty acyl-CoA, content. In conclusion, these data strongly support the hypothesis that n-3 fatty acids protect against fat-induced insulin resistance by serving as peroxisome proliferator-activated receptor-alpha ligands and thereby induce hepatic, but not intramuscular, peroxisome proliferation. In turn, an increased hepatic beta-oxidative capacity results in lower hepatic triglyceride/diacylglycerol and intramyocellular triglyceride/fatty acyl-CoA content.

Macrophage migration inhibitory factor expression in male and female ethanol-fed rats.

Macrophage migration inhibitory factory (MIF) regulates macrophage accumulation at sites of injury and can promote the inflammatory response. We studied MIF expression in the intragastric feeding rat model for alcoholic liver injury. Male and age-matched female rats were fed ethanol or dextrose with fish oil. Two groups of male rats were fed medium-chain triglycerides with ethanol or dextrose. Analysis of liver histopathology, lipid peroxidation, endotoxin, mRNA, and immunohistochemistry for MIF, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were carried out. Male and female rats fed fish oil and ethanol showed necroinflammatory liver injury and had the highest expression of MIF, TNF-alpha, and IFN-gamma in the liver. Decreased levels of MIF protein were seen in rats with higher endotoxin levels, suggesting that preformed MIF is released into the circulation. MIF is an important mediator of the inflammatory response in alcoholic liver disease and a potential therapeutic target.

Effects of cellular redox balance on induction of apoptosis by eicosapentaenoic acid in HT29 colorectal adenocarcinoma cells and rat colon in vivo

BACKGROUND AND AIMSEpidemiological evidence suggests n-3 polyunsaturated lipids may protect against colorectal neoplasia. Consumption of fish oil modulates crypt cytokinetics in humans, and crypt apoptosis in animal models. To explore...

Reduced Hepatic Triglyceride Secretion in Rats Fed Docosahexaenoic Acid–Rich Fish Oil Suppresses Postprandial Hypertriglyceridemia

To evaluate the mechanisms of suppression of postprandial hypertriglyceridemia by fish oil rich in docosahexaenoic acid, the effect on the intestinal absorption of triglyceride, activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) and metabolism of chylomicrons (CM) and CM remnants were compared with that of safflower oil in Sprague-Dawley rats in a series of studies. The feeding of fish oil for 3 wk suppressed postprandial hypertriglyceridemia (study 1). Dietary fish oil did not alter the rate of lymphatic absorption of triglyceride (study 2). The activities of LPL and HTGL were measured at 5 h after the beginning of feeding, when serum triglyceride concentrations were highest in both dietary groups. The activities of LPL in adipose tissue and heart were greater (P < 0.05) and those of HTGL were lower (P < 0.05) in the rats fed fish oil (study 3). In contrast, there were no differences in the activities of LPL and HTGL in postheparin plasma between the fish and safflower oil groups (study 4). The clearance rates of CM and CM remnants were measured by injecting intravenously CM collected from rats fed safflower or fish oils with [14C]triolein and [3H]cholesterol (study 5). Dietary oil did not influence the half-lives of CM or CM remnants. The secretion of triglyceride from the liver of rats injected with Triton WR-1339 was lower (P < 0.05) in the rats fed docosahexaenoic acid, a major component of fish oil, than those fed linoleic acid, a major component of safflower oil (study 6). These observations strongly support the hypothesis that in rats, the principal cause of the suppression of postprandial hypertriglyceridemia by fish oil is the depression of triglyceride secretion from the liver.

Low Arachidonic Acid Rather than α-Tocopherol Is Responsible for the Delayed Postnatal Development in Offspring of Rats Fed Fish Oil Instead of Olive Oil during Pregnancy and Lactation

This study was designed to compare in rats the effects of dietary fish oil and olive oil during pregnancy and lactation on offspring development, fatty acid profile and vitamin E concentration. From d 0 of pregnancy, female Sprague-Dawley rats were divided into two groups that were fed purified diets that differed only in their nonvitamin lipid components. One diet contained 10 g fish oil/100 g diet (FOD), whereas the other contained 10 g olive oil/100 g diet (OOD). At d 20 of gestation, maternal adipose tissue fatty acid profile did not differ between rats fed the two diets, whereas both maternal and fetal plasma and liver arachidonic acid (AA) contents were proportionally lower and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid contents were higher in the FOD group than in the OOD group. alpha-Tocopherol concentration was lower in maternal and fetal plasma, liver and brain in the FOD group than in the OOD group. The postnatal increase in body weight and length was less and body and psychomotor maturation indices were delayed in pups from FOD-fed dams compared with those from OOD-fed dams. This difference was maintained when pups were cross-fostered at birth, with the delay in postnatal development present in the pups suckling dams fed FOD during lactation. At age 21 d, pups suckling dams fed FOD had lower AA and higher EPA and DHA concentrations in brain phospholipids. Although alpha-tocopherol in plasma and liver was lower in pups suckling dams fed FOD rather than OOD, brain alpha-tocopherol concentrations did not differ. Milk yield and milk alpha-tocopherol and AA concentrations were lower and EPA and DHA were higher in the milk of dams fed FOD compared with those fed OOD. Postnatal development indices and the proportion of plasma, liver and brain AA concentrations, although not plasma, liver and brain alpha-tocopherol concentrations, recovered to the values found in dams fed OOD when the FOD was supplemented with gamma-linolenic acid. However, postnatal development indices were not recovered when the FOD was supplemented with sufficient exogenous vitamin E to increase plasma and liver alpha-tocopherol concentrations above those in dams fed OOD. Thus, although feeding FOD during pregnancy and lactation decreases both alpha-tocopherol and AA concentrations, the latter deficiency rather than the former seems to be responsible for delayed postnatal development of rat pups.

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.

Comparative effects of perilla and fish oils on the activity and gene expression of fatty acid oxidation enzymes in rat liver

The activity and mRNA level of hepatic enzymes in fatty acid oxidation and synthesis were compared in rats fed diets containing either 15% saturated fat (palm oil), safflower oil rich in linoleic acid, perilla oil rich in α-linolenic acid or fish oil rich in eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) for 15 days. The mitochondrial fatty acid oxidation rate was 50% higher in rats fed perilla and fish oils than in the other groups. Perilla and fish oils compared to palm and safflower oils approximately doubled and more than tripled, respectively, peroxisomal fatty acid oxidation rate. Compared to palm and safflower oil, both perilla and fish oils caused a 50% increase in carnitine palmitoyltransferase I activity. Dietary fats rich in n-3 fatty acids also increased the activity of other fatty acid oxidation enzymes except for 3-hydroxyacyl-CoA dehydrogenase. The extent of the increase was greater with fish oil than with perilla oil. Interestingly, both perilla and fish oils decreased the activity of 3-hydroxyacyl-CoA dehydrogenase measured using short- and medium-chain substrates. Compared to palm and safflower oils, perilla and fish oils increased the mRNA level of many mitochondrial and peroxisomal enzymes. Increases were generally greater with fish oil than with perilla oil. Fatty acid synthase, glucose-6-phosphate dehydrogenase, and pyruvate kinase activity and mRNA level were higher in rats fed palm oil than in the other groups. Among rats fed polyunsaturated fats, activities and mRNA levels of these enzymes were lower in rats fed fish oil than in the animals fed perilla and safflower oils. The values were comparable between the latter two groups. Safflower and fish oils but not perilla oil, compared to palm oil, also decreased malic enzyme activity and mRNA level. Examination of the fatty acid composition of hepatic phospholipid indicated that dietary α-linolenic acid is effectively desaturated and elongated to form EPA and DHA. Dietary perilla oil and fish oil therefore exert similar physiological activity in modulating hepatic fatty acid oxidation, but these dietary fats considerably differ in affecting fatty acid synthesis.

Effect of n-3 polyunsaturated fatty acid supplementation on lipid peroxidation of rat organs.

The present study was undertaken in order to reexamine the effect of n-3 polyunsaturated fatty acid (PUFA)-rich diet supplementation on lipid peroxidation and vitamin E status of rat organs. Male Wistar rats were fed a diet containing safflower or fish oil at 50 g/kg diet and an equal amount of vitamin E at 59 mg/kg diet (1.18 g/kg oil; and 1.5 g/kg PUFA in safflower oil diet, and 4.3 g/kg PUFA in fish oil diet) for 6 wk. Fatty acid composition of total lipids of brain, liver, heart, and lung of rats fed fish oil was rich in n-3 PUFA, whereas that of each organ of rats fed safflower oil was rich in n-6 PUFA. The vitamin E levels in liver, stomach, and testis of the fish oil diet group were slightly lower than those of the safflower oil diet group, but the levels in brain, heart, lung, kidney, and spleen were not different between the two diet groups. The levels of phospholipid hydroperoxides were determined by the high-performance liquid chromatography-chemiluminescence method and the levels of thiobarbituric acid-reactive substances (TBARS) were determined at pH 3.5 in the presence of butylated hydroxytoluene with or without EDTA. Levels of phospholipid hydroperoxides and TBARS in the brain, liver, heart, lung, kidney, spleen, stomach and testis of the fish oil diet group were similar to those of the safflower oil diet group. The results indicate that high fish oil intake does not induce increased levels of phospholipid hydroperoxides and TBARS in rat organs.

Effect of dietary polyunsaturated fatty acids on contractile function of hearts isolated from sedentary and trained rats.

Moderate physical training induced a decrease in arterial blood pressure in fish oil-fed rats as compared to sunflower seed oil-fed rats. The purpose of this study was to determine if these changes were due to modifications of the left ventricular function of the heart. Forty rats were fed a semi-purified diet containing either 10% sunflower seed oil or 10% fish oil (EPAX 3000TG, Pronova). Each dietary group was assigned to two sub-groups, one being constituted by sedentary animals and the other by trained animals. Training was achieved by daily running for 60 minutes at moderate intensity for three weeks. At the end of the training period, the animals were sacrificed and their hearts were immediately perfused according to the working mode. The phospholipid fatty acid composition and parameters of the left ventricular function were determined. Feeding fish oil markedly reduced the proportion of n-6 polyunsaturated fatty acids (PUFA, 18:2 n-6, 20:4 n-6, 22:4 n-6 and 22:5 n-6) in cardiac phospholipids. The n-6 PUFA were replaced by n-3 PUFA (mainly docosahexaenoic acid). In sedentary animals, the fluid dynamic (aortic and coronary flow, cardiac output) was not modified by the diet. The heart rate was reduced (-10%) in n-3 PUFA-rich hearts. Physical training did not markedly alter the polyunsaturated fatty acid profile of cardiac phospholipids. Conversely, it reduced the heart rate, aortic flow and cardiac output (-11, -21 and -14%, respectively) at a similar extent in the two dietary groups. In a second set of experiments, the training period was repeated in animals fed a commercially available diet (A103, UAR) which simultaneously provided n-6 and n-3 fatty acids. In these dietary conditions, neither the aortic flow nor the heart rate was decreased by physical exercise. These results suggest that both n-6 and n-3 PUFA in the diet are necessary to ensure a good cardiac adaptation to moderate physical training. Furthermore, the fish oil-induced decrease in arterial blood pressure in trained animals was not related to changes in cardiac contractility, but to a decrease in vascular resistances. Moderate physical training + dietary n-3 PUFA might be used to prevent hypertension and cardiovascular diseases.

Effect of stable fish oil on arterial thrombogenesis, platelet aggregation, and superoxide dismutase activity.

We examined the influence of dietary stable fish oil on aortic thrombosis, platelet aggregation, and superoxide dismutase (SOD) activity in a rat model. Twenty-nine Sprague-Dawley rats were fed regular chow supplemented with stable fish oil preparation (for 1 or 3 weeks), and 37 rats fed regular chow served as controls. The abdominal cavity was opened, and the abdominal aorta isolated. Whatman paper impregnated with 35% FeCl3 was wrapped around the surface of the aorta, and aortic flow was continuously recorded. In control rats, an occlusive platelet-fibrin-rich thrombus was formed in 21 +/- 3 min. Dietary fish oil in a time-dependent fashion delayed time to thrombus formation (24 +/- 2 min in rats fed fish oil for 1 week and 31 +/- 2 min in rats fed fish oil for 3 weeks), inhibited platelet aggregation (21 +/- 5% vs. 45 +/- 6%; p < 0.01) and increased SOD activity (p < 0.01). We conclude that dietary supplementation with stable fish oil delays formation of arterial thrombus, probably by reducing platelet aggregation and oxidative stress-associated arterial injury.

Increased diaphragm expression of GLUT4 in control and streptozotocin-diabetic rats by fish oil-supplemented diets.

Dietary fat intake influences plasma glucose concentration through modifying glucose uptake and utilization by adipose and skeletal muscle tissues. In this paper, we studied the effects of a low-fat diet on diaphragm GLUT4 expression and fatty acid composition in control and streptozotocin-induced diabetic rats. Control as well as diabetic rats were divided into three different dietary groups each. Either 5% olive oil, 5% sunflower oil, or 5% fish oil was the only fat supplied by the diet. Feeding these low-fat diets for 5 wk induced major changes in fatty acid composition, both in control and in diabetic rats. Arachidonic acid was higher in diabetic olive and sunflower oil-fed rats with respect to fish oil-fed, opposite to docosahexaenoic acid which was higher in diabetic fish oil-fed rats with respect to the other two groups. Animals receiving a fish oil diet had the lowest plasma glucose concentration. GLUT4 expression in diaphragm, as indicated by GLUT4 protein and mRNA, is modulated both by diabetes and by diet fatty acid composition. Diabetes induced a decrease in expression in all dietary groups. Plasma glucose levels correlated well with the increased amount of GLUT4 protein and mRNA found in fish oil-fed groups. Results are discussed in terms of the influence that arachidonic and n-3 polyunsaturated fatty acids may exert on the transcriptional and translational control of the GLUT4 gene.

Coordinate induction of peroxisomal acyl-CoA oxidase and UCP-3 by dietary fish oil: a mechanism for decreased body fat deposition

Rats fed dietary fats rich in 20- and 22-carbon polyenoic fatty acids deposit less fat and expend more energy at rest than rats fed other types of fats. We hypothesized that this decrease in energetic efficiency was the product of: (a) enhanced peroxisomal fatty acid oxidation and/or (b) the up-regulation of genes encoding proteins that were involved with enhanced heat production, i.e. mitochondrial uncoupling proteins (UCP-2, UCP-3) and peroxisomal fatty acid oxidation proteins. Two groups of male Fisher 344 rats 3–4 week old ( n=5 per group) were pair fed for 6 weeks a diet containing 40% of its energy fat derived from either fish oil or corn oil. Epididymal fat pads from rats fed the fish oil diet weighed 25% ( P < 0.05) less than those found in rats fed corn oil. The decrease in fat deposition associated with fish oil ingestion was accompanied by a significant increase in the abundance of skeletal muscle UCP-3 mRNA. The level of UCP-2 mRNA skeletal muscle was unaffected by the type of dietary oil, but the abundance of UCP-2 mRNA in the liver and heart were significantly lower ( P < 0.05) in rats fed fish oil than in rats fed corn oil. In addition to inducing UCP-3 expression, dietary fish oil induced peroxisomal acyl-CoA oxidase gene expression 2–3 fold in liver, skeletal muscle and heart. These data support the hypothesis that dietary fish oil reduces fat deposition by increasing the expression of mitochondrial uncoupling proteins and increasing fatty acid oxidation by the less efficient peroxisomal pathway.