Effect of dietary n-3 and n-6 oils with and without food restriction on activity of antioxidant enzymes and lipid peroxidation in livers of cyclophosphamide treated autoimmune-prone NZB/W female mice

OBJECTIVE: Cyclophosphamide (CTX), an alkylating agent, is extensively used in the treatment of lupus nephritis, but its administration has been associated with free radical mediated oxidative stress. The present study was designed to investigate the effect of dietary corn oil (CO), fish oil (FO) and food restriction (FR) on the activities of hepatic antioxidant enzymes, fatty acid composition and lipid peroxidation following CTX administration in autoimmune-prone NZB/W female mice. METHODS: Autoimmune-prone NZB/W female mice were fed either ad libitum (AL) or food restricted (60% of AL intake), semipurified diets containing 5% CO or 5% FO supplemented with equal levels of antioxidants and injected with either phosphate buffered saline (PBS), or CTX (50 mg/kg body weight) every 10 days. Proteinuria was measured biweekly. The treatment was stopped at 10 months and diets were continued until the mice were killed at 12 months. Fatty acid composition, activity of antioxidant enzymes and lipid peroxidation were analyzed in liver homogenates, and anti-DNA antibodies were analyzed in the serum. RESULTS: Mice in the FO/AL dietary group exhibited significantly higher liver catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities compared to the CO/AL dietary group. CTX significantly decreased SOD and GSH-Px activity in the FO/AL group and CAT and GSH-Px in the CO/AL group. In AL fed mice given CTX, activities of CAT, GSH-Px and GST were significantly higher in mice fed FO diets than in mice fed CO diets. FR increased the activity of enzymes in both the CO and FO diet groups. In FR mice, CTX decreased CAT and GSH-Px activity in both the CO and FO dietary groups, but glutathione S-transferase (GST) only in the CO group. The decrease in SOD activity was not significant in either of the restricted groups. CTX significantly increased generation of thiobarbituric acid reactive substances (TBARS) in both AL groups. FR significantly decreased lipid peroxidation in both the CO and FO groups, with or without CTX. CTX decreased serum anti-DNA antibody levels in both the CO and FO dietary groups. FR also decreased antibody titer in both the CO and FO dietary groups, and it was decreased further with CTX treatment. FO fed animals had higher levels of n-3 fatty acids, whereas CO fed animals had high levels of n-6 fatty acids. CTX significantly increased 20:4 and decreased 18:1 in CO/AL fed animals, whereas it increased 18:1 and decreased 22:6 in FO/AL fed animals. CONCLUSIONS: Results obtained in the present study suggests that FO and, more significantly, FO combined with FR can have a beneficial effect in hepatic tissues subjected to CTX induced oxidative stress by regulating the activity of antioxidant enzymes. In addition, the study also indicates that n-3 and n-6 dietary lipids are susceptible to lipid peroxidation, particularly in the presence of a prooxidant like CTX, and that FR is beneficial in decreasing lipid peroxidation. The study also suggests that FO and CTX can have additive effects in preventing kidney disease in NZB/W mice.     

Hydroxymatairesinol and its mammalian metabolite enterolactone reduce the growth and metastasis of subcutaneous AH109A hepatomas in rats

Both epidemiological and experimental evidence is accumulating to show that a lignan-rich diet may reduce the risk of human breast cancer. Possible anti-cancer effects of dietary lignans on hepatomas or hepatoma cells have not been the topic of earlier studies. In the present study, we examined the effect of 7-hydroxymatairesinol (HMR) and its mammalian metabolite, enterolactone (ENL), on AH109A hepatoma cell proliferation and invasion in vitro. HMR and ENL inhibited the proliferation and invasion of AH109A hepatoma cells in vitro. The 50% inhibitory concentration (IC50) of hepatoma cell proliferation was lower for ENL (10 microM) than HMR (> 200 microM). Likewise, IC50 of hepatoma cell invasion was lower for ENL (9 microM) than HMR (144 microM). ENL suppressed hepatoma cell proliferation by accumulating cells in G1 phase and elongating doubling time of these cells, and by increasing the rate of apoptosis. Subsequently, we investigated in vivo the effect of dietary HMR and ENL on growth and metastasis of AH109A hepatomas in rats. Both of these compounds reduced the growth and metastasis of solid AH109A hepatomas in rats. These in vitro and in vivo findings suggest that HMR has inhibitory activities on tumor growth and metastasis in the hepatoma-bearing rats, and that this anti-tumor effect is mediated at least partially by ENL, a metabolite of HMR.     

Apple flavonols and n-3 polyunsaturated fatty acid–rich fish oil lowers blood C-reactive protein in rats with hypercholesterolemia and acute inflammation

Both quercetin glycosides and omega-3 polyunsaturated fatty acids (n-3 PUFA) are well established for their individual health benefits in ameliorating metabolic disease. However, their combined effects are not well documented. It was hypothesized that the beneficial properties of quercetin glycosides can be enhanced when provided in combination with n-3 PUFA. Therefore, the aim of the present study was to investigate the effects of apple flavonols (AF) and fish oil (FO), alone and in combination, on proinflammatory biomarkers and lipid profiles in rats fed a high-fat diet. Sixty male Wistar rats were randomly divided into 5 groups (n = 12) and fed a high-fat diet for 4 weeks. One of the 5 groups of rats was used as the high-fat control. The other 4 groups of rats were injected with lipopolysaccharide (LPS) (5 mg/kg body weight) intraperitoneally, 5 hours before euthanization. One of these 4 groups was used as the hypercholerolemic and inflammatory control (high-fat with lipopolysaccharide [HFL]), and the other 3 received AF (HFL + 25 mg/kg per day AF), FO (HFL + 1 g/kg per day FO), or the combination (HFL + AF + FO). Compared to the HFL group, the AF, FO, and AF + FO groups showed lower serum concentrations of interleukin-6 and C-reactive protein (CRP) levels. The AF, FO, and AF + FO also had lowered serum triacylglycerol and non–high-density lipoprotein cholesterol (HDL-C) concentrations, but higher HDL-C levels relative to the HFL group. An additive effect was observed on serum CRP in the AF + FO group as compared with the AF or FO groups. The results demonstrated that AF and FO inhibited the production of proinflammatory mediators and showed an improved efficacy to lower serum CRP when administered in combination, and they significantly improved blood lipid profiles in rats with diet-induced hyperlipidemia and LPS-induced acute inflammation.     

Growth of Dunning transplantable prostate adenocarcinomas in rats fed diets with various fat contents

The effects of dietary fat concentration (5 vs. 20% corn oil, 0.5 vs. 20% corn oil and fat-free vs. 20% corn oil) on the growth of the Dunning R3327-H (hormone-sensitive, well-differentiated, slow-growing) and R3327-150 (hormone-insensitive, anaplastic, rapidly growing) transplantable prostate tumor sublines were studied in Copenhagen x Fisher F1 male rats. Rats fed 5 vs. 20% corn oil or 0.5 vs. 20% corn oil showed no differences in either R3327-H or R3327-150 tumor growth. Fat-free diets had no effect on the growth of R3327-150 tumors. However, the mean weight of the R3327-H tumor at necropsy, 16 wk after implantation, was reduced by 40% in rats fed a fat-free diet compared with 20% corn oil (P less than 0.05). Energy intake, weight gain and the weight of the pituitary and prostate glands in rats bearing either tumor was lower in rats fed the fat-free diet than in those fed the 20% corn oil diet. There were no differences in serum prolactin, pituitary prolactin or serum testosterone associated with dietary fat concentration in any study. In summary, no differences in transplantable prostate tumor growth were seen over a wide range of lipid intake (0.5-20%), although a fat-free diet reduced the growth of the R3327-H prostate adenocarcinoma.     

Effects of simultaneous dietary fish oil ingestion and sulfur amino acid supplementation on the lipid metabolism in hepatoma-bearing rats with hyperlipidemia

The effects of simultaneous dietary fish oil ingestion and sulfur amino acid (L-methionine and L-cystine) supplementation on serum lipid concentrations and various parameters related to the lipid metabolism were studied in Donryu rats subcutaneously implanted with an ascites hepatoma cell line, AH109A. A diet containing 10% fish oil was found to reduce serum triglyceride, total cholesterol, (very-low-density lipoprotein plus low-density lipoprotein)-cholesterol, phospholipid and nonesterified fatty acid (NEFA) concentrations in these animals, and dietary supplementation of 1.2% L-methionine and L-cystine also suppressed these serum lipid concentrations. Hepatic fatty acid synthesis and the availability of serum NEFA were decreased, and epididymal adipose tissue lipoprotein lipase (LPL) activity was elevated by dietary fish oil, while LPL activity in various tissues and hepatic fatty acid oxidation were increased by dietary sulfur amino acids, resulting in a reduction in the serum triglyceride concentration by dietary fish oil and sulfur amino acids, respectively. Dietary fish oil suppressed the hepatoma-induced increase in cholesterogenesis in the host liver, and dietary methionine and cystine enhanced bile acid excretion into feces, which were the causes of the hypocholesterolemic effect. In these serum lipid concentrations, there were significant effects of fish oil ingestion and sulfur amino acid supplementation, but no significant interaction between these two factors was seen. These results indicate that dietary fish oil and sulfur amino acid, L-methionine and L-cystine, have hypolipidemic effects in cancer-related hyperlipidemia, and that the effects of these two factors on the decrease in these serum lipid concentrations are additive; these two factors may affect the lipid metabolism via different pathways and mechanisms.     

Hydroxymatairesinol and Its Mammalian Metabolite Enterolactone Reduce the Growth and Metastasis of Subcutaneous AH109A Hepatomas in Rats

Both epidemiological and experimental evidence is accumulating to show that a lignan-rich diet may reduce the risk of human breast cancer. Possible anti-cancer effects of dietary lignans on hepatomas or hepatoma cells have not been the topic of earlier studies. In the present study, we examined the effect of 7-hydroxymatairesinol (HMR) and its mammalian metabolite, enterolactone (ENL), on AH109A hepatoma cell proliferation and invasion in vitro. HMR and ENL inhibited the proliferation and invasion of AH109A hepatoma cells in vitro. The 50% inhibitory concentration (IC ₅₀ ) of hepatoma cell proliferation was lower for ENL (10 μ M) than HMR (> 200 μ M). Likewise, IC ₅₀ of hepatoma cell invasion was lower for ENL (9 μ M) than HMR (144 μ M). ENL suppressed hepatoma cell proliferation by accumulating cells in G ₁ phase and elongating doubling time of these cells, and by increasing the rate of apoptosis. Subsequently, we investigated in vivo the effect of dietary HMR and ENL on growth and metastasis of AH109A hepatomas in rats. Both of these compounds reduced the growth and metastasis of solid AH109A hepatomas in rats. These in vitro and in vivo findings suggest that HMR has inhibitory activities on tumor growth and metastasis in the hepatoma-bearing rats, and that this anti-tumor effect is mediated at least partially by ENL, a metabolite of HMR.     

Fish oil combined with SCFA synergistically prevent tissue accumulation of NEFA during weight loss in obese mice

Based on their proposed metabolic effects, we examined whether fish oil (FO) and SCFA, alone or in combination, accelerate weight loss and the resultant metabolic improvements. Obesity was induced in male C57BL/6J mice by high-energy feeding for 10 weeks. The mice were transferred to a low-fat diet (2·5w%) for 4 weeks, the source of fat being either FO, a lard-safflower oil mix (control), or both types combined with SCFA. Weight, fasting insulin, tissue and serum lipid concentrations, as well as mRNA amount of genes related to adipose inflammation and hepatic fat oxidation were determined. All groups lost weight and showed reduced fasting insulin concentrations and reduced liver TAG. However, weight loss on the control-fat diet caused significant increase in hepatic and cardiac NEFA. Substituting 20?% of the fat with SCFA increased weight loss by 48?% and reduced fasting insulin 1·5-fold more than the no-SCFA diets. It furthermore significantly increased the amount of mRNA for PPAR-α, and decreased the mRNA amount for NF-κB in the liver and white adipose tissue. The FO diets enhanced improvement of tissue lipid levels. Thus, FO improved liver TAG and NEFA levels compared with weight loss on the control diet. Combining FO and SCFA further reduced tissue NEFA accumulation. In conclusion, we found that dietary SCFA had a significant impact on gene expression in the liver and adipose tissue, and that the effect of FO on tissue NEFA content was modified by SCFA. Thus, interactions between fatty acids should be considered when studying the effects of specific fatty acids.     

Inhibitory effect of coffee on hepatoma proliferation and invasion in culture and on tumor growth, metastasis and abnormal lipoprotein profiles in hepatoma-bearing rats

We have already reported that instant coffee powder (ICP) and ICP-loaded rat sera could suppress proliferation and invasion of rat ascites hepatoma cell line of AH109A in vitro. In this report, we examined the mechanisms for suppression of tumor cell proliferation and invasion by ICP, and the effect of ICP on in vivo tumor growth, metastasis and abnormal lipoprotein profiles in hepatoma-bearing rats. ICP, when directly added to the culture media, induced cell cycle arrest (elongation of S phase) at a lower concentration (0.3 mg/mL) and apoptosis at a higher concentration (0.6-1.2 mg/mL). ICP and ICP-loaded rat sera showed reactive oxygen species (ROS)-scavenging property and canceled the enhancement of invasive activity of hepatoma cells induced by ROS in vitro. These results suggest that ICP suppresses the proliferation by inducing cell cycle arrest and apoptosis, and the invasion by scavenging ROS and that ICP could retain these properties after their gastrointestinal absorption. The hepatoma-bearing rats were fed with a 20% casein diet (20C) or 20C supplemented with 0.1%, ICP for 14 d. Dietary ICP significantly reduced solid tumor growth and tended to reduce hepatoma metastases to lung and lymphatic nodes, suggesting that ICP could suppress tumor cell proliferation and invasion in vivo. In addition, dietary ICP significantly increased serum high-density lipoprotein (HDL)-cholesterol and tended to reduce very low-density and low-density lipoprotein (VLDL+LDL)-cholesterol, resulting in amelioration of abnormal lipoprotein profiles occurred in hepatoma-bearing rats. In conclusion, ICP has the ability to induce cell cycle arrest and apoptosis in hepatoma cells and to suppress tumor cell invasion by reducing oxidative stresses in vitro, and it could also exhibit these effects in vivo, leading to the inhibition of tumor growth and metastases.     

Anti-oxidant properties of N-acetyl-L-cysteine do not improve the immune resistance of mice fed dietary lipids to Listeria monocytogenes infection

BACKGROUND & AIMS: Current knowledge of the potential effects that several dietary lipids exert on immune functions indicates that these substances participate actively in the modulation of immune system by which they contribute to the improvement of the conditions of patients suffering from inflammatory disorders. However, long-chain n-3 polyunsaturated fatty acids induce an immunosuppressive status that leads to a reduction of the host natural resistance to infectious agents as well as to an enhancement of oxidative damage. Hence, the present study has been designed to evaluate the effects on the immune system of the antioxidant N-acetyl-L-cysteine (NAC) in mice fed dietary lipids and infected with Listeria monocytogenes. METHODS: Balb/c mice were fed for 4 weeks with diets containing either olive oil (OO, 20% by weight), fish oil (FO, 20% by weight) or hydrogenated coconut oil (HCO, 20% by weight). After dietary lipid administration mice were experimentally infected with L. monocytogenes or treated with NAC (25mg/ml intraperitoneally). RESULTS: NAC at a concentration of 1mM promoted a loss of cell viability, although no differences were observed among the four groups. After injection of NAC in combination with L. monocytogenes, 25% of mice fed a low-fat (LF) diet survived. However, in the groups fed dietary lipids no effect on survival of mice was found. NAC participated in the reduction of superoxide anion generation measured with nitroblue tetrazolium (NBT) in the group fed a FO diet. Finally, NAC reduced the recovery of L. monocytogenes from spleen of mice fed diets containing LF or HCO. CONCLUSIONS: On the basis of these results, we can confirm that the administration of NAC improves survival in mice fed LF diet, whereas a reduction in the generation of superoxide radicals was measured in mice fed a FO diet and infected with L. monocytogenes. Similarly, bacterial recovery was diminished in mice fed diets containing LF or HCO. Hence, these data reveal a beneficial effect of NAC in mice fed LF or HCO and a detrimental action of this antioxidant in mice fed diets containing FO or OO.     

Effects of dietary methionine and glycine on serum lipoprotein profiles and fecal sterol excretion in normal and hepatoma-bearing rats

The effects of concurrent addition of methionine (Met) and glycine (Gly) to a 20% casein diet on serum lipoprotein profiles and fecal sterol excretion were studied in male Donryu rats with or without subcutaneous implantation of an ascites hepatoma line of AH109A cells. The hepatoma-bearing rats fed on the 20% casein diet had a notable elevation in the very-low-density lipoprotein + low-density lipoprotein (VLDL + LDL)-cholesterol (Ch) level with a slight but significant decrease in high-density lipoprotein (HDL)-Ch level when compared to the hepatoma-free (normal) rats fed on the same diet. The dietary addition of 1.2% Met and 2.5% Gly in combination suppressed the hepatoma-induced elevation in the (VLDL + LDL)-Ch level with a prevention of the hepatoma-induced decrease in the HDL-Ch level. The addition of the two amino acids also lowered significantly the (VLDL + LDL)-Ch level without affecting the HDL-Ch level in tumor-free rats. Fecal excretion of both neutral and acidic sterols were reduced with growth of the hepatoma. The dietary addition of Met and Gly exerted no or little influence on neutral sterol excretion in both the tumor-free and -bearing states, but it enhanced acidic sterol excretion into feces in both states, especially in the hepatoma-bearing state at the last stage of feeding. These results suggest that the excretion and catabolism of Ch might be impaired in hepatoma-bearing rats with growth of the tumor, and that the supplemental Met and Gly in combination might enhance Ch catabolism by stimulating either synthesis or conjugation of bile acids, leading to a reduction of the (VLDL + LDL)-Ch level in the normal and hepatoma-bearing states.     

Influence of dietary fat on oxidative stress and inflammation in murine macrophages

ObjectiveMany studies have shown that the nature of the lipid consumed in the diet significantly affects the development of inflammatory diseases. In this study, we compared the effect of diets supplemented with 15% by weight of fish oil (FO), refined olive oil (ROO), and pomace olive oil (POO) with that of a low-fat diet, 2% by weight of corn oil, considered as the basal diet (BD), on the ability to modify reactive oxidative species and proinflammatory mediator generation by stimulated murine macrophages.MethodsMice were fed the different oil-enriched diets for 8 wk. Peritoneal macrophages were isolated from these mice and subsequently stimulated. Reactive oxygen species and proinflammatory mediators were measured in the corresponding supernatants. Data were statistically treated by one-way analysis of variance and Tukey's multiple comparison post hoc test.ResultsThe ROO and POO significantly reduced the hydrogen peroxide production compared with BD, whereas FO stimulated its production. Moreover, the generation of nitric oxide was significantly prevented in all the experimental oil-enriched dietary groups. The ROO and FO groups showed significantly reduced cytokine (tumor necrosis factor-α, interleukin-1β, interleukin-6) and prostaglandin E₂ production.ConclusionThese results confirm the prevention action on proinflammatory mediator generation exerted by FO and demonstrate the protective antioxidant properties not only of olive oil but also of POO. The consumption of these olive oils may help to prevent cellular oxidative stress and inflammation.     

Ethanol effects on lipid peroxidation and glutathione-mediated defense in rat small intestine: Role of dietary fats

The effect of ethanol feeding for 5 weeks on lipid peroxidation status of small intestine was studied in rats maintained on either a rat pellet (RP) or a semisynthetic diet containing coconut oil (CCO), corn oil (CO), or fish oil (FO). Highest rate of iron/ascorbate-induced lipid peroxidation was observed in intestinal mucosa of FO-fed rats, which was further elevated (p < 0.05) upon ethanol administration. Purified brush borders from all the ethanol-treated dietary groups were more susceptible to iron-induced lipid peroxidation. Level of nonprotein thiols was increased by ethanol feeding to rats given CO or FO. FO-fed rats exhibited increased activities of glutathione reductase (GR), glutathione-S-transferase (GST), and catalase (Cat). Glutathione peroxidase (GPx) was the lowest in the CCO group. Ethanol-treated FO group exhibited increased GST and GPx activities compared to controls, whereas in rats fed the RP or CO diet, ethanol feeding significantly decreased GST activity. GR and Cat activities were not affected under these conditions. Thus, ethanol exposes the small intestinal mucosa to oxidative stress. The effects were more pronounced in rats fed n-3 fatty acid-rich (FO) diet. The corresponding rise in GPx and GST levels may reflect the adaptive changes in intestine.     

Altered fatty acid compositions in atlantic salmon (Salmo salar) fed diets containing linseed and rapeseed oils can be partially restored by a subsequent fish oil finishing diet

Atlantic salmon postsmolts were fed a control diet or one of 9 experimental diets containing various blends of two vegetable oils, linseed (LO) and rapeseed oil (RO), and fish oil (FO) in a triangular trial design, for 50 wk. After sampling, fish previously fed 100% FO, LO and RO were switched to a diet containing 100% FO for a further 20 wk. Fatty acid compositions of flesh total lipid were linearly correlated with dietary fatty acid compositions (r = 0.99-1.00, P < 0.0001). Inclusion of vegetable oil at 33% of total oil significantly reduced the concentrations of the highly unsaturated fatty acids, eicosapentaenoate [20:5(n-3)] and docosahexaenoate [22:6(n-3)], to approximately 70 and 75%, respectively, of the values in fish fed 100% FO. When vegetable oil was included at 100% of total dietary lipid, the concentrations of 20:5(n-3) and 22:6(n-3) were significantly reduced to approximately 30 and 36%, respectively, of the values in fish fed FO. Transfer of fish previously fed 100% vegetable oil to a 100% FO diet for 20 wk restored the concentrations of 20:5(n-3) and 22:6(n-3) to approximately 80% of the value in fish fed 100% FO for 70 wk, although the values were still significantly lower. However, in fish previously fed either 100% LO or RO, concentrations of 18:2(n-6) remained approximately 50% higher than in fish fed 100% FO. This study suggests that RO and LO can be used successfully to culture salmon through the seawater phase of their growth cycle; this will result in reductions in flesh 20:5(n-3) and 22:6(n-3) concentrations that can be partially restored by feeding a diet containing only marine FO for a period before harvest.     

Dietary fish oil upregulates intestinal lipid metabolism and reduces body weight gain in C57BL/6J mice

Fish oils (FO) rich in (n-3) PUFA exert hypolipidemic and antiobesity effects in association with modulated hepatic lipid metabolism. We recently demonstrated the possible involvement of intestinal lipid metabolism in the development of obesity. In this study, we examined the effect of FO ingestion on intestinal lipid metabolism in relation to obesity. When diet-induced obesity-prone C57BL/6J mice were fed an 8% FO, high-fat (30%) diet for 5 mo, body weight gain was significantly reduced compared with mice fed a 30% triacylglycerol (TG) diet without FO. In addition to modulating messenger RNA (mRNA) levels in the liver, FO ingestion for 2 wk affected the intestinal mRNA levels of lipid metabolism-related genes; those of carnitine palmitoyltransferase 1a, cytochrome P450 4A10, and malic enzyme were significantly higher in mice fed the 8% FO diet compared with mice fed the 30% TG diet. Northern blot analysis revealed that the expression levels of most lipid metabolism-related genes in the small intestine of mice fed the 8% FO diet were comparable to those in the liver. Furthermore, reflecting the difference at the mRNA level, FO ingestion affected lipid metabolism-related enzyme activity; fatty acid beta-oxidation, omega-oxidation, and malic enzyme activities in the small intestine of mice fed the 8% FO diet were 1.2-, 1.6-, and 1.7-fold those in mice fed the 30% TG diet, respectively. These findings suggest that an upregulation of intestinal lipid metabolism is associated with the antiobesity effect of FO.     

Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid mediators and anti-DNA antibodies in a mouse model for rheumatoid arthritis

OBJECTIVE: Omega-3 (omega-3) fatty acid rich-fish oil (FO) and vitamin E (vit-E) may delay the progress of certain autoimmune diseases. The present study examined the mechanism of action of omega-3 and omega-6 lipids and vit-E on the serum cytokines and lipid mediators in autoimmune-prone MRL/lpr mice (a model for rheumatoid arthritis, RA). The lpr (lymphoproliferative) gene is overexpressed in these mice causing extensive lymphoproliferation, lupus-like symptoms and accelerated aging. METHODS: Weanling female MRL/lpr and congenic control MRL/++ mice were fed 10% corn oil (CO, omega6) or FO-based semipurified diets containing two levels of vitamin E (vit-E-75, I.U. and vit-E-500 I.U./Kg diet) for four months. At the end of the experiment, serum anti-DNA antibodies, cytokines and lipid mediators levels were determined. RESULTS: The appearance of enlarged lymph nodes was delayed in the mice fed FO, and the FO-500 IU vit-E diet offered further protection against enlargement of lymph nodes. The MRL/lpr mice exhibited significantly higher levels of serum anti-dsDNA antibodies. The FO-fed mice had significantly lower serum IL-6, IL-10, IL-12, TNF-alpha, PGE2, TXB2 and LTB4 levels compared with CO-fed mice. In mice fed 500 IU vit-E diets, the serum IL-6, IL-10, IL-12 and TNF-alpha levels were significantly lower and serum IL-1beta was significantly higher compared to 75 IU-vit-E-fed mice in CO/FO or both. The levels of anti-DNA antibodies, IL-4, IL-6, TNF-alpha, IL-10 and IL-12 were higher in the sera of MRL/lpr mice. The FO diet lowered the levels of these cytokines (except IL-4) and lipid mediators. Adding 500 IU of vit-E to the FO diet further lowered the levels of IL-6, IL-10, IL-12, and TNF-alpha. CONCLUSION: It is clear from our observations that the beneficial effects of FO can be enhanced by the addition of 500 IU of vit-E in the diet. The FO diet containing 500 IU of vit-E may specifically modulate the levels of IL-6, IL-10, IL-12 and TNF-alpha and thereby may delay the onset of autoimmunity in the MRL/lpr mouse model. The observations from this study may form a basis for selective nutrition intervention based on specific fatty acids and antioxidants in delaying the progress of RA.     

合成油的营养评价——(二)合成油饲料对实验性高胆固醇血症大鼠体重、血脂和肝脂成分的影响

在88g基础饲料中加入12g不同种类的油脂(合成油、猪油和豆油)和1％胆固醇喂养大鼠5周以诱导动物产生高脂血症,并以不加入胆固醇的豆油饲料作为正常对照。比较各组动物在实验期内的生长、血清脂质、肝脏脂质和某些内脏器官重量的改变。结果如下: (1)大鼠摄食含不同油脂的致高胆固醇血症饲料5周后,各组雄鼠的体重增加无明显的不同,雌鼠的体重增加则有显著的差别,即合成油组动物的增重显著较猪油组和对照组的为低。 (2)在各种油脂饲料中加入胆固醇都可使动物的肝重增大。猪油组和豆油组动物的肝脏有明显的脂肪肝病变。肝脂含量增加,肝胆固醇和甘油三酯大量积存(分别约为对照组的9-10倍和2-3倍)。而合成油组动物的肝脏外观表现正常,肝脂含量、肝胆固醇和甘油三酯水平则接近对照组的正常水平。 (3)在各种油脂饲料中加入胆固醇喂养大鼠,对雄鼠血清胆固醇水平的影响不明显,但引起雌鼠血清胆固醇的改变和对照组比较,猪油饲料使动物的血清胆固醇含量明显增高,豆 油和合成油饲料则可维持动物的血胆固醇含量于正常水平。血清甘油三酯水平则以合成油饲料组动物的为最高。 (4)在各种饲料中加入胆固醇除增大肝脏重量外,也使雌鼠的主动脉重量增高,但饲料油脂种类对其重量的影响不明显。 上述结果表明,当饲料中含有高水?     

Substituting fish oil with crude palm oil in the diet of Atlantic salmon (Salmo salar) affects muscle fatty acid composition and hepatic fatty acid metabolism

Supplies of marine fish oils (FO) are limited and continued growth in aquaculture production dictates that substitutes must be found that do not compromise fish health and product quality. In this study the suitability of crude palm oil (PO) as a replacement for FO in diets of Atlantic salmon was investigated. Duplicate groups of Atlantic salmon post-smolts were fed four practical-type diets in which the added lipid was either 100% FO and 0% crude PO (0% PO); 75% FO and 25% PO (25% PO); 50% FO and 50% PO (50% PO); and 100% PO, for 30 wk. There were no effects of diet on growth rate or feed conversion ratio nor were any histopathological lesions found in liver, heart or muscle. Lipid deposition was greatest in fish fed 0% PO and was significantly greater than in fish fed 50% and 100% PO. Fatty acid compositions of muscle total lipid were correlated with dietary PO inclusion such that the concentrations of 16:0, 18:1(n-9), 18:2(n-6), total saturated fatty acids and total monoenoic fatty acids increased linearly with increasing dietary PO. The concentration of eicosapentaenoic acid [20:5(n-3)] was reduced significantly with increasing levels of dietary PO but the concentration of docosahexaenoic acid [22:6(n-3)] was significantly reduced only in fish fed 100% PO, compared with the other three treatments. Similar diet-induced changes were seen in liver total lipid fatty acid compositions. Hepatic fatty acid desaturation and elongation activities were approximately 10-fold greater in fish fed 100% PO than in those fed 0% PO. This study suggests that PO can be used successfully as a substitute for FO in the culture of Atlantic salmon in sea water. However, at levels of PO inclusion above 50% of dietary lipid, significant reductions in muscle 20:5(n-3), 22:6(n-3) and the (n-3):(n-6) PUFA ratio occur, resulting in reduced availability of these essential (n-3) highly unsaturated fatty acids to the consumer.     

Serum lipid concentrations and mean life span are modulated by dietary polyunsaturated fatty acids in the senescence-accelerated mouse

The senescence-accelerated mouse (SAMP8) is an animal model used in studies of aging. This study was undertaken to investigate the effects of dietary PUFA on longevity (Experiment 1) and serum lipid concentrations (Experiment 2) in SAMP8 mice. Male mice were fed either an (n-3) PUFA-rich (9 g/100 g perilla oil) or an (n-6) PUFA-rich (9 g/100 g safflower oil) diet beginning at 6 wk of age. Experiment 1: The groups did not differ in body weight gain, but those fed perilla oil had significantly lower scores of senescence relative to those fed safflower oil (P<0.05). The mean life span of mice fed perilla oil was 357+/-21 d and of those fed safflower oil, 426+/-24 d (P<0.05). Pathological studies revealed that the incidence of tumors was significantly lower in the perilla oil group than in the safflower oil group (P<0.05). Approximately half the mice fed perilla oil had died after 10 mo, and the direct causes closely connected with death could not be specified. Experiment 2: The serum total cholesterol, HDL cholesterol, triglyceride and phospholipid concentrations were significantly lower in the perilla oil group than in the safflower oil group (P<0.01). A marked decrease of serum HDL cholesterol and apolipoprotein A-II (ApoA-II)concentrations in advanced age were observed in the mice fed perilla oil (P<0.01). Ten-month-old mice fed perilla oil had a significantly greater ratio of apolipoprotein A-I (ApoA-I) to ApoA-II than those fed safflower oil. Separation of HDL subfractions revealed that the smaller HDL species were much more abundant than the larger HDL species in both dietary oil groups. These findings suggest that dietary (n-3) and (n-6) PUFA differ in their effects on serum lipid metabolism which may modulate the mean life span of SAMP8 mice fed each dietary oil.     

Ratio of n6 to n-3 fatty acids in the diet affects tumor growth and cachexia in Walker 256 tumor-bearing rats

In this study we investigate the impact of the dietary ratio of n-6 to n-3 fatty acids (FAs) from postweaning until adult age upon tumor growth, lipid peroxidation in tumor tissue, and metabolic indicators of cancer cachexia in Walker 256 tumor-bearing rats. Weanling male Wistar rats received a normal low-fat (40 g/kg diet) chow diet or high-fat diets (300 g/kg) that included fish oil (FO) or sunflower oil or blends of FO and sunflower oil to yield n-6 to n-3 FA ratios of approximately 6:1, 30:1, and 60:1 ad libitum. After 8 wk, half of each group was inoculated with 1 ml of 2 x 10(7) Walker 256 cells. At the 14th day after tumor inoculation, the animals were killed, and tumors and blood were removed. The different diets did not modify the blood parameters in the absence of tumor bearing, except the high-FO diet, which decreased serum cholesterol and triacylglycerol concentrations. Tumor weight in chow-fed rats was 19 g, and these rats displayed cancer cachexia, characterized by hypoglycemia, hyperlacticidemia, hypertriacylglycerolemia, loss of body weight, and food intake reduction. Tumor weight in FO-fed rats was 7.7 g, and these animals gained body weight (14.6 g) and maintained blood metabolic parameters similar to non-tumor-bearing animals. Tumor weight in rats fed the diet with an n-6 to n-3 FA ratio of 6:1 was similar to tumor-bearing, chow-fed rats, but they gained 2 g in the body weight and blood metabolic parameters were similar to those in non-tumor-bearing rats. However, a further increase in the n-6 FA content of the diet did not change the cachectic state associated with tumor bearing. In this experimental model, a dietary n-6 to n-3 FA ratio of 6:1 was able to increase food intake and body weight, restore the biochemical blood parameters of cachexia, and prevent the development of cancer cachexia.     

Krill oil versus fish oil in modulation of inflammation and lipid metabolism in mice transgenic for TNF-α

Purpose

Biological effects of marine oils, fish oil (FO) and krill oil (KO), are mostly attributed to the high content of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The study was aimed to investigate the influence of FO and KO on lipid homeostasis and inflammation in an animal model of persistent low-grade exposure to human tumor necrosis factor α (hTNF-α) and to evaluate whether these effects depend on the structural forms of EPA and DHA [triacylglycerols (TAG) vs. phospholipids].

Methods

Male C57BL/6 hTNF-α mice were fed for 6 weeks a high-fat control diet (24.50 % total fats, w/w) or high-fat diets containing either FO or KO at similar doses of n-3 PUFAs (EPA: 5.23 vs. 5.39 wt%, DHA: 2.82 vs. 2.36 wt% of total fatty acids).

Results

We found that KO, containing bioactive n-3 PUFAs in the form of phospholipids, was capable of modulating lipid metabolism by lowering plasma levels of TAG and cholesterol and stimulating the mitochondrial and peroxisomal fatty acid β-oxidation, as well as improving the overall carnitine turnover. Though the administration of FO was not as effective as KO in the lowering of plasma TAG, FO significantly improved the levels of all cholesterol classes in plasma. Except from the increase in the levels of IL-17 in FO-fed mice and a trend to decrease in MCP-1 levels in KO-fed animals, the levels of pro-inflammatory cytokines were not substantially different between treatment groups.

Conclusion

Our findings demonstrate that FO and KO are comparable dietary sources of n-3 PUFAs. However, when quantitatively similar doses of n-3 PUFAs are administered, KO seems to have a greater potential to promote lipid catabolism. The effect of dietary oils on the levels of inflammatory markers in hTNF-α transgenic mice fed a high-fat diet needs further investigations.