Fed Corn Oil Research Articles

Granulocyte Marker Protein Is Increased in Stools from Rats with Azoxymethane-Induced Colon Cancer

Background: We wanted to investigate the relationship between the fecal levels of granulocyte marker protein (GMP) and the presence of aberrant crypt foci (ACF) and colorectal cancer in rats given injections of azoxymethane (AOM) and fed either of two different diets, a basal diet plus 20% corn oil or 20% beef suet, respectively. Methods: The rats received intraperitoneal injections of AOM, 15 mg/kg, once weekly for 6 weeks and were killed after 22 weeks. Results: In the group fed beef suet 17 of 19 rats developed colon cancer, whereas in the group fed corn oil 4 of 14 rats developed cancer. None of the 20 control rats fed either the beef suet or corn oil diets developed cancer or aberrant crypts, and GMP remained unchanged. Surprisingly, the numbers of ACF were significantly higher (467 versus 295; P = 0.004) in the group fed corn oil than in the group fed beef suet. On the other hand, the size (crypts/focus) of the ACF was significantly higher (P = 0.03) in the beef suet group. Furthermore, fecal GMP was significantly higher in the beef suet group than in the corn oil group after 18 weeks, and this difference increased further toward the end of the study. GMP was greatly increased in all rats with colorectal cancer. Conclusions: Fecal GMP may have provided us with a valuable tool for further studies of the induction and progression of neoplasia in rats and, possibly, in mice, since the anti-GMP antibody cross-reacts with feces extracts from mice.

Dietary Menhaden and Corn Oils and the Red Blood Cell Membrane Lipid Composition and Fluidity in Hyper- and Normocholesterolemic Miniature Swine

Fatty acids in the diet are readily incorporated into lipids in various tissues. However, it is not clear whether all tissues have the same level of incorporation. Second, (n-6) unsaturated fatty acids increase the fluidity of membranes, but this has not been shown for (n-3) fatty acids. In this study, we measured the incorporation of (n-6) and (n-3) fatty acids into erythrocyte membrane lipids and studied their effects on the fluidity of erythrocyte membranes. One group of female miniature swine was made hypercholesterolemic by feeding the swine cholesterol and lard for 2 mo; the other group served as controls and was fed a stock diet. Both groups were then fed either corn oil or menhaden oil or a mixture of the two for 23 additional weeks. Blood was collected at 0, 2, 4, 12 and 23 wk after initialization of the experimental diets, and fatty acid composition of phospholipids was assessed. Membrane phospholipids of pigs fed menhaden oil had elevated (n-3) fatty acids (20:5 and 22:6), and lower 18:2 than those fed corn oil. There was no difference in 20:4 content. The fatty acid changes occurred as early as 2 wk after consumption of the corn oil or menhaden oil in pigs previously fed a stock diet, but it took longer in pigs previously fed lard + cholesterol, indicating residual effects of pretreatment. Menhaden oil increased anisotropy (indicating decreased fluidity) more than corn oil for the nonpolar probe diphenylhexatriene (DPH) at earlier time points, but not at 23 wk. Erythrocyte membrane fluidity was significantly related to membrane polyunsaturate content, with (n-6) fatty acids having a greater influence than (n-3) fatty acids. A comparison of the present red blood cell fatty acid compositions with brain synaptosome fatty acid compositions for the same animals showed poor correlations for some of the fatty acids. There was no significant direct relationship between docosahexaenoate (DHA) concentrations in erythrocyte membranes with DHA concentrations in brain synaptosomes from cerebellum, forebrain and caudate nucleus.

Effect of dietary lipid on γ-glutamyl transferase-positive foci during hepatocarcinogenesis in rats

The effect of dietary lipid on γ-glutamyl transferase-positive (GGT-positive) foci was investigated. Female Sprague-Dawley rats were dosed with diethylnitrosamine (15 mg/kg) at 24 h of age. After weaning, they were fed nutritionally complete semipurified diets for 3 months. Rats fed 15% corn oil had significantly lower hepatic phospholipid eicosapentaenoate and docosahexaenoate than rats fed 7.5% corn oil plus 7.5% fish oil, 5% corn oil plus 10% fish oil ( P < 0.05). However, rats fed 15% corn oil had significantly greater hepatic phospholipid arachidonate than rats fed the other two diets ( P <0.05), suggesting that n-3 polyunsaturated fatty acids were incorporated into hepatic phospholipid at the expense of n-6 polyunsaturated fatty acids. Hepatic PGF 2α content was significantly greater in rats fed 15% corn oil than in rats fed the other two diets ( P < 0.05). Rats fed fish oil had significantly lower hepatic vitamin E content than rats fed corn oil ( P < 0.05). Hepatic lipid peroxidation (TBARS) tended to increase with increased dietary fish oil ( P < 0.05). Dietary lipid did not influence GGT-positive foci area or number. In conclusion, dietary lipid affected hepatic PGF 2α production, however, showed no effect on GGT-positive foci area and number. This may suggest that PGF 2α is not the underlying mechanism for GGT-positive foci during hepatocarcinogenesis.

Brain and heart membrane fatty acid composition in miniature swine fed diets containing corn and menhaden oils

Thirty-six female minipigs, from 4.7–10.6 years old, were fed corn oil (CO) and/or menhaden oil (MO) in diets containing 0, 0.75, or 15% MO and sufficient CO to provide 15% total oil for 6 months. Half the animals were made hypercholesterolemic by feeding them a 13% lard, 2% cholesterol diet for 2 months prior to the experimental feeding period. Samples were taken from the same location in each animal from forebrain, caudate nucleus, cerebellum, and heart to isolate brain synaptosomes and heart plasma membranes. Pretreatment of the minipigs with cholesterol had no effect on the fatty acid composition of the fractions isolated and their membrane fluidity. Despite MO feeding, the long chain n-3 fatty acids were low in the heart plasma membranes compared to heart tissue homogenates from the same animals. Minipigs fed 15% MO showed significant increases in synaptosomal eicosapentaenoate (EPA) and docosapentaenoate (DPA). Docosahexaenoate (DHA) was incorporated into synaptosomes in animals fed 0.75% MO, at concentrations significantly higher than in the CO-fed pigs. Pigs fed 15% MO showed significantly lower brain DHA than those fed CO. The synaptosomal data for the pigs fed the various diets suggest that metabolic synthesis from linolenate, 18:3(n-3), may be a more important source of brain DHA than diet, but that dietary n-6 n-3 ratios and levels of 18:3(n-3), EPA, DPA and DHA may require careful attention. The fatty acid changes did not affect fluidity determined by fluorescence anisotropy of diphenylhexatriene or its polar derivatives.

Fatty acid composition of microsomal phospholipids in rats fed different oils and antioxidant vitamins supplement

The aim of the study was to examine effects of feeding diets containing different oils and antioxidant vitamins supplementation on the fatty acid composition of hepatic microsomal phospholipids in the rat. Forty-eight male Sprague Dawley rats were fed for 20 days diets containing 15% corn, olive, fish, or hazelnut oil, without or with the addition of β-carotene (30 mg/kg) and dl-α-tocopherylacetate (500 mg/kg), n = 6 per group. Microsomal phospholipids of rats fed corn oil exhibited higher content of linoleic, arachidonic, and docosatetraenoic acids ( P < 0.05). Compared with corn oil (control group), olive oil intake increased palmitic, oleic, and vaccenic acids in phosphatidylcholine and phosphatidylserine + phosphatidylinositol, and vaccenic acid in phosphatidylethanolamine ( P < 0.05). Fish oil intake increased the level of n-3 long-chain polyunsaturated fatty acids, and decreased arachidonic acid in all phospholipids ( P < 0.05). On the other hand, the intake of hazelnut oil increased palmitoleic and oleic acids in phosphatidylcholine and phosphatidylethanolamine, and palmitoleic and vaccenic acids in phosphatidylserine + phosphatidylinositol ( P < 0.05). Vitamin supplementation increased microsomal retinol in rats fed corn oil, and α-tocopherol in all groups fed vegetable oils ( P < 0.05). The intake of vitamins supplement induced slight modifications of the fatty acid profile of microsomal phospholipids: a higher level of monounsaturated fatty acids, mainly oleic acid, with a reduction of polyunsaturated fatty acids was observed. These results manifest that the composition of microsomes is affected by the fatty acid profile of dietary oils and the intake of antioxidant vitamins supplements.

Dietary fish oil or lofrin, a 5-lipoxygenase inhibitor, decrease the growth-suppressing effects of coccidiosis in broiler chicks

Broiler chicks were fed a diet containing 4% of either corn oil or fish oil from 3 to 14 d of age. From Days 15 to 23, half of the chicks in each dietary treatment were fed Lofrin (an experimental 5-lipoxygenase inhibitor) at 33 micrograms/kg feed. The remaining chicks within each dietary treatment were the untreated controls. At 24 d of age, half of the chicks within each diet-Lofrin treatment group were each infected with 4.6 x 10(4) sporulated Eimeria tenella oocysts, resulting in a 2 x 2 x 2 factorial arrangement of treatments. Body weight gain, feed consumption, and feed conversion efficiency were determined throughout the study. At 27 d of age, blood, liver, and ceca were sampled. Plasma tumor necrosis factor and hemopexin, hepatic fatty acid composition, and cecal inflammatory cell infiltration were determined. Liver fatty acid composition tended to reflect that of the diet. Chicks fed fish oil had livers that were enriched in (n-3) polyunsaturated fatty acids (PUFA) at the expense of (n-6) PUFA. Chicks fed fish oil gained body weight more rapidly than those fed corn oil. Infection of chicks with Eimeria decreased body weight gain of chicks fed corn oil, but not of chicks fed fish oil. The addition of Lofrin to the corn oil diets abrogated the growth-suppressing effects of infection, although there was no Lofrin effect among chicks fed fish oil. There was a diet by Lofrin interaction in which Lofrin treatment of birds fed corn oil decreased feed consumption and increased feed conversion efficiency, but had no effect on chicks fed diets containing fish oil. Plasma hemopexin was greater, but tumor necrosis factor was lower, in chicks fed fish oil than in chicks fed corn oil. Eimeria infection significantly increased cecal inflammatory cell infiltration across all dietary treatments. There were no clear relationships between growth rate or efficiency and the severity of the inflammatory response to Eimeria infection, as indicated by hemopexin levels and cecal inflammatory scores. These results indicate that Lofrin or fish oil, both of which modify eicosanoid metabolism, attenuate the growth-depressing effects of an Eimeria tenella infection.

Dietary Fat and Fiber Modulate the Effect of Carcinogen on Colonic Protein Kinase C λ Expression in Rats , ,

To elucidate the mechanisms by which dietary factors influence the risk of colon cancer, we investigated the effect of select dietary fats and fibers on atypical protein kinase C (PKC) λ expression. Azoxymethane- and saline (control)-injected rats were fed diets containing either corn oil or fish oil (15 g/100 g) and either cellulose or pectin (6 g/100 g) and killed at two time points (15 and 37 wk) in a 2 × 2 × 2 × 2 factorial design. Colonic PKC λ protein and mRNA levels were determined using immunoblotting and relative competitive polymerase chain reaction, respectively. Azoxymethane suppressed cytosolic PKC λ protein levels compared with the saline controls at both time points, and this suppression was partially blocked by fish oil feeding at 15 wk and pectin at 37 wk. Also, at 15 wk, azoxymethane-injected rats fed corn oil had higher levels of membrane PKC λ relative to the other treatment groups. Overall, expression of PKC λ mRNA was not correlated with differences in the respective isozyme protein levels. Therefore, the chemopreventive effects of dietary fish oil and pectin are associated with the blockage of azoxymethane-induced alterations in colonic PKC λ protein expression.

Acetaldehyde-modified and 4-hydroxynonenal-modified proteins in the livers of rats with alcoholic liver disease

Liver proteins form adducts with acetaldehyde and are modified by products of lipid peroxidation in alcohol-fed animals. It has been hypothesized that the formation of these modified liver proteins may contribute to liver injury in alcoholic liver disease. The present work was performed to determine the extent of protein modification in rats with experimental alcoholic liver disease. Rats were fed ethanol intragastrically with medium chain triglycerides (MCTs), palm oil, corn oil, or fish oil. The group fed MCTs and ethanol showed no liver injury, rats fed palm oil and ethanol showed only fatty liver, rats fed corn oil and ethanol showed fatty liver with moderate necrosis and inflammation, and rats fed fish oil and ethanol showed fatty liver with severe necrosis and inflammation. Antibodies were raised by using keyhole limpet hemocyanin modified in vitro by 4-hydroxynonenal (4-HNE) or acetaldehyde as immunogens. When liver extracts were examined by Western blot analysis, the intensities of the acetaldehyde-modified protein band (37 kd) in the alcohol-fed animals were significantly different among the ethanol-treated groups and correlated with plasma acetaldehyde concentrations. It was strongest in rats fed fish oil and ethanol, followed by rats fed palm oil and ethanol and rats fed corn oil and ethanol, whereas rats fed MCTs and ethanol showed the weakest intensity. The 37-kd protein-adetaldehyde adduct was located mainly in the pericentral region of the liver. No acetaldehyde adduct was detected in the control rats that were pair-fed with isocaloric amounts of dextrose. Western blot analysis using the anti-4-HNE antibody showed four distinctive bands (48, 45, 40, and 38 kd) in the liver extracts of alcohol-fed rats. Control animals showed only a weak 38-kd band. Although the intensities of the 48-, 40-, and 38-kd bands were similar among the different ethanol-treated groups, the intensity of the 45-kd band decreased from MCTs and ethanol > palm oil and ethanol > or = corn oil and ethanol > fish oil and ethanol. The data indicate that the degree of liver protein modification by acetaldehyde correlates well with the severity of liver injury in ethanol-fed rats, whereas modification by the lipid peroxidation product 4-HNE shows no correlation with the severity of liver injury. (Hepatology 1997 Sep;26(3):650-7)

Acetaldehyde-modified and 4-hydroxynonenal-modified proteins in the livers of rats with alcoholic liver disease.

Liver proteins form adducts with acetaldehyde and are modified by products of lipid peroxidation in alcohol-fed animals. It has been hypothesized that the formation of these modified liver proteins may contribute to liver injury in alcoholic liver disease. The present work was performed to determine the extent of protein modification in rats with experimental alcoholic liver disease. Rats were fed ethanol intragastrically with medium chain triglycerides (MCTs), palm oil, corn oil, or fish oil. The group fed MCTs and ethanol showed no liver injury, rats fed palm oil and ethanol showed only fatty liver, rats fed corn oil and ethanol showed fatty liver with moderate necrosis and inflammation, and rats fed fish oil and ethanol showed fatty liver with severe necrosis and inflammation. Antibodies were raised by using keyhole limpet hemocyanin modified in vitro by 4-hydroxynonenal (4-HNE) or acetaldehyde as immunogens. When liver extracts were examined by Western blot analysis, the intensities of the acetaldehyde-modified protein band (37 kd) in the alcohol-fed animals were significantly different among the ethanol-treated groups and correlated with plasma acetaldehyde concentrations. It was strongest in rats fed fish oil and ethanol, followed by rats fed palm oil and ethanol and rats fed corn oil and ethanol, whereas rats fed MCTs and ethanol showed the weakest intensity. The 37-kd protein-adetaldehyde adduct was located mainly in the pericentral region of the liver. No acetaldehyde adduct was detected in the control rats that were pair-fed with isocaloric amounts of dextrose. Western blot analysis using the anti-4-HNE antibody showed four distinctive bands (48, 45, 40, and 38 kd) in the liver extracts of alcohol-fed rats. Control animals showed only a weak 38-kd band. Although the intensities of the 48-, 40-, and 38-kd bands were similar among the different ethanol-treated groups, the intensity of the 45-kd band decreased from MCTs and ethanol > palm oil and ethanol > or = corn oil and ethanol > fish oil and ethanol. The data indicate that the degree of liver protein modification by acetaldehyde correlates well with the severity of liver injury in ethanol-fed rats, whereas modification by the lipid peroxidation product 4-HNE shows no correlation with the severity of liver injury.

Dietary Soybean Protein Increases Insulin Receptor Gene Expression in Wistar Fatty Rats when Dietary Polyunsaturated Fatty Acid Level Is Low ,

To investigate the effects of different dietary fatty acids and proteins on glucose tolerance and insulin receptor gene expression, Wistar fatty rats (genetically obese, noninsulin-dependent diabetes mellitus) and their lean littermates (8 wk old) were fed a casein or soybean protein diet containing 9% partially saturated beef tallow (plus 1% corn oil), 10% corn oil or 10% fish oil for 3 wk. In glucose tolerance tests, plasma insulin concentrations were significantly higher in obese rats fed corn oil or fish oil than in those fed partially saturated beef tallow, particularly in the soybean protein groups. However, plasma glucose concentrations were not significantly affected by dietary protein or fat. The insulin receptor mRNA concentrations in livers and adipose tissues were higher in rats fed soybean protein/partially saturated beef tallow than in those fed any other protein/fat combination. Dietary soybean protein may help to reduce the insulin resistance, but only when a diet low in polyunsaturated fatty acids is consumed. On the other hand, the insulin receptor mRNA concentrations in adipose tissue were generally lower in the obese rats of all dietary groups than in the lean rats, suggesting that insulin resistance may be due to a defect of insulin receptor gene expression.

Dietary fish oil blocks carcinogen-induced down-regulation of colonic protein kinase C isozymes.

In order to elucidate the influence of dietary constituents on colonic intracellular signal transduction, the effect of different fats on rat colonic epithelial protein kinase C (PKC) alpha (classical), delta (novel) and lambda-zeta (atypical) expression was determined in carcinogen-treated animals. Sprague-Dawley rats were provided with one of two fats (corn oil and fish oil); plus or minus the carcinogen azoxymethane (AOM) and killed at two time points (15 and 37 weeks) in a 2x2x2 factorial design. At 5 and 6 weeks of age, animals were injected s.c. with either AOM at a dose of 15 mg/kg body weight or saline once a week for 2 weeks and continued on the same diet until termination of the study. At 15 and 37 weeks after the second injection, 10 rats from each treatment group were killed. Colonic PKC alpha, delta and lambda-zeta steady-state protein and mRNA levels were determined using immunoblotting and relative quantitative polymerase chain reaction, respectively. Colonic mucosa from rats injected with AOM had significantly suppressed membrane and cytosolic PKC alpha and cytosolic lambda-zeta protein levels (P < 0.05) as compared to saline-injected control animals at both time points. In contrast, rats fed fish oil diets had significantly higher (P < 0.05) cytosolic PKC delta and lambda-zeta protein levels relative to animals fed corn oil diets. However, the effect of diet and AOM on the steady-state expression of PKC alpha, delta and zeta mRNA was not consistent with changes in the respective isozyme protein levels, suggesting regulation at the post-transcriptional level. These data demonstrate that dietary fish oil blocks the carcinogen-induced decrease in the steady-state levels of colonic mucosal PKC delta and lambda-zeta, which may in part explain why this fat source protects against colon cancer development.

Dietary n-3 fatty acids increase spleen size and postendotoxin circulating TNF in mice; role of macrophages, macrophage precursors, and colony-stimulating factor-1.

In experimental studies in mice, dietary supplementation with n-3 fatty acids (FA) alleviates inflammation and increases resistance to infection. Nevertheless, TNF production capacity was found to be increased in n-3 FA-fed mice. We previously found increased relative spleen weights in n-3 FA-fed mice. In this study, the nature of this increased spleen size was further investigated. Spleen cellularity was increased significantly in mice fed n-3 FA (fish oil 15% w/w), compared with controls fed corn oil (15%) or normal lab chow (p < 0.05). Experiments with T cell-deficient nude mice and experiments using macrophage depletion through liposomal dichloromethylene-biphosphonate revealed that the increase in spleen cellularity is T cell independent and largely due to macrophage accumulation in the spleen. Accumulation of marginal zone and red pulp macrophages was histologically and immunohistochemically confirmed. n-3 FA induced peripheral blood monocytosis and an aspecific increase in bone marrow cellularity. Postendotoxin circulating TNF concentrations were increased significantly in n-3 FA-fed mice compared with controls. Splenectomy did not abolish this increase in circulating TNF. However, after macrophage depletion through liposomal dichloromethylene-biphosphonate, circulating TNF was not detectable after endotoxin challenge. Circulating concentrations of CSF-1 did not differ between the various experimental groups. It is suggested that the cellular changes observed relate to increased constitutive production of TNF.

Regulatory effects of dietary n-3 and n-6 lipids on plasma and hepatic lipid levels, liver cell number and microsomal protein content in spontaneously hypertensive rats

Weanling male spontaneously hypertensive rats were fed semipurified diets containing either corn or fish oil for 8 weeks. Rats fed on fish oil diet had significantly lower plasma triglyceride, total cholesterol and HDL-cholesterol levels than rats fed on corn oil diet ( P < 0.05). Moreover, rats fed on fish oil diet had significantly lower liver total lipid and triglyceride concentrations than rats fed on corn oil diet ( P < 0.05). Dietary lipids were reflected in plasma fatty acid composition. Rats fed on fish oil diet had significantly greater plasma eicosapentaenoate (EPA) and docosahexaenoate (DHA) (n-3 PUFAs) with an accompanying decrease in plasma linoleate (LA) and arachidonate (AA) (n-6 PUFAs), in comparison with the rats fed corn oil ( P < 0.05). Those results would suggest that the n-3 PUFAs were incorporated into plasma lipids at the expense of the n-6 PUFAs. Rats fed on corn oil diet had significantly greater liver DNA content than rats fed on fish oil diet ( P < 0.05), thereby implying that the n-3 PUFAs in fish oil had an inhibitory effect on liver cell proliferation. Furthermore, rats fed on fish oil diet had significantly greater hepatic microsomal protein content than rats fed on corn oil diet ( P < 0.05), indicating that fish oil exerted a stimulatory effect on hepatic microsomal enzymes.

Manganese protects against heart mitochondrial lipid peroxidation in rats fed high levels of polyunsaturated fatty acids.

We demonstrated previously that dietary manganese (Mn) deficiency depressed Mn concentrations in most tissues and consistently depressed Mn superoxide dismutase (MnSOD) levels in heart. To examine the functional consequences of these effects, we fed weanling male Sprague-Dawley rats (n = 12/diet) diets containing 20% (wt/wt) corn oil or 19% menhaden oil + 1% corn oil by weight and 0.75 or 82 mg Mn/kg diet for 2 mo (the fish oil mixture was supplemented with (+)-(mixed)-alpha-tocopherol to the level in corn oil). Heart and liver Mn concentrations in the Mn-deficient rats were 56% of those in Mn-adequate rats (P < 0.0001), confirming Mn deficiency. The Mn-deficient rats had more conjugated dienes in heart mitochondria than Mn-adequate rats (P < 0.001); rats fed fish oil had more conjugated dienes than those fed corn oil (P < 0.001). The MnSOD activity was inversely correlated with conjugated dienes (r = -0.71, P < 0.005), and Mn-deficient rats had 37% less MnSOD activity in the heart than did Mn-adequate rats (P < 0.0001). The dietary treatments did not affect heart microsomal conjugated diene formation, possibly because of compensation by copper-zinc (CuZn) SOD activity; CuZnSOD activities were 35% greater in the hearts of Mn-deficient animals (P < 0.01). Liver was less sensitive to Mn deficiency than was the heart as judged by MnSOD activity and conjugated diene formation. This work is the first to demonstrate that dietary Mn protects against in vivo oxidation of heart mitochondrial membranes.

Dietary fat and fiber differentially alter intracellular second messengers during tumor development in rat colon.

The effect of fat, fiber and carcinogen on colonic epithelial intracellular second messengers 1,2-diacyl-sn-glycerol (DAG), ceramide, and the steady-state level of phospholipase C (PLC-gamma1) was determined in 160 male Sprague-Dawley rats (10 rats per group). The study was a 2 x 2 x 2 x 2 factorial design with two types of fat (corn oil or fish oil), two types of fiber (cellulose or pectin), two injected subgroups (with or without azoxymethane (AOM), and two time points (15 and 37 weeks). At the final time point (37 weeks) there were an additional 20 rats per diet in each of the carcinogen-treated groups for tumor analyses only (n = 80), for a total of 240 animals in the entire study. At each time point (15 and 37 weeks), 80 rats were killed and colonic mucosa obtained for DAG, ceramide and PLC-gamma1 assays. At the first time point (15 weeks), there was no microscopic evidence of tumors. At the final time point (37 weeks), fish oil resulted in a lower proportion of animals with adenocarcinomas relative to corn oil feeding (56.1 % versus 69.6 %, P < 0.05). There was no significant main effect of fiber on the percentage of animals with tumors. At 15 weeks post-injection, AOM injected animals fed corn oil-containing diets had a significantly (P < 0.001) higher DAG mass and steady-state levels of PLC-gamma1 compared with AOM-injected animals fed fish oil and saline injected rats on all diets. Animals fed corn oil diets also had a significantly (P < 0.01) elevated mucosal ceramide mass compared with fish oil fed animals. Moreover, rats injected with AOM had a significantly (P < 0.02) elevated colonic mucosal DAG/ceramide ratio versus saline injected animals. In contrast, dietary fiber had no effect on any of the parameters measured at 15 weeks. However, at 37 weeks post-injection, dietary fiber significantly altered DAG (P < 0.02), and PLC-gamma1 expression (P < 0.05) in the absence of an effect on tumor incidence. These data demonstrate that the ability of dietary fish oil to reduce experimental colon carcinogenesis may be mediated by changes in colonic intracellular mediators during the initial stages of tumorigenesis.

Anti-inflammatory properties of docosahexaenoic and eicosapentaenoic acids in phorbol-ester-induced mouse ear inflammation.

Laboratory animal models and clinical studies suggest that dietary n-3 fatty acids are beneficial in diseases with an inflammatory component such as rheumatoid arthritis or psoriasis. In the present study we investigated the effect of purified docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on phorbol ester (TPA)-induced acute inflammation. Mice were fed for 6 weeks a diet containing 5% corn oil enriched with either 1% DHA or 1% EPA and compared with a group receiving 6% corn oil only. The dietary treatment with DHA or EPA elevated the n-3 polyunsaturated fatty acids as expected in the spleen and ear phospholipids, associated with a reduction in arachidonic acid levels. The degree of ear inflammation was quantified by measuring the four parameters including (1) edema as the increase in ear biopsy weight, (2) polymorphonuclear cell infiltration as myeloperoxidase activity (MPO) at the site of inflammation, (3) prostaglandin E2 (PGE2) and (4) leukotriene B4 (LTB4) concentrations in ear edema. The addition of DHA to the diet reduced significantly the edema formation and the MPO activity 24 h after TPA challenge. Both DHA and EPA significantly reduced the PGE2 and LTB4 levels compared with animals fed corn oil. This result suggests that DHA rather than EPA may be useful in the adjuvant treatment of diseases where acute inflammatory processes play a role.

Coconut oil and beef tallow, but not tricaprylin, can replace menhaden oil in the diet of red drum (Sciaenops ocellatus) without adversely affecting growth or fatty acid composition.

The ability of juvenile red drum (Sciaenops ocellatus) to utilize medium-chain triglycerides (MCT) and other saturated dietary lipids was investigated in two 6-wk feeding experiments. Diets contained solvent-extracted menhaden fish meal to which menhaden fish oil (control), coconut oil, corn oil, beef tallow or various levels of MCT as tricaprylin (30, 46, 65 and 80% of total lipid) were added. Diets were fed to triplicate groups of juvenile red drum in aquaria containing brackish (6%) water. In the first feeding experiment, red drum fed the control diet had the greatest weight gains and feed efficiencies. Weight gain, but not feed was slightly, of fish fed corn oil and fish fed coconut oil was slightly (P < 0.05) lower. In the second feeding experiment, fish fed coconut oil and those fed beef tallow had significantly higher weight gains and feed efficiencies than did fish fed the control diet. Fish fed the diets containing tricaprylin at all inclusion levels in both feeding experiments had significantly lower weight gains and feed efficiencies and higher levels of beta-hydroxybutyric acid in plasma. Fish fed diets with high levels of MCT also had lower (n-3) and greater (n-6) fatty acid levels in the neutral lipid fraction of muscle tissue compared with fish fed the control diet. Coconut oil and beef tallow consistently resulted in greater liver lipid deposition but had variable effects on other tissue indices. Saturated dietary lipids had variable effects on fatty acid composition of muscle polar and neutral lipid fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide production in experimental alcoholic liver disease in the rat: Role in protection from injury

Background & Aims : Regulation of blood flow and oxygen supply are important pathogenetic factors in alcoholic liver disease. Because nitric oxide may have an important role, its effects on alcoholic liver injury were investigated. Methods : Rats were fed ethanol intragastrically with either saturated fat or corn oil. Spontaneous production of NO by liver nonparenchymal cells was compared in the two dietary groups. Two additional groups of rats fed corn oil and ethanol were treated with either an NO inhibitor ( l-NAME) or supplemented with l-arginine. Liver pathology and plasma NO production were evaluated. Results : In the corn oil and ethanol group, a progressive decrease in liver nonparenchymal cell NO production and increased plasma NO levels were associated with liver injury. Reduced nicotinamide adenine dinucleotide phosphate diaphorase staining showed increased centrilobular staining of hepatocytes in the corn oil and ethanol group and l-NAME-treated group. Moreover, l-NAME increased the severity, whereas l-arginine supplementation completely prevented liver injury. In the saturated fat and ethanol group, in which there was no liver injury, the levels of NO 2 − in nonparenchymal supernatant were 5–10-fold higher than in the corn oil and ethanol group. Conclusions : Decreased NO production by nonparenchymal cells may contribute to liver injury in ethanol-fed rats, and the compensatory increase in hepatocyte NO production may contribute to centrilobular liver injury.

Dietary fat and vitamin E have differential effects on serum lipid levels

The experiment was designed to study the effects of dietary fat and vitamin E on serum lipid status, an important indicator of risk for atherosclerosis. The influences of dietary fat and d,1-α-tocopheryl acetate (vitamin E) on serum fatty acid profiles, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride concentrations were studied in 40 weanling male Sprague-Dawley rats. Rats were fed semipurified diets containing corn oil or lard and graded levels (0, 100, 5000 or 15000 ppm) of vitamin E for 8 weeks. Serum vitamin E level was significantly greater in the corn oil group with 100 ppm vitamin E than in the lard group with 100 ppm vitamin E (p<0.05). Lipid status was verified by serum fatty acid profiles. Serum C18:0 (stearic acid) and C18:1 n-9 (oleic acid) of rats were significantly greater in the lard groups than in the corn oil groups with an equal amount of vitamin E except with the 100 ppm vitamin E, serum C18:2 n-6 (linoleic acid) of rats was significantly greater in the corn oil groups than in the lard groups with an equal amount of vitamin E, and C20:4 n-6 (arachidonic acid) of rats was significantly greater in the corn oil group with 15000 ppm vitamin E than in the lard group with 15000 ppm vitamin E (p<0.05). Rats fed corn oil had significantly greater serum HDL-cholesterol than rats fed lard with 100 or 15000 ppm vitamin E (p<0.05). However, serum LDL-cholesterol level was significantly greater in the rats fed corn oil with 100 ppm vitamin E compared with that in the rats fed lard with 100 ppm vitamin E (p<0.05). Both dietary fat and vitamin E had effects on serum HDL-cholesterol, however, no interaction existed between dietary fat and vitamin E on serum HDL-cholesterol. With regard to serum LDL-cholesterol, only vitamin E had a significant effect. The results suggested that both dietary fat and vitamin E can influence atherosclerosis progression via their effects on serum lipid status, but no interaction between them on serum lipid status was found.

Animal and Plant Fats Selectively Modulate Oxidizability of Rabbit LDL and LDL-Mediated Disruption of Endothelial Barrier function1

Enrichment of lipoproteins with fatty acids derived from animal and/or plant fats may modify the oxidizability of lipoproteins and their effects on endothelial barrier function. To test this hypothesis, rabbits were fed for 30 days diets containing 2 g corn oil/100 g diet (low fat diet) or low fat supplemented with 16 g/100 g diet of corn oil, corn oil with added cholesterol, milk fat, chicken fat, beef tallow or lard. Compared with those fed the low fat, serum and LDL cholesterol concentrations were significantly lower in rabbits fed corn oil and greater in animals fed corn oil with added cholesterol or chicken fat. In contrast to the cholesterol data, lipid hydroperoxide levels were highest in oxidized LDL derived from rabbits fed corn oil or lard. LDL vitamin E levels were highest in rabbits fed corn oil with added cholesterol. The significant elevations in linoleic acid [18:2(n-6)] in serum and LDL may partially explain the high oxidizability of LDL in rabbits fed corn oil. LDL isolated from animals fed corn oil, lard or milk fat had significantly greater albumin transfer across cultured endothelial monolayers compared with those of the low fat diet group. Their oxidative modification further contributed to endothelial barrier dysfunction. Dietary cholesterol supplementation to the corn oil diet decreased the oxidizability of LDL and partially protected the oxidized LDL-mediated endothelial cell dysfunction as compared with the corn oil diet group. These data suggest that beef tallow and chicken fat are the least atherogenic fats if oxidative modification of LDL is a critical issue in atherosclerosis.