Effects of dietary corn oil and salmon oil on lipids and prostaglandin E2 in rat gastric mucosa

Three groups of male rats were fed either a corn oilenriched diet (17%, w/w), a salmon oil-enriched diet (12.5%) supplemented with corn oil (4.5%) or a low-fat diet (4.4%) for eight wk to investigate the possible relationships between dietary fatty acids and lipid composition, and prostaglandin E₂ level and phospholipase A₂ activity in the rat gastric mucosa. High-fat diets induced no important variation in total protein, phospholipid and cholesterol contents of gastric mucosa. Compared with a low-fat diet, corn oil produced a higher n−6/n−3 ratio in mucosal lipids, whereas this ratio was markedly lowered by a fish oil diet. In comparison with the low-fat diet, the production of prostaglandin E₂(PGE₂) in gastric mucosa of rats fed salmon oil was significantly, decreased by a factor of 2.8. In the corn oil group, PGE₂ production tended to decrease, but not significantly. In comparison with the low-fat diet, both specific and total gastric mucosal phospholipase A₂ activities were increased (+18 and 23%, respectively) in the salmon oil group; they were unchanged in the corn oil group. It is suggested that the decrease of gastric PGE₂ in rats fed fish oil is not provoked by a decrease in phospholipase A₂ activity but may be the result of the substitution of arachidonic acid by n−3 PUFA or activation of PGE₂ catabolism.     

Phospholipid profile and production of prostanoids by murine colonic epithelium: Effect of dietary fat

Dietary fat and abnormal production of various prostanoids have been linked to various disease states of the large bowel, including cancer of the colon. Studies were conducted to determine the effect of dietary fat (beef tallow or corn oil) on the lipid composition and prostanoid production of the murine colon. Female C57BL/6J mice were fed high-fat (HF) diets (47% of calories as fat) or low-fat (LF) diets (10% of calories as fat). After four wk of dietary treatment, the mucosa was scraped, and lipids were extracted from the mucosal and muscle layers. The fat content of the diets did not significantly alter the amount of phospholipid (PL) or neutral lipid in the colonic tissue. However, the HF affected the PL profile of the colonic mucosa. For example, the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) was significantly higher for both the HF groups compared with that of the two LF groups (0.76±0.15 and 0.80±0.13 vs 0.31±0.20 and 0.34±0.18). Production of 13,14-dihydro-15-keto-PGE₂ (measured as bicyclic PGE₂) and TXB₂ (a stable metabolite of TXA₂) and PGF_1α (a stable metabolite of PGI₂) was unaffected by the dietary treatments. The muscle had a different PL profile (PC:PE is 2.6±0.1) than the mucosa and contributed a larger proportion of the prostanoids formed. This study demonstrates that the phospholipid polar head group composition of normal colonic mucosa is altered by dietary fat, but the ability of the mucosa to synthesize metabolites of PGE₂, TXA₂ and PGI₂ is not affected. ARC Contribution No. 1504.     

Arachidonic acid,prostaglandin E2 and leukotriene C4 levels in gingiva and submandibular salivary glands of rats fed diets containing n−3 fatty acids

The effect of dietary n−3 fatty acids on prostaglandin E₂ (PGE₂) and leukotriene C₄ (LTC₄) levels in rat salivary glands and gingiva was examined in two separate nutritional studies. In the first set of experiments, two groups of male weanling Sprague-Dawley rats were fed semipurified diets containing 10% corn oil (control group) or 10% menhaden oil (experimental group). Rats were killed after 8 wk on the diets; the fatty acid composition of total phospholipids and the concentrations of PGE₂ and its precursor, arachidonic acid, were measured in gingiva and submandibular salivary glands (SMSG). Dietary n−3 fatty acids were incorporated into the tissue phospholipids. Arachidonic acid levels were reduced by 56% in gingiva and SMSG of rats fed menhaden oil compared with the control rats fed the diet containing corn oil. The concentrations of PGE₂ in SMSG and gingiva of rats fed the diet containing menhaden oil were reduced by 74% and 83%, respectively. In a subsequent nutritional study, we tested whether the diet-induced reduction in tissue arachidonic acid levels would also result in a corresponding decrease in LTC₄ production. Three groups of rats were fed diets containing 5% corn oil (group 1), 4% ethyl ester concentrate of n−3 fatty acids plus 1% corn oil (group 2), or 5% ethyl ester concentrate of n−3 fatty acids (group 3). After 6 wk of feeding, gingiva and SMSG were analyzed for arachidonic acid content andin vitro production of LTC₄. Arachidonic acid content of total phospholipids was about 60% lower in gingiva and 69% lower in SMSG of rats fed the ethyl ester concentrate of n−3 fatty acids (groups 2 and 3) than those of the control group fed the corn oil diet (group 1). Upon incubation with calcium ionophore, gingiva and SMSG from rats fed the n−3 fatty acids rich diet produced significantly less TLC₄ than those from rats of the control group. Because PGE₂ and LTC₄ are believed to be important biochemical mediators of periodontal disease, one may speculate that a diet-induced reduction in their levels may have a beneficial effect upon the course of the disease. The function of salivary glands may also be altered because of the role of these eicosanoids in salivary secretions. Presented in part for the Hatton Award Competition at the American Association for Dental Research Meeting, San Francisco, California, March 15–19, 1989, and at the International Association for Dental Research Meeting, Acapulco, Mexico, April 17–21, 1991.     

Effect of dietary fat on colonic protein kinase C and induction of aberrant crypt foci

A major objective of the present study was to determine whether a high-fat diet affects early events during colon carcinogenesis. Female Sprague-Dawley rats were injected with saline or azoxymethane (20 mg/kg) and fed either a normal (5% corn oil w/w) or a high (5% corn oil and 15% beef tallow w/w) fat diet. To assess the effect of a known tumor-promoting diet on the early events of neoplastic transformation, Study 1 examined the induction and growth of aberrant crypt foci (ACF) as well as of proliferative indices. The total number of ACF were similar in both groups even after 8 wk of dietary treatment; however, ACF with accelerated growth characteristics (≥4 crypts/focal lesions) were more prevalent (P≤0.05) in the colons of animals fed the high-fat diet. Metaphase arrest cells and 5′-bromo-2′-deoxyuridine labelled cells showed no appreciable response to dietary changes. To determine whether changes in colonic signal transduction pathways represent an early response to dietary modification, Study 2 evaluated the activity of protein kinase C (PKC), proliferative indices and changes in phospholipid fatty acid profiles. In comparison to the normal fat group, the colons of high-fat fed animals exhibited higher (P≤0.05) membranes and lower soluble PKC activity; however, proliferation patterns of these colons were not altered. Changes in the membrane lipid composition were minor; however, an increase in the phosphatidylcholine/phosphatidylethanolamine ratio and in 20∶4n−6 was noted. Our results demonstrate that in comparison to a normal-fat diet, a high-fat diet stimulated the growth of a population of ACF, i.e., preneoplastic lesions leading to advanced growth characteristics. In addition, a high-fat diet exerted a marked influence on total, cytosolic and membrane associated PKC activities. The findings suggest that modulation of PKC may play a critical role at the early stages of colon carcinogenesis. This work was presented by L.M.Z. Lafave as a recipient of the Honored Student Award at the American Oil Chemists' Society annual meeting, Anaheim, California, 1993. L.M.Z. Lafave is the recipient of a Natural Sciences and Engineering Research Council Postgraduate Scholarship.     

Effects of flaxseed derivatives in experimental polycystic kidney disease vary with animal gender

Flaxseed derivatives, including both oil and flax lignan, modify progression of renal injury in animal models, including Han:SPRD-cy polycystic kidney disease (PKD). Gender is a significant factor in the rates of progression of many forms of human renal disease, but the role of gender in the response to nutrition intervention in renal disease is unexplored. In this study, male and female Han:SPRD-cy rats or normal littermates were fed either corn oil (CO) or flax oil (FO) diets, with or without 20 mg/kg of the diet flax lignan secoisolaricinoresinol dyglycoside (SDG). Renal injury was assessed morphometrically and biochemically. Renal and hepatic PUFA composition was assessed by GC and renal PGE₂ release by ELISA. FO preserved body weight in PKD males, with no effect in females. SDG reduced weight in both normal and PKD females. FO reduced proteinuria in both male and female PKD. FO reduced cystic change and renal inflammation in PKD males but reduced cystic change, fibrosis, renal inflammation, tissue lipid peroxides, and epithelial proliferation in PKD females. SDG reduced renal inflammation in all animals and lipid peroxides in PKD fenales. A strong interaction between SDG and FO was observed in renal FA composition of female kidneys only, suggesting increased conversion of C₁₈ PUFA to C₂₀ PUFA. FO reduced renal release of PGE₂ in both genders. Gender influences the effects of flaxseed derivatives in Han:SPRD-cy rats. Gender-based responses to environmental factors, such as dietary lipid sources and micronutrients, may contribute to gender-based differences in disease progression rates.     

The effect of long-chain monoenes on prostaglandin E2 synthesis by rat skin

In order to ascertain whether the dermal lesions observed in male rats fed rapeseed oils are due to impaired prostaglandin biosynthesis, endogenous levels of prostaglandin E₂ (PGE₂) in skin and the capacity of this tissue to synthesize PGE₂ from arachidonic acid was investigated. Male Sprague-Dawley rats were fed from weaning for 8 weeks either a standard rat diet (chow) or semisynthetic diets containing 20% by weight of the following fat sources: corn oil; commercial lard; commercial lard to which was added 5.4% free erucic acid; rendered pig fat; or the following rapeseed oils:Brassica napus var. Zephyr;B. campestris var. Span;B. campestris var. Arlo (15%) and var. Echo (85%) designated HEAR (high erucic acid rapeseed). The long-chain monoene content (18∶1, 20∶1, and 22∶1) of the diets fed ranged from 30 to 71 mole % and that of skin from 27 to 74 mole %. A significant (P<0.01) correlation was found between the level of 18∶2n−6 in the diet and the endogenous PGE₂ levels in skin and the capacity of this tissue to synthesize PGE₂. No relationship was found between these two PGE₂ parameters and the level of erucic acid in the diet. The rate of turnover of PGE₂ appeared to be lower in rats fed rapeseed oil as evidenced by the relatively high endogenous PGE₂ levels when these oils were fed (96 to 105 μg/g). On the other hand, the lowest capacity for PGE₂ synthesis was found with skin from rats fed Zephyr rapeseed oil, rats which also had the most severe incidence of hair loss and dermal lesions. Significant (P<0.01) negative correlations were observed between the level of monoenes and specifically the level of oleic (18∶1n−9) acid in the diets and PGE₂ synthesis capacity of skin, possibly confirming the known inhibitory effect of 18∶1n−9 on the prostaglandin synthesizing enzyme system. Contribution No. 687, Animal Research Institute.     

Effect of high fat corn oil,olive oil and fish oil on phospholipid fatty acid composition in male F344 rats

Epidemiological and laboratory animal model studies have provided evidence that the effect of dietary fat on colon tumorigenesis depends on the amount of fat and its composition. Because of the importance of the composition of dietary fat and of tissue membrane fatty acid composition in tumor promotion, experiments were designed to investigate the relative effects of high fat diets rich in ω3, ω6 and ω9 fatty acids and colon carcinogen on the phospholipid fatty acid composition of liver, colon, small intestine, erythrocytes and blood plasma. At 6 wk of age, groups of animals were fed diets containing 5% corn oil (LFCO), 23.5% corn oil (HFCO), 23.5% olive oil (HFOO), and 20.5% fish oil plus 3% corn oil (HFFO). Two weeks later all the animals except the vehicle-treated animals received azoxymethanes.c. once weekly for 2 wk at a dose rate of 15 mg/kg body weight. Animals were sacrificed 5 d later and liver, colon, small intestine and erythrocytes and blood plasma were analyzed for phospholipid fatty acids. The results indicate that the phospholipid fatty acid composition of liver, colon and small intestine of HFCO diet fed animals, were not significantly different from those fed the LFCO diet. The levels of palmitoleic acid and linoleic acid were increased in erythrocytes and blood plasma of the animals fed the HFCO diet compared to those fed the LFCO diet. Feeding the HFCO diet significantly increased the oleic acid content and decreased the linoleic acid and arachidonic acid levels in various organs when compared to the HFCO diet. Animals fed the HFFO diet showed a marked increase in eicosapentaenoic acid and docosahexaenoic acid and a decrease in linoleic acid and arachidonic acid levels as compared to those fed the HFCO diet. The results also indicate that carcinogen treatment had only a minimal effect on the phospholipid fatty acid composition.     

Influence of omega-3 and omega-6 fatty acid sources on prostaglandin levels in mice

Studies from this laboratory, employing a hairless mouse model, have indicated that a polyunsaturated fatty acid source rich in omega-3 (n−3) fatty acid (FA) inhibits ultraviolet (UV)-carcinogenic expression, when compared to that of diets containing predominantly n−6 fatty acids. Omega-3 FA is a poor substrate for cyclo-oxygenase, the rate-limiting step in prostaglandin (PG) synthesis—the latter, particularly PGE₂, are known to influence tumor biology. Based upon this rationale, plasma and cutaneous PGE₂ levels were determined from hairless mice fed diets containing either 4% or 12% corn or menhaden oil. After two weeks on the respective diets, plasma PGE₂ levels of corn oil-fed animals were approximately 6-fold greater than those of the menhaden oil-fed groups. A similar response was found in the dermis. Although the relationship to carcinogenic expression is unknown, dietary n−3 FA content can have a pronounced effect upon PGE₂ levels and possesses the potential for influencing other immunomodulators.     

Acetoacetate metabolism of rats fed high fat or restricted calorie diets

Ethyl-¹⁴C-acetoacetate was used to trace oxidation and metabolism of acetoacetate when rats were fed a high fat diet (80% of total calories from beef tallow or corn oil, carbohydrate free), a high carbohydrate diet (2% corn oil) or a high carbohydrate diet with restriction of calories to one half of ad lib. consumption for two weeks. The rate of expiration of¹⁴CO₂ in all groups of animals did not differ significantly and was not related to plasma concentration of acetoacetate. The high fat diets slightly enhanced the oxidation of acetoacetate to¹⁴CO₂ over a 3 hr period compared to other diets. Incorporation of acetoacetate into fatty acids did not differ significantly among groups. Rats fed the high carbohydrate diet ad lib. incorporated into liver cholesterol more acetoacetate than did any other group, but dietary unsaturated fat resulted in greater incorporation of acetoacetate into cholesterol than saturated fat. High calorie and high beef tallow groups were ketonemic but the low concentration of plasma acetoacetate in rats fed a high corn oil diet indicates that unsaturated fatty acids are not ketogenic. The data show that utilization of acetoacetate is not significantly reduced in a ketonemic condition and support the premise that overproduction of ketone bodies is the cause of ketonemia. Rats appeared to be normal during the two-week period when no carbohydrate was included in the diet. Presented at the AOCS Meeting, Chicago, October, 1967.     

Dietary n-3 and n-6 PUFA Enhance DHA Incorporation in Retinal Phospholipids Without Affecting PGE<Subscript>1</Subscript> and PGE<Subscript>2</Subscript> Levels

The purpose of this study was to determine whether dietary n-3 and n-6 PUFA may affect retinal PUFA composition and PGE₁ and PGE₂ production. Male Wistar rats were fed for 3 months with diets containing: (1) 10% eicosapentaenoic acid (EPA) and 7% docosahexaenoic acid (DHA), or (2) 10% γ-linolenic acid (GLA), or (3) 10% EPA, 7% DHA and 10% GLA, or (4) a balanced diet deprived of EPA, DHA, and GLA. The fatty acid composition of retinal phospholipids was determined by gas chromatography. Prostaglandin production was measured by enzyme immunoassay. When compared to rats fed the control diet, the retinal levels of DHA were increased in rats fed both diets enriched with n-3 PUFA (EPA + DHA and EPA + DHA + GLA diets) and decreased in those supplemented with n-6 PUFA only (GLA diet). The diet enriched with both n-6 and n-3 PUFA resulted in the greatest increase in retinal DHA. The levels of PGE₁ and PGE₂ were significantly increased in retinal homogenates of rats fed with the GLA-rich diet when compared with those of animals fed the control diet. These higher PGE₁ and PGE₂ levels were not observed in animals fed with EPA + DHA + GLA. In summary, GLA added to EPA + DHA resulted in the highest retinal DHA content but without increasing retinal PGE₂ as seen in animals supplemented with GLA only.     

A comparative study of the nutritive value of thermally oxidized oils

Summary Thermal oxidation of corn oil under laboratory conditions, at 200°C., led to the formation of an oil exhibiting definite growth-depressing action under bothad libitum and paired feeding conditions. Under similar conditions margarine base stock gave only slight growth depression, and none was noted with butter oil. The effect was not a permanent one as animals that were changed to a normal diet quickly recovered and grew to maturity. It appeared that the products formed during the thermal treatment were related to the unsaturated or polyunsaturated portions of the oil. The growth-depressing effect appeared to be multiple in nature, it had an irritant or diarrhea effect and possibly an enzyme-inhibiting or vitamin-destroying effect. Funds for partial support of these studies were made available by the American Dairy Association and research grant No. C-1932 from the National Institute of Health, Public Health Service.     

Potential of Magnetic Resonance Spectroscopy in Assessing the Effect of Fatty Acids on Inflammatory Bowel Disease in an Animal Model

People with inflammatory bowel disease (IBD) are at risk for developing colorectal cancer, and this risk increases at a rate of 1% per year after 8–10 years of having the disease. Saturated and ω-6 polyunsaturated fatty acids (PUFAs) have been implicated in its causation. Conversely, ω-3 PUFAs may have the potential to confer therapeutic benefit. Since proton magnetic resonance spectroscopy (¹H MRS) combined with pattern recognition methods could be a valuable adjunct to histology, the objective of this study was to analyze the potential of ¹H MRS in assessing the effect of dietary fatty acids on colonic inflammation. Forty male Sprague-Dawley rats were administered one of the following dietary regimens for 2 weeks: low-fat corn oil (ω-6), high-fat corn oil (ω-6), high-fat flaxseed oil (ω-3) or high-fat beef tallow (saturated fatty acids). Half of the animals were fed 2% carrageenan to induce colonic inflammation similar to IBD. ¹H MRS and histology were performed on ex vivo colonic samples, and the ¹H MR spectra were analyzed using a statistical classification strategy (SCS). The histological and/or MRS studies revealed that different dietary fatty acids modulate colonic inflammation differently, with high-fat corn oil being the most inflammatory and high-fat flaxseed oil the least inflammatory. ¹H MRS is capable of identifying the biochemical changes in the colonic tissue as a result of inflammation, and when combined with SCS, this technique accurately differentiated the inflamed colonic mucosa based on the severity of the inflammation. This indicates that MRS could serve as a valuable adjunct to histology in accurately assessing colonic inflammation. Our data also suggest that both the type and the amount of fatty acids in the diet are critical in modulating IBD.     

Impact of dietary FA and energy restriction on plasma leptin and ob gene expression in mice

The aim of the present study was to elucidate whether the qualitative compositiion of dietary fat influences plasma leptin and adipose tissue ob gene expression differentially. Two high-fat diets and a diet rich in carbohydrate were each administered both ad libitum and with a 25% energy restriction. The high-fat diets contained 58 energy percent as either monounsaturated FA (MUFA) or saturated FA (SAFA), whereas the carbohydrate-rich diet (CH) contained 7 energy percent as fat. We aimed at obtaining the same final weight for the animals in the ad libitum group as in the energy-restricted groups. This goal was reached at he same time (days 22–24) for all groups except for the ad libitum animals fed on saturated fat (day 36). The plasma leptin concentrations on ad libitum CH and MUFA diets did not differ significantly (24.3 ± 2.1 and 34.7 ± 6.7 ng/mL, respectively) whereas the saturated fat diet caused a lower concentration (13.9 ± 1.9 ng/mL; P < 0.05). Interestingly, no differences in plasma leptin levels between groups were seen in the energy-restricted groups (mean 8.0 + 1.0 ng/mL). The type of diet did not alter the ob gene expression in intraabdominal white adipose tissue; however, a lower expression level was found in the energy-restricted groups. The percentage of body fat in the three ad libitum fed groups did not differ (23 ± 1%). Thus, short-term administration of a diet rich in SAFA suppresses circulating leptin levels without altering the adipose tissue ob gene expression. This indicates that saturated fat may alter protein handling by adipose tissue or the whole body clearance of leptin.     

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

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

Borage or primrose oil added to standardized diets are equivalent sources for γ-linolenic acid in rats

The aim of this study was to evaluate the effect of different doses and sources of dietary γ-linolenic acid (GLA) on the tissue phospholipid fatty acid composition. Rats fed four different levels of GLA (2.3, 4.6, 6.4 and 16.2 g of GLA/kg diet) in the form of either borage oil or evening primrose oil during 6 wk were compared with animals fed corn oil. The levels of dihomo-γ-linolenic acid (DHLA) and GLA showed a significant dose-related increase in liver, erythrocyte and aorta phospholipids. Moreover, the arachidonic acid/DHLA ratios in tissues decreased with increasing intake of dietary GLA. There was no significant difference in tissue GLA and DHLA levels within groups given equal amounts of dietary GLA either as borage oil or evening primrose oil. The amount of dietary GLA administered did not significantly influence prostaglandin E₂ production in stimulated aortic rings and thromboxane B₂ levels in serum; however, an increase in prostaglandin E₁ derived from DHLA was observed in the supernatants of stimulated aorta.     

Effect of fish oil on cancer cachexia and host liver metabolism in rats with prostate tumors

The aim of this study was to investigate whether tumor-induced cachexia and aberrations in host liver metabolism, induced by the MAT-LyLu variant of the Dunning prostate tumor, could be prevented by ω3 fatty acids from fish oil. On day 0, adult Copenhagen-Fisher rats fed normal chowad libitum were inoculated with 10⁶ MAT-LyLu cells (n=14) or saline (n=9). On day 7, when tumors were palpable, four tumor-bearing (TB) and four nontumorbearing (NTB) rats were put on isocaloric diets with 50% of total energy as fish oil. The introduction of fish oil-enriched diets caused a reduction in energy intake to less than half of the energy intake by animals fed normal diets during days 7–14 (difference by dietary group: NTB,P<0.001; TB,P<0.001). During days 14–21, energy intake in fish oil-fed animals returned to approximately 75% of energy intake by animals fed normal diets (difference by dietary group: NTB,P<0.003; TB,P=0.001). Carcass weight of animals on day 21, when the study was terminated, was significantly related to initial weight (P=0.05) and mean food intake during the study (P=0.01). When data were adjusted for these variables using analysis of covariance, with NTB animals on normal diets being the reference group, significant loss of carcass weight was observed in TB animals on normal diets only (mean ±SEM 58±10 g loss,P<0.001), but not in TB animals on fish oil diets (8±18 g loss,P=0.67). This positive effect of fish oil diets on carcass weight in TB animals was statistically significant (50±19 g,P<0.02), implicating that the fish oil enriched diet inhibited tumor-induced weight loss by more than 85%. No effect of fish oil diets on tumor growth was detected. In all TB animals, regardless of diet, hepatic [P_i]/adenosine triphosphate] ratios measured by³¹P magnetic resonance spectroscopy (MRS)in vivo andin vitro were elevated, and absolute concentrations of phosphocholine, glycerophosphocho-line, glycerophosphoethanolamine and glucose-6-phosphate as determined by³¹P MRSin vitro were reduced. Ultrastructural studies of liver tissue revealed increased numbers of mitochondria and increased amounts of endoplasmic reticulum in the host liver of TB animals, without differences between dietary group. In conclusion, fish oil supplementation partially inhibited MAT-LyLu tumor-induced cachexia, but did not prevent the majority of³¹P MRS-detectable alterations in host liver metabolism.     

Refeeding varying fatty acid and cholesterol diets alters phospholipids in rat intestinal brush border membrane

Refeeding a diet initially given shortly after weaning results in a different adaptive change in the in vitro intestinal uptake of sugars and lipids than if the diet is given for the first time at a later age. This study was undertaken in rats to test the hypothesis that changes in nutrient uptake associated with refeeding diets containing beef tallow (S), beef tallow plus 1% cholesterol (Sc), fish oil (F), or fish oil plus cholesterol (Fc) are associated with changes in the brush border membrane (BBM) phospholipids and phospholipid fatty acids. Weanling Sprague-Dawley rats were fed ad libitum one of the four diets. At 35 d of age (about 2 wk after weaning), the rats were maintained on either the same diet used at weaning, or were switched to one of the other semisynthetic diets which were then fed for a further 7 wk. At week nine (2+7) the rats were either continued on the same diet or were switched back to the original diet for 2 wk (2+7+2). The groups of animals which were compared included SSSc vs. ScSSc; ScScS vs. SScS; FFFc vs. FcFFc; and FcFcF vs. FFcF. Refeeding S, Sc, F, or Fc had no effect on food consumption or on body weight gain. Refeeding Fc resulted in increased ileal BBM total phospholipids, whereas rechallenge with F resulted in a decline in the jejunal BBM ratio of phospholipid/cholesterol. Refeeding Sc resulted in a decrease in the ileal BBM phosphatidylcholine (PC). In rats rechallenged with Fc, there was increased ileal BBM sphingomyelin (SM), increased ileal BBM phosphatidylethanolamine (PE), decreased ileal BBM PC/PE, and an increased ileal BBM SM/PC. Refeeding had no effect on the fatty acyl constituents of the jejunal or ileal BBM PC or PE. These results suggest that there are late effects of the early introduction of dietary cholesterol on intestinal BBM phospholipid content and composition that may contribute to the previously reported changes in intestinal nutrient absorption.     

Effect of dietarytrans fatty acids on some membrane-associated enzymes and receptors in rat heart

Three groups of male weanling Sprague-Dawley rats were fed diets containing 20% corn oil, 20% partially hydrogenated soybean oil (PHSBO) or 18% PHSBO +2% corn oil. PHSBO contained about 48% of its total fatty acids astrans-octadecenoate. Rats were killed after 16–18 weeks of feeding the various diets, hearts were dissected and crude sarcolemma was prepared by differential centrifugation. The activities of ouabain-sensitive (Na⁺+K⁺)ATPase were significantly lower in membranes of rats fed 20% PHSBO than the control rats fed 20% corn oil. The feeding of 2% corn oil with 18% PHSBO resulted in partial restoration of the enzyme activity. The maximum number of [³H]ouabain-binding sites (B_max) was also lower in cardiac membranes of rats fed 20% PHSBO than those fed 20% corn oil. Similar to (Na⁺+K⁺)ATPase activity, some restoration of the number of [³H]ouabain-binding sites was observed when 2% corn oil was fed with 18% PHSBO-containing diet. There was no difference in the binding affinity of the radioligand for the receptor among the 3 dietary groups. Adenylate cyclase activities (fluoride-, isoproterenol- and forskolinstimulated) were lower in membranes of rats fed 20% PHSBO or 18% PHSBO +2% corn oil than in the control group fed 20% corn oil. Density of the β-adrenergic receptor was the lowest in cardiac membranes of rats fed 20% PHSBO. The feeding of 2% corn oil with 18% PHSBO resulted in partial restoration of the maximum number of [³H]dihydroalprenolol (DHA)-binding sites. The affinity of the binding sites was, however, not affected by the type of the dietary fat. The results of this study suggest that dietarytrans fatty acids can affect the activities of (Na⁺+K⁺)ATPase and adenylate cyclase and the density of digitalis and β-adrenergic receptors in rat heart.     

Dietary flax oil reduces renal injury,oxidized LDL content,and tissue n-6/n-3 FA ratio in experimental polycystic kidney disease

As whole flaxseed is beneficial in the treatment of experimental renal disease, we undertook a study to determine whether previously documented benefits of whole flaxseed could be reproduced with dietary low-lignan flax oil (FO), a rich source of α-linolenic acid, in experimental polycystic kidney disease. Male offspring of Han:SPRD-cy heterozygous rats were fed a synthetic diet containing FO or corn oil (CO) for 8 wk from the time of weaning. Renal inflammation, fibrosis, proliferation, cystic change, and oxidized-LDL were assessed morphometrically. Hepatic and renal lipid composition was assessed using GC. FO feeding produced hepatic and renal enrichment of n−3 PUFA and an increase in C18∶>C18 PUFA ratios (18-carbon PUFA compared to longer-chain PUFA), with a reduction in proportion of hepatic long-chain PUFA. The FO-based diet was associated with lower mean cystic change by 29.7% (P=0.018), fibrosis by 21.7% (P=0.017), macrophage infiltration by 31.5% (P< 0.0001), epithelial proliferation by 18.7% (P=0.0035), and ox-LDL detection by 31.4% (P<0.0001) in Han:SPRD-cy heterozygotes. Serum creatinine was significantly lower in FO-fed diseased animals. A small hypocholesterolemic effect was noted in all animals fed FO. FO feeding moderates renal injury, modifies the profile of substrates available for elongation to eicosanoid precursors, and inhibits the elongation of C₁₈ PUFA in this model. The consumption of FO-based products may prove a more practical way of obtaining health benefit than attempts to increase dietary content of unrefined seed.     

Resource Availability and Quality Influence Patterns of Diet Mixing by Sheep

In grazing systems, forage availability is a function of herbivore density, which can influence an animal's ability to be selective. In turn, the influence of food availability on selectivity has the potential to influence plant biodiversity. We hypothesized that the ability of herbivores to mix toxin-containing foods in their diets is a function of the availability of nontoxic foods and the nutritional characteristics of the toxin-containing foods. We evaluated this hypothesis in two trials simulating different diet qualities (high-quality foods in trial 1, low-quality foods in trial 2). Within each trial, the four treatment groups were offered with different amounts of nutritious, familiar foods—10, 30, 50, and 70% of ad libitum intake—but were offered with ad libitum access to toxin-containing foods. Each lamb was presented with five foods, including three toxin-containing unfamiliar foods (terpenes, tannins, and oxalates) and two nutritious familiar foods (alfalfa and barley). In trial 1, as the availability of nutritious familiar foods decreased, animals ate more of all three toxin-containing foods. As the availability of nutritious alternatives increased, the pattern of selection shifted from terpenes to tannins and oxalates. In trial 2, animals also ate more toxins as the availability of nutritious alternatives decreased, but their pattern of diet mixing changed. Low availability of nutritious alternatives resulted in the animals eating more oxalates. During preference tests when all five foods were offered ad libitum, animals fed with 10, 30, 50, and 70% of ad libitum intake from trial 1 ate 49, 47, 41, and 38% of the three toxin-containing foods, respectively. The lower diet quality in trial 2 affected intake of the toxin-containing foods such that animals fed with 10, 30, 50, and 70% of ad libitum intake ate 37, 36, 29, and 27%, respectively, of the three toxin-containing foods. Thus, the quality of toxin-containing foods and the availability of nutritious alternatives interacted to modify the pattern of diet mixing by lambs.