Search

The present study was designed to examine the effects of increasing dietary levels of vaccenic acid (VA) and cis-9, trans-11 conjugated linoleic acid (CLA) on chemically induced mammary carcinogenesis in rats. Both fatty acids were provided as a natural component in butter fat. The conversion of VA to CLA by delta9-desaturase was documented previously in several species, including rats and humans. Specifically, our objective was to determine the relative contribution of dietary VA and CLA to the tissue concentration of CLA and its ability to inhibit the development of mammary carcinomas. A total of 7 diets were formulated with varying levels of CLA and VA. The overall dietary treatment scheme was designed to evaluate the modulation of mammary cancer risk by 1). small increases of CLA in the presence of a low level of VA and 2). more substantial increases of VA against a background of low levels of CLA. As expected, small increases in dietary CLA at the low end of the CLA dose-response range did not reduce tumorigenesis. In contrast, there was a distinct and marked inhibitory response to VA that was dose dependent. The effect of VA was magnified in this experiment because the dose range of VA tested was much broader than that of CLA. Fatty acid analysis showed that the conversion of dietary VA to CLA resulted in a dose-dependent increase in the accumulation of CLA in the mammary fat pad, which was accompanied by a parallel decrease in tumor formation in the mammary gland. The finding confirms that the conversion of VA to CLA is as important for cancer prevention as the dietary supply of CLA. Thus, VA is also anticarcinogenic, and VA and CLA represent functional food components that are present in ruminant fat.

Conjugated linoleic acid (CLA) is a term used to describe the different conjugated isomers of linoleic acid. CLA has been found to be anticarcinogenic in mammary cancer, but its effects on colon carcinogenesis are still inconclusive. In this study, the isomer-specific effects of the cis-9, trans-11 and trans-10, cis-12 CLA isomers were investigated in the Min mouse model for intestinal carcinogenesis. The Min mice (n = 10/group) were fed either an AIN-93G control diet or a diet containing 1 g/100 g cis-9, trans-11 or trans-10, cis-12 CLA for 8 wk. The number and size of adenomas were measured and the proteins from the small intestinal tissues extracted for immunoblotting analysis. The number of adenomas did not differ, but the size of the adenomas was greater in the distal part of the small intestine in mice fed the trans-10, cis-12 isomer than in controls (1.19 +/- 0.16 vs. 0.94 +/- 0.21 mm, mean +/- SD, P < 0.01). The same isomer caused an increase in lipid peroxidation, measured as urinary 8-iso-prostaglandin (PG)F(2alpha). Nuclear p65 protein of the mucosal tissue was not detectable in the trans-10, cis-12 group, which differed (P < 0.05) from the control group. Cyclin D1, a target for the nuclear factor (NF)-kappaB pathway, was elevated in the trans-10, cis-12 group compared with the control group (P < 0.01), but cyclooxygenase-2 levels were not higher. There was no difference in beta-catenin protein levels between the groups. The results indicate that the trans-10, cis-12 isomer of CLA can act as a cancer promoter in colon carcinogenesis possibly through pathways affecting NF-kappaB and cyclin D1.

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in beef and dairy products. However, when 1 g CLA/100 g diet was given to mice in a low fat diet (4 g fat/100 g diet), they showed a marked decrease in fat mass, but demonstrated symptoms of lipoatrophic diabetes, i.e., marked hepatomegaly and insulin resistance. In this study, to determine whether the decrease in adipose tissue was responsible for these adverse effects, mice were fed different doses of CLA and dietary fat. In Experiment 1, mice were fed different doses of CLA (0, 0.1 and 1 g CLA/100 g diet) in a fixed 4 g fat/100 g diet; in those fed 0.1 g CLA, subcutaneous white adipose tissue (WAT) weight was 48% lower than in mice fed 0 g CLA. The mice fed 0.1 g CLA did not exhibit hepatomegaly and insulin resistance. In Experiment 2, mice were fed for 5 mo different amounts of dietary fat (4, 13 and 34 g fat/100 g diet) in 0 or 1 g CLA/100 g diet; in mice fed 1 g CLA with 34 g fat, retroperitoneal and subcutaneous WAT weights were 76 and 79% lower, respectively, than those of mice fed 0 g CLA with 34 g fat. Mice fed 1 g CLA in the diet with 34 g fat had normal plasma insulin concentrations and a 45% greater liver weight. These data suggested that the percentage of CLA in dietary fat might be a determinant of CLA-mediated lipodystrophy.

Studies suggest that heated oils contribute to the presence of oxidized components in the circulating lipoproteins and to the development of atherosclerosis in animals. We evaluated the effects of 11-13 wk of consumption of a well defined dietary oxidized fatty acid, 13-hydroxylinoleic acid (13-HODE) (8 mg), on atherosclerotic lesion development and plasma cholesterol concentrations in mice fed diets varying in fat and cholesterol contents. LDL receptor knockout mice were used in two feeding studies. In study 1, oxidized fatty acid consumption in association with a high fat diet increased aortic lesion areas by >100% (P < 0.05). Surprisingly, oxidized fatty acid intake also tended to increase plasma total cholesterol (P = 0.12) and LDL cholesterol (P < 0.05) as well as oxidative stress as measured by higher levels of autoantibodies to oxidatively modified proteins (P = 0.008). However, in mice fed a nonpurified diet, oxidized fatty acids were not atherogenic and may even have been beneficial, as indicated by a lower plasma triglyceride (TG) concentration (P < 0.05). In study 2, mice were fed either a high fat, medium fat or low fat diet to evaluate whether the increase in aortic lesions due to oxidized fatty acid consumption in study 1 was a result of the associated higher plasma total and LDL cholesterol concentrations. In study 2, 13-HODE-treated mice in the medium and low fat diet groups but not those fed the high fat diet had larger atherosclerotic lesions (P < 0.05). Additionally, plasma total and LDL cholesterol as well as TG were not affected by HODE treatment. However, the total cholesterol:HDL cholesterol ratio was higher in treated mice (P < 0.05) and HDL cholesterol was lower in HODE-treated mice that were fed the low fat diet (P < 0.05). Our results suggest that, in mice fed cholesterol, oxidized fatty acids may be atherogenic, both in terms of increased oxidative stress (as seen in study 1) and by increasing the atherogenicity of the plasma cholesterol profile.

A study was conducted to examine the effects of dietary conjugated linoleic acids (CLA; 0, 0.5 or 1.0 g/100 g total CLA) and lipid source (menhaden oil, soybean oil or a 1:1 mixture of menhaden:soybean oil) on growth rates and fatty acid composition of yellow perch. Dietary treatments were fed to apparent satiation to triplicate groups of fish initially weighing 37.9 g/fish. At the end of the 9-wk feeding trial, no significant differences were detected in weight gain or feed intake among fish fed any of the dietary treatments. Dietary CLA, lipid source and/or their interaction significantly affected feed efficiency, total liver lipid concentration, and muscle and liver fatty acid concentrations. Feed efficiency (g gain/g feed) was significantly lower in fish fed diets containing soybean oil (0.51) compared with fish fed menhaden oil (0.58) or menhaden:soybean oil (0.60). Liver total lipid concentrations were significantly reduced in fish fed 0.5 and 1.0 g/100 g CLA compared with fish fed the diets containing no CLA and in fish fed menhaden oil compared with those fed soybean oil or a 1:1 mixture of menhaden:soybean oil. Total CLA levels increased in both liver and muscle as dietary CLA concentration increased, irrespective of lipid source. However, total CLA concentrations were significantly lower in liver and muscle of fish fed soybean oil. Total muscle CLA concentrations were 0, 1.26 and 2.92 g/100 g fatty acids in fish fed diets containing menhaden oil and 0, 0.5 and 1.0 g/100 g CLA, respectively. Mono- and polyunsaturated fatty acid (PUFA) concentrations were significantly lower in muscle and liver of fish fed CLA compared with fish fed the diets containing no CLA. In contrast, liver concentrations of saturated fatty acids, 14:0, 16:0 and 18:0, were significantly higher in fish fed 1.0 g/100 g CLA.

Conjugated linoleic acids (CLA) have been shown to affect fatty acid synthesis in various tissues. The objective of the study was to compare the effect of a commercial source of CLA with a linoleic acid-enriched oil (LA), supplied to 12 multiparous sows during gestation and lactation, on adipose tissue and milk fatty acid composition. The CLA isomers detected in the CLA oil were (in order of magnitude) c9,t11; t10,c12; c9,c11; t9,t11/t10,t12 and c10,c12 and amounted to 58.9 g/100 g fat. Biopsies were taken from the backfat on d 7 and 97 of gestation and milk samples were collected on d 2, 9, 16 and 23 after farrowing. Collection of colostrum and mature milk samples took place at 1100 h for sows who farrowed in the morning or at 1500 h for those who farrowed in the afternoon. All major CLA isomers in the supplement were transferred to the tissue and milk fat and, compared with the LA group, significantly increased saturated fatty acid and decreased monounsaturated fatty acid levels in the tissue and milk. These findings suggest a distinct involvement of CLA in the de novo fatty acid synthesis and desaturation process in the adipose tissue and mammary gland. Estimated transfer efficiency of dietary CLA isomers was 41-52% for the backfat and 55-69% for the mature milk. The incorporation and uptake efficiency seemed to be selective with the highest values found for c9,t11-CLA. Overall, dietary CLA supplementation of sows during gestation and lactation markedly altered backfat and milk fatty acid composition.

Effects of conjugated linoleic acids (CLA) on a series of metabolic events are expected to depend on the feeding regimen and levels of energy ingested. This study was the first examining the mode of action of CLA on body composition, tissue lipids, lipoproteins and hepatic enzymes in situations of enhanced fat store mobilization. Two groups of male growing Sprague-Dawley rats were fed for 3 wk a diet containing 0 (control group) or 3 g/100 g of a CLA mixture at the expense of sunflower oil, and were then subjected to a weight-loss feeding regimen for another 18 d. Rats fed the CLA-fortified diet gained 11% less weight than the control rats (P<0.05). Rats fed the high CLA diet had less body fat (1.47+/-0.16 vs. 1.07+/-0.09 g/100g, P<0.05) and a higher lean deposition (25.6+/-0.2 vs. 28.4+/-0.3 g/100 g, P<0.05) than control rats. CLA-fed rats had a 41% lower cholesterol concentration in liver than the control rats (P<0.05). Some differences in glycerophospholipid subclass profile of liver and erythrocyte membrane were observed; the hepatic concentrations of phosphatidylethanolamine (4.76+/-0.46 vs. 6.86+/-0.99 micromol/g, P = 0.07) and phosphatidylcholine (12.9+/-0.5 vs. 15.3+/-1.2 micromol/g, P = 0.09) tended to be greater and the level of phosphatidylcholine in erythrocyte membranes was significantly greater (1.40+/-0.12 vs. 1.83 +/-0.16 micromol/g, P<0.05) in the CLA-treated group than in the control group. The activities of catalase and ornithine decarboxylase in liver did not differ between the groups. Further, CLA-treated rats had significantly lower serum concentrations of VLDL lipids than control rats, whereas concentrations of LDL and HDL lipids were unaffected. The results indicate that a high dose of a CLA mixture is a strong repartitioning agent and a modulator of lipid metabolism under conditions of enhanced fat store mobilization in rats.

We report the effect of an atherogenic diet supplemented with cis-9, trans-11-octadecadienoic acid (c9t11), linoleic acid (LA) or an isomeric mixture of conjugated linoleic acids (CLA) on plasma lipids, weight gain and food intake of male Golden Syrian hamsters. Animals were assigned to three diet groups (n = 10), and fed nonpurified diet, supplemented with 10% hydrogenated coconut oil and 0.05% cholesterol for 6 wk. The first diet group was further supplemented with 1% CLA (CLA group), the second diet group with 0.2% c9t11 (c9t11 group) and the third group with 0.2% LA (LA group). The diets were designed to have equivalent levels of c9t11 in the CLA and c9t11 groups. At 2 and 6 wk of feeding, the CLA group had significantly lower plasma triglyceride and total cholesterol concentrations than either the c9t11 or the LA groups. HDL-cholesterol did not differ among diet groups. The CLA group had significantly lower weight gain but greater food intake than either the c9t11 or the LA groups. There were no significant differences between the c9t11 and the LA groups in any of the variables measured. We conclude that under our experimental conditions of short-term feeding, c9t11, thought to be the active compound in CLA, does not produce the same effect as the isomer mixture.

This study examined the effects of diets deficient (D) in linoleic [18:2(n-6)] and linolenic acid [18:3(n-3)] at 0.8 and 0.05% energy, respectively, or adequate (C) in 18:2(n-6) and 18:3(n-3) at 8.3 and 0.8% energy, respectively, without (-) or with (+) 0.2% energy arachidonic [20:4(n-6)] and 0.16% energy docosahexaenoic [22:6(n-3)] acid in piglets fed from birth to 18 d. Frontal cortex dopaminergic and serotoninergic neurotransmitters and phospholipid fatty acids were measured. Piglets fed the D- diet had significantly lower frontal cortex dopamine, 3,4-dihydroxyphenylacetic (DOPAC), homovanillic acid (HVA), serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations than did piglets fed the C- diets. Frontal cortex dopamine, norepinephrine, DOPAC, HVA, serotonin and 5-HIAA were higher in piglets fed the D+ compared to those fed the D- diet (P < 0.05) and not different between piglets fed the D+ and those fed the C- diets or the C- and C+ diets. Piglets fed the D- diet had lower frontal cortex phosphatidylcholine (PC) and phosphatidylinositol (PI) 20:4(n-6) and PC and phosphatidylethanolamine (PE) 22:6(n-3) than did piglets fed the C- diet (P < 0.05). Piglets fed the D+ diet had higher frontal cortex PC and PI 20:4(n-6) and PC, PE, PS and PI 22:6(n-3) than did piglets fed the D- diet. These studies show that dietary essential fatty acid deficiency fed for 18 d from birth affects frontal cortex neurotransmitters in rapidly growing piglets and that these changes are specifically due to 20:4(n-6) and/or 22:6(n-3).

Conjugated linoleic acids (CLA) decrease the body fat content of rodents; the aim of this study was to determine whether dietary CLA altered carcass composition of pigs. Female Large White x Landrace pigs (n = 66) were used in this study. To obtain initial body composition, six pigs were slaughtered at 57 kg live weight, whereas the remaining pigs were allocated to one of six dietary treatments (0, 1.25, 2.5, 5.0, 7.5 and 10.0 g/kg CLA, containing 55% of CLA isomers). The diets, containing 14.3 MJ digestible energy (DE) and 9. 3 g available lysine per kg, were fed ad libitum for 8 wk. Dietary CLA had no significant effect on average daily gain (861 vs. 911 g/d for pigs fed diets with and without CLA, P = 0.15) or feed intake (2. 83 vs. 2.80 kg/d, P = 0.74). The gain to feed ratio was increased by dietary CLA by 6.3% (0.328 vs. 0.348, P = 0.009). Fat deposition decreased linearly (-8.2 +/- 2.09 g/d for each gram per kilogram increase in CLA concentration; P < 0.001) with increasing inclusion of CLA. At the highest level of CLA inclusion, fat deposition was decreased by 88 g/d (-31%). Similarly, the ratio of fat to lean tissue deposition decreased linearly (-0.093 +/- 0.0216 for each gram per kilogram increase in CLA concentration; P < 0.001) with increasing dietary CLA. The carcass lean tissue deposition response to dietary CLA was quadratic in nature and was maximized (+25%) at 5. 0 g/kg dietary CLA. Overall, dietary CLA increased the gain to feed ratio and lean tissue deposition and decreased fat deposition in finisher pigs.

Conjugated linoleic acids (CLA) have positive health effects in experimental models. Our objective was to determine the effect of CLA supplementation on milk of dairy cows. A commercial source of CLA was infused abomasally to by-pass rumen fermentation. The supplement contained 61.2% CLA; the major CLA isomers were cis/trans 8,10, cis/trans 9,11, cis/trans 10,12 and cis/trans 11,13. Four Holstein cows were used in a 4 x 4 Latin square design. Treatments were 5-d infusions of 0, 50, 100 and 150 g/d of CLA supplement. Infusion increased milk fat content of CLA from 6.8 mg/g fat (zero dose) to 63.6 mg/g fat (highest dose). All of the major CLA isomers in the supplement were transferred to milk fat in a dose-dependent manner. Apparent efficiency of transfer to milk fat was 22.5, 22.5, 10.2 and 26.3% for cis/trans 8,10, cis/trans 9,11, cis/trans 10,12 and cis/trans 11,13, respectively. CLA infusion had no effect on milk protein and little effect on milk yield (21.5, 20.4, 20.9 and 18.3 kg/d for 0, 50, 100 and 150 g/d CLA supplement, respectively). However, CLA infusion dramatically reduced milk fat. On average, the content and yield of milk fat were reduced by 52 and 55%, respectively. The role of specific CLA isomers and mechanism(s) for the reduction in milk fat have not been established, although the pattern of milk fatty acids demonstrated effects were most pronounced on de novo fatty acid synthesis and the desaturation process. Overall, dietary supplemention of CLA increased milk fat content of CLA, altered milk fatty acid composition and markedly reduced the content and yield of milk fat.

Conjugated linoleic acid (CLA) is a potent anticarcinogen secreted in milk of ruminants, but it inhibits de novo fatty acid synthesis and desaturation in mammary cell cultures. The potential for increasing CLA content of milk fat and the effects of elevated CLA availability on milk fat secretion were investigated. Four Holstein cows were used in a single crossover design with repeated measures to determine milk fatty acid concentration in response to a 24-h infusion of 200 g linoleic acid (LA) or a mixture of 100 g LA plus 100 g CLA (LCLA). Milk and blood samples were obtained 12 h before infusion and at 12-h intervals from 0 to 72 h. Compared with LA infusion, total CLA concentration in blood plasma at 24 h in response to LCLA was elevated fivefold, whereas CLA content of plasma triglycerides was increased 10-fold. Milk fat yield from 24 to 72 h was approximately 34% lower in response to LCLA compared with LA, due primarily to reduced yield of fatty acids with six to 16 carbons. Amount of CLA in milk increased from 0.5 g/100 g total fatty acids at 0 h to 3.3 g/100 g at 36 h in response to LCLA. Concentration of stearic acid in milk fat at 36 h in response to LCLA was nearly double the stearic acid concentration in response to LA. Oleic and arachidonic acid concentrations in milk declined as stearic acid increased in response to LCLA. Results indicated CLA content of milk fat reflects the amount available for absorption from the small intestine, and CLA appeared to be a potent inhibitor of de novo fatty acid synthesis and desaturation in the mammary gland.

Increasing dietary fat content increases mammary gland tumorigenesis in laboratory rodents. The effect can be attributed only in part to increasing energy intake, which itself increases tumorigenesis. Restriction of dietary or energy intake, sufficient to reduce body weight, reduces mammary gland tumorigenesis. Consideration of these effects has led to discussion of the possible need for changes in the feeding of laboratory rodents in carcinogenesis bioassays and other chronic studies. Studies of endocrine or other growth factors for the mammary gland have not identified specific effects of dietary fat or energy. In addition, tumorigenesis in other organs responds similarly to increased fat or decreased energy intake, indicating that the mechanisms are not, or not entirely, specific for the mammary gland. Extrapolations of results between species must always be made with caution, but the marked effects of dietary fat and energy in rodent tumorigenesis models must be considered in designing diet advice for humans.

To study the effect of maternal linoleic acid [18:2(n-6), LA] supplementation during pregnancy on neonatal essential fatty acid status, pregnant women with relatively low plasma linoleic acid concentrations before 16 wk of gestation (n = 21) were supplied with foods rich in linoleic acid, resulting in an additional intake of 10 g/d of linoleic acid from the 20th week of gestation until delivery. One of the two control groups consisted of pregnant women with comparably low plasma linoleic acid concentrations at the start of the study (LL-control group, n = 22); the other consisted of women with habitually high plasma linoleic acid concentrations (HL-control group, n = 21). The neonatal essential fatty acid status was assessed by determining the fatty acid composition of phospholipids (PL) isolated from umbilical plasma and umbilical vessel walls. The maternal linoleic acid status in the LA-supplemented group increased to a level comparable to that of the HL-control group, but the neonatal linoleic acid status did not differ from that of either control group. Linoleic acid supplementation did result in slightly, but significantly, higher total amounts of (n-6) long-chain polyenes in umbilical plasma and vein vessel wall phospholipids compared with the LL-control group. This increase was associated with significantly lower total amounts of (n-3) long-chain polyenes. In the HL-control group, the concentration of (n-3) long-chain polyenes in umbilical plasma and vessel walls was significantly lower than in the LA-supplemented and the LL-control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Mice were fed for 2 mo diets having ratios of alpha-linolenate [18:3 (n-3)] to linoleate [18:2(n-6)] of < 0.01, 0.36, 1.0 and 3.9. Proportions of safflower seed oil and perilla seed oil were adjusted to obtain these ratios. The dietary alpha-linolenate to linoleate balance was reflected in the proportion of (n-3) and (n-6) highly unsaturated fatty acids with 20- and 22-carbon chains in spleen phospholipids, but the ratio did not affect the proportion of T lymphocyte subsets expressing CD4 and CD8 antigens in splenic leukocytes. The immunoglobulin (Ig) G and IgM responses against sheep red blood cells when estimated as plaque-forming cells present in spleen, were not affected significantly by the diets. However, the serum hemagglutinin titer was slightly but significantly higher in the high alpha-linolenate diet group [18:3(n-3)/18:2(n-6) = 3.9] than in the dietary group with 18:3(n-3) to 18:2(n-6) ratios of 0.36 and < 0.01. In contrast, the IgE antibody response against egg albumin, as well as the mortality from anaphylactic shock induced by a second challenge with antigen, was significantly lower in the high alpha-linolenate diet group [18:3(n-3)/18:2(n-6) = 3.9] than in the high linoleate diet [18:3(n-3)/18:2(n-6) < 0.01] group. These results, together with the reported suppressive effects of a high alpha-linolenate diet on the formation of lipid-derived allergic mediators, support the hypothesis that raising the (n-3) to (n-6) ratios of diets would be effective in reducing the severity of immediate-type allergic hypersensitivity.

We investigated the effects of various levels of dietary 18:2(n-6) (linoleic acid) and 18: 3(n-3) (alpha-linolenic acid) on the growth, feeding, body composition and metabolism of polyunsaturated fatty acids in liver and muscle of Arctic charr. Fish were fed 8 or 12 casein-based semipurified diets in two separate experiments for 12 or 14 wk, respectively. Low levels of dietary 18:2(n-6) and 18:3(n-3) supplemented with pure methyl esters or linseed (flax) oil had an additive effect on fish growth. For each 100 g of diet, the addition of 1.6-1.7 g of 18:3(n-3) and 2.6 g of 18:2(n-6) led to significantly lower fish growth compared with the treatment diets with lower amounts of 18:2(n-6). Whereas 18:2(n-6) was converted to 20:4(n-6) and 22: 5(n-6) in the absence or presence of dietary 18: 3(n-3), the dominant product of 18:3(n-3) conversion was consistently 22:6(n-3). High levels of dietary 18: 3(n-3) markedly inhibited the conversion of 18:2(n-6), whereas the inhibition of dietary 18:2(n-6) on 18: 3(n-3) conversion was noted only when the ratio of dietary 18:2(n-6) to 18:3(n-3) changed from 1.0 to 1.5. Feeding diets rich in 18:3(n-3) led to a marked accumulation of 18:3(n-3) and 18:4(n-3) in fish muscle but a negligible change in 20:5(n-3) and 22:6(n-3), regardless of the level of 18:3(n-3) in the diets.

Conjugated linoleic acid (CLA) is an anticarcinogen in several model animal systems. Conjugated linoleic acid occurs naturally in food and is present at higher concentrations in products from ruminant animals. Given that certain rumen microorganisms produce CLA from free linoleic acid, we studied the effect of feeding free or esterified linoleic acid on tissue CLA concentrations using conventional and germ-free rats. Conventional rats were fed a 5% (wt/wt) corn oil control diet alone or supplemented with 5% free linoleic acid or 8.63% corn oil (equivalent to 5% linoleic acid in triglyceride). Germ-free rats were fed autoclavable nonpurified diet alone or supplemented with 5% free linoleic acid. Analyses of CLA concentrations were performed on lipids extracted from liver, lung, kidney, skeletal muscle and abdominal adipose tissue, and on liver phospholipid and neutral lipid fractions. Tissue CLA concentrations were higher in conventional rats fed free linoleic acid (the major isomers were cis-9, trans-11 and trans-9, cis-11) than in control animals. Conjugated linoleic acid concentrations in free linoleic acid-fed rats were maximal at 4 wk, and levels were 5-10 times higher than those of controls. Elevated CLA concentrations were also observed in liver phospholipid and neutral lipid fractions. In contrast, CLA concentrations in the tissues of germ-free rats were not affected by diet. Feeding the corn oil-fortified diet to conventional rats did not increase CLA concentration in the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Peritoneal cells (PEC) and splenocytes were obtained from Listeria monocytogene (LM)-infected or noninfected mice fed a 20% fat diet rich in either (n-3) polyunsaturated fatty acids [(n-3) PUFA diet], linoleate [(n-6) PUFA diet], oleate (MONO diet), or saturated fatty acids (SAT diet) for 6 wk and were assessed for T cells, B cells, macrophages and Ia expression by flow cytometric analysis. In the peritoneum of noninfected mice, dietary fat did not affect total cell yield or the percentage of B cells, macrophages or Ia+ cells, but the (n-3) PUFA-fed group had a greater percentage of T cells than did the other groups. Among the LM-infected mice, the (n-3) PUFA-fed group generally had the highest percentage of B cells and the lowest percentages of T cells, macrophages and Ia+ cells in the peritoneum. Listeria monocytogene infection elevated peritoneal T cell numbers in all mice except the (n-3) PUFA-fed group. The density of Ia molecules on PEC was 40% lower in mice fed the (n-3) PUFA diet. In the spleen, dietary fat also influenced the immune cell populations and Ia+ cells. Two-color staining of spleen cells revealed that Ia+ splenocytes were predominately B cells. These data demonstrate that dietary fats influence Ia expression and immune cell populations and that the effects observed in one immune tissue or cell type may not be readily extrapolated to others.

For 16 wk Atlantic salmon (Salmo salar) post-smolts were fed practical-type diets that contained either fish oil (FO) or sunflower oil (SO) as the lipid component. Both diets contained adequate (n-3) polyunsaturated fatty acids (PUFA). All the phospholipids of heart and liver from SO-fed fish had increased levels of 18:2(n-6), 20:2(n-6) and 20:3(n-6); phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) also had increased 20:4(n-6). There was a general decrease in 20:5(n-3) in the phospholipids, reflected in an increase in the 20:4(n-6)/20:5(n-3) ratio, especially in PC and PE. The fatty acid compositions of phospholipids from brain and retina were much less affected by dietary linoleate than those of heart and liver. Fish fed SO developed severe heart lesions that caused thinning of the ventricular wall and muscle necrosis. The fish fed SO also were susceptible to a transportation-induced shock syndrome that caused 30% mortality. These results establish that a diet with a low (n-3)/(n-6) ratio can cause changes in fatty acid metabolism that are deleterious to the health of salmonid fish, especially when subjected to stress.

The present work tests the hypothesis that high fat/low carbohydrate diets elevate the level of liver microsomal cytochrome P450IIE1. Male Sprague-Dawley rats were fed liquid diets containing varied ratios of corn oil/carbohydrate for 4 d. Rats fed diets with higher fat/carbohydrate ratios produced higher serum acetone levels and higher hepatic microsomal P450IIE1 content and N-nitrosodimethylamine demethylase activity than those fed diets with lower fat/carbohydrate ratios. This dietary fat/carbohydrate effect on P450IIE1 also was observed with modified semipurified AIN-76A diets. In addition, both the quantity and the extent of unsaturation of dietary lipids affected P450IIE1 regulation. At moderate fat levels (5 and 20% diet), rats fed corn oil and menhaden oil diets produced higher P450IIE1 activity than those fed lard and olive oil diets. Rats fed a diet containing 20% corn oil or an amount of linoleic acid equivalent to the 20% corn oil diet showed twofold to threefold increases in the level of P450IIE1 over those fed a fat-free diet. Rats fed a 25% corn oil diet showed twofold higher enflurane metabolism in vivo than those fed a 0.5% corn oil diet. The present results suggest that the constitutive P450 enzyme level is regulated by dietary fat/carbohydrate ratios.

Mice of the C57Bl/6J strain were maintained on diets in which the unsaturated fatty acids were all cis fatty acids (CFA) or a mixture of CFA and trans fatty acids (TFA). The fats used were mixtures of corn oil, olive oil, cocoa butter, margarine and shortening blended to yield similar fatty acid compositions, except for the ratio of the CFA to TFA and the percentage of linoleic acid (EFA). Regardless of the level of fat (20 or 40 energy %) or the level of EFA (2 to 12 energy %), diets with TFA decreased the percentage of fat in mouse milk. When lactating females raised on the CFA diets were crossed to the TFA diets, TFA appeared in the milk at 12 h postcross, and within 4 d postcross the percent of milk fat was decreased to levels similar to that of nursing females raised continuously on the TFA diets. Conversely, lactating females crossed from TFA to CFA diets produced milk with percentage fat values and fatty acid compositions that approached those seen in nursing females fed the CFA diets continuously. The possible involvement of TFA in the classical milk fat depression phenomenon in ruminants and its potential relevance in human lactation are discussed.

Evidence that biosynthesis of prostaglandins (PG) in tissues of animals deficient in essential fatty acids is dependent on the availability of their precursors has been demonstrated. The purpose of this study was to determine the following: (1) effects of dietary linoleate enrichment on PG biosynthesis in rats; (2) effects of exogenous PGE2 and dietary linoleate on plasma free fatty acids and serum cholesterol in fed and fasted rats. Rats were fed three different concentrations of dietary linoleate as beef tallow, hydrogenated vegetable fat, or corn oil. The concentrations of PGE1 and PGF2a measured by radioimmunoassay were higher in rats fed the fed the beef tallow diet independent of energy status. A decrease in the concentration of PG between fasted and fed rats receiving hydrogenated vegetable fat is discussed in respect to the possible influence of trans isomers of unsaturated fatty acids on the biosynthesis of PG. There were significant effects of fasting on serum cholesterol concentration regardless of diet and significant interactions among effects of PGE2, fasting, and diet, suggesting regulatory effects of PGE2 on serum cholesterol concentration. The increase in plasma free fatty acids associated with fasting was prevented by PGE2 for all diets, but had the most marked effect on rats fed hydrogenated vegetable fat.

The effects of seven levels of dietary linoleic acid (18:2), with and without trans-octadecenoic acid (18:1t), on the fatty acid composition and prostaglandin content of milk were investigated in lactating rat dams. At parturition, 14 groups of 4 rats each were fed diets containing 20% fat, with mixtures of coconut and safflower oils providing seven concentrations of 18:2 ranging from 3.6 +/- 0.5 to 44.5 + 2.3% of total fatty acids. Hydrogenated soybean oil was added such that 18:1t comprised 10.3 +/- 0.3% of total fatty acids. Milk samples were collected on day 12 postpartum for prostaglandin analyses and on day 16 for fatty acid analyses. The relationship of dietary 18:2 to milk 18:2 was linear (r = 0.98; P = 0.0001), with milk 18:2 ranging from 2.6 +/- 0.1% of total fatty acids at the lowest level of dietary 18:2 to 27.9 +/- 1.6% at the highest. Milk 18:1t was highly correlated (r = 0.99; P = 0.0001) with the amount of dietary 18:1t. In rats fed hydrogenated fat, milk 18:1t averaged 7.0 +/- 0.2% of total fatty acids. Transfer from diet to milk was 46.4 +/- 4.2% for 18:2 and 37.5 +/- 1.7% for 18:1t. Mean concentrations of prostaglandin F2 alpha and E in rat milk were 269 +/- 16 pg/mL and 477 +/- 24 pg/mL respectively. There were no significant differences in the concentrations of either prostaglandin relative to 18:1t consumption at any level of 18:2.

Rats were fed linoleate- or triolein-supplemented total parenteral solutions by continuous intragastric infusion for 7 or 14 d to characterize plasma lipid and apolipoprotein (apo) levels, and the high density lipoprotein (HDL) profile associated with essential fatty acid deficiency (EFAD). Results indicate that plasma cholesterol and triglyceride levels tend to be lower with EFAD, whereas plasma levels of apolipoproteins E and B are lower and apo A-I levels are higher in EFAD animals. EFAD was also associated with 30% fewer apo E--enriched HDL1 particles and a decrease from 11.4 to 11.1 nm in the mean peak diameter of HDL (P less than 0.05). These observations emphasize the sensitivity of apo E content to alterations in plasma cholesterol level and suggest that cholesterol transport is decreased during EFAD in the rat.

Weanling rats were fed high fat diets containing 40% of energy as fat for 23 d. Diets were formulated to contain equivalent content of essential nutrients per calorie for the nonfat components. Four oil mixtures provided high dietary levels of either oleic, linoleic, linolenic or erucic acid. Effect of dietary fatty acid composition on the fatty acid composition of phosphatidylcholine, phosphatidylethanolamine and cardiolipin isolated from cardiac mitochondria was examined in conjunction with the effect of diet on the oxidative activity of cardiac mitochondria. Dietary treatments that reduced the content of C16:0 in the sn-1 and sn-2 positions of phosphatidylcholine were associated with increased content of C20:1 and C22:1 fatty acids into the sn-2 position and resulted in decreased oxidative activity of cardiac mitochondria utilizing palmitylcarnitine as a substrate for oxidation. Diets high in linoleic acid did not increase membrane phospholipid content of omega 3 fatty acids, but resulted in decreased level of C20:4 omega 6. In a subsequent perfusion experiment, hearts were removed from animals fed either high erucic or high linoleic acid diets and were perfused to examine rates of fatty acid oxidation and simultaneous synthesis of high energy phosphate compounds in cardiac muscle. Diet did not affect the levels of creatine phosphate or adenine nucleotides present in the tissue on a per-gram-wet-weight basis, but production of 14CO2 from beta-oxidation of palmitic acid was lower for animals fed the high erucic acid diet than for those fed the high linoleic acid diet. Since this diet did not alter oxidation of palmitylcarnitine in vitro and as beta-oxidation of lauric acid was not decreased in the perfused heart, we conclude that mitochondrial oxidation of fatty acid was not altered by diet and that low rates observed for palmitate oxidation are attributable to reduced palmitylcarnitine synthesis.

Diets supplying 20 or 40% of the calories as fat with linoleate to saturated fatty acid ratios of 0.4, 0.8 and 5.5 were fed to male weanling rats for 8 and 11 weeks. Recalcification clotting time was not affected by dietary treatment. Concentration of cAMP in the platelets was significantly elevated at the highest level of dietary linoleate. Cyclic AMP was negatively correlated with concentration of dihomo-gamma-linolenic acid in platelet phospholipids and positively correlated with prostaglandin E1, suggesting that dihomo-gamma-linolenic acid is rapidly converted to prostaglandin E1 causing a rise of cAMP due to stimulation of adenylate cyclase. Dietary treatment did not markedly change the composition of the platelet phospholipid fatty acids and, therefore, resulted in no change in synthesis of the proaggregatory prostaglandin by platelets during clotting. Although the fatty acid composition of the platelet phospholipids remained constant, dietary treatment did affect the total amount of phospholipid fatty acid present in the platelet. Serum concentrations of cholesterol were significantly higher in rats fed the 20% fat diet than in rats fed the 40% fat diet. Platelet cholesterol followed the same trend as serum cholesterol indicating that the cholesterol content of platelets appears to reflect the lipid environment of the plasma.

To investigate whether dietary linoleic acid inhibits lymphocyte proliferation, rabbits were fed diets containing 35% of the digestible energy (35 en%) as sunflower seed oil (25 en% linoleic acid) or palm oil (3.5 en% linoleic acid). No differences in the mitogen-induced proliferation of peripheral blood lymphocytes (PBL) or splenocytes or in the effect of sera on PBL proliferation were observed. To investigate whether the amount of dietary fat affects lymphocyte proliferation, rats were fed diets containing 10 or 35 en% as fat. No difference in the mitogen-induced proliferation of splenocytes was obtained. However, serum from fed rats but not from fasted rats of the 35 en% fat group inhibited splenocyte proliferation, in comparison with serum from rats of the 10 en% fat group. Removing chylomicrons from the sera did not affect proliferation. The very low density lipoprotein + chylomicron fraction of the plasma inhibited proliferation. The inhibition was stronger for the 35 en% fat group than for the 10 en% fat group and was increased by fasting. No systematic differences in the effects on proliferation were obtained with the low or high density lipoprotein fractions of both groups. Diets containing a high amount of linoleic acid do not inhibit lymphocyte proliferation. The amount of dietary fat might affect lymphocyte proliferation through one or more factors in the plasma.

Experiments were conducted to determine how 20 weeks of deprivation of vitamin B-12 (B-12) would influence polyunsaturated fatty acid (PUFA) patterns in cerebral and liver phospholipids of female rats. All experimental diets included 24% soybean protein and either 3.5 of 0.35% of linoleate (18:2). Deprivation of B-12 and restricted intakes of 18:2 significantly inhibited growth of the rats. Rats depleted of B-12 had 6.7 times more methylmalonic acid in their liver, and significantly more odd-numbered acids (15:0 + 17:0) were present in phosphatidyl choline (PC) of their liver and cerebrum. Deprivation of B-12 promoted 63.3 to 97.3% increases of 18:2 in PC and phosphatidyl ethanolamine (PE) of the liver. Rats deprived of B-12 had significantly less arachidonate (20:4 omega 6) and 22:5 omega 6 in their liver PC, as well as smaller amounts of 20:4 omega 6 and 22:6 omega 3 in their cerebral PC. Some of the observed changes appear to be due to a significant interaction between the effects of B-12 and linoleate. Changes in PUFA patterns of cerebral and hepatic PC suggest that B-12 deprivation may interfere with the conversion of 18:2 omega 6 leads to 20:4 omega 6 leads to 22:5 omega 6. Some of the observed changes may also be related to an inhibited ability to convert PE to PC.

Rats from an inbred Sprague-Dawley strain were fed purified diets with a low (0.3% of the total energy), normal (3%) or high (10%) content of essential fatty acids (EFA) for several generations. Thirty- to 34-d-old male rats of at least the sixth generation to be fed these diets were given a single intragastric dose of [1-14C]linoleic acid in olive oil, and the respiratory CO2, urine and feces were collected for 20 h. The 14C activity was determined in the respiratory CO2, urine and feces as well as in total lipids and lipid classes of the whole animal and in nine tissue groups. The content of total lipids and lipid classes was similar in all groups. The rats in the low EFA group retained significantly more radioactivity (51%) in the tissues than the rats fed the normal EFA (34%) or the high EFA (27%) diets. In all groups most of the radioactivity was found in the skeletal muscles, skin, liver and white fat, but the retention was greater in the low EFA group than in the other groups, except in the white and brown fat. In the carcass and most tissues, the proportion of the retained 14C activity recovered in the phospholipids increased with decreasing EFA level in the diet, whereas in the triglycerides the opposite was found. Expressed as percent of administered dose, the total retention of radioactivity in the phospholipids was 31, 13 and 8% in the low, normal and high EFA group, respectively, while the retention in the triglycerides was about the same in all groups (17-18%).

Male Sprague-Dawley rats were fed diets varying in fatty acid composition for 24 d. Liver plasma membranes were isolated, and the effect of diet on phospholipid fatty acyl tail composition and glucagon-stimulated adenylate cyclase activity was measured. Dietary linolenic acid influenced membrane phospholipid fatty acid composition and altered the effect of different dietary levels of linoleic acid on membrane composition. At low dietary intakes of linolenic acid, membrane fatty acids derived from linolenic acid increased as dietary intake of C18:2(9,12) increased. At high dietary linolenic acid levels membrane content of fatty acids derived from linolenic acid decreased as dietary intake of linoleic acid increased. Glucagon-stimulated adenylate cyclase activity decreased at high levels of both dietary linoleic acid and linolenic acid. These observations suggest that dietary balance between linoleic and linolenic acids has a role in plasma membrane composition and may control glucagon-stimulated adenylate cyclase activity.

Rats were fed a diet either deficient (0.05%) in essential fatty acids (EFA), or providing 4% (control) and 10% (surplus) of the total energy intake in the form of linoleic acid. All diets were isoenergetic and provided 13.9% of the energy as fat. The rats were kept at 29 or 5 degrees C. Growth and food intake of rats fed linoleic acid surplus at either temperature for 10 wk were not different from that of controls; basal metabolism, norepinephrine-induced nonshivering thermogenesis (NST) and thermogenic variables in the brown adipose tissue (amount of mitochondria and mitochondrial uncoupling protein) also were not different. The effects of EFA deficiency were drastically enhanced in the cold: After 10 wk of consuming a diet low in EFA at 5 degrees C, the body weight of rats was 75% of that of controls (87% at 29 degrees C); the food intake was 135% of controls at 5 degrees C (120% at 29 degrees C). The resting respiration in deficient rats was 125% of controls at 5 degrees C (110% at 29 degrees C); body temperatures as low as 35.1 degrees C were measured in deficient rats after 3 wk at 5 degrees C; the cold tolerance of the rats was significantly diminished (30% died within 3 wk at 5 degrees C), thus emphasizing the essential role of dietary EFA during cold stress. Norepinephrine-induced NST and the thermogenic parameters in brown fat were not influenced by EFA deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)