Dietary polyunsaturated fat in relation to mammary carcinogenesis in rats

High fat diets promote the development of mammary tumors induced in rats by 7,12-dimethylbenz(a)anthracene (DMBA), and polyunsaturated fats are more effective than saturated fats. This difference is related to the linoleic acid content of polyunsaturated vegetable oils, but the amount of linolealte required for maximum tumor promotion appears to be higher than indicated by earlier experiments. Comparison of the effects of a polyunsaturated vegetable oil (corn oil) containing linoleate with a fish oilo (menhaden oil) containing polyunsaturated fatty acids derived from linolenic acid showed that higher dietary mammary tumors, while corresponding levels of menhaden oil had an inhibitory effect. This is further evidence that promotion of mammary tumorigenesis by polyunsaturated vegetable oils may be mediated by prostaglandins or other biologically active eicosanoids derived from n−6 fatty acids.     

Fats in human nutrition

Summary Dietary fats represent the most compact chemical energy available to man. They contain twice the caloric value of an equivalent weight of sugar. However dietary fats should not be thought of solely as providers of unwanted calories as fats are as vital to cell structure and biological function as protein. If an individual consumes food items of high fat content, an adequate protein and vitamin intake should be assured in order to provide the lipotropic factors necessary for normal fat metabolism. It may be more judicious to control the total caloric intake under such circumstances rather than to resort to periods of semi-starvation or to drastically decrease the dietary fat intake which could result in an increase in hunger pangs and an actual increase in total caloric intake. If the excess calories furnished by carbohydrates are converted to fatin vivo, the problem of obesity could not be solved under conditions of increased total caloric intake. The problem could be solved by a curtailed intake of a diet which includes meat, milk, eggs, vegetables, fruits, and sufficient cereals and bread to provide for an adequate protein, vitamin, and caloric intake. Dietary fats provide the essential linoleic acid which seems to have both a structural and functional role in animal tissue. Although the optimum total intake of linoleic acid by man has not been established, it is evident that the level of intake in the American dietary pattern could be increased. However the indiscriminate substitution of soft for hard fats seems undesirable as an excess consumption of highly unsaturated fatty acids may change the functional value of the triglycerides in the depot fats and may put an undue stress on the antioxidant supply availablein vivo.     

Effect of varying proportions of dietary menhaden and corn oil on experimental rat mammary tumor promotion

Dose-related effects of long-chain highly unsaturated n−3 fatty acids on the development ofN-nitrosomethylurea (NMU)-induced rat mammary tumors were assessed in female F344 rats. Four test groups (36 rats/group) were fed the following high-fat (HF) diets (23% fat, w/w): Group 1, 18% menhaden oil (MO) and 5% corn oil (CO); Group 2, 11% MO and 11.8% CO; Group 3,5% MO and 18% CO; Group 4, CO alone. A fifth group, serving as an internal control, was fed a low-fat diet containing 5% CO alone. Experimental diets were begun after initiation with NMU, and the experiment was terminated 31 wk later. Total tumor numbers in the five groups were 28, 16, 32, 26 and 11, respectively, indicating that the promotion phase of NMU-induced carcinogenesis was significantly suppressed only when equal parts of CO and MO (Group 2) were fed or when CO alone was fed at 5% (w/w). At high (Group 1) or low (Group 3) levels of MO, tumor numbers were indistinguishable from the HF CO group (Group 4). The same pattern was observed when assessed in terms of cumulative tumor incidence and multiplicity. However, when expressed in terms of final tumor incidence, dietary MO did not suppress tumor promotion in a statistically significant fashion at any concentration. Animals fed MO gained weight at the same rate as those fed CO, indicating that the presence of MO in the diet did not result in food avoidance behavior. Measurement of total serum cholesterol indicated an inverse trend with respect to the MO content of the diet. Analysis of serum fatty acid profiles indicated that the proportion of n−3 and n−6 polyun-saturated fatty acids (PUFA) in the serum reflected that of the diet. These results support the hypothesis that the relative proportions of dietary n−3/n−6 fatty acids play an important role in the suppression of experimental mammary tumorigenesis and suggest that changes in circulating cholesterol or n−3 PUFA levels, induced by dietary MO, are not directly related to tumor development. Presented in part at the 81st Annual Meeting of the American Association for Cancer Research, Washington, D.C., May 1990     

Dietary polyunsaturated fat versus saturated fat in relation to mammary carcinogenesis

High levels of dietary fat have been shown to promote the development of mammary tumors induced in rats by 7,12-dimethylbenz(α)anthracene, and polyunsaturated fats were found to be more effective than saturated fats. In further studies it was found that diets containing 3% sunflowerseed oil (polyunsaturated fat) and 17% beef tallow or coconut oil (saturated fats) enhance tumorigenesis as much as a diet containing 20% sunflowerseed oil. Rats on these diets developed at least twice as many tumors as those fed diets containing either 3% sunflowerseed oil or 20% of the saturated fats alone. These results are in accord with human epidemiological data which show that breast cancer mortality in different countries is positively correlated with total fat intake but not with intake of polyunsaturated fat. Total fat intake varies greatly in different countries, but most human diets probably contain levels of polyunsaturated fat at least equivalent to 3% sunflowerseed oil.     

Dietary fat and colon cancer: Animal model studies

Since it was first suggested that high dietary fat is a risk factor in colon cancer, there have been several studies to test this hypothesis. Epidemiologic studies suggested a positive association between dietary fat and colon cancer. Laboratory animal model studies demonstrated that not only the amount of rat, but also types of fat differing in fatty acid composition are important determining factors in colon tumor development. Chemically-induced colon tumor incidence was increased in rats fed the semipurified diets containing 23% corn oil, safflower oil, lard or beef tallow (high-fat) as compared to those fed 5% corn oil, safflower oil, lard or beef tallow diets (low-fat). Diets containing 23% conconut oil, olive oil or fish oil, or high-fat diets containing varying levels oftrans fat, had no colon tumor-enhancing effect compared to their respective low fat diets. The stage at which the effect of dietary fat is exerted appears to be mostly during the post-initiation phase of colon carcinogenesis. Lack of a colon tumor enhancing effect of dietary fish oil is observed both during the initiation and postinitiation phases. The mechanisms by which various dietary fats increase colon carcinogenesis are not fully understood. In most instances, however, the high-fat diet appears to enhance tumorigenesis through elevation of agents, such as secondary bile acids, that act as promoters of tumor development. Lack of colon tumor promotion by dietary fish oil andtrans fat appears to be mediated through their effect on mucosal ornithine decarboxylase activity, colonic secondary bile acids and/or prostaglandin synthesis. Based on a paper presented at the Symposium on Lipids in Cancer held at the AOCS Annual Meeting, Baltimore, MD, April 1990.     

Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue

Omega-3 PUFA of marine origin reduce adiposity in animals fed a high-fat diet. Our aim was to learn whether EPA and DHA could limit development of obesity and reduce cellularity of adipose tissue and whether other dietary FA could influence the effect of EPA/DHA. Weight gain induced by composite high-fat diet in C57BL/6J mice was limited when the content of EPA/DHA was increased from 1 to 12% (wt/wt) of dietary lipids. Accumulation of adipose tissue was reduced, especially of the epididymal fat. Low ratio of EPA to DHA promoted the effect. A higher dose of EPA/DHA was required to reduce adiposity when admixed to diets that did not promote obesity, the semisynthetic high-fat diets rich in EFA, either α-linolenic acid (ALA, 18∶3 n−3, the precursor of EPA and DHA) or linoleic (18∶2 n−6) acid. Quantification of adipose tissue DNA revealed that except for the diet rich in ALA the reduction of epididymal fat was associated with 34–50% depression of tissue cellularity, similar to the 30% caloric restriction in the case of the high-fat composite diet. Changes in plasma markers and adipose gene expression indicated improvement of lipid and glucose metabolism due to EPA/DHA even in the context of the diet rich in ALA. Our results document augmentation of the antiadipogenic effect of EPA/DHA during development of obesity and suggest that EPA/DHA could reduce accumulation of body fat by limiting both hypertrophy and hyperplasia of fat cells. Increased dietary intake of EPA/DHA may be beneficial regardless of the ALA intake.     

Dietary intake of essential and long-chain polyunsaturated fatty acids in pregnancy

The dietary intake of EFA and long-chain PUFA (LCPUFA) by women with (n=14) and without (n=31) gestational diabetes mellitus (GDM) was determined by repeated 24-h recalls. Women with GDM consumed significantly more energy as fat compared with women who had uncomplicated pregnancies; absolute dietary fat did not differ. Dietary n−3 LCPUFA was substantially lower than the current recommendation for pregnancy, whereas intake of saturated FA (SFA) exceeded it. We conclude that replacing dietary sources of SFA with those of EFA and LCPUFA, especially n−3 LCPUFA, would benefit the dietary fat profiles of all pregnant women.     

Effects of dietary fats on fatty acid composition and Δ5 desaturase in normal and diabetic rats

We have studied the effect of various diets on the phospholipid fatty acid composition andin vitro Δ5 desaturase activity of hepatic microsomes derived either from the normal or streptozotocin-induced diabetic rat. The diets studied were the standard rat chow diet and a basal fat-free diet supplemented either with 20 percent saturated fat, 20 percent unsaturated fat, or 20 percent menhaden oil. Phospholipid fatty acid composition analysis revealed that the normal rat fed the saturated fat or menhaden oil diet had significantly decreased arachidonate levels, consistent with decreased Δ5 desaturase activities and decreased 18∶2n−6 intake. On the contrary, the unsaturated fat diet decreased dihomo-γ-linolenate and increased arachidonate levels, without increased Δ5 desaturase activity. Streptozotocininduced diabetes resulted in decreased arachidonate and Δ5 desaturase activity. The unsaturated fat diet fed to the diabetic rat also failed to correct this decreased Δ5 desaturase activity. The unsaturated fatty acids in this diet also displaced a substantial amount of n−3 fatty acids in both normal and diabetic microsomes, due to the competition between these two fatty acid families for incorporation into the membrane phospholipids. Conversely, the menhaden oil diet fed to the normal and diabetic rats displaced n−6 fatty acids, reduced Δ5 desaturase activity, and enhanced 22∶6n−3 incorporation into diabetic microsomes.     

Fatty acid composition of habitual omnivore and vegetarian diets

High-fat diets are implicated in the onset of cardiovascular disease (CVD), cancer, and obesity. Large intakes of saturated and trans FA, together with low levels of PUFA, particularly long-chain (LC) omega-3 (n−3) PUFA, appear to have the greatest impact on the development of CVD. A high n−6∶n−3 PUFA ratio is also considered a marker of elevated risk of CVD, though little accurate data on dietary intake is available. A new Australian food composition database that reports FA in foods to two decimal places was used to assess intakes of FA in four habitual dietary groups. Analysis using the database found correlations between the dietary intakes of LC n−3 PUFA and the plasma phospholipid LC n−3 PUFA concentrations of omnivore and vegetarian subjects. High meat-eaters (HME), who consumed large amounts of food generally, had significantly higher LC n−3 PUFA intakes (0.29 g/d) than moderate meat-eaters (MME) (0.14 g/d), whose intakes in turn were significantly higher than those of ovolacto-vegetarians or vegans (both 0.01 g/d). The saturated FA intake of MME subjects (typical of adult male Australians) was not different from ovolacto-vegetarian intakes, whereas n−6∶n−3 intake ratios in vegetarians were significantly higher than in omnivores. Thus, accurate dietary and plasma FA analyses suggest that regular moderate consumption of meat and fish maintains a plasma FA profile possibly more conducive to good health.     

Comparative effects of α- and γ-linolenic acids on rat liver fatty acid oxidation

It has been reported that both n−3 and n−6 octadecatrienoic acids can increase hepatic fatty acid oxidation activity. It remains unclear, however, whether different enzymes in fatty acid oxidation show a similar response to n−3 and n−6 octadecatrienoic acids. The activity of hepatic fatty acid oxidation enzymes in rats fed an oil mixture rich in α-linolenic acid (18:3n−3) and borage oil rich in γ-linolenic acid (18:3n−6) was therefore compared to that in rats fed an oil mixture rich in linoleic acid (18:2n−6) and a saturated fat (palm oil) in this study. Linseed oil served as the source of 18:3n−3 for the oil mixture rich in this octadecatrienoic acid and contained 30.6% 18:3n−3 but not 18:3n−6. Borage oil contained 25.7% 18:3n−6 and 4.5% 18:3n−3. Groups of seven rats each were fed diets containing 15% various fats for 15 d. The oxidation rate of palmitoyl-CoA in the peroxisomes was higher in rats fed a fat mixture rich in 18:3n−3 (3.03 nmol/min/mg protein) and borage oil (2.89 nmol/min/mg protein) than in rats fed palm oil (2.08 nmol/min/mg protein) and a fat mixture rich in 18:2n−6 (2.15 nmol/min/mg protein). The mitochondrial palmitoyl-CoA oxidation rate was highest in rats fed a fat mixture rich in 18:3n−3 (1.93 nmol/min/mg protein), but no significant differences in this parameter were seen among the other groups (1.25–1.46 nmol/min/mg protein). Compared to palm oil and fat mixtures rich in 18:2n−6, a fat mixture rich in 18:3n−3 and borage oil significantly increased the hepatic activity of carnitine palmitoyl-transferase and acyl-CoA oxidase. Compared to palm oil and a fat mixture rich in 18:2n−6, a fat mixture rich in 18:3n−3, but not fats rich in 18:3n−6, significantly decreased 3-hydroxyacyl-CoA dehydrogenase activity. Compared to palm oil and a fat mixture rich in 18:2n−6, borage oil profoundly decreased mitochondrial acyl-CoA dehydrogenase activity, but a fat mixture rich in 18:3n−3 increased it. 2,4-Dienoyl-CoA reductase activity was significantly lower in rats fed palm oil than in other groups. Compared to other fats, borage oil significantly increased Δ³, Δ²-enoyl-CoA isomerase activity. Activity was also significantly higher in rats fed 18:2n−6 oil than in those fed palm oil. It was confirmed that both dietary 18:3n−6 and 18:3n−3 increased fatty acid oxidation activity in the liver. These two dietary octadecatrienoic acids differ considerably, however, in how they affect individual fatty acid oxidation enzymes.     

Dietary fat,fatty acids and prostate cancer

International comparisons suggest a relationship between prostate cancer incidence and dietary fat, an inference supported by migration studies, the changing incidence rates and levels of animal fat consumption in Japan and the results from some case-control studies. Overall, however, epidemiological studies have been inconclusive, and although prostate cancer is one of the hormone-dependent tumors, evidence of interactions between dietary fats and male endocrine function is incomplete. Laboratory experimentation has shown that n−6 fatty acids stimulate and n−3 fatty acids inhibit human prostate cancer cells in culture; also, feeding diets rich in marine oils suppresses growth of these cells as solid tumors in athymic nude mice. These growth effects of polyunsaturated fatty acids appear to involve both prostaglandins and leukotrienes and to interconnect with autocrine regulation by epidermal growth factor-related polypeptides. Based on a paper presented at the Sympsoium on Lipids in Cancer held at the AOCS Annual Meeting, Baltimore, MD, April 1990.     

Skeletal muscle membrane lipids and insulin resistance

Skeletal muscle plays a major role in insulin-stimulated glucose disposal. This paper reviews the range of evidence in humans and experimental animals demonstrating close associations between insulin action and two major aspects of muscle morphology: fatty acid composition of the major structural lipid (phospholipid) in muscle cell membranes and relative proportions of major muscle fiber types. Workin vitro andin vivo in both rats and humans has shown that incorporation of more unsaturated fatty acids into muscle membrane phospholipid is associated with improved insulin action. As the corollary, a higher proportion of saturated fats is linked to impairment of insulin action (insulin resistance). Studiesin vitro suggest a causal relationship. Among polyunsaturated fatty acids (PUFA) there is some, but not conclusive, evidence that ω-3 (n−3) PUFA may play a particular role in improving insulin action; certainly a high n−6/n−3 ratio appears deleterious. In relation to fiber type, the more highly oxidative, insulin-sensitive type 1 and type 2a fibers have a higher percentage of unsaturated fatty acids, particularly n−3, in their membrane phospholipid, compared to the insulin-resistant, glycolytic, type 2b fibers. These variables, however, can be separated and may act in synergy to modulate insulin action. It remains to establish whether lifestyle (e.g., dietary fatty acid profile and physical activity), genetic predisposition, or a combination are the prime determinants of muscle morphology (particularly membrane lipid profile) and hence insulin action.     

Mitochondrial membrane fatty acid composition in the marmoset monkey following dietary lipid supplementation

Diets supplemented with high levels of saturated fatty acids derived from sheep kidney (perirenal) fat or unsaturated fatty acids derived from sunflowerseed oil were fed to marmoset monkeys for 22 wk. The effect of such diets on plasma, red blood cell phospholipids, and liver, heart, kidney and brain mitochondrial phospholipid fatty acids was determined. Despite large differences in the level and type of lipid present in the experimental diets, there was little effect on the proportion of saturated to unsaturated fatty acids in the phospholipids of the membranes examined. The diets did, however, alter the proportion of the various classes of polyunsaturated fatty acids in the membrane phospholipids, with the sunflower-seed oil diet elevating and the sheep kidney fat diet reducing the n−6/n−3 unsaturated fatty acid ratio, relative to a low (mixed fat) reference diet. This change occurred in all membranes except brain, in which only a small response to altered dietary lipid intake was observed. Elevation of dietary linoleic acid led to an increase in membrane linoleic acid and a marked decrease in membrane arachidonic acid, such that the membranes from animals fed the sunflowerseed oil diet exhibited the lowest proportion of arachidonic acid. In this latter respect, the response of the marmoset monkey to dietary lipid supplementation differs markedly from the rat. Our inability to alter significantly membrane lipid saturation/unsaturation supports the notion that a homeostatic mechanism is in some way responsible for buffering membranes from the effects of significant changes in the nature of the dietary lipid intake.     

Effects of fatty acids on gap junctional communication: Possible role in tumor promotion by dietary fat

Dietary lipids, in particular unsaturated fat, promote the development of many experimental tumors. However, no mechanisms to fully explain these effects have been elucidated. Recent reports, which we summarize here, suggest a role for gap junction-mediated intercellular communication in the process of tumor promotion. We also review tumor-promoting effects of dietary fat on experimental, particularly mammary, carcinogenesis. Our main focus is to review recent data examining the inhibitory effects of unsaturated fatty acids on metabolic cooperation in Chinese hamster V79 cells. These data suggest that inhibition of junctional communication may be involved mechanistically in the promotion of tumors by high levels of dietary unsaturated fat. Finally, potential mechanisms by which unsaturated fatty acids inhibit metabolic cooperation are examined. Presented at the symposium on “Specialty Lipids and Their Biofunctionality” at the annual meeting of the American Oil Chemists' Society, Philadelphia, May 1985.     

Comparative bioavailability of dietary alpha-linolenic and docosahexaenoic acids in the growing rat

Animal and human studies have indicated that developing mammals fed only α-linolenic acid (18∶3n−3) have lower docosahexaenoic acid (22∶6n−3) content in brain and tissue phospholipids when compared with mammals fed 18∶3n−3 plus 22∶6n−3. The aim of this study was to test the hypothesis that low bioavailability of dietary 18∶−3 to be converted to 22∶6n−3 could partly explain this difference in fatty acid accretion. For that purpose, we determined the partitioning of dietary 18∶3n−3 and 22∶6n−3 between total n−3 fatty acid body accumulation, excretion, and disappearance (difference between the intake and the sum of total n−3 fatty acids accumulated and excreted). This was assessed using the quantitative method of whole-body fatty acid balance in growing rats fed the same amount of a 5% fat diet supplying either 18∶3n−3 or 22∶6n−3 at a level of 0.45% of dietary energy (i.e., 200 mg/100 g diet). We found that 58.9% of the total amount of 18∶3n−3 ingested disappeared, 0.4% was excreted in feces, 21.2% accumulated as 18∶3n−3 (50% in total fats and 46% in the carcass-skin compartment), and 17.2% accumulated as long-chain derivatives (14% as 22∶6n−3 and 3.2% as 20∶5n−3+22∶5n−3). Similar results were obtained from the docosahexaenoate balance (as % of the total amount ingested): disappearance, 64.5%; excretion, 0.5%; total accumulation, 35% with 30.1% as 22∶6n−3. Thus, rats fed docosahexaenoate accumulated a twofold higher amount of 22∶6n−3, which was mainly deposited in the carcass-skin compartment (68%). Similar proportions of disappearance of dietary 18∶−3 and 22∶6n−3 lead us to speculate that these two n−3 polyunsaturated fatty acids were β-oxidized in the same amount.     

Incorporation of n−3 fatty acids into plasma and liver lipids of rats: Importance of background dietary fat

The health benefits of long-chain n−3 PUFA (20∶5n−3 and 22∶6n−3) depend on the extent of incorporation of these FA into plasma and tissue lipids. This study aimed to investigate the effect of the background dietary fat (saturated, monounsaturated, or n−6 polyunsaturated) on the quantitative incorporation of dietary 18∶3n−3 and its elongated and desaturated products into the plasma and the liver lipids of rats. Female weanling Wistar rats (n=54) were randomly assigned to six diet groups (n=9). The fat added to the semipurified diets was tallow (SFA), tallow plus linseed oil (SFA-LNA), sunola oil (MUFA), sunola oil plus linseed oil (MUFA-LNA), sunflower oil (PUFA), or sunflower oil plus linseed oil (PUFA-LNA). At the completion of the 4-wk feeding period, quantitative FA analysis of the liver and plasma was undertaken by GC. The inclusion of linseed oil in the rat diets increased the level of 18∶3n−3, 20∶5n−3, and, to a smaller degree, 22∶6n−3 in plasma and liver lipids regardless of the background dietary fat. The extent of incorporation of 18∶3n−3, 20∶5n−3, and 22∶5n−3 followed the order SFA-LNA>MUFA-LNA>PUFA-LNA. Levels of 22∶6n−3 were increased to a similar extent regardless of the type of major fat in the rat diets. This indicates that the background diet affects the incorporation in liver and plasma FA pools of the n−3 PUFA with the exception of 22∶6n−3 and therefore the background diet has the potential to influence the already established health benefits of long-chain n−3 fatty acids.     

Dietary fat composition and age affect synaptosomal and retinal phospholipid fatty acid composition in C57BL/6 mice

The purpose of this study was (i) to determine whether dietary fat-induced differences in neural and retinal membranes occur when dietary fat treatment is implemented in aged animals and (ii) to characterize the effect of long-term differences in dietary fat on neural and retinal membrane composition. For the first objective, young (six-week-old) and old (95-week-old) mice were randomly assigned to beef tallow (TAL) or soybean oil (SBO) diets for eight weeks. For the second objective, young (four-week-old) mice consumed either TAL or SBO diets for 99 weeks. Young and old mice challenged with a change in dietary fat for an eight-week period showed both diet and age effects on neural and retinal phospholipid fatty acid composition (P<0.05). In addition, significant diet by age interactions were evident. In mice that consumed TAL and SBO diets throughout their life, only retinal phosphatidylethanolamine (PE) 18∶2n−6 and neural phosphatidylserine 22∶5n−6, PE 18∶2n−6 and phosphatidylcholine 18∶2n−6 differed between dietary treatments (P<0.05). Neither the unsaturation index nor the n−6/n−3 ratio was affected by diet. Neural and retinal phospholipid fatty acid composition were responsive to changes in dietary fat even when the treatment was implemented beyond developmental or post-weanling stages. In contrast, when mice consumed TAL or SBO diets throughout their life, fewer differences in phospholipid fatty acid composition were detected, suggesting that the effect of the dietary treatment was mitigated by aging.     

High dietary 18∶3n−3 increases the 18∶3n−3 but not the 22∶6n−3 content in the whole body, brain, skin, epididymal fat pads, and muscles of suckling rat pups

The objective of this study was to test the hypothesis that increasing maternal dietary 18∶3n−3 by decreasing the 18∶2n−6/18∶3n−3 ratio will increase the 18∶3n−3 and 22∶6n−3 content of the whole body, liver, skin (epidermis, dermis, and subcutaneous tissue), epididymal fat pads, and muscles (arms and legs) of 2-wk-old rat pups. Sprague-Dawley dams at parturition were fed semipurified diets containing either a low (18∶2n−6 to 18∶3n−3 ratio of 24.7∶1) or a high (18∶2n−6 to 18∶3n−3 ratio of 1.0∶1) 18∶3n−3 fatty acid content. During the first 2 wk of life, rat pups received only their dams' milk. Fatty acid composition of the pups' stomach contents (dams' milk), whole body, brain, liver, skin, epididymal fat pads, and muscles was determined. The stomach fatty acid composition of 18∶3n−3 reflected the dams' diet. The content of 18∶3n−3 in whole body, brain, liver, skin, epididymal fat pads, and muscles was significantly (P<0.05) greater in rat pups fed the high compared with the low 18∶3n−3 fatty acid diet. The 22∶6n−3 content of the whole body, brain, skin, epididymal fat pads, and muscles was not quantitatively different in rat pups fed either the low or high 18∶3n−3 fatty acid diet. The 20∶5n−3 and 22∶5n−3 content of the whole body, skin, and epididymal fat pads was significantly increased in rat pups fed the high compared with the low 18∶3n−3 fatty acid diet. High content of 18∶3n−3 was found in the skin of rat pups fed either a low or high 18∶3n−3 fatty acid diet. These findings demonstrate that high maternal dietary 18∶3n−3 significantly increases the 18∶3n−3 but not the 22∶6n−3 content of the whole body, brain, skin, epididymal fat pads, and muscles with approximately 39 and 41% of the whole body 18∶3n−3 content being deposited in the skin of suckling rat pups fed either the low or high 18∶3n−3 diet, respectively.     

The effect of dietary n−6 and n−3 polyunsaturated fatty acids on blood pressure and tissue fatty acid composition in spontaneously hypertensive rats

Effects of dietary n−6 and n−3 fatty acids (FAs) on blood pressure (BP) and tissue phospholipid (PL) FA composition in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were compared. Male weanling SHR and WKY were fed a fat-free semisynthetic diet supplemented with 10% (w/w) fats containing (a) 78% 18∶2n−6 (LA-rich), (b) 20% LA and 55% 18∶3n−3 (LN-rich), or (c) 11% LA and 3% LN (CON) for seven weeks. Dietary fats did not affect the BP elevation, but significantly altered the FA composition of brain, adrenal gland, renal medulla and cortex PL in SHR. The LA-rich diet increased n−6 FA while it reduced n−3 FA levels. The levels of 20∶4n−6 were not significantly different between animals fed the LA-rich and the CON diets. LN-rich diet increased the levels of n−3 FAs, while it reduced those of n−6 FAs. However, the extent of change was significantly less in SHR than in WKY. In all dietary groups, SHR, as compared to WKY, had a relatively higher level of the 2 series prostaglandin (PG) precursor, 20∶4n−6, and a relatively lower level of the 1 and 3 series PG precursors, 20∶3n−6 and 20∶5n−3. The possibility that the unbalanced eicosanoid FA precursor levels might contribute to the development of hypertension in this animal model is discussed.     

Dietary modulation of fatty acid profiles and oxidative status of rat hepatocyte nodules: Effect of different n−6/n−3 fatty acid ratios

Male Fischer rats were fed the AIN76A diet containing varying n−6/n−3 FA ratios using sunflower oil (SFO), soybean oil (SOY), and SFO supplemented with EPA-50 and GLA-80 (GLA) as fat sources. Hepatocyte nodules, induced using diethylnitrosamine followed by 2-acetylaminofluorene/partial hepatoctomy promotion, were harvested, with surrounding and respective dietary control tissues, 3 mon after partial hepatectomy. The altered growth pattern of hepatocyte nodules in rats fed SFO is associated with a distinct lipid pattern entailing an increased concentration of PE, resulting in increased levels of 20∶4n−6. In addition, there is an accumulation of 18∶1n−9 and 18∶2n−6 and a decrease in the end products of the n−3 metabolic pathway in PC, suggesting a dysfunctional Δ-6-desaturase enzyme. The hepatocyte nodules of the SFO-fed rats exhibited a significantly reduced lipid peroxidation level that was associated with an increaser in the glutathione (GSH) concentration. The low n−6/n−3 FA ratio diets significantly decreased 20∶4n−6 in PC and PE phospholipid fractions with a concomitant increase in 20∶5n−3, 22∶5n−3, and 22∶6n−3. The resultant changes in the 20∶4/20∶5 FA ratio and the 20∶3n−6 FA level in the case of the GLA diet suggest a reduction of prostaglandin synthesis of the 2-series. The GLA diet also counteracted the increased level of 20∶4n−6 in PE by equalizing the nodule/surrounding ratio. The low n−6/n−3 ratio diets significantly increased lipid peroxidation levels in hepatocyte nodules, mimicking the level in the surrounding and control tissue while GSH was decreased. An increase in n−3 FA levels and oxidative status resulted in a reduction in the number of glutathione-S-transferase positive foci in the liver of the GLA-fed rats. Modulation of cancer development with low n−6/n−3 ratio diets containing specific dietary FA could be a promising tool in cancer intervention in the liver.