The influence of dietary fatty acid composition on N-ethyl-Nnitrosourea-induced mammary tumour incidence in the rat and on the composition of inositol- and ethanolamine-phospholipids of normal and tumour mammary tissue

This study has investigated the influence of dietary fatty acid composition on mammary tumour incidence in N-ethyl-N-nitrosourea (ENU)-treated rats and has compared the susceptibility to dietary fatty acid modification of the membrane phospholipids phosphatidyliuositol (PI) and phosphatidylethanolamine (PE) from normal and tumour tissue of rat mammary gland. The incidence of mammary tumours was significantly lower in fish oil- (29%), compared with olive oil- (75%; P < 0.04) but not maize oil- (63%; P < 0.1) fed animals. No differences in PI fatty acid composition were found in normal or tumour tissue between rats fed on maize oil, olive oil or fish oil in diets from weaning. When normal and tumour tissue PI fatty acids were compared, significantly higher amounts of stearic acid (18:O) were found in tumour than normal tissue in rats given olive oil (P < 0.05). A similar trend was found in animals fed on maize oil, although differences between normal and tumour tissue did not reach a level of statistical significance (P < 0.1). In mammary PE, maize oil-fed control animals had significantly higher levels of linoleic acid (18:2n-6) than either olive oil- or fish oil-fed animals (P < 0.05, both cases) and levels of arachidonic acid were also higher in maize oil- compared with fish oil-fed animals (P < 0.05). In tumourbearing animals no differences in PE fatty acid composition were found between the three dietary groups. When normal and tumour tissue PE fatty acids were compared, significantly lower amounts of liuoleic acid (18:2n-6; P < 0.01) and significantly greater amounts of arachidonic acid (20:4n-6; P < 0.05) were found in tumour than normal tissue of rats fed on maize oil. The present study shows that the fatty acid composition of PI from both normal and tumour tissue of the mammary gland is resistant to dietary fatty acid modification. The PE fraction is more susceptible to dietary modification and in this fraction there is evidence of increased conversion of linoleic acid to arachidonic acid in tumour compared with normal tissue. Lower tumour incidence rates in rats given fish oils may in part be due to alteration in prostanoid metabolism secondary to displacement of arachidonic acid by eicosapentaenoic acid, but PE rather than PI would appear to be the most likely locus for diet-induced alteration in prostanoid synthesis in this tissue. Effects of dietary fatty acids other than on the balance of n-6 and n-3 fatty acids, and on prostanoid metabolism, should also be considered. The significance of increased stearic acid content of PI in tumours of olive oil-fed animals and the possible influence of dietary fatty acids on the capacity for stearic acid accumulation requires further study.

Pretranslational regulation of the expression of the lipoprotein lipase (EC 3.1, l.34) gene by dietary fatty acids in the rat

Although there have been a number of studies of effects of diet and hormones on lipoprotein lipase (EC 3.1.1.34; LPL) activity and levels of LPL mRNA (Raynolds et al. 1990), there have been no studies which have investigated effects of different dietary fatty acids on LPL gene expression. In the present study male Wistar Albino rats were pair-fed diets containing 50 g fat/kg of different fatty acid composition for 2 weeks. The diets fed were (1) a mixed oil (450 g saturated fatty acids, 420 g monounsaturated fatty acids, 130 g polyunsaturated fatty acids/kg; n 8), (2) maize oil (n 8), or (3) fish oil (n 8). Animals were killed, RNA was extracted from liver and perirenal and epididymal fat pads, and analysed by ‘Northern methodology’. Samples were hybridized to a human cDNA probe for LPL (Gotoda et al. 1989). Two transcripts were identified in epididymai and perirenal adipose tissue which were approximately 3·7 and 1·7 kb in size. The results suggested that (1) fish oil-fed animals had significantly greater production of LPL mRNA in epididymai adipose tissue compared with maize oil-fed animals (P < 0·05), (2) maize oil-fed animals had significantly greater production of LPL mRNA in perirenal fat compared with the other dietary groups (P < 0·05), (3) expression in the liver was not significant. Rats fed on a fish oil diet had significantly reduced plasma triacylglycerol concentrations compared with the mixed-oil group (P < 0·05), but there were no significant differences in plasma cholesterol. The differences in LPL could not be explained directly by the changes in plasma immunoreactive-insulin and glucose-dependent insulinotrophic polypeptide levels in the three groups.

Effect of dietary fatty acid composition on inositol-, choline- and ethanolamine-phospholipids of mammary tissue and erythrocytes in the rat

The present study investigated the effect of feeding maize-oil, olive-oil and fish-oil diets, from weaning to adulthood, on rat mammary tissue and erythrocyte phospholipid fatty acid compositions. Effects of diet on the relative proportions of membrane phospholipids in the two tissues were also investigated. Mammary tissue phosphatidylinositol (PI) fatty acids were unaltered by diet, but differences in phosphatidylethanolamine (PE) and, to a lesser extent, phosphatidylcholine (PC) fractions were found between animals fed on different diets from weaning. Differences observed were those expected from the dietary fatty acids fed; n-6 fatty acids were found in greatest amounts in maize-oil-fed rats, n-9 in olive-oil-fed rats, and n-3 in fish-oil-fed rats. In erythrocytes the relative susceptibilities of the individual phospholipids to dietary modification were: PE > PC > PI, but enrichment with n-9 and n-3 fatty acids was not observed in olive-oil- and fish-oil-fed animals and in PC and PE significantly greater amounts of saturated fatty acids were found when animals fed on olive oil or fish oil were compared with maize-oil-fed animals. The polyunsaturated:saturated fatty acid ratios of PE and PC fractions were significantly lower in olive-oil- and fish-oil-fed animals. No differences in the relative proportions of phospholipid classes were found between the three dietary groups. It is suggested that differences in erythrocyte fatty acid composition may reflect dietary-induced changes in membrane cholesterol content and may form part of a homoeostatic response the aim of which is to maintain normal erythrocyte membrane fluidity. The resistance of mammary tissue PI fatty acids to dietary modification suggests that alteration of PI fatty acids is unlikely to underlie effects of dietary fat on mammary tumour incidence rates.

Plasma lipids and prolactin in patients with breast cancer

In a comparative study of pre- and postmenopausal women with benign and malignant breast disease, a number of differences were observed in circulating plasma prolactin and lipid concentrations. Plasma lipids, phospholipids, triglycerides, cholesterol and free fatty acids were all higher in blood obtained from breast cancer patients prior to surgery. HDL-Cholesterol levels were significantly lower in these patients. These differences remained when the patient groups were sub-divided according to menopausal status. Plasma prolactin concentrations were also found to be higher in cancer compared with non-cancer patients, this effect being more marked in premenopausal than in postmenopausal patients. Premenopausal patients with invasive or poorly differentiated disease had significantly higher prolactin levels than those with non-invasive disease. No correlations were found between plasma prolactin and any of the lipid fractions.

Dietary monounsaturated fatty acids and haemostasis

Diets high in monounsaturated fatty acids (MUFA) are increasingly being recommended as a highly-effective cholesterol-lowering strategy in populations at risk of CHD. However, the need for a re-appraisal of the benefits of diets rich in MUFA became apparent as a result of recent studies showing that meals high in olive oil cause greater postprandial activation of blood coagulation factor VII than meals rich in saturated fatty acids. The present review evaluates the evidence for the effects of MUFA-rich diets on fasting and postprandial measurements of haemostasis, and describes data from a recently-completed long-term controlled dietary intervention study. The data show that a background diet high in MUFA has no adverse effect on fasting haemostatic variables and decreases the postprandial activation of factor VII in response to a standard fat-containing meal. Since the same study also showed a significant reduction in the ex vivo activation of platelets in subjects on the high-MUFA diet, the overall findings suggest that there is no reason for concern regarding adverse haemostatic consequences of high-MUFA diets.

Dietary fatty acids and human health

A considerable amount of evidence has accumulated to support the view that the very long chain omega 3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) have beneficial cardiovascular and anti-inflammatory properties and that levels of their consumption are insufficient in most Western diets. More recently, attention has been given to the possibility that the precursor omega-3 PUFA, alpha linolenic acid (ALNA), may share some of the beneficial actions of EPA/DHA on human health. Further research into the metabolism and physiological actions of ALNA, and comparisons with EPA/DHA, is needed before conclusions regarding the optimal amounts and types of omega-3 PUFA for human health can be defined. Conjugated linoleic acid (CLA), which arises as a metabolic by-product of rumen hydrogenation and which is found in foods of animal origin, has been proposed to possess potent health promoting properties, but much of this research has been conducted in experimental animals. There is an urgent need for complementary studies in human volunteers, to confirm the putative anti-carcinogenic, anti-atherogenic, anti-lipogenic and immuno-suppressive properties of CLA.

Dietary interventions affecting chylomicron and chylomicron remnant clearance

Interest in effects of diet on postprandial lipoproteins has increased in recent years as a result of accumulating evidence for adverse cardiovascular consequences of elevated concentrations of triglyceride rich lipoproteins. Particular attention has been given to ability of different fatty acids to modulate postprandial lipoprotein responses because of evidence for both harmful and protective cardiovascular properties of the saturated, monounsaturated and ω-6 and ω-3 polyunsaturated fatty acid (PUFA) classes. Evidence for direct atherogenic properties of chylomicron remnants has led to attempts to monitor effects of diet specifically on this lipoprotein class. Limitations in the methods employed to measure chylomicron remnants and the small number of human studies which have evaluated effects of meal, and background diet, fatty acid composition, makes it difficult to draw definitive conclusions at the present time. However consideration of data from both animal and human studies tends to support the conclusion that diets, and meals, rich in PUFA (particularly long chain ω-3 PUFA), result in attenuated postprandial responses of the intestinally-derived lipoproteins. Attenuated responses to high PUFA meals appear to be due to greater rates of clearance and greater activation of lipoprotein lipase (LPL). Attenuated responses to high PUFA background diets may be due to adaptive changes involving both accelerated rates of clearance in peripheral tissues and liver, as well as decreased output of the competitor for chylomicron clearance, very low density lipoprotein (VLDL).