Showing papers by "Philip C. Calder published in 1996"

The ratio of n‐6 to n‐3 polyunsaturated fatty acids in the rat diet alters serum lipid levels and lymphocyte functions

Abstract: Previous studies have reported that feeding rats diets rich in fish oils, which contain high proportions of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic and docosahexaenoic acids, results in lowering of blood lipid levels and suppression of lymphocyte functions testedex vivo andin vivo. The effects of other n-3 PUFA, such as α-linolenic acid, which is found in high proportions in linseed oil, are not as well documented. Therefore, in the present study, weanling male rats were fed for six weeks on one of five high-fat (20% by weight) diets made by mixing together sunflower and linseed oils; the resulting blends had n-6/n-3 PUFA ratios of 112.5:1 (pure sunflower oil), 14.8:1, 6.5:1, 0.8:1, and 0.33:1 (pure linseed oil); the levels of all other components in the diet were identical. The final body weight and total dissectable fat were lowest in rats fed the pure linseed oil diet. Serum cholesterol, triacylglycerol and nonesterified fatty acid concentrations decreased as the n-6/n-3 PUFA ratio of the diet decreased. The fatty acid composition of the serum and of spleen lymphocytes was influenced by the diet fed-there was a progressive decrease in the proportions of linoleic and arachidonic acids and a progressive increase in the proportion of α-linolenic acid as the n-6/n-3 PUFA ratio of the diet decreased. Eicosapentaenoic and docosahexaenoic acids were detected in the serum but not in spleen lymphocytes. Inclusion of α-linolenic acid in the diet resulted in significant suppression of spleen lymphocyte proliferation in response to the T-cell mitogen concanavalin A and in spleen lymphocyte natural killer cell activity, both measuredex vivo. The localized graft vs. host response, a measure of cellmediated immunityin vivo, progressively decreased as the n-6/n-3 PUFA ratio of the diet decreased. Thus, this study shows that dietary α-linolenic acid results in lowered blood lipid levels and suppressed lymphocyte functionsex vivo andin vivo. With respect to these effects, α-linolenic acid is as potent as dietary fish oil.

The effects of olive oil upon rat serum lipid levels and lymphocyte functions appear to be due to oleic acid.

Abstract: In order to investigate whether previously reported effects of feeding olive oil (OO) upon rat serum lipid concentrations and immune cell functions are due to oleic acid, weanling rats were fed for 6 weeks on diets containing 20% by weight of OO, safflower oil (SO), or high oleic acid sunflower oil (HOSO); a low-fat (LF) diet containing 2.5% by weight of lipid was used as a control. Feeding the OO or HOSO diets resulted in an elevated serum triacylglycerol concentration as compared with feeding the LF or SO diets. The serum total cholesterol concentrations were raised in the animals fed the high-fat diets and were highest in animals fed the OO or the HOSO diet. The fatty acid composition of the serum and of spleen lymphocytes reflected that of the diet fed. The mitogen-stimulated spleen lymphocyte proliferation ex vivo was significantly lower following OO or HOSO feeding as compared with LF or SO feeding. Similarly, feeding the OO or the HOSO diet resulted in lower spleen natural killer cell activity as compared with LF or SO feeding. These observations indicate that the effects of OO feeding are most likely due to oleic acid rather than to other components of OO.

Can n-3 polyunsaturated fatty acids be used as immunomodulatory agents?

Abstract: 261, 472-475 23 Chedid, M., Shirakawa, F., Naylor, P. and Mizel, S. (1989) J. Immunol. 142,4301-4306 24 Guy, G. R., Cao, X. and Tan, Y. H. (1992) J. Biol. Chem. 267, 1846-1852 25 Kracht, M., Shiroo, M., Marshall, C. J., Hsuan, J. J. and Saklatvala, J. (1994) Biochem. J. 302, 897-905 26 Saklatvala, J., Rawlinson, L. M., Marshall, C. J. and Kracht, M. (1993) FEBS Lett. 334, 189-192 27 Kracht, M., Truong, O., Totty, N. F., Shiroo, M. and Saklatvala, J. (1994) J. Exp. Med. 180, 20 17-2026 28 Freshney, N. W., Rawlinson, L., Guesdon, F., Jones, E., Cowley, S. and Saklatvala, J. (1994) Cell

Glutamine requirement of proliferating T lymphocytes.

Abstract: Glutamine is required for lymphocyte proliferation but the site of glutamine action is not yet known. In this study, the effect of glutamine on key events that occur during lymphocyte activation [interleukin-2 (IL-2) production, IL-2 use, IL-2 receptor expression, transferrin receptor expression] was investigated. Rat or mouse spleen lymphocytes were cultured in the presence of the T-cell mitogen concanavalin A (Con A) and various concentrations of glutamine. There was a trend (not significant) for the ratio of CD4+:CD8+ spleen lymphocytes to increase (from 1.9 to 2.6) as the concentration of glutamine in culture medium increased from 0 to 2 mmol/L. As the concentration of glutamine increased, there was an increase in the proportion of cells expressing the IL-2 receptor (from 30 to 45%) and the transferrin receptor (from 34% to 55%). As the concentration of glutamine increased there was a 2.7-fold increase in the concentration of IL-2 in the culture medium. The IL-2 concentration was decreased when an IL-2 receptor-blocking antibody was included in the culture medium; the IL-2 concentrations measured were taken to indicate the initial Con A-stimulated production of IL-2. In these conditions, the IL-2 concentration in the medium increased 39-fold as the glutamine concentration increased. The use of IL-2 by an IL-2-dependent cell line was dependent on the glutamine concentration in the culture medium. Thus, all four components of lymphocyte activation investigated (IL-2 production, IL-2 use, IL-2 receptor expression, transferrin receptor expression) were dependent on the concentration of glutamine present in the culture medium. Thus, glutamine might provide an early signal in the lymphocyte activation process.

Characterization of lipoprotein composition in rats fed different dietary lipids and of the effects of lipoproteins upon lymphocyte proliferation

Abstract: Weanling Lewis rats were fed for 10 weeks on a low fat (2.5% by weight; LF) diet or on diets containing 20% by weight of hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO), or menhaden (fish) oil (MO); all other components of the diets were identical. The chylomicron (CM), very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions were isolated from the serum. The serum from MO-fed animals had lower LDL and HDL cholesterol concentrations than the serum from animals fed each of the other diets. The apolipoprotein A-1 concentration in the HDL fraction from animals fed the MO diet was also low. The serum from HCO-fed animals had a higher CM triacylglycerol concentration than serum from animals fed each of the other diets. The serum from OO-fed animals had a higher VLDL triacylglycerol concentration than serum from animals fed each of the other diets. The concentration of apolipoprotein B was also high in the VLDL fraction from OO-fed animals. The fatty acid composition of each lipoprotein fraction was affected by the nature of the lipid in the diet; the greatest effects were observed in the CM and VLDL fractions. Each lipoprotein fraction isolated from LF-fed rats inhibited mitogen-stimulated rat spleen lymphocyte proliferation in a concentration-dependent manner; LDL and HDL caused greater inhibition than CM and VLDL. Dietary lipid manipulation did not alter the inhibitory effects of any of the lipoprotein fractions upon lymphocyte proliferation, except that CM and HDL from MO-fed animals and HDL from OO-fed animals resulted in enhanced proliferation compared with either CM or HDL from animals fed the other diets. We conclude that the inhibition of lymphocyte proliferation caused by feeding rats certain dietary lipids (OO, EPO, MO) may be mediated by non-lipoprotein serum components.