Replacement of Dietary Saturated by Unsaturated Fatty Acids: Effects on Platelet Protein Kinase C Activity, Urinary Content of 2,3-dinor-TXB₂ and In Vitro Platelet Aggregation in Healthy Man

Summary

The present study was conducted to compare the effects of oleic (OA) and linoleic acids (LA) on platelet function in healthy subjects. After a 4-week period on a diet rich in saturated fatty acids (SAFA), 38 volunteers (20 female, 18 male) had a high OA (18.0 en%) diet or a high LA diet (11.5 en%) for four weeks in a controlled manner. A control group of 13 subjects consumed their habitual diet throughout the study.

Replacing the SAFA diet by the OA or LA diet did not affect the membrane-associated activity of platelet protein kinase C (PKC). However, both diets tended to increase the cytosolic activity to a comparable extent. Both the OA and the LA diets increased urinary excretion of 2,3-dinor-TXB₂, as compared to the SAFA diet, whereas the urinary excretion of β-thromboglobulin remained unchanged. As compared to the initial SAFA diet, platelet aggregation to collagen increased after both diets, while ADP induced aggregation showed no diet-induced changes. The results indicate increased platelet activity after both oil diets with no differences between the OA and LA diet and confirm in vitro findings that cis-unsaturated fatty acids have a distinct effect on cytosolic PKC, in particular.

• References

• 1 Mattson FH, Grundy SM. Comparison of the effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on plasma lipids and lipoproteins in man. J Lipid Res 1985; 26: 194-202.
• 2 Valsta LM, Jauhiainen M, Aro A, Katan MB, Mutanen M. Effects of a monounsaturated rapeseed oil and a polyunsaturated sunflower oil diet on lipoprotein levels in humans. Arteriosclerosis Thromb 1992; 12 (01) 50-7.
• 3 Sirtori CR, Tremoli E, Gatti E, Montanari G, Sirtori M, Colli S, Gianfranceschi G, Maderna P, Dentone CZ, Testolin G, Galli C. Controlled evaluation of fat intake in the Mediterranean diet: comparative activities of olive oil and corn oil on plasma lipids and platelets in high-risk patients. Am J Clin Nutr 1986; 44: 635-42.
• 4 Reaven P, Parthasarathy S, Grasse BJ, Miller E, Almazan F, Mattson FH, Khoo JC, Steinberg D, Witztum JL. Feasibility of using an oleate-rich diet to reduce the susceptibility of low-density lipoprotein to oxidative modification in humans. Am J Clin Nutr 1991; 54: 701-6.
• 5 Abbey M, Belling GB, Noakes M, Hirata F, Nestel PJ. Oxidation of low-density lipoproteins: intraindividual variability and the effect of dietary linoleate supplementation. Am J Clin Nutr 1993; 57: 391-8.
• 6 Mutanen M, Freese R, Valsta LM, Ahola I, Ahlström A. Rapeseed oil and sunflower oil diets enhance platelet in vitro aggregation and thromboxane production in healthy men when compared with milk fat or habitual diets. Thromb Haemost 1992; 67 (03) 352-6.
• 7 Barradas MA, Christofides JA, Jeremy JY, Mikhailidis DP, Fry DE, Dandona P. The effect of olive oil supplementation on human platelet function, serum cholesterol-related variables and plasma fibrinogen concentrations: a pilot study. Nutr Res 1990; 10: 403-11.
• 8 Mutanen M. Cis-unsaturated fatty acids and platelet function. Prostaglandins Leukot Essent Fatty acids 1997; 57 (04) 403-10.
• 9 Hornstra G, Lewis B, Chait A, Turpeinen O, Karvonen MJ, Vergroesen AJ. Influence of dietary fat on platelet function in men. Lancet 1973; i: 1155-7.
• 10 Fleischman AI, Justice D, Bierenbaum ML, Stier A, Sullivan A. Beneficial effect of increased dietary linoleate upon in vivo platelet function in man. J Nutr 1975; 105 (10) 1286-90.
• 11 Fleischman AI, Bierenbaum ML, Justice D, Stier A, Sullivan A, Fleischman M. Titrating dietary linoleate to in vivo platelet function in man. Am J Clin Nutr 1975; 28 (06) 601-5.
• 12 Renaud S. Linoleic acid, platelet aggregation and myocardial infarction. Atherosclerosis 1990; 80: 255-6.
• 13 Folch J, Lees M, Sloane-Stanley GHS. A simple method for isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 226: 497-509.
• 14 Stoffel W, Chu F, Ahrens Jr. EH. Analysis of long-chain fatty acids by gas-liquid chromatography. Anal Chem 1959; 31: 307-8.
• 15 Prisco D, Rogasi PG, Matucci M, Abbate R, Gensini GF, Serneri GGN. Increased thromboxane A2 generation and altered membrane fatty acid composition in platelets from patients with active angina pectoris. Thromb Res 1986; 44: 101-2.
• 16 Turpeinen AM, Wübert J, Aro A, Lorenz R, Mutanen M. Similar effects of diets rich in stearic acid or trans fatty acids on platelet function and endothelial prostacyclin production in humans. Arterioscler Thromb Vasc Biol 1998; 18: 316-22.
• 17 Khan WA, Blobe GC, Hannun YA. Activation of protein kinase C by oleic acid. J Biol Chem 1992; 267: 3605-12.
• 18 Berens ME, Salmon SE, Davis TP. Quantitative analysis of prostaglandins in cell culture medium by high-resolution gas chromatography with electron capture detection. J Chrom 1984; 307: 251-60.
• 19 Pradelles P, Grassi J, Maclouf J. Enzyme immunoassays of eicosanoids using acetylcholinesterase. Methods Enzymol 1990; 187: 24-34.
• 20 Hjemdahl P, Perneby C, Theodorsson E, Egberg N, Larsson PT. A new assay for β-thromboglobulin in urine. Thromb Res 1991; 64: 33-43.
• 21 Born GVR. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-9.
• 22 Systat: Statistics, Version 5.2 Edition. Evanston IL. Systat, Inc.; 1992: 724 pp.
• 23 Hannun YA, Greenberg CS, Bell RM. Sphingosine inhibition of agonist-dependent secretion and activation of human platelets implies that protein kinase C is a necessary and common event of the signal transduction pathways. J Biol Chem 1987; 262: 13620-6.
• 24 Naor Z, Shearman MS, Kishimoto A, Nishizuka Y. Calcium-independent activation of hypothalamic type I PKC by unsaturated fatty acids. Mol Endocr 1988; 2: 1043-8.
• 25 Yoshida K, Asaoka Y, Nishizuka Y. Platelet activation by simultaneous actions of diacylglycerol and polyunsaturated fatty acids. Proc Natl Acad Sci USA 1992; 89: 6443-6.
• 26 Khan WA, Blobe G, Halpern A, Taylor W, Wetsel WC, Burns D, Loomis C, Hannun YA. Selective regulation of protein kinase C isoenzymes by oleic acid in human platelets. J Biol Chem 1993; 268 (07) 5063-8.
• 27 Baldassare JJ, Henderson PA, Burns D, Loomis C, Fisher GJ. Translocation of protein kinase C isozymes in thrombin-stimulated human platelets. J Biol Chem 1992; 267 (22) 15585-90.
• 28 Blair IA, Prakash C, Phillips MA, Dougherty RM, Iacono JM. Dietary modification of w6 fatty acid intake and its effect on urinary eicosanoid excretion. Am J Clin Nutr 1993; 57: 154-60.
• 29 Adam O, Wolfram G. Effect of different lionleic acid intakes on prostaglandin biosynthesis and kidney function in man. Am J Clin Nutr 1984; 40: 763-70.
• 30 Epstein M, Lifschitz M, Rappaport K. Augmentation of prostaglandin production by linoleic acid in man. Clin Sci 1982; 63: 565-71.
• 31 Freese R, Mutanen M. Alpha-linolenic acid and marine long-chain n-3 fatty acids only slightly differ in their effects on hemostatic factors in healthy subjects. Am J Clin Nutr 1997; 66: 591-5.
• 32 van Oost BA, Veldhuyzen B, Timmermans APM, Sixma JJ. Increased urinary β-thromboglobulin excretion in diabetes assayed with a modified RIA kit-techique. Thromb Haemost 1983; 49 (01) 18-20.
• 33 de Boer AC, Han P, Turpie AGG, Zielinsky A, Genton E. Plasma and urine beta-thromboglobulin concentration in patients with deep vein thrombosis. Blood 1981; 58 (04) 693-8.
• 34 Doyle DJ, Chesterman CN, Cade JF, McGready JR, Rennie GC, Morgan FJ. Plasma concentrations of platelet specific proteins with platelet survival. Blood 1980; 55: 82-4.
• 35 Ghaddar HM, Cortes J, Salomaa V, Kark JD, Davis CE, Folsom AR, Heiss G, Stinson V, Wu KK. Correlation of specific platelet activation markers with carotid arterial wall thickness. Thromb Haemost 1995; 74 (03) 943-8.
• 36 Burri BJ, Dougherty RM, Kelley DS, Iacono JM. Platelet aggregation in humans is affected by replacement of dietary linoleic acid with oleic acid. Am J Clin Nutr 1991; 54: 359-62.
• 37 Kwon JS, Snook JT, Wardlaw GM, Hwang DH. Effects of diets high in saturated fatty acids, canola oil, or safflower oil on platelet function, thromboxane B₂ formation, and fatty acid composition of platelet phospholipids. Am J Clin Nutr 1991; 54: 359-62.
• 38 McDonald BE, Gerrard JM, Bruce VM, Corner EJ. Comparison of the effect of canola oil and sunflower oil on plasma lipids and lipoproteins and on in vivo thromboxane A₂ and prostacyclin production in healthy young men. Am J Clin Nutr 1989; 50: 1382-8.
• 39 Renaud S, Godsey F, Dumont E, Thevenon C, Ortchanian E, Martin JL. Influence of long-term diet modification on platelet function and composition in Moselle farmers. Am J Clin Nutr 1986; 43: 136-50.
• 40 Freese R, Mutanen M, Valsta LM, Salminen I. Comparison of the effects of two diets rich in monounsaturated FAs differing in their linoleic/a-linolenic scid ratio on platelet aggregation. Thromb Haemost 1994; 71: 73-7.
• 41 Challen AD, Branch WJ, Cummings JH. The effects of aspirin and linoleic acid on platelet aggregation, platelet fatty acid composition and haemostasis in man. Hum Nutr Clin Nutr 1983; 37C: 197-208.