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The hypocholesterolaemic effects of sitostanol in the guinea pig are in part related to changes in hepatic lipids and lipoprotein composition

Published online by Cambridge University Press:  09 March 2007

Tripurasundari Ramjiganesh*
Affiliation:
Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA
Suheeta Roy
Affiliation:
Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA
Jonathan C. McIntyre
Affiliation:
Monsanto Company, St. Louis, MO, 63167, USA
Maria Luz Fernandez
Affiliation:
Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA
*
*Corresponding author: fax +1 860 486 3674, email: [email protected]
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Abstract

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To evaluate some of the mechanisms involved in the plasma cholesterol lowering of sitostanol (SI), male Hartley guinea pigs were fed diets containing cholesterol (0.25 g/100 g) and four doses of SI: either 0 (control), 0.75, 1.5 or 2.25 g/100 g. In addition a negative control (-C) group with dietary cholesterol (0.04 g/100 g) was included. Corn oil was used as the source of fat and the contribution of fat energy was 35 %. Plasma total cholesterol was 43, 49 and 53 % (P<0.0001) lower after SI intake compared to the control. Plasma LDL concentrations were 47, 53 and 61 % lower with increasing doses of SI. In addition, intake of SI resulted in 26–42 % lower hepatic total cholesterol. Hepatic esterified cholesterol and triacylglycerols were 32–60 % and 55–61 % lower after SI intake. SI intake resulted in favourable plasma and hepatic cholesterol concentrations similar to those in guinea pigs fed low levels of dietary cholesterol (-C). The LDL obtained from the control group had a higher number of molecules of free and esterified cholesterol than the SI groups. SI intake resulted in 69–71 % higher cholesterol excretion compared to the control. SI treatment enhanced the total faecal neutral sterol excretion by 54–58 % compared to control and by 70–76 % compared to the (-C) group. These results suggest that SI might have its hypocholesterolaemic effect by reducing cholesterol absorption, which results in lower concentration of cholesterol in liver. This reduction in hepatic cholesterol might possibly alter hepatic cholesterol metabolism and affect lipoprotein concentration and composition.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2001

References

Allain, C, Poon, L, Chan, C, Richmond, W & Fu, P (1974) Enzymatic determination of total serum cholesterol. Clinical Chemistry 20, 470475.CrossRefGoogle ScholarPubMed
Becker, M, Staab, D & Von-Bergmann, K (1993) Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. Journal of Pediatrics 122, 292296.CrossRefGoogle ScholarPubMed
Carr, T, Andressen, CJ & Rudel, LL (1993) Enzymatic determination of triglyceride, free cholesterol and total cholesterol in tissue lipid extracts. Clinical Biochemistry 26, 3942.CrossRefGoogle ScholarPubMed
Chapman, JM, Mills, GL & Ledford, JH (1975) The distribution and partial characterization of the serum apolipoproteins in the guinea pig. Biochemistry Journal 149, 423436.CrossRefGoogle ScholarPubMed
Child, P & Kuksis, A (1986) Investigation in the role of micellar phospholipid in the preferential uptake of cholesterol over sitosterol by dispersed rat jejunal villus cells. Biochemistry and Cell Biology 64, 847853.CrossRefGoogle ScholarPubMed
Daggy, BP, O'Connell, NC, Jerdack, GR, Stinson, GR & Setchell, KDR (1997) Additive hypocholesterolemic effect of psyllium and cholestyramine in the hamster: influence on fecal sterol and bile acid profiles. Journal of Lipid Research 38, 491502.CrossRefGoogle ScholarPubMed
Dietshy, JM, Turley, SD & Spady, DK (1993) Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. Journal of Lipid Research 34, 16371657.CrossRefGoogle Scholar
Fernandez, ML & McNamara, DJ (1994) Regulation of cholesterol and lipoprotein metabolism in the guinea pig mediated by dietary fat quality and quantity. Journal of Nutrition 121, 934943.CrossRefGoogle Scholar
Fernandez, ML, Lin, ECK & McNamara, DJ (1992) Regulation of low density lipoprotein kinetics by dietary fat saturation. Journal of Lipid Research 33, 97109.CrossRefGoogle ScholarPubMed
Fernandez, ML, Abdel-Fattah, G & McNamara, DJ (1993) Dietary fat saturation modifies the metabolism of LDL subfractions in guinea pigs. Arteriosclerosis and Thrombosis 13, 14181428.CrossRefGoogle Scholar
Fernandez, ML, Sun, DM, Montano, C & McNamara, DJ (1995) Carbohydrate-fat exchange and regulation of hepatic cholesterol and plasma lipoprotein metabolism in the guinea pig. Metabolism 44, 855864.CrossRefGoogle ScholarPubMed
Fernandez, ML, Wilson, TA, Conde, K, Vegara-Jimnez, M & Nicolosi, RJ (1999) Hamsters and guinea pigs differ in the plasma lipoprotein cholesterol when fed diets varying in animal protein, soluble fiber or cholesterol content. Journal of Nutrition 129, 13231332.CrossRefGoogle ScholarPubMed
Fungwe, TV, Cagan, LM, Cook, GA, Wolcox, HG & Heimberg, M (1993) Dietary cholesterol stimulates hepatic bio-synthesis of triglyceride and reduces oxidation of fatty acids in the rat. Journal of Lipid Research 34, 933941.CrossRefGoogle Scholar
Ginsberg, HN (1990) Lipoprotein physiology and its relationships to atherogenesis. Endocrinology and Metabolism Clinics of North America 19, 211222.CrossRefGoogle ScholarPubMed
Gylling, H & Miettinen, TA (1996) Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin dependent diabetic men. Journal of Lipid Research 837, 17761785.CrossRefGoogle Scholar
Gylling, H, Puska, P, Vartiainen, E & Miettinen, TA (1999) Serum sterols during stanol ester feeding in a mildly hypercholesterolemic population. Journal of Lipid Research 40, 593600.CrossRefGoogle Scholar
Hallikainen, MA, Sarkkinen, ES & Uusitupa, MI (2000) Plant stanol esters affect serum cholesterol concentrations of hypercholesterolemic men and women in a dose-dependent manner. Journal of Nutrition 130. 4767–776.CrossRefGoogle ScholarPubMed
Heinemann, T, Pietruck, B, Kullak-Ublick, G & Von-Bergmann, K (1988) Comparison of sitosterol and sitostanol inhibition of intestinal cholesterol absorption. Agents and Actions 26, S117-S122.Google ScholarPubMed
Heinemann, T, Pietruck, B, Kullak-Ublick, G & Von-Bergmann, K (1991) Mechanisms of action of plant sterols on inhibition of cholesterol absorption. Comparison of sitosterol and sitostanol. European Journal of Clinical Pharmacology 40, S59-S63.CrossRefGoogle ScholarPubMed
Heinemann, T, Axtmann, G & Von-Bergmann, K (1993) Comparison of intestinal absorption of cholesterol with different plant sterols in man. European Journal of Clinical Investigation 23, 827831.CrossRefGoogle ScholarPubMed
Holmquit, L, Carlson, K & Carlson, AL (1987) Comparisons between the use of isopropanol and tetramethyl urea for the solubilization and quantitation of human serum very low-density lipoproteins. Analytical Biochemistry 88, 457460.Google Scholar
Ikeda, I & Sugango, M (1983) Some aspects of mechanism of inhibition of cholesterol absorption by beta-sitosterol. Biochimica et Biophysica Acta 732, 651658.CrossRefGoogle ScholarPubMed
Lees, AM, Mok, HY, Lees, RS, McCluskey, MA & Grundy, SM (1977) Plant sterols as cholesterol lowering agents: clinical trials in patients with hypercholesterolemia and studies of sterol balance. Atherosclerosis 28, 325338.CrossRefGoogle ScholarPubMed
Lin, ECK, Fernandez, ML & McNamara, DJ (1994) Dietary fat type and cholesterol quantity interact to affect cholesterol metabolism in guinea pigs. Journal of Nutrition 122, 20192029.CrossRefGoogle Scholar
Markwell, MAS, Haas, SM, Bieber, LL & Tolbert, NE (1978) A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Annals of Biochemistry 87, 206210.CrossRefGoogle ScholarPubMed
Mattson, FH, Volpenhein, RA & Erickson, BA (1977) Effect of plant sterol esters on the absorption of dietary cholesterol. Journal of Nutrition 107, 11391146.CrossRefGoogle Scholar
McNamara, DJ (1992) Dietary fatty acids, lipoproteins and cardiovascular disease. Advances in Food and Nutrition Research 36, 251253.Google ScholarPubMed
Miettinen, TA, Puska, P, Gylling, H, Vanhanen, H & Vartiainen, E (1995) Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. New England Journal of Medicine 333, 13081312.CrossRefGoogle Scholar
Nestel, P, Billington, N, Tada, P, Nugent, P & Fidge, N (1983) Heterogenity of very-low-density lipoprotein metabolism in hyperlipidemic subjects. Metabolism 32, 810817.CrossRefGoogle ScholarPubMed
Ntanios, FY & Jones, PJ (1998) Effects of variable dietary sitostanol concentrations on plasma lipid [profile and phytosterol metabolism in hamsters]. Biochimica et Biophysica Acta 1390, 237244.CrossRefGoogle ScholarPubMed
Ntanios, FY & Jones, PJ (1999) Dietary sitostanol reciprocally influences cholesterol absorption in hamsters and rabbits. Atherosclerosis 143, 341351.CrossRefGoogle ScholarPubMed
Ntanios, FY, MacDougall, DE & Jones, PJ (1998) Gender effects of tall oil versus soybean phytosterols as cholesterol lowering agents in hamsters. Candian Journal of Physiology and Pharmacology 76, 780787.CrossRefGoogle ScholarPubMed
Oshry, R, Olivecrona, T, Deckelbaum, RJ & Eisenberg, S (1985) Is hypertriglyceridemic very low density lipoprotein a precursor of normal low density lipoprotein? Journal of Lipid Research 26, 158167.CrossRefGoogle Scholar
Pelletier, X, Belbraouet, S, Mirabel, D, Mordret, F, Perrin, JL, Pages, X & Debry, G (1995) A diet moderately enriched in phytosterols lowers plasma cholesterol concentrations in normocholesterolemic men. Annals of Nutrition and Metabolism 39, 291295.CrossRefGoogle Scholar
Redgrave, T, Roberks, C & West, C (1975) Separation of plasma lipoproteins by density gradient ultracentrifugation. Annals of Biochemistry 65, 4249.CrossRefGoogle ScholarPubMed
Rong, N, Ausman, LM & Nicolosi, RJ (1997) Oryzanol decreases cholesterol absorption and aortic fatty streak in hamsters. Lipids 32, 303309.CrossRefGoogle ScholarPubMed
Salen, G, Ahrens, EH & Grundy, SM (1970) Metabolism of beta-sitosterol in man. Journal of Clinical Investigation 49, 952967.CrossRefGoogle ScholarPubMed
Stamler, J, Wentforth, D & Neaton, JD (1986) Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356 222 primary screens of the multiple risk factor intervention trial (MR-FIT). JAMA 256, 28232828.CrossRefGoogle Scholar
Sugano, M, Kamo, F & Ikeda, I (1976) Lipid lowering effect of phytostanols in rats. Atherosclerosis 24, 301309.CrossRefGoogle ScholarPubMed
Sugano, M, Morioka, H & Ikeda, I (1977) A comparison of hypocholesterolemic activity of beta sitosterol and beta-sitostanol in rats. Journal of Nutrition 107, 20112019.CrossRefGoogle ScholarPubMed
Swell, L, Field H, Jr & Treadwell, CR (1960) Absorption of cholesterol-4-C14 oleate. Proceedings for the Society of Experimental Biology and Medicine 103, 263266.CrossRefGoogle ScholarPubMed
Swell, L, Boiter, TA, Field H, Jr & Treadwell, CR (1955) Absorption of dietary cholesterol esters. American Journal of Physiology. 180, 129132.CrossRefGoogle ScholarPubMed
Warnick, GR, Bederson, J & Albers, JJ (1992) Dextran-sulfate-Mg+2 precipitation procedure for quantitation of high density lipoprotein cholesterol. Clinical Chemistry 28, 1397–1388.Google Scholar
Weihrauch, JL & Gardner, JM (1978) Sterol content of foods of plant origin. Journal of American Dietetics Association 73, 3947.CrossRefGoogle ScholarPubMed
Weststrate, JA & Meijer, GW (1998) Plant sterol-enriched margarines and reduction of plasma total- and LDL-cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects. European Journal of Clinical Nutrition 52, 334343.CrossRefGoogle ScholarPubMed
Wilson, MD & Rudel, LL (1994) Review of cholesterol absorption with emphasis on dietary and biliary cholesterol. Journal of Lipid Research 35, 943953.CrossRefGoogle ScholarPubMed
VanHeek, M & Zilversmit, D (1991) Mechanisms of hypertriglyceridemia in the coconut oil/cholesterol-fed rabbit. Increased secretion and decreased catabolism of VLDL. Arteriosclerosis and Thrombosis. 11, 918927.CrossRefGoogle Scholar
Vuorio, AF, Gylling, H, Turtola, H, Kontula, K, Ketonen, P & Miettinen, TA (2000) Stanol ester margarine alone and with Simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-north karelia mutation. Arteriosclerosis, Thrombosis and Vascular Biology 20, 500506.CrossRefGoogle ScholarPubMed