Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-26T01:16:39.996Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of esterified 4-desmethylsterols and -stanols or 4,4′-dimethylsterols on cholesterol and bile acid metabolism in hamsters

Published online by Cambridge University Press:  09 March 2007

Elke A. Trautwein ,
Claudia Schulz ,
Dörte Rieckhoff ,
Angelika Kunath-Rau ,
Helmut F. Erbersdobler ,
W. Arjan de Groot  and
Gert W. Meijer
Elke A. Trautwein*
Affiliation:
Unilever Research, Vlaardingen, The Netherlands
Claudia Schulz
Affiliation:
University of Kiel, Institute of Human Nutrition and Food Science, Kiel, Germany
Dörte Rieckhoff
Affiliation:
University of Kiel, Institute of Human Nutrition and Food Science, Kiel, Germany
Angelika Kunath-Rau
Affiliation:
University of Kiel, Institute of Human Nutrition and Food Science, Kiel, Germany
Helmut F. Erbersdobler
Affiliation:
University of Kiel, Institute of Human Nutrition and Food Science, Kiel, Germany
W. Arjan de Groot
Affiliation:
Unilever Research, Vlaardingen, The Netherlands
Gert W. Meijer
Affiliation:
Lipton, 800 Sylvan Ave, Englewood Cliffs, New Jersey, USA
*
*Corresponding author: Elke A. Trautwein, fax +31 10 460 5993, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

4-Desmethylsterols and -stanols reduce plasma total cholesterol (TC) and LDL cholesterol by inhibition of intestinal cholesterol absorption, while the cholesterol-lowering potential of 4,4′-dimethylsterols is less well defined. The present study aimed to compare the effects of 4-desmethylsterols, -stanols, and 4,4′-dimethylsterols on plasma and hepatic cholesterol, sterol excretion and bile acid metabolism. Male golden Syrian hamsters were fed diets containing 13 g/100 g fat, 0·08 g/100 g cholesterol and 0 (control), 0·24 or 0·48 % (w/w) esterified 4-desmethylsterols (sterols) and esterified hydrogenated 4-desmethylsterols (stanols) from common vegetable oils or esterified 4,4′-dimethylsterols from rice bran oil for 5 weeks. Sterol and stanol esters at the dose of 0·24 % were equally effective and significantly (P<0·05) lowered TC by 15 %, while 0·24 % 4,4-dimethylsterols reduced TC by 10 %. Liver total and esterified cholesterol concentrations were significantly (P<0·05) lowered by 40, 22, 43 and 31 % in hamsters fed 0·48 % sterols, 0·24 % stanols, 0·48 % stanols or 0·48 % dimethylsterols, respectively. Daily faecal bile acid excretion and hepatic cholesterol 7α-hydroxylase activity were not altered, indicating that sterols, stanols and dimethylsterols had no effect on the intestinal re-absorption of bile acids or on hepatic bile acid synthesis. Daily excretion of cholesterol was significantly higher in hamsters fed esterified sterols and stanols, but was only slightly increased in those fed dimethylsterols. The results indicate that esterified sterols and stanols were equally effective in lowering plasma TC and LDL cholesterol, while dimethylsterol esters caused a weaker cholesterol-lowering effect. Sterols and stanols achieve their cholesterol-lowering effect by stimulating faecal cholesterol excretion through inhibiting intestinal cholesterol absorption, but do not affect bile acid excretion. Other mechanisms need to be considered to explain the effect on plasma and hepatic cholesterol of dimethylsterols.

Keywords

4-Desmethylsterols4-Desmethylstanols4,4-DimethylsterolsPlasma lipidsBile acidsFaecal sterol excretionHamster
Type
Research Article
Information
British Journal of Nutrition , Volume 87 , Issue 3 , March 2002 , pp. 227 - 237
Copyright
Copyright © The Nutrition Society 2002

References

Begemann, F, Bandomer, G & Herget, HJ (1978) The influence of beta-sitosterol on biliary cholesterol saturation and bile acid kinetics in man. Scandinavian Journal of Gastroenterology 13, 57–63.CrossRefGoogle ScholarPubMed
Boberg, KM, Akerlund, J-E & Björkhem, I (1989) Effect of sitosterol on the rate-limiting enzymes in cholesterol synthesis and degradation. Lipids 24, 9–12.CrossRefGoogle ScholarPubMed
Chiang, JYL (1991) Reversed-phase high-performance liquid chromatography assay of cholesterol 7α-hydroxylase. Methods of Enzymology 206, 483–491.CrossRefGoogle Scholar
DeDeckere, EAM & Korver, O (1996) Minor constituents of rice bran oil as functional foods. Nutrition Reviews 54, S120–S126.CrossRefGoogle Scholar
Goulinet, S & Chapman, MJ (1993) Plasma lipoproteins in the golden Syrian hamster (Mesocricetus auratus): heterogeneity of apo B- and apo A1-containing particles. Journal of Lipid Research 34, 943–959.CrossRefGoogle Scholar
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 37, 1776–1785.CrossRefGoogle ScholarPubMed
Gylling, H, Siimes, MA & Miettinen, TA (1995) Sitostanol ester margarine in dietary treatment of children with familiar hypercholesterolemia. Journal of Lipid Research 36, 1807–1812.CrossRefGoogle Scholar
Hallikainen, MA, Sarkkinen, ES & Uusitupa, MIJ (2000) Plant stanol esters affect serum cholesterol concentrations of hypercholesterolemic men and women in a dose-dependent manner. Journal of Nutrition 130, 767–776.CrossRefGoogle ScholarPubMed
Havel, RJ, Eder, HA & Bragdon, JH (1955) The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. Journal of Clinical Investigation 34, 1345–1353.CrossRefGoogle ScholarPubMed
Hayes, KC, Stephan, ZF, Pronczuk, A, Lindsey, S & Verdon, C (1989) Lactose protects against estrogen-induced pigment gallstones in hamsters fed nutritionally adequate purified diets. Journal of Nutrition 119, 1726–1736.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, 827–831.CrossRefGoogle ScholarPubMed
Hendriks, HFJ, Weststrate, JA, Van Vliet, T & Meijer, GW (1999) Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocho-lesterolaemic and mildly hypercholesterolaemic subjects. European Journal of Clinical Nutrition 153, 319–327.CrossRefGoogle Scholar
Hylemon, PB, Studer, EJ, Pandak, WM, Heuman, DM, Vlahcevic, ZR & Chiang, JYL (1989) Simultaneous measurement of cholesterol 7α-hydroxylase activity by reversed-phase high performance liquid chromatography using both endogenous and exogenous [4-14C]cholesterol as substrate. Analytical Biochemistry 182, 212–216.CrossRefGoogle Scholar
Ikeda, I, Kawasaki, A, Samezima, K & Sugano, M (1981) Antihypercholesterolemic activity of β-sitostanol in rabbits. Journal of Nutritional Science and Vitaminology 27, 243–251.CrossRefGoogle ScholarPubMed
Ikeda, I, Nakashima-Yoshida, K & Sugano, M (1985) Effects of cycloartenol on absorption and serum levels of cholesterol in rats. Journal of Nutritional Science and Vitaminology 31, 375–384.CrossRefGoogle ScholarPubMed
Ikeda, I & Sugano, M (1978) Comparison of absorption and metabolism of β-sitosterol and β-sitostanol in rats. Atherosclerosis 30, 227–237.CrossRefGoogle ScholarPubMed
Ikeda, I & Sugano, M (1983) Some aspects of mechanism of inhibition of cholesterol absorption by β-sitosterol. Biochimica et Biophysica Acta 732, 651–658.CrossRefGoogle ScholarPubMed
Ikeda, I, Tanaka, K, Sugano, M, Vahouny, GV & Gallo, LL (1988) Inhibition of cholesterol absorption in rats by plant sterols. Journal of Lipid Research 29, 1573–1582.CrossRefGoogle ScholarPubMed
Imray, CHE, Minoura, T, Davis, A, Radley, S, Newbold, KM, Lavelle-Jones, M, Lawson, AM, Baker, PR & Neoptolemos, JP (1992) Comparability of hamsters with human faecal unconjugated bile acids in a model of colorectal cancer. Anticancer Research 12, 553–558.Google Scholar
Jones, PJH, MacDougall, DE, Ntanios, F & Vanstone, C (1997) Dietary phytosterols as cholesterol-lowering agents in humans. Canadian Journal of Physiology and Pharmacology 75, 217–227.CrossRefGoogle ScholarPubMed
Jones, PJH, Raeini-Sarjaz, M, Ntanios, F, Vanstone, CA, Feng, JY & Parsons, W (2000) Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. Journal of Lipid Research 41, 697–705.CrossRefGoogle ScholarPubMed
Kris-Etherton, PM & Dietschy, J (1997) Design criteria for studies examining individual fatty acid effects on cardiovascular disease risk factors: human and animal studies. American Journal of Clinical Nutrition 65 Suppl., 1590S–1596S.CrossRefGoogle ScholarPubMed
Kuroki, S, Muramoto, S, Kuramoto, T & Hoshita, T (1983) Effect of feeding cholesterol and sitosterol on hepatic steroid 12α-hydroxylase activity in female hamsters. Journal of Pharmcological Dynamics 6, 551–557.Google ScholarPubMed
Ling, WH & Jones, PJH (1995 a) Dietary phytosterols. A review of metabolism, benefits and side effects. Life Sciences 57, 195–206.CrossRefGoogle ScholarPubMed
Ling, WH & Jones, PJH (1995 b) Enhanced efficacy of sitostanol-containing versus sitostanol-free phytosterols mixtures in altering lipoprotein cholesterol levels and synthesis in rats. Atherosclerosis 118, 319–331.CrossRefGoogle ScholarPubMed
Markwell, MAK, Haas, SM, Bieber, LL & Tolbert, NE (1978) A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Analytical Biochemistry 87, 206–210.CrossRefGoogle 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, 1308–1312.CrossRefGoogle Scholar
Miettinen, TA & Vanhanen, HT (1994) Dietary sitosterol related to absorption, synthesis and serum levels of cholesterol in different apolipoprotein E phenotypes. Atherosclerosis 106, 217–226.CrossRefGoogle Scholar
Miettinen, TA, Vuoristo, M, Nissinen, M, Järvinen, HJ & Gylling, H (2000) Serum, biliary, and fecal cholesterol and plant sterols in colectomized patients before and during consumption of stanol ester margarine. American Journal of Clinical Nutrition 71, 1095–1102.CrossRefGoogle ScholarPubMed
Nagao, K, Sato, M, Takenaka, M, Ando, M, Iwamoto, M & Imaizumi, K (2001) Feeding unsaponifiable compounds from rice bran oil does not alter hepatic mRNA abundance for cholesterol metabolism-related proteins in hypercholesterolemic rats. Bioscience, Biotechnology & Biochemistry 65, 371–377.CrossRefGoogle Scholar
Nguyen, TT, Dale, LC, von Bergmann, K & Croghan, IT (1999) Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women: a randomized controlled trial. Mayo Clinic Proceedings 74, 1198–1206.CrossRefGoogle Scholar
Normen, L, Dutta, P, Lia, A & Andersson, H (2000) Soy sterol esters and β-sitostanol ester as inhibitors of cholesterol absorption in human small bowel. American Journal of Clinical Nutrition 71, 908–913.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, 237–244.CrossRefGoogle ScholarPubMed
Pollak, OJ & Kritchevsky, D (1981) Sitosterol. In Monographs on Atherosclerosis, Vol. 10, [Clarkson, TB and Kritchevsky, D, editors]. New York, Basel: CABI Publishing on behalf of the Nutrition Society.Google Scholar
Rossi, SS, Converse, JL & Hofmann, AF (1987) High pressure liquid chromatographic analysis of conjugated bile acids in human bile: simultaneous resolution of sulfated and unsulfated lithocholyl amidates and the common conjugated bile acids. Journal of Lipid Research 28, 589–595.CrossRefGoogle ScholarPubMed
Shefer, S, Hauser, S, Lapar, V & Mosbach, EH (1973) Regulatory effects of sterols and bile acids on hepatic 3-hydroxy-3-methylglutaryl CoA reductase and cholesterol 7α-hydroxylase in the rat. Journal of Lipid Research 14, 573–580.CrossRefGoogle Scholar
Shefer, S, Salen, G, Bullock, J, Nguyen, LB, Ness, GC, Vhao, Z, Belamarich, PF, Chowdhary, I, Lerner, S, Batta, AK & Tint, GS (1994) The effect of increased hepatic sitosterol on the regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7α-hydroxylase in the rat and sitosterolemic homozygotes. Hepatology 20, 213–219.Google Scholar
Sierksma, A, Weststrate, JA & Meijer, GW (1999) Spreads enriched with plant sterols, either esterified 4,4 dimethylsterols or free 4-desmethylsterols, and plasma total and LDL-cholesterol concentrations. British Journal of Nutrition 82, 273–282.CrossRefGoogle ScholarPubMed
Spady, DK, Stange, EF, Bilhartz, LE & Dietschy, JM (1986) Bile acids regulate hepatic low density lipoprotein receptor activity in the hamster by altering cholesterol flux across the liver. Proceedings of the National Academy Sciences USA 83, 1916–1920.CrossRefGoogle ScholarPubMed
Spady, DK, Turley, SD & Dietschy, JM (1985) Rates of low density lipoprotein uptake and cholesterol synthesis are regulated independently in the liver. Journal of Lipid Research 26, 465–472.CrossRefGoogle ScholarPubMed
Suckling, KE, Benson, GM, Bond, B, Gee, A, Glen, A, Haynes, C & Jackson, B (1991) Cholesterol lowering and bile acid excretion in the hamster with cholestyramine treatment. Atherosclerosis 89, 183–190.CrossRefGoogle ScholarPubMed
Sugano, M, Kamo, F, Ikeda, I & Morioka, H (1976) Lipid-lowering activity of phytostanols in rats. Atherosclerosis 24, 301–309.CrossRefGoogle ScholarPubMed
Sugano, M, Morioka, H & Ikeda, I (1977) A comparison of hypocholesterolemic activity of β-sitosterol and β-sitostanol in rats. Journal of Nutrition 107, 2011–2019.Google Scholar
Sugano, M & Tsuji, E (1997) Rice bran oil and cholesterol metabolism. Journal of Nutrition 127, 521S–524S.CrossRefGoogle ScholarPubMed
Tangedahl, TN, Thiste, JL, Hofmann, AF & Matsehe, JW (1979) Effect of beta-sitosterol alone or in combination with chenic acid on cholesterol saturation of bile and cholesterol absorption in gallstones patients. Gastroenterology 76, 1341–1346.CrossRefGoogle ScholarPubMed
Trautwein, EA, Kunath-Rau, A, Dietrich, J, Drusch, S & Erbersdobler, HF (1997) Effect of dietary fats rich in lauric, myristic, palmitic, oleic or linoleic acid on plasma, hepatic and biliary lipids in cholesterol-fed hamsters. British Journal of Nutrition 77, 605–620.CrossRefGoogle ScholarPubMed
Trautwein, EA, Liang, J & Hayes, KC (1993 a) Cholesterol gallstone induction in hamsters reflect strain differences in plasma lipoproteins and bile acid profiles. Lipids 28, 305–312.CrossRefGoogle ScholarPubMed
Trautwein, EA, Siddiqui, A & Hayes, KC (1993 b) Modeling plasma lipoprotein–bile lipid relationships: differential impact of psyllium and cholestyramine in hamsters fed a lithogenic diet. Metabolism 42, 1531–1540.CrossRefGoogle ScholarPubMed
Uchida, K, Takase, H, Nomura, Y, Takeda, K, Takeuchi, N & Ishikawa, Y (1984) Changes in biliary and fecal bile acids in mice after treatments with diosgenin and β-sitosterol. Journal of Lipid Research 25, 236–245.CrossRefGoogle ScholarPubMed
Vanhanen, HT, Kajander, J, Lehtovirta, H & Miettinen, TA (1994) Serum levels, absorption efficiency, faecal elimination and synthesis of cholesterol during increasing doses of dietary sitostanol esters in hypercholesterolaemic subjects. Clinical Science 87, 61–67.CrossRefGoogle ScholarPubMed
Vissers, MN, Zock, PL, Meijer, GW & Katan, MB (2000) Effect of plant sterols from rice bran oil and triterpene alcohols from sheanut oil on serum lipoprotein concentrations in humans. American Journal of Clinical Nutrition 72, 1510–1515.CrossRefGoogle ScholarPubMed
Weststrate, JA, Ayesh, R, Bauer-Plank, C & Drewitt, PN (1999) Safety evaluation of phytosterol esters. Part 4. Faecal concentrations of bile acids and neutral sterols in healthy normolipidaemic volunteers consuming a controlled diet either with or without a phytosterol ester-enriched margarine. Food and Chemistry Toxicology 37, 1063–1071.CrossRefGoogle ScholarPubMed
Weststrate, JA & Meijer, GW (1998) Plant sterol-enriched margarines and reduction of plasma total and LDL-cholesterol concentrations in normocholesterolemic and mildly hypercholesterolemic subjects. European Journal of Clinical Nutrition 52, 334–343.CrossRefGoogle Scholar