Metabolism - Clinical and Experimental
Volume 55, Issue 3 , Pages 292-299 , March 2006

Stigmasterol reduces plasma cholesterol levels and inhibits hepatic synthesis and intestinal absorption in the rat

  • Ashok K. Batta

      Affiliations

    • Department of Medicine, UMDNJ-NJ Medical School, Newark, NJ 07103, USA
    • Department of Veterans Affairs, NJ Health Care System, East Orange, NJ 07018, USA
    • Corresponding Author InformationCorresponding author. GI Section (15A), VA Medical Center, East Orange, NJ 07019, USA. Tel.: +1 201 676 1000/2289; fax: +1 201 676 2991.
    • ,
  • Guorong Xu

      Affiliations

    • Department of Medicine, UMDNJ-NJ Medical School, Newark, NJ 07103, USA
    • Department of Veterans Affairs, NJ Health Care System, East Orange, NJ 07018, USA
    • ,
  • Akira Honda

      Affiliations

    • Division of Gastroenterology and Hepatology, Ibaraki Prefectural Institute of Public Health and University of Tsukuba, Mito, Ibaraki 310-0852, Japan
    • ,
  • Teruo Miyazaki

      Affiliations

    • Division of Gastroenterology and Hepatology, Ibaraki Prefectural Institute of Public Health and University of Tsukuba, Mito, Ibaraki 310-0852, Japan
    • ,
  • Gerald Salen

      Affiliations

    • Department of Medicine, UMDNJ-NJ Medical School, Newark, NJ 07103, USA

Received 1 July 2005 ,Accepted 5 August 2005.

References 

  1. Salen G, Arhens EH, Grundy SM. Metabolism of β-sitosterol in man. J Clin Invest. 1970;49:952–967
  2. Mellies MJ, Ishikawa TT, Glueck CJ, et al. Phytosterols in aortic tissue in adults and infants. J Lab Clin Med. 1976;88:914–921
  3. Koivisto PV, Miettenen TA. Plasma and biliary cholestanol related to steroid metabolism in familial hypercholesterolemia patients with and without ileal exclusion. Clin Chim Acta. 1988;174:197–205
  4. Miettenen TA. Diurnal variation of cholesterol precursors squalene and methyl sterols in human plasma lipoproteins. J Lipid Res. 1982;23:466–473
  5. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292–296
  6. Kuksis A, Myher JJ, Marai L. Usefulness of gas chromatographic profiles of plasma total lipids in diagnosis of phytosterolemia. J Chromatogr. 1986;381:1–12
  7. Miettenen TA, Tilvis RS, Kesaniemi YA. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol. 1990;131:20–31
  8. Lee M-H, Lu K, Hazard S, et al. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet. 2001;27:79–83
  9. Berge KE, Tian H, Graf GA, et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science. 2000;290:1771–1775
  10. Lu K, Lee M-H, Hazard S, et al. Two genes that match to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2 encoded by ABCG5 and ABCG8, respectively. Am J Hum Genet. 2001;69:278–290
  11. Salen G, Tint GS, Shefer S, et al. Increased sitosterol absorption is offset by rapid elimination to prevent accumulation in heterozygotes with sitosterolemia. Arterioscler Thromb. 1992;12:563–568
  12. Aringer L. 7-Hydroxylation of 3-oxygenated C27-, C28-, and C29-steroids in rat liver 18,000 g supernate. J Lipid Res. 1978;19:933–944
  13. Slota T, Kozlov NA, Ammon HV. Comparison of cholesterol and β-sitosterol: effects on jejunal fluid secretion induced by oleate, and absorption from mixed micellar solutions. Gut. 1983;24:653–658
  14. Igel M, Giesa U, Lütjohann D, et al. Comparison of the intestinal uptake of cholesterol, plant sterols, and stanols in mice. J Lipid Res. 2003;44:533–538
  15. Batta AK, Xu G, Bollineni LS, et al. Effect of high plant sterol-enriched diet and cholesterol absorption inhibitor, ezetimibe, on plant sterol absorption and plasma concentrations in hypercholesterolemic wild-type Kyoto (WKY) rats. Metabolism. 2005;54:38–48
  16. Schonheimer R, Behring H, Hummel RH. Uber die spezifitat der resorption von sterin, abhanging von ihren konstitution. Hoppe-Seyler Z Physiol Chem. 1930;192:117–124
  17. Vahouny GV, Connor WE, Subramaniam S, et al. Comparative lymphatic absorption of sitosterol, stigmasterol, and fucosterol and differential inhibition of cholesterol absorption. Am J Clin Nutr. 1983;37:805–809
  18. Lees AM, Mok HYI, McCluskey MA, et al. Plant sterols as cholesterol-lowering agents: clinical trial in patients with hypercholesterolemia and studies of sterol balance. Atherosclerosis. 1977;28:325–338
  19. Grundy SM, Arhens EH, Davignon J. The interaction of cholesterol absorption and cholesterol synthesis in man. J Lipid Res. 1969;10:304–315
  20. Heinemann T, Aztmann G, von Bergmann K. Comparison of intestinal absorption of cholesterol with different plant sterols in man. Eur J Clin Invest. 1993;23:827–831
  21. Scoggan KA, Gruber H, Lariviere K. A missense mutation in the rat Abcg5 gene causes phytosterolemia in stroke-prone spontaneously hypertensive (SHRSP), spontaneously hypertensive (SHR), and normotensive (WKY inbred) rats. J Lipid Res. 2003;44:911–916
  22. Yu H, Pandit B, Klett E, et al. The rat STSL locus: characterization, chromosomal assignment, and genetic variations in sitosterolemic hypertensive rats. BMC Cardiovasc Disord. 2003;3:4
  23. Salen G, Shore V, Tint GS, et al. Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. J Lipid Res. 1989;30:1319–1330
  24. Batta AK, Salen G, Batta P, et al. Simultaneous quantitation of fatty acids, sterols and bile acids in human stool by capillary gas-liquid chromatography. J Chromatogr B. 2002;775:153–161
  25. Honda A, Salen G, Matsuzaki Y, et al. Differences in hepatic levels of intermediates in bile acid biosynthesis between Cyp27−/− mice and CTX. J Lipid Res. 2001;42:291–300
  26. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–254
  27. Nguyen LB, Shefer S, Salen G, et al. A molecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis. J Clin Invest. 1990;86:923–931
  28. Honda A, Salen G, Shefer S, et al. Bile acid synthesis in the Smith-Lemli-Opitz syndrome: effects of dehydrocholesterols on cholesterol 7α-hydroxylase and 27-hydroxylase activities in rat liver. J Lipid Res. 1999;40:1520–1528
  29. Zilversmit DB, Hughes LB. Validation of a dual-isotope plasma ratio method for measurement of cholesterol absorption in rats. J Lipid Res. 1974;15:465–473
  30. Ikeda I, Nakagiri H, Sugano M, et al. Mechanism of phytosterolemia in stroke-prone spontaneously hypertensive and WKY rats. Metabolism. 2001;50:1361–1368
  31. McNamara DJ, Proia A, Miettinen TA. Thin-layer and gas-liquid chromatographic identification of neutral steroids in human and rat feces. J Lipid Res. 1981;22:474–484
  32. Fernandez C, Suarez Y, Ferruelo AJ, et al. Inhibition of cholesterol biosynthesis by Δ22-unsaturated phytosterols via competitive inhibition of sterol Δ24-reductase in mammalian cells. Biochem J. 2002;366(Pt 1):109–119
  33. Yang C, Yu L, Li W, et al. Disruption of cholesterol homeostasis by plant sterols. J Clin Invest. 2004;114:813–822
  34. Owsley E, Chiang JYL. Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7a-hydroxylase gene. Biochem Biophys Res Commun. 2003;304:191–195
  35. Mattson FH, Volpenhein RA, Erickson BA. Effect of plant sterol esters on the absorption of dietary cholesterol. J Nutr. 1977;107:1139–1146
  36. Katan MB, et al. for the Stresa Workshop participants Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc. 2003;78:965–978

PII: S0026-0495(05)00348-3

doi: 10.1016/j.metabol.2005.08.024

Metabolism - Clinical and Experimental
Volume 55, Issue 3 , Pages 292-299 , March 2006

Article Tools

* Image Usage & Resolution