| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Journal of Lipid Research, Vol 30, 1319-1330, Copyright © 1989 by Lipid Research, Inc.
ARTICLES |
G Salen, V Shore, GS Tint, T Forte, S Shefer, I Horak, E Horak, B Dayal, L Nguyen and AK Batta
Medical Service, Veterans Administration Medical Center, East Orange, NJ 07019.
We measured the turnover and absorption of sitosterol and cholesterol, along with plasma sterol and lipoprotein concentrations, in one control and two subjects with sitosterolemia with xanthomatosis. All individuals consumed the same diet which contained approximately 500 mg/day of cholesterol and 250 mg/day of sitosterol. Sterol absorption was measured by the plasma dual-isotope ratio method and turnover by plasma isotope-kinetic analysis. In two sitosterolemic subjects, 28% and 63% of the sitosterol and 69% and 49% of the cholesterol were absorbed, respectively, compared to 4% of the sitosterol and 44% of the cholesterol in the control. As expected, plasma sitosterol specific activities decayed much more rapidly than cholesterol in the control subject. In contrast, plasma sitosterol and cholesterol specific activity-time curves were similar and decayed more slowly in the sitosterolemic subjects. In the control subject, the total sitotterol pool was 290 mg and was linearly related to low absorption (18 mg/day); whereas the total sitosterol pool was 17 times (4800 mg) and 13 times (3500 mg) larger, respectively, in the sitosterolemic subjects and was expanded out of proportion to increased absorption because of decreased removal. Daily cholesterol turnover and synthesis were markedly reduced in the sitosterolemic subjects. In four sitosterolemic subjects, plasma concentrations of total sterols, low density lipoproteins, and apolipoprotein B were increased, while those of high density lipoproteins and apolipoprotein A-I were low to normal. The low density lipoproteins were very similar to those of normal control subjects in density distribution, peak flotation rate, sterol-to-protein (apolipoprotein B) ratio, particle size, and morphology. These results demonstrate in patients with sitosterolemia with xanthomatosis that: 1) the absorption of sitosterol and cholesterol is enhanced; 2) tissue recognition between cholesterol and sitosterol is lost; 3) total exchangeable sitosterol pools are expanded out of proportion to absorption because of decreased excretion; 4) plasma sterol and lipoprotein concentrations favor tissue deposition; and 5) cholesterol synthesis is diminished. We postulate that the changes in sitosterol metabolism (increased absorption, loss of tissue sterol structural recognition, expanded pools, and hepatic retention) are a response to reduced cholesterol synthesis in these subject.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S Kidambi and S B Patel Sitosterolaemia: pathophysiology, clinical presentation and laboratory diagnosis J. Clin. Pathol., May 1, 2008; 61(5): 588 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ikonen Mechanisms for cellular cholesterol transport: defects and human disease. Physiol Rev, October 1, 2006; 86(4): 1237 - 1261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yu, K. von Bergmann, D. Lutjohann, H. H. Hobbs, and J. C. Cohen Ezetimibe normalizes metabolic defects in mice lacking ABCG5 and ABCG8 J. Lipid Res., August 1, 2005; 46(8): 1739 - 1744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, T. Joy, D. Mymin, J. Frohlich, and R. A. Hegele Phenotypic heterogeneity of sitosterolemia J. Lipid Res., December 1, 2004; 45(12): 2361 - 2367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Wilund, L. Yu, F. Xu, H. H. Hobbs, and J. C. Cohen High-level expression of ABCG5 and ABCG8 attenuates diet-induced hypercholesterolemia and atherosclerosis in Ldlr-/- mice J. Lipid Res., August 1, 2004; 45(8): 1429 - 1436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-P. Duan, H. H. Wang, and D. Q-H. Wang Cholesterol absorption is mainly regulated by the jejunal and ileal ATP-binding cassette sterol efflux transporters Abcg5 and Abcg8 in mice J. Lipid Res., July 1, 2004; 45(7): 1312 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Graf, J. C. Cohen, and H. H. Hobbs Missense Mutations in ABCG5 and ABCG8 Disrupt Heterodimerization and Trafficking J. Biol. Chem., June 4, 2004; 279(23): 24881 - 24888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Wu, F. Basso, R. D. Shamburek, M. J. A. Amar, B. Vaisman, G. Szakacs, C. Joyce, T. Tansey, L. Freeman, B. J. Paigen, et al. Hepatic ABCG5 and ABCG8 Overexpression Increases Hepatobiliary Sterol Transport but Does Not Alter Aortic Atherosclerosis in Transgenic Mice J. Biol. Chem., May 28, 2004; 279(22): 22913 - 22925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Field, E. Born, and S. N. Mathur LXR/RXR ligand activation enhances basolateral efflux of {beta}-sitosterol in CaCo-2 cells J. Lipid Res., May 1, 2004; 45(5): 905 - 913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. H. Ju, L. M. Clausen, K. F. Allred, A. L. Almada, and W. G. Helferich {beta}-Sitosterol, {beta}-Sitosterol Glucoside, and a Mixture of {beta}-Sitosterol and {beta}-Sitosterol Glucoside Modulate the Growth of Estrogen-Responsive Breast Cancer Cells In Vitro and in Ovariectomized Athymic Mice J. Nutr., May 1, 2004; 134(5): 1145 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Salen, K. von Bergmann, D. Lutjohann, P. Kwiterovich, J. Kane, S.B. Patel, T. Musliner, P. Stein, B. Musser, and the Multicenter Sitosterolemia Study Group Ezetimibe Effectively Reduces Plasma Plant Sterols in Patients With Sitosterolemia Circulation, March 2, 2004; 109(8): 966 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Graf, L. Yu, W.-P. Li, R. Gerard, P. L. Tuma, J. C. Cohen, and H. H. Hobbs ABCG5 and ABCG8 Are Obligate Heterodimers for Protein Trafficking and Biliary Cholesterol Excretion J. Biol. Chem., November 28, 2003; 278(48): 48275 - 48282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sehayek Genetic regulation of cholesterol absorption and plasma plant sterol levels: commonalities and differences J. Lipid Res., November 1, 2003; 44(11): 2030 - 2038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Khovidhunkit, A. H. Moser, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold Endotoxin down-regulates ABCG5 and ABCG8 in mouse liver and ABCA1 and ABCG1 in J774 murine macrophages: differential role of LXR J. Lipid Res., September 1, 2003; 44(9): 1728 - 1736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O. Kwiterovich Jr., S. C. Chen, D. G. Virgil, A. Schweitzer, D. R. Arnold, and L. E. Kratz Response of obligate heterozygotes for phytosterolemia to a low-fat diet and to a plant sterol ester dietary challenge J. Lipid Res., June 1, 2003; 44(6): 1143 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yu, J. York, K. von Bergmann, D. Lutjohann, J. C. Cohen, and H. H. Hobbs Stimulation of Cholesterol Excretion by the Liver X Receptor Agonist Requires ATP-binding Cassette Transporters G5 and G8 J. Biol. Chem., April 25, 2003; 278(18): 15565 - 15570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Igel, U. Giesa, D. Lutjohann, and K. von Bergmann Comparison of the intestinal uptake of cholesterol, plant sterols, and stanols in mice J. Lipid Res., March 1, 2003; 44(3): 533 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yu, R. E. Hammer, J. Li-Hawkins, K. von Bergmann, D. Lutjohann, J. C. Cohen, and H. H. Hobbs Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion PNAS, December 10, 2002; 99(25): 16237 - 16242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Sudhop, Y Sahin, B Lindenthal, C Hahn, C Luers, H K Berthold, and K von Bergmann Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion Gut, December 1, 2002; 51(6): 860 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Repa, K. E. Berge, C. Pomajzl, J. A. Richardson, H. Hobbs, and D. J. Mangelsdorf Regulation of ATP-binding Cassette Sterol Transporters ABCG5 and ABCG8 by the Liver X Receptors alpha and beta J. Biol. Chem., May 17, 2002; 277(21): 18793 - 18800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Lu, M.-H. Lee, H. Yu, Y. Zhou, S. A. Sandell, G. Salen, and S. B. Patel Molecular cloning, genomic organization, genetic variations, and characterization of murine sterolin genes Abcg5 and Abcg8 J. Lipid Res., April 1, 2002; 43(4): 565 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Salen, G. Xu, G. S. Tint, A. K. Batta, and S. Shefer Hyperabsorption and retention of campestanol in a sitosterolemic homozygote: comparison with her mother and three control subjects J. Lipid Res., November 1, 2000; 41(11): 1883 - 1889. [Abstract] [Full Text]
|
|
|
|
|
|
W. M. N. Ratnayake, M. R. L’Abbé, R. Mueller, S. Hayward, L. Plouffe, R. Hollywood, and K. Trick Vegetable Oils High in Phytosterols Make Erythrocytes Less Deformable and Shorten the Life Span of Stroke-Prone Spontaneously Hypertensive Rats J. Nutr., May 1, 2000; 130(5): 1166 - 1178. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. A Hallikainen and M. I. Uusitupa Effects of 2 low-fat stanol ester–containing margarines on serum cholesterol concentrations as part of a low-fat diet in hypercholesterolemic subjects Am. J. Clinical Nutrition, March 1, 1999; 69(3): 403 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. B. Berger, R. J. Pegoraro, S. B. Patel, P. Naidu, L. Rom, H. Hidaka, A. D. Marais, A. Jadhav, R. P. Naoumova, and G. R. Thompson HMG-CoA reductase is not the site of the primary defect in phytosterolemia J. Lipid Res., May 1, 1998; 39(5): 1046 - 1054. [Abstract] [Full Text]
|
|
|
|
|
|
S. B. Patel, A. Honda, and G. Salen Sitosterolemia: exclusion of genes involved in reduced cholesterol biosynthesis J. Lipid Res., May 1, 1998; 39(5): 1055 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Honda, G. Salen, L. B. Nguyen, G. S. Tint, A. K. Batta, and S. Shefer Down-regulation of cholesterol biosynthesis in sitosterolemia: diminished activities of acetoacetyl-CoA thiolase, 3-hydroxy-3-methylglutaryl-CoA synthase, reductase, squalene synthase, and 7-dehydrocholesterol {Delta}7-reductase in liver and mononuclear leukocytes J. Lipid Res., January 1, 1998; 39(1): 44 - 50. [Abstract] [Full Text]
|
|
|
|
 |
|
 G S. Tint, M. Irons, E. R. Elias, A. K. Batta, R. Frieden, T. S. Chen, and G. Salen Defective Cholesterol Biosynthesis Associated with the Smith-Lemli-Opitz Syndrome N. Engl. J. Med., January 13, 1994; 330(2): 107 - 113. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. E. Ostlund Jr., J. B. McGill, C.-M. Zeng, D. F. Covey, J. Stearns, W. F. Stenson, and C. A. Spilburg Gastrointestinal absorption and plasma kinetics of soy Delta 5-phytosterols and phytostanols in humans Am J Physiol Endocrinol Metab, April 1, 2002; 282(4): E911 - E916. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
