Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis

G. Salen, V. Shore, G. S. Tint, T. Forte, S. Shefer, I. Horak, E. Horak, B. Dayal, L. Nguyen, A. K. Batta, F. T. Lindgren, P. O. Kwiterovich

Research output: Contribution to journalArticle

Abstract

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 sitosterol 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 subjects.

Original languageEnglish (US)
Pages (from-to)1319-1330
Number of pages12
JournalJournal of Lipid Research
Volume30
Issue number9
StatePublished - 1989
Externally publishedYes

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Xanthomatosis
Cholesterol
Sterols
Plasmas
Apolipoproteins B
Tissue
LDL Lipoproteins
Isotopes
Lipoproteins
gamma-sitosterol
Sitosterolemia
VLDL Lipoproteins
Apolipoprotein A-I
HDL Lipoproteins
Nutrition
Flotation
Particle Size
Metabolism

ASJC Scopus subject areas

  • Endocrinology

Cite this

Salen, G., Shore, V., Tint, G. S., Forte, T., Shefer, S., Horak, I., ... Kwiterovich, P. O. (1989). Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. Journal of Lipid Research, 30(9), 1319-1330.

Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. / Salen, G.; Shore, V.; Tint, G. S.; Forte, T.; Shefer, S.; Horak, I.; Horak, E.; Dayal, B.; Nguyen, L.; Batta, A. K.; Lindgren, F. T.; Kwiterovich, P. O.

In: Journal of Lipid Research, Vol. 30, No. 9, 1989, p. 1319-1330.

Research output: Contribution to journalArticle

Salen, G, Shore, V, Tint, GS, Forte, T, Shefer, S, Horak, I, Horak, E, Dayal, B, Nguyen, L, Batta, AK, Lindgren, FT & Kwiterovich, PO 1989, 'Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis', Journal of Lipid Research, vol. 30, no. 9, pp. 1319-1330.
Salen, G. ; Shore, V. ; Tint, G. S. ; Forte, T. ; Shefer, S. ; Horak, I. ; Horak, E. ; Dayal, B. ; Nguyen, L. ; Batta, A. K. ; Lindgren, F. T. ; Kwiterovich, P. O. / Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. In: Journal of Lipid Research. 1989 ; Vol. 30, No. 9. pp. 1319-1330.
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AU - Shore, V.

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AU - Forte, T.

AU - Shefer, S.

AU - Horak, I.

AU - Horak, E.

AU - Dayal, B.

AU - Nguyen, L.

AU - Batta, A. K.

AU - Lindgren, F. T.

AU - Kwiterovich, P. O.

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N2 - 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 sitosterol 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 subjects.

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