Chenodeoxycholic acid normalizes elevated lipoprotein secretion and catabolism in cerebrotendinous xanthomatosis.
Cerebrotendinous xanthomatosis (CTX) is a rare inherited lipid storage disease caused by a defect in bile acid synthesis in which cholesterol and its product cholestanol are deposited in neurological and vascular tissue. Therapy with chenodeoxycholic acid but not with the 7 beta-epimeric ursodeoxych...
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1989-05-01
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Series: | Journal of Lipid Research |
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doaj-b35800a2df8c4609afc849611cc23f262021-04-25T04:18:36ZengElsevierJournal of Lipid Research0022-22751989-05-01305633640Chenodeoxycholic acid normalizes elevated lipoprotein secretion and catabolism in cerebrotendinous xanthomatosis.G S Tint0H Ginsberg1G Salen2N A Le3S Shefer4Department of Medicine, VA Medical Center, East Orange, NJ 07019.Department of Medicine, VA Medical Center, East Orange, NJ 07019.Department of Medicine, VA Medical Center, East Orange, NJ 07019.Department of Medicine, VA Medical Center, East Orange, NJ 07019.Department of Medicine, VA Medical Center, East Orange, NJ 07019.Cerebrotendinous xanthomatosis (CTX) is a rare inherited lipid storage disease caused by a defect in bile acid synthesis in which cholesterol and its product cholestanol are deposited in neurological and vascular tissue. Therapy with chenodeoxycholic acid but not with the 7 beta-epimeric ursodeoxycholic acid is usually successful. In an untreated patient, total and low density lipoprotein (LDL) cholesterol were found to be low (134 +/- 11 and 78 +/- 8 mg/dl, respectively). The production rate (PR) and fractional catabolic rate (FCR) of very low density (VLDL) apolipoprotein B (apoB) were, however, both markedly increased (34.7 mg/kg per day and 13.7 pools/day, respectively vs. 15.1 +/- 5.0 mg/kg per day and 6.2 +/- 3.8 pools/day in controls) while the PR and FCR of LDL apoB were moderately elevated (16.3 mg/kg per day and 0.65 pools/day, respectively vs. 12.9 +/- 1.2 mg/kg per day and 0.52 +/- 0.10 pools/day in controls). After 1 month of 750 mg/day of chenodeoxycholic acid, the FCR and PR of both VLDL and LDL apoB became normal while total plasma cholesterol increased significantly to 145 +/- 18 mg/dl. In a second patient who had been receiving 750 mg/day of chenodeoxycholic acid for 6 months lipoprotein kinetics were normal. These parameters did not change when the subject was switched to 750 mg/day ursodeoxycholic acid. We postulate that cholesterol biosynthesis in CTX is derepressed by a diminished hepatic pool of chenodeoxycholic acid and that the elevated secretion of apoB is a response to the increased rate of cholesterol production.http://www.sciencedirect.com/science/article/pii/S0022227520383255 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
G S Tint H Ginsberg G Salen N A Le S Shefer |
spellingShingle |
G S Tint H Ginsberg G Salen N A Le S Shefer Chenodeoxycholic acid normalizes elevated lipoprotein secretion and catabolism in cerebrotendinous xanthomatosis. Journal of Lipid Research |
author_facet |
G S Tint H Ginsberg G Salen N A Le S Shefer |
author_sort |
G S Tint |
title |
Chenodeoxycholic acid normalizes elevated lipoprotein secretion and catabolism in cerebrotendinous xanthomatosis. |
title_short |
Chenodeoxycholic acid normalizes elevated lipoprotein secretion and catabolism in cerebrotendinous xanthomatosis. |
title_full |
Chenodeoxycholic acid normalizes elevated lipoprotein secretion and catabolism in cerebrotendinous xanthomatosis. |
title_fullStr |
Chenodeoxycholic acid normalizes elevated lipoprotein secretion and catabolism in cerebrotendinous xanthomatosis. |
title_full_unstemmed |
Chenodeoxycholic acid normalizes elevated lipoprotein secretion and catabolism in cerebrotendinous xanthomatosis. |
title_sort |
chenodeoxycholic acid normalizes elevated lipoprotein secretion and catabolism in cerebrotendinous xanthomatosis. |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
1989-05-01 |
description |
Cerebrotendinous xanthomatosis (CTX) is a rare inherited lipid storage disease caused by a defect in bile acid synthesis in which cholesterol and its product cholestanol are deposited in neurological and vascular tissue. Therapy with chenodeoxycholic acid but not with the 7 beta-epimeric ursodeoxycholic acid is usually successful. In an untreated patient, total and low density lipoprotein (LDL) cholesterol were found to be low (134 +/- 11 and 78 +/- 8 mg/dl, respectively). The production rate (PR) and fractional catabolic rate (FCR) of very low density (VLDL) apolipoprotein B (apoB) were, however, both markedly increased (34.7 mg/kg per day and 13.7 pools/day, respectively vs. 15.1 +/- 5.0 mg/kg per day and 6.2 +/- 3.8 pools/day in controls) while the PR and FCR of LDL apoB were moderately elevated (16.3 mg/kg per day and 0.65 pools/day, respectively vs. 12.9 +/- 1.2 mg/kg per day and 0.52 +/- 0.10 pools/day in controls). After 1 month of 750 mg/day of chenodeoxycholic acid, the FCR and PR of both VLDL and LDL apoB became normal while total plasma cholesterol increased significantly to 145 +/- 18 mg/dl. In a second patient who had been receiving 750 mg/day of chenodeoxycholic acid for 6 months lipoprotein kinetics were normal. These parameters did not change when the subject was switched to 750 mg/day ursodeoxycholic acid. We postulate that cholesterol biosynthesis in CTX is derepressed by a diminished hepatic pool of chenodeoxycholic acid and that the elevated secretion of apoB is a response to the increased rate of cholesterol production. |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520383255 |
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