Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption
The absorption of cholesterol by the small intestine is a major route for the net entry of cholesterol into the body and can therefore affect the plasma low density lipoprotein-cholesterol (LDL-C) concentration. These studies used ezetimibe, a potent inhibitor of cholesterol absorption, to delineate...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-04-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752034013X |
| _version_ | 1830187373135134720 |
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| author | Joyce J. Repa Stephen D. Turley Gang Quan John M. Dietschy |
| author_facet | Joyce J. Repa Stephen D. Turley Gang Quan John M. Dietschy |
| author_sort | Joyce J. Repa |
| collection | DOAJ |
| description | The absorption of cholesterol by the small intestine is a major route for the net entry of cholesterol into the body and can therefore affect the plasma low density lipoprotein-cholesterol (LDL-C) concentration. These studies used ezetimibe, a potent inhibitor of cholesterol absorption, to delineate the biochemical and molecular changes in intrahepatic metabolism and biliary lipid secretion when there is a major reduction in chylomicron cholesterol delivery to the liver. In female LDL receptor (LDLR)-deficient (LDLR−/−) mice fed a basal diet containing ezetimibe (0–10 mg/day/kg body weight), cholesterol absorption was reduced up to 91%, fecal neutral sterol excretion was increased up to 4.7-fold, and plasma total cholesterol concentrations decreased by up to 18%. Blocking cholesterol absorption prevented the accumulation of very low density lipoproteins and LDL in the circulation of LDLR−/− mice fed a lipid-rich diet. In female LDLR+/+ mice fed the lipid-rich diet with ezetimibe, the relative mRNA level for the LDLR in the liver was 2-fold greater than in matching mice given the lipid-rich diet alone.We conclude that in the mouse the reduction in plasma LDL-C levels induced by blocking cholesterol absorption reflects both a diminished rate of LDL-C production and a modest increase in hepatic LDLR expression. |
| first_indexed | 2024-12-17T22:27:29Z |
| format | Article |
| id | doaj.art-5d7ba2b2b52a401e873ca841d7d6bc9f |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T22:27:29Z |
| publishDate | 2005-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-5d7ba2b2b52a401e873ca841d7d6bc9f2022-12-21T21:30:19ZengElsevierJournal of Lipid Research0022-22752005-04-01464779789Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorptionJoyce J. Repa0Stephen D. Turley1Gang Quan2John M. Dietschy3Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887The absorption of cholesterol by the small intestine is a major route for the net entry of cholesterol into the body and can therefore affect the plasma low density lipoprotein-cholesterol (LDL-C) concentration. These studies used ezetimibe, a potent inhibitor of cholesterol absorption, to delineate the biochemical and molecular changes in intrahepatic metabolism and biliary lipid secretion when there is a major reduction in chylomicron cholesterol delivery to the liver. In female LDL receptor (LDLR)-deficient (LDLR−/−) mice fed a basal diet containing ezetimibe (0–10 mg/day/kg body weight), cholesterol absorption was reduced up to 91%, fecal neutral sterol excretion was increased up to 4.7-fold, and plasma total cholesterol concentrations decreased by up to 18%. Blocking cholesterol absorption prevented the accumulation of very low density lipoproteins and LDL in the circulation of LDLR−/− mice fed a lipid-rich diet. In female LDLR+/+ mice fed the lipid-rich diet with ezetimibe, the relative mRNA level for the LDLR in the liver was 2-fold greater than in matching mice given the lipid-rich diet alone.We conclude that in the mouse the reduction in plasma LDL-C levels induced by blocking cholesterol absorption reflects both a diminished rate of LDL-C production and a modest increase in hepatic LDLR expression.http://www.sciencedirect.com/science/article/pii/S002222752034013Xcholesterol synthesischolesterol excretionbile acid excretionenterocytehepatocytebiliary lipid composition |
| spellingShingle | Joyce J. Repa Stephen D. Turley Gang Quan John M. Dietschy Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption Journal of Lipid Research cholesterol synthesis cholesterol excretion bile acid excretion enterocyte hepatocyte biliary lipid composition |
| title | Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption |
| title_full | Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption |
| title_fullStr | Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption |
| title_full_unstemmed | Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption |
| title_short | Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption |
| title_sort | delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption |
| topic | cholesterol synthesis cholesterol excretion bile acid excretion enterocyte hepatocyte biliary lipid composition |
| url | http://www.sciencedirect.com/science/article/pii/S002222752034013X |
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