Abstract
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. DD 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.
Original language | English (US) |
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Pages (from-to) | 779-789 |
Number of pages | 11 |
Journal | Journal of lipid research |
Volume | 46 |
Issue number | 4 |
DOIs | |
State | Published - 2005 |
Keywords
- Adenosine triphosphate binding cassette transporters
- Apolipoprotein composition
- Bile acid excretion
- Biliary lipid composition
- Cholesterol excretion
- Cholesterol synthesis
- Enterocyte
- Hepatocyte
- Liver X receptor
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology