| First Author | Repa JJ | Year | 2005 |
| Journal | J Lipid Res | Volume | 46 |
| Issue | 4 | Pages | 779-89 |
| PubMed ID | 15654122 | Mgi Jnum | J:98574 |
| Mgi Id | MGI:3578705 | Doi | 10.1194/jlr.M400475-JLR200 |
| Citation | Repa JJ, et al. (2005) Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption. J Lipid Res 46(4):779-89 |
| abstractText | 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. |
