| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
Papers In Press, published online ahead of print January 16, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8887
Corresponding Author: john.dietschy{at}utsouthwestern.edu
The absorption of cholesterol by the small intestine is a major route for the net entry of cholesterol into the body and can therefore impact 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 mice fed a basal diet containing ezetimibe (0 to 10 mg/day/kg body weight), cholesterol absorption was reduced up to 91%, fecal neutral sterol excretion increased up to 4.7-fold and plasma total cholesterol concentrations fell by up to 18%. Blocking cholesterol absorption prevented 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 as well as a modest increase in hepatic LDLR expression.
Revised on January 10, 2005
Accepted on January 12, 2005
Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption: Impact on low density lipoprotein production
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Li, S. D. Turley, B. Liu, J. J. Repa, and J. M. Dietschy GM2/GD2 and GM3 gangliosides have no effect on cellular cholesterol pools or turnover in normal or NPC1 mice J. Lipid Res., August 1, 2008; 49(8): 1816 - 1828. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Steinberg, E. J. Eichhorn, W. E. Connor, G. A. Diamond, S. Kaul, J. A. Blake, H. R. Davis Jr., N. J. Murgolo, M. P. Graziano, T. Kaye, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N. Engl. J. Med., July 31, 2008; 359(5): 529 - 530. [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Repa, H. Li, T. C. Frank-Cannon, M. A. Valasek, S. D. Turley, M. G. Tansey, and J. M. Dietschy Liver X Receptor Activation Enhances Cholesterol Loss from the Brain, Decreases Neuroinflammation, and Increases Survival of the NPC1 Mouse J. Neurosci., December 26, 2007; 27(52): 14470 - 14480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Valasek, S. L. Clarke, and J. J. Repa Fenofibrate reduces intestinal cholesterol absorption via PPAR{alpha}-dependent modulation of NPC1L1 expression in mouse J. Lipid Res., December 1, 2007; 48(12): 2725 - 2735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Getz and C. A. Reardon Nutrition and Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2499 - 2506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. Beltroy, B. Liu, J. M. Dietschy, and S. D. Turley Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C disease J. Lipid Res., April 1, 2007; 48(4): 869 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Telford, B. G. Sutherland, J. Y. Edwards, J. D. Andrews, P. H. R. Barrett, and M. W. Huff The molecular mechanisms underlying the reduction of LDL apoB-100 by ezetimibe plus simvastatin J. Lipid Res., March 1, 2007; 48(3): 699 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Basso, L. A. Freeman, C. Ko, C. Joyce, M. J. Amar, R. D. Shamburek, T. Tansey, F. Thomas, J. Wu, B. Paigen, et al. Hepatic ABCG5/G8 overexpression reduces apoB-lipoproteins and atherosclerosis when cholesterol absorption is inhibited J. Lipid Res., January 1, 2007; 48(1): 114 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Huff, R. L. Pollex, and R. A. Hegele NPC1L1: Evolution From Pharmacological Target to Physiological Sterol Transporter Arterioscler. Thromb. Vasc. Biol., November 1, 2006; 26(11): 2433 - 2438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Ness, R. C. Holland, and D. Lopez Selective Compensatory Induction of Hepatic HMG-CoA Reductase in Response to Inhibition of Cholesterol Absorption. Experimental Biology and Medicine, May 1, 2006; 231(5): 559 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Tremblay, B. Lamarche, J. S. Cohn, J.-C. Hogue, and P. Couture Effect of Ezetimibe on the In Vivo Kinetics of ApoB-48 and ApoB-100 in Men With Primary Hypercholesterolemia Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1101 - 1106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Valasek, J. Weng, P. W. Shaul, R. G. W. Anderson, and J. J. Repa Caveolin-1 Is Not Required for Murine Intestinal Cholesterol Transport J. Biol. Chem., July 29, 2005; 280(30): 28103 - 28109. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
