| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Lipid Research, Vol. 46, 1205-1212, June 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology
* Arteriosclerosis Research Program, Departments of Pathology and Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC
Department of Anatomy, University of California, San Francisco, San Francisco, CA
Published, JLR Papers in Press, April 1, 2005. DOI 10.1194/jlr.M500018-JLR200
1 To whom correspondence should be addressed. e-mail: lrudel{at}wfubmc.edu
The relative contributions of ACAT2 and LCAT to the cholesteryl ester (CE) content of VLDL and LDL were measured. ACAT2 deficiency led to a significant decrease in the percentage of CE (37.2 ± 2.1% vs. 3.9 ± 0.8%) in plasma VLDL, with a concomitant increase in the percentage of triglyceride (33.0 ± 3.2% vs. 66.7 ± 2.5%). Interestingly, the absence of ACAT2 had no apparent effect on the percentage CE in LDL, whereas LCAT deficiency significantly decreased the CE percentage (38.6 ± 4.0% vs. 54.6 ± 1.9%) and significantly increased the phospholipid percentage (11.2 ± 0.9% vs. 19.3 ± 0.1%) of LDL. When both LCAT and ACAT2 were deficient, VLDL composition was similar to VLDL of the ACAT2-deficient mouse, whereas LDL was depleted in core lipids and enriched in surface lipids, appearing discoidal when observed by electron microscopy. We conclude that ACAT2 is important in the synthesis of VLDL CE, whereas LCAT is important in remodeling VLDL to LDL. Liver perfusions were performed, and perfusate apolipoprotein B accumulation rates in ACAT2-deficient mice were not significantly different from those of controls; perfusate VLDL CE decreased from 8.0 ± 0.8% in controls to 0 ± 0.7% in ACAT2-deficient mice.
In conclusion, our data establish that ACAT2 provides core CE of newly secreted VLDL, whereas LCAT adds CE during LDL particle formation.
Supplementary key words acyl-CoA:cholesterol acyltransferase 2 • lecithin:cholesterol acyltransferase • low density lipoprotein • very low density lipoprotein • hepatocyte • apolipoprotein B
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Minehira, S. G. Young, C. J. Villanueva, L. Yetukuri, M. Oresic, M. K. Hellerstein, R. V. Farese Jr., J. D. Horton, F. Preitner, B. Thorens, et al. Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice J. Lipid Res., September 1, 2008; 49(9): 2038 - 2044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Brown, T. A. Bell III, H. M. Alger, J. K. Sawyer, T. L. Smith, K. Kelley, R. Shah, M. D. Wilson, M. A. Davis, R. G. Lee, et al. Targeted Depletion of Hepatic ACAT2-driven Cholesterol Esterification Reveals a Non-biliary Route for Fecal Neutral Sterol Loss J. Biol. Chem., April 18, 2008; 283(16): 10522 - 10534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Temel, L. Hou, L. L. Rudel, and G. S. Shelness ACAT2 stimulates cholesteryl ester secretion in apoB-containing lipoproteins J. Lipid Res., July 1, 2007; 48(7): 1618 - 1627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Spector and W. G. Haynes LDL Cholesteryl Oleate: A Biomarker for Atherosclerosis? Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1228 - 1230. [Full Text] [PDF]
|
|
|
|
|
|
T. A. Bell III, K. Kelley, M. D. Wilson, J. K. Sawyer, and L. L. Rudel Dietary Fat-Induced Alterations in Atherosclerosis Are Abolished by ACAT2-Deficiency in ApoB100 Only, LDLr-/- Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1396 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. W. Joyce, E. M. Wagner, F. Basso, M. J. Amar, L. A. Freeman, R. D. Shamburek, C. L. Knapper, J. Syed, J. Wu, B. L. Vaisman, et al. ABCA1 Overexpression in the Liver of LDLr-KO Mice Leads to Accumulation of Pro-atherogenic Lipoproteins and Enhanced Atherosclerosis J. Biol. Chem., November 3, 2006; 281(44): 33053 - 33065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhou, Y. Zhai, Y. Mu, H. Gong, H. Uppal, D. Toma, S. Ren, R. M. Evans, and W. Xie A Novel Pregnane X Receptor-mediated and Sterol Regulatory Element-binding Protein-independent Lipogenic Pathway J. Biol. Chem., May 26, 2006; 281(21): 15013 - 15020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zhao, R. Natarajan, and S. Ghosh Human liver cholesteryl ester hydrolase: cloning, molecular characterization, and role in cellular cholesterol homeostasis Physiol Genomics, November 17, 2005; 23(3): 304 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Temel, R. G. Lee, K. L. Kelley, M. A. Davis, R. Shah, J. K. Sawyer, M. D. Wilson, and L. L. Rudel Intestinal cholesterol absorption is substantially reduced in mice deficient in both ABCA1 and ACAT2 J. Lipid Res., November 1, 2005; 46(11): 2423 - 2431. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
