| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Departments of Atherosclerosis and Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065
Bioinformatics, Merck Research Laboratories, Rahway, New Jersey 07065
1 To whom correspondence should be addressed. e-mail: tianquan_cai{at}merck.com
Angiopoietins are members of the vascular endothelial growth factor family. One family member, angiopoietin-like protein 3 (Angptl3), was recently shown to be predominantly expressed in the liver and to play an important role in regulating lipid metabolism. In this study, we show that the Angptl3 gene is a direct target of the liver X receptor (LXR). Mice fed a high cholesterol diet exhibited a significant increase in Angptl3 expression in the liver. Oral administration to mice of T0901317, a synthetic LXR-selective agonist, increases levels of plasma lipids and Angptl3 mRNA in the liver. Treatment of HepG2 cells with LXR selective agonists led to a dose-dependent increase of Angptl3 mRNA. Analysis of the DNA sequence just 5' of the Angptl3 transcriptional start site revealed the presence of several potential transcription factor binding sites, including that for LXR. When transfected into HepG2 cells, the promoter activity of Angptl3 was significantly induced by LXR- or retinoid X receptor-selective agonists. Mutation of the predicted LXR binding site (DR4 element) completely abolished the LXR agonist-mediated activation of the promoter.
Together, these studies show that Angptl3 is transcriptionally regulated by LXR, and reveals a novel mechanism by which LXR may regulate lipid metabolism.
Abbreviations: ABCA1, ATP-binding cassette transporter 1; Angptl3, angiopoietin-like protein 3; FCS, fetal calf serum; LXR, liver X receptor; OH Ch, hydroxycholesterol; 9-RA, 9-cis retinoic acid; SREBP, sterol regulatory element-binding protein; TG, triglycerides
Supplementary key words lipid metabolism • angiopoietin • transcriptional regulation • nuclear receptor
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Shimamura, M. Matsuda, H. Yasumo, M. Okazaki, K. Fujimoto, K. Kono, T. Shimizugawa, Y. Ando, R. Koishi, T. Kohama, et al. Angiopoietin-Like Protein3 Regulates Plasma HDL Cholesterol Through Suppression of Endothelial Lipase Arterioscler. Thromb. Vasc. Biol., February 1, 2007; 27(2): 366 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Reue and L. Vergnes Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Approaches to lipid metabolism gene identification and characterization in the postgenomic era J. Lipid Res., September 1, 2006; 47(9): 1891 - 1907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Fugier, J.-J. Tousaint, X. Prieur, M. Plateroti, J. Samarut, and P. Delerive The Lipoprotein Lipase Inhibitor ANGPTL3 Is Negatively Regulated by Thyroid Hormone J. Biol. Chem., April 28, 2006; 281(17): 11553 - 11559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Koster, Y. B. Chao, M. Mosior, A. Ford, P. A. Gonzalez-DeWhitt, J. E. Hale, D. Li, Y. Qiu, C. C. Fraser, D. D. Yang, et al. Transgenic Angiopoietin-Like (Angptl)4 Overexpression and Targeted Disruption of Angptl4 and Angptl3: Regulation of Triglyceride Metabolism Endocrinology, November 1, 2005; 146(11): 4943 - 4950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ge, J.-Y. Cha, H. Gopal, C. Harp, X. Yu, J. J. Repa, and C. Li Differential regulation and properties of angiopoietin-like proteins 3 and 4 J. Lipid Res., July 1, 2005; 46(7): 1484 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ge, G. Yang, X. Yu, T. Pourbahrami, and C. Li Oligomerization state-dependent hyperlipidemic effect of angiopoietin-like protein 4 J. Lipid Res., November 1, 2004; 45(11): 2071 - 2079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Akiyama, G. Lambert, C. J. Nicol, K. Matsusue, J. M. Peters, H. B. Brewer Jr., and F. J. Gonzalez Peroxisome Proliferator-activated Receptor {beta}/{delta} Regulates Very Low Density Lipoprotein Production and Catabolism in Mice on a Western Diet J. Biol. Chem., May 14, 2004; 279(20): 20874 - 20881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Masson, B. Staels, T. Gautier, C. Desrumaux, A. Athias, N. Le Guern, M. Schneider, Z. Zak, L. Dumont, V. Deckert, et al. Cholesteryl ester transfer protein modulates the effect of liver X receptor agonists on cholesterol transport and excretion in the mouse J. Lipid Res., March 1, 2004; 45(3): 543 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Steffensen and J.-A. Gustafsson Putative Metabolic Effects of the Liver X Receptor (LXR) Diabetes, February 1, 2004; 53(90001): S36 - 42. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ge, G. Yang, L. Huang, D. L. Motola, T. Pourbahrami, and C. Li Oligomerization and Regulated Proteolytic Processing of Angiopoietin-like Protein 4 J. Biol. Chem., January 16, 2004; 279(3): 2038 - 2045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kaneko, M. Matsuda, Y. Yamada, Y. Tachibana, I. Shimomura, and M. Makishima Induction of Intestinal ATP-binding Cassette Transporters by a Phytosterol-derived Liver X Receptor Agonist J. Biol. Chem., September 19, 2003; 278(38): 36091 - 36098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Inaba, M. Matsuda, M. Shimamura, N. Takei, N. Terasaka, Y. Ando, H. Yasumo, R. Koishi, M. Makishima, and I. Shimomura Angiopoietin-like Protein 3 Mediates Hypertriglyceridemia Induced by the Liver X Receptor J. Biol. Chem., June 6, 2003; 278(24): 21344 - 21351. [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 |
