J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M600020-JLR200 on February 28, 2006

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
M600020-JLR200v1
47/6/1281    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brusq, J.-M.
Right arrow Articles by Issandou, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brusq, J.-M.
Right arrow Articles by Issandou, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Journal of Lipid Research, Vol. 47, 1281-1288, June 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine

Jean-Marie Brusq1, Nicolas Ancellin, Pascal Grondin, Raphaelle Guillard, Sandrine Martin, Yannick Saintillan and Marc Issandou

GlaxoSmithKline, 91951 Les Ulis, Cedex, France

Published, JLR Papers in Press, February 28, 2006.

1 To whom correspondence should be addressed. e-mail: jean-marie.g.brusq{at}gsk.com

The alkaloid drug berberine (BBR) was recently described to decrease plasma cholesterol and triglycerides (TGs) in hypercholesterolemic patients by increasing expression of the hepatic low density lipoprotein receptor (LDLR). Using HepG2 human hepatoma cells, we found that BBR inhibits cholesterol and TG synthesis in a similar manner to the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide 1-ß-ribofuranoside (AICAR). Significant increases in AMPK phosphorylation and AMPK activity were observed when the cells were incubated with BBR. Activation of AMPK was also demonstrated by measuring the phosphorylation of acetyl-CoA carboxylase, a substrate of AMPK, correlated with a subsequent increase in fatty acid oxidation. All of these effects were abolished by the mitogen-activated protein kinase kinase inhibitor PD98059. Treatment of hyperlipidemic hamsters with BBR decreased plasma LDL cholesterol and strongly reduced fat storage in the liver. These findings indicate that BBR, in addition to upregulating the LDLR, inhibits lipid synthesis in human hepatocytes through the activation of AMPK. These effects could account for the strong reduction of plasma TGs observed with this drug in clinical trials.

Supplementary key words low density lipoprotein cholesterol • PD98059 • 5-aminoimidazole-4-carboxamide 1-ß-ribofuranoside • fatty acid oxidation • phosphorylation of acetyl-coenzyme A carboxylase


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
F. Qiu, Z. Zhu, N. Kang, S. Piao, G. Qin, and X. Yao
Isolation and Identification of Urinary Metabolites of Berberine in Rats and Humans
Drug Metab. Dispos., November 1, 2008; 36(11): 2159 - 2165.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. Zhou, X. Wang, L. Shao, Y. Yang, W. Shang, G. Yuan, B. Jiang, F. Li, J. Tang, H. Jing, et al.
Berberine Acutely Inhibits Insulin Secretion from {beta}-Cells through 3',5'-Cyclic Adenosine 5'-Monophosphate Signaling Pathway
Endocrinology, September 1, 2008; 149(9): 4510 - 4518.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
N. Turner, J.-Y. Li, A. Gosby, S. W.C. To, Z. Cheng, H. Miyoshi, M. M. Taketo, G. J. Cooney, E. W. Kraegen, D. E. James, et al.
Berberine and Its More Biologically Available Derivative, Dihydroberberine, Inhibit Mitochondrial Respiratory Complex I: A Mechanism for the Action of Berberine to Activate AMP-Activated Protein Kinase and Improve Insulin Action
Diabetes, May 1, 2008; 57(5): 1414 - 1418.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. Yin, Z. Gao, D. Liu, Z. Liu, and J. Ye
Berberine improves glucose metabolism through induction of glycolysis
Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E148 - E156.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
P. Abidi, W. Chen, F. B. Kraemer, H. Li, and J. Liu
The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms
J. Lipid Res., October 1, 2006; 47(10): 2134 - 2147.
[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 
Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.