Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M203912200 on July 11, 2002

J. Biol. Chem., Vol. 277, Issue 37, 34117-34124, September 13, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/37/34117    most recent
M203912200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hyogo, H.
Right arrow Articles by Cohen, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hyogo, H.
Right arrow Articles by Cohen, D. E.
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?

Leptin Promotes Biliary Cholesterol Elimination during Weight Loss in ob/ob Mice by Regulating the Enterohepatic Circulation of Bile Salts*

Hideyuki HyogoDagger §, Suheeta RoyDagger , Beverly Paigen, and David E. CohenDagger ||**

From the Departments of Dagger  Medicine and || Biochemistry, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461 and  The Jackson Laboratory, Bar Harbor, Maine 04609

Leptin administration to obese C57BL/6J (ob/ob) mice results in weight loss by reducing body fat. Because adipose tissue is an important storage depot for cholesterol, we explored evidence that leptin-induced weight loss in ob/ob mice was accompanied by transport of cholesterol to the liver and its elimination via bile. Consistent with mobilization of stored cholesterol, cholesterol concentrations in adipose tissue remained unchanged during weight loss. Plasma cholesterol levels fell sharply, and microscopic analyses of gallbladder bile revealed cholesterol crystals as well as cholesterol gallstones. Surprisingly, leptin reduced biliary cholesterol secretion rates without affecting secretion rates of bile salts or phospholipids. Instead, cholesterol supersaturation of gallbladder bile was due to marked decreases in bile salt hydrophobicity and not to hypersecretion of biliary cholesterol per se, such as occurs in humans during weight loss. In addition to regulating bile salt composition, leptin treatment decreased bile salt pool size. The smaller, more hydrophilic bile salt pool was associated with substantial decreases in intestinal cholesterol absorption. Within the liver, leptin treatment reduced the activity of 3-hydroxy-3-methylglutaryl-CoA reductase, but it did not change activities of cholesterol 7alpha -hydroxylase or acyl-CoA:cholesterol acyltransferase. These data suggest that leptin regulates biliary lipid metabolism to promote efficient elimination of excess cholesterol stored in adipose tissue. Cholesterol gallstone formation during weight loss in ob/ob mice appears to represent a pathologic consequence of an adaptive response that prevents absorption of biliary and dietary cholesterol.

* This work was supported by National Institutes of Health Grants DK48873 (to D. E. C.) and DK51568 (to B. P.) and Grant DK 20514 from the Albert Einstein College of Medicine Diabetes Research & Training Center.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Recipient of a grant from the Japan-North America Medical Exchange Foundation and a Dr. Charles Trey Memorial American Liver Foundation Postdoctoral Fellowship.

** To whom correspondence should be addressed: Liver Research Center, Ullmann 625, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Tel.: 718-430-2098; Fax: 718-430-8975; E-mail: dcohen@aecom.yu.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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
 FASEB J.Home page
E. F. Scapa, A. Pocai, M. K. Wu, R. Gutierrez-Juarez, L. Glenz, K. Kanno, H. Li, S. Biddinger, L. A. Jelicks, L. Rossetti, et al.
Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2
FASEB J, July 1, 2008; 22(7): 2579 - 2590.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
C. R. Wooton-Kee, D. E. Cohen, and M. Vore
Increased cholesterol 7{alpha}-hydroxylase expression and size of the bile acid pool in the lactating rat
Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G1009 - G1016.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
D. J. Lloyd, J. McCormick, J. Helmering, K. W. Kim, M. Wang, P. Fordstrom, S. A. Kaufman, R. A. Lindberg, and M. M. Veniant
Generation and characterization of two novel mouse models exhibiting the phenotypes of the metabolic syndrome: Apob48-/-Lepob/ob mice devoid of ApoE or Ldlr
Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E496 - E505.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. S. Sabeva, E. J. Rouse, and G. A. Graf
Defects in the Leptin Axis Reduce Abundance of the ABCG5-ABCG8 Sterol Transporter in Liver
J. Biol. Chem., August 3, 2007; 282(31): 22397 - 22405.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
W.-J. Wang, J. M. Baez, R. Maurer, H. M. Dansky, and D. E. Cohen
Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E-deficient mice
J. Lipid Res., November 1, 2006; 47(11): 2400 - 2407.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
W. Huang, N. Dedousis, A. Bandi, G. D. Lopaschuk, and R. M. O'Doherty
Liver Triglyceride Secretion and Lipid Oxidative Metabolism Are Rapidly Altered by Leptin in Vivo
Endocrinology, March 1, 2006; 147(3): 1480 - 1487.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. K. Wu and D. E. Cohen
Phosphatidylcholine transfer protein regulates size and hepatic uptake of high-density lipoproteins
Am J Physiol Gastrointest Liver Physiol, December 1, 2005; 289(6): G1067 - G1074.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. K. Wu and D. E. Cohen
Altered hepatic cholesterol metabolism compensates for disruption of phosphatidylcholine transfer protein in mice
Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G456 - G461.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. K. Wu, H. Hyogo, S. K. Yadav, P. M. Novikoff, and D. E. Cohen
Impaired response of biliary lipid secretion to a lithogenic diet in phosphatidylcholine transfer protein-deficient mice
J. Lipid Res., March 1, 2005; 46(3): 422 - 431.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Lundasen, W. Liao, B. Angelin, and M. Rudling
Leptin Induces the Hepatic High Density Lipoprotein Receptor Scavenger Receptor B Type I (SR-BI) but Not Cholesterol 7{alpha}-Hydroxylase (Cyp7a1) in Leptin-deficient (ob/ob) Mice
J. Biol. Chem., October 31, 2003; 278(44): 43224 - 43228.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S. Guilmeau, M. Buyse, A. Tsocas, J. P. Laigneau, and A. Bado
Duodenal Leptin Stimulates Cholecystokinin Secretion: Evidence of a Positive Leptin-Cholecystokinin Feedback Loop
Diabetes, July 1, 2003; 52(7): 1664 - 1672.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
H. Hyogo, S. Roy, and D. E. Cohen
Restoration of gallstone susceptibility by leptin in C57BL/6J ob/ob mice
J. Lipid Res., June 1, 2003; 44(6): 1232 - 1240.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
S. K. Erickson, S. R. Lear, S. Deane, S. Dubrac, S. L. Huling, L. Nguyen, J. S. Bollineni, S. Shefer, H. Hyogo, D. E. Cohen, et al.
Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice
J. Lipid Res., May 1, 2003; 44(5): 1001 - 1009.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement