| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Papers In Press, published online ahead of print October 1, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Lipid Research, Vol. 47, 2280-2290, October 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology
,
* Department of Medicine, University of California, San Francisco, San Francisco, CA
Liver Center, University of California, San Francisco, San Francisco, CA
Gladstone Institute of Cardiovascular and Neurological Disease, San Francisco, CA
** KineMed, Emeryville, CA
Arkansas Children's Nutrition Center, University of Arkansas, Little Rock, AR
Department of Pathology, University of California, San Francisco, San Francisco, CA
The online version of this article (available at http://www.jlr.org) contains additional table.
Published, JLR Papers in Press, July 8, 2006.
1 Present address of L. Arnaboldi: Department of Pharmacological Sciences, University of Milan, Italy.
2 To whom correspondence should be addressed. e-mail: jmaher{at}medsfgh.ucsf.edu
Lipogenic diets that are completely devoid of methionine and choline (MCD) induce hepatic steatosis. MCD feeding also provokes systemic weight loss, for unclear reasons. In this study, we found that MCD feeding causes profound hepatic suppression of the gene encoding stearoyl-coenzyme A desaturase-1 (SCD-1), an enzyme whose regulation has significant effects on metabolic rate. Within 7 days of MCD exposure, hepatic SCD-1 mRNA decreased to nearly undetectable levels. By day 21, SCD-1 protein was absent from hepatic microsomes and fatty acids showed a decrease in monounsaturated species. These changes in hepatic SCD-1 were accompanied by signs of hypermetabolism. Calorimetry revealed that MCD-fed mice consumed 37% more energy than control mice (P = 0.0003). MCD feeding also stimulated fatty acid oxidation, although fatty oxidation genes were not significantly upregulated. Interestingly, despite their increased metabolic rate, MCD-fed mice did not increase their food consumption, and as a result, they lost 26% of their body weight in 21 days. In summary, MCD feeding suppresses SCD-1 in the liver, which likely contributes to hypermetabolism and weight loss. MCD feeding also induces hepatic steatosis, by an independent mechanism. Viewed together, these two disparate consequences of MCD feeding (weight loss and hepatic steatosis) give the appearance of an unusual form of lipodystrophy.
Supplementary key words liver • fatty liver • steatosis • lipogenesis • fatty acid • oxidation • stearoyl-coenzyme A desaturase-1
Abbreviations: ACC, acetyl-coenzyme A carboxylase; AMPK, AMP-activated protein kinase; BHT, butylated hydroxytoluene; CPT-1, carnitine palmitoyltransferase-1; DNL, de novo lipogenesis; MCD, methionine-choline-deficient; MCS, methionine-choline-sufficient; MTP, microsomal triglyceride transfer protein; SCD-1, stearoyl-coenzyme A desaturase-1; SREBP-1, sterol-regulatory element binding protein-1
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G Serviddio, F Bellanti, R Tamborra, T Rollo, N Capitanio, A D Romano, J Sastre, G Vendemiale, and E Altomare Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia-reperfusion injury Gut, July 1, 2008; 57(7): 957 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Depke, G. Fusch, G. Domanska, R. Geffers, U. Volker, C. Schuett, and C. Kiank Hypermetabolic Syndrome as a Consequence of Repeated Psychological Stress in Mice Endocrinology, June 1, 2008; 149(6): 2714 - 2723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Rinella, M. S. Elias, R. R. Smolak, T. Fu, J. Borensztajn, and R. M. Green Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet J. Lipid Res., May 1, 2008; 49(5): 1068 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Baumgardner, K. Shankar, L. Hennings, T. M. Badger, and M. J. J. Ronis A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G27 - G38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Romestaing, M.-A. Piquet, D. Letexier, B. Rey, A. Mourier, S. Servais, M. Belouze, V. Rouleau, M. Dautresme, I. Ollivier, et al. Mitochondrial adaptations to steatohepatitis induced by a methionine- and choline-deficient diet Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E110 - E119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Lee, J. S. Yan, R. K. Ng, S. Kakar, and J. J. Maher Polyunsaturated fat in the methionine-choline-deficient diet influences hepatic inflammation but not hepatocellular injury J. Lipid Res., August 1, 2007; 48(8): 1885 - 1896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kohli, X. Pan, P. Malladi, M. S. Wainwright, and P. F. Whitington Mitochondrial Reactive Oxygen Species Signal Hepatocyte Steatosis by Regulating the Phosphatidylinositol 3-Kinase Cell Survival Pathway J. Biol. Chem., July 20, 2007; 282(29): 21327 - 21336. [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 |
