J. Lipid Res.
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A more recent version of this article appeared on October 1, 2006

Papers In Press, published online ahead of print July 8, 2006
J. Lipid Res., doi:10.1194/jlr.M600198-JLR200
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Submitted on May 9, 2006
Revised on June 27, 2006
Accepted on July 7, 2006

Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1

Gizem Rizki, Lorenzo Arnaboldi, Bianca Gabrielli, Jim Yan, Gene S. Lee, Ray K. Ng, Scott M. Turner, Thomas M. Badger, Robert E. Pitas, and Jacquelyn J. Maher

Liver Center and Department of Medicine, University of California, San Francisco, San Francisco, CA 94110

Corresponding Author: 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-CoA desaturase-1 (SCD-1), an enzyme whose regulation has significant effects on metabolic rate. Within 7 days of MCD exposure, hepatic SCD-1 mRNA fell to nearly undetectable levels. By day 21, SCD-1 protein was absent from hepatic microsomes and fatty acids showed a drop 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 up-regulated. Interestingly, despite their increased metabolic rate, MCD-fed mice did not increase their food consumption, and as a result, 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. When viewed together, these two disparate consequences of MCD feeding (weight loss and hepatic steatosis) give the appearance of an unusual form of lipodystrophy.


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