Loss of stearoyl–CoA desaturase-1 function protects mice against adiposity
- James M. Ntambi*,†,‡,
- Makoto Miyazaki*,
- Jonathan P. Stoehr*,
- Hong Lan*,
- Christina M. Kendziorski§,
- Brian S. Yandell¶,
- Yang Song‡,
- Paul Cohen∥,
- Jeffrey M. Friedman¶, and
- Alan D. Attie*
- Departments of *Biochemistry, †Nutritional Sciences,§ Biostatistics and Medical Informatics, and¶ Statistics and Horticulture, University of Wisconsin, Madison, WI 53706; and ∥Laboratory of Molecular Genetics and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021
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Contributed by Jeffrey M. Friedman
Abstract
Stearoyl–CoA desaturase (SCD) is a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (C18:1) and palmitoleate (C16:1), which are components of membrane phospholipids, triglycerides, wax esters, and cholesterol esters. Several SCD isoforms (SCD1-3) exist in the mouse. Here we show that mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased insulin sensitivity, and are resistant to diet-induced weight gain. The protection from obesity involves increased energy expenditure and increased oxygen consumption. Compared with the wild-type mice the SCD1−/− mice have increased levels of plasma ketone bodies but reduced levels of plasma insulin and leptin. In the SCD1−/− mice, the expression of several genes of lipid oxidation are up-regulated, whereas lipid synthesis genes are down-regulated. These observations suggest that a consequence of SCD1 deficiency is an activation of lipid oxidation in addition to reduced triglyceride synthesis and storage.
Footnotes
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↵ ‡ To whom reprint requests should be addressed. E-mail: ntambi{at}biochem.wisc.edu.
- Abbreviations:
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SCD, stearoyl–CoA desaturase
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- Copyright © 2002, The National Academy of Sciences
