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Journal of Lipid Research, Vol. 49, 1456-1465, July 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Inhibition of stearoyl CoA desaturase activity induces hypercholesterolemia in the cholesterol-fed hamster¹

Catherine A. Major^*, Kevin Ryan^*, Andrew J. Bennett^*, Adam L. Lock^2,, Dale E. Bauman and Andrew M. Salter^3,*

^* Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire, United Kingdom, LE12 5RD
Department of Animal Science, Cornell University, Ithaca, NY 14853

¹ This work was presented in abstract form at the British Nutrition Society Summer Meeting, Norwich, UK, 2005.

This work was supported in part by a studentship (C.A.M.) from the British Heart Foundation.

Published, JLR Papers in Press, March 2, 2008.

² Present address of A. L. Lock: Department of Animal Science, University of Vermont, 208 Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0148.

³ To whom correspondence should be addressed. e-mail: Andrew.salter{at}nottingham.ac.uk

Reduction of stearoyl CoA desaturase (SCD) activity has been shown to induce resistance to diet-induced obesity in mice. In the present study, SCD was inhibited by feeding sterculic oil (SO) to male Golden Syrian Hamsters fed high-fat diets with or without added dietary cholesterol. In the absence of cholesterol, SO had little impact on adipose tissue mass or plasma lipoprotein concentrations. When cholesterol was included in the diet, inhibition of SCD resulted in reduced body weight, adipose tissue mass, and feed efficiency. These animals also exhibited a marked hypercholesterolemia, with an accumulation of free-cholesterol–rich particles within the LDL density range, and reduced hepatic cholesterol esterification. This was accompanied by a 20-fold increase in plasma alanine aminotransferase, which was suggestive of significant hepatic damage. Hepatic acetyl CoA carboxylase and fatty acid synthase mRNA concentrations were reduced by feeding cholesterol and SO, whereas lipoprotein lipase and SCD mRNA were increased. These changes were associated with decreased hepatic sterol regulatory element binding protein 1a and 1c mRNA concentrations. Thus, inhibition of SCD activity in the cholesterol-fed hamster results in a reduction in overall body weight and adipose tissue deposition. However, this also causes marked hypercholesterolemia and potential liver damage.

Supplementary key words sterculic oil • lipoproteins • hamsters • gene expression

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