Submitted on December 21, 2007
Revised on February 19, 2008
Accepted on March 1, 2008
Inhibition of stearoyl coenzyme a desaturase activity induces hypercholesterolemia in the cholesterol-Fed Hamster
Catherine A. Major, Kevin Ryan, Andrew J. Bennett, Adam L. Lock, Dale E. Bauman, and Andrew M. Salter
Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Loughborough, Leicestershire LE12 5RD
Corresponding Author: andrew.salter{at}nottingham.ac.uk
Reduction of stearoyl Coenzyme A 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 to male Golden Syrian Hamsters fed high fat diets with or without added dietary cholesterol. In the absence of cholesterol, sterculic oil 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 coenzyme A carboxylase and fatty acid synthase mRNA concentrations were reduced by feeding cholesterol and sterculic oil, while 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.
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