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Journal of Lipid Research, Vol. 43, 1899-1907, November 2002
Copyright © 2002 by Lipid Research, Inc.

Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia

Alan D. Attie^1,*, Ronald M. Krauss, Mark P. Gray-Keller^*,, Alison Brownlie, Makoto Miyazaki^*, John J. Kastelein^**, Aldons J. Lusis, Anton F. H. Stalenhoef, Jonathan P. Stoehr^*, Michael R. Hayden^,*** and James M. Ntambi^*,

^* Department of Biochemistry, University of Wisconsin-Madison, Madison, WI
Lawrence Berkeley National Laboratory, University of California-Berkeley, Berkeley, CA
Xenon Genetics, Inc., Burnably, B.C., Canada
^** Academic Medical Center, Amsterdam, The Netherlands
Department of Medicine, UCLA School of Medicine, Los Angeles, CA
University Medical Center Nijmegen, Nijmegen, The Netherlands
^*** Center for Molecular and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI

¹ To whom correspondence should be addressed. e-mail: attie{at}biochem.wisc.edu

Stearoyl-CoA desaturase (SCD) is expressed at high levels in several human tissues and is required for the biosynthesis of oleate (18:1) and palmitoleate (16:1). These monounsaturated fatty acids are the major components of phospholipids, triglycerides, wax esters, and cholesterol esters. Mice with a targeted disruption of the SCD1 gene have very low levels of VLDL and impaired triglyceride and cholesterol ester biosynthesis. In the HYPLIP mouse, a model of hyperlipidemia, there was a 4-fold increase in hepatic SCD activity, a 1.8-fold increase in the desaturation index, and a 2-fold increase in plasma triglycerides. We used the plasma ratio of 18:1/18:0 (the "desaturation index") as an in vivo measure of SCD activity in human subjects. In human subjects with triglycerides ranging from 0.3 to 20 mM, the desaturation ratio accounted for one-third of the variance in plasma triglyceride levels. A 2-fold increase in the desaturation index was associated with a 4-fold increase in plasma triglycerides. In human subjects exposed to a high carbohydrate diet, the desaturation index explained 44% of the variance in triglycerides.

We propose that many of the factors that influence plasma triglyceride levels do so by converging upon the regulation of SCD activity.

Supplementary key words metabolic syndrome • hyperlipidemia • monounsaturated fatty acids

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