Molecular, Genetic, and Biochemical Nutrition Commons^™

Inhibition Of Stearoyl-Coa Desaturase 1 (Scd1) Dissociates Insulin Resistance And Obesity From Atherosclerosis, J. Mark Brown, Soonkyu Chung, Janet K. Sawyer, Chiara Degirolamo, Heather M. Alger, Tam Nguyen, Xuewei Zhu, My-Ngan Duong, Amanda L. Wibley, Ramesh Shah, Matthew A. Davis, Kathryn Kelley, Martha D. Wilson, Carol Kent, John S. Parks, Lawrence L. Rudel

Department of Nutrition and Health Sciences: Faculty Publications

Background—Stearoyl-CoA Desaturase 1 (SCD1) is a well-known enhancer of the metabolic syndrome. The purpose of the present study was to investigate the role of SCD1 in lipoprotein metabolism and atherosclerosis progression.

Methods and Results—Antisense oligonucleotides were used to inhibit SCD1 in a mouse model of hyperlipidemia and atherosclerosis (LDLr^-/-Apob^100/100). In agreement with previous reports, inhibition of SCD1 protected against diet-induced obesity, insulin resistance, and hepatic steatosis. However, unexpectedly SCD1 inhibition strongly promoted aortic atherosclerosis, which could not be reversed by dietary oleate. Further analyses revealed that SCD1 inhibition promoted accumulation of saturated fatty acids …