Combined Therapy of Dietary Fish Oil and Stearoyl-CoA Desaturase 1 Inhibition Prevents the Metabolic Syndrome and Atherosclerosis

Authors

J. Mark Brown, Wake Forest University School of Medicine
Soonkyu Chung, University of Nebraska-LincolnFollow
Janet K. Sawyer, Wake Forest University School of MedicineFollow
Chiara Degirolamo, Wake Forest University School of Medicine
Heather M. Alger, Wake Forest University School of Medicine
Tam M. Nguyen, Wake Forest University School of Medicine
Xuewei Zhu, Wake Forest University School of Medicine
My-Ngan Duong, Department of Cell Biology, Cleveland Clinic, Ohio
Amanda L. Brown
Caleb Lord, Wake Forest University School of Medicine
Ramesh Shah, Wake Forest University School of Medicine
Matthew A. Davis, Wake Forest University School of Medicine
Kathryn Kelley, Wake Forest University School of Medicine
Martha D. Wilson, Wake Forest University School of Medicine
Jennifer Madenspacher, United States Department of Health and Human Services, Research Triangle Park, NC
Michael B. Fessler, United States Department of Health and Human Services, Research Triangle Park, NC
John S. Parks, Wake Forest University School of Medicine
Lawrence L. Rudel, Wake Forest University School of Medicine

Document Type

Article

Date of this Version

2010

Citation

Arteriosclerosis, Thrombosis, and Vascular Biology. 2010; 30: 24-30

Comments

U.S. Government Work

Abstract

Background—Stearoyl-CoA desaturase 1 (SCD1) is a critical regulator of energy metabolism and inflammation. We have previously reported that inhibition of SCD1 in hyperlipidemic mice fed a saturated fatty acid (SFA)-enriched diet prevented development of the metabolic syndrome, yet surprisingly promoted severe atherosclerosis. In this study we tested whether dietary fish oil supplementation could prevent the accelerated atherosclerosis caused by SCD1 inhibition.

Methods and Results—LDLr^-/-, ApoB^100/100 mice were fed diets enriched in saturated fat or fish oil in conjunction with antisense oligonucleotide (ASO) treatment to inhibit SCD1. As previously reported, in SFA-fed mice, SCD1 inhibition dramatically protected against development of the metabolic syndrome, yet promoted atherosclerosis. In contrast, in mice fed fish oil, SCD1 inhibition did not result in augmented macrophage inflammatory response or severe atherosclerosis. In fact, the combined therapy of dietary fish oil and SCD1 ASO treatment effectively prevented both the metabolic syndrome and atherosclerosis.

Conclusions—SCD1 ASO treatment in conjunction with dietary fish oil supplementation is an effective combination therapy to comprehensively combat the metabolic syndrome and atherosclerosis in mice.