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

被引:50
作者
Brown, J. Mark [1 ]
Chung, Soonkyu [1 ]
Sawyer, Janet K. [1 ]
Degirolamo, Chiara [1 ]
Alger, Heather M. [2 ]
Nguyen, Tam M. [1 ]
Zhu, Xuewei [1 ]
Duong, My-Ngan [4 ]
Brown, Amanda L. [3 ]
Lord, Caleb [1 ]
Shah, Ramesh [1 ]
Davis, Matthew A. [1 ]
Kelley, Kathryn [1 ]
Wilson, Martha D. [1 ]
Madenspacher, Jennifer [5 ]
Fessler, Michael B. [5 ]
Parks, John S. [1 ]
Rudel, Lawrence L. [1 ]
机构
[1] Wake Forest Univ, Sch Med, Dept Pathol, Sect Lipid Sci, Winston Salem, NC 27157 USA
[2] Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA
[3] Wake Forest Univ, Sch Med, Dept Mol Med, Winston Salem, NC 27157 USA
[4] Cleveland Clin, Dept Cell Biol, Cleveland, OH USA
[5] NIEHS, Lab Resp Biol, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA
基金
美国国家卫生研究院;
关键词
saturated fat; fish oil; atherosclerosis; inflammation; metabolic syndrome; FATTY-ACIDS; INSULIN-RESISTANCE; DEFICIENCY PROTECTS; MICE; OBESITY; MODULATION; GENE; TRIGLYCERIDES; INFLAMMATION; DISRUPTION;
D O I
10.1161/ATVBAHA.109.198036
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (Arterioscler Thromb Vasc Biol. 2010;30:24-30.)
引用
收藏
页码:24 / U63
页数:25
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