| Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 inhibition prevents the metabolic syndrome and atherosclerosis. | |
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MedLine Citation:
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PMID: 19834103 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J Mark Brown; Soonkyu Chung; Janet K Sawyer; Chiara Degirolamo; Heather M Alger; Tam M Nguyen; Xuewei Zhu; My-Ngan Duong; Amanda L Brown; Caleb Lord; Ramesh Shah; Matthew A Davis; Kathryn Kelley; Martha D Wilson; Jennifer Madenspacher; Michael B Fessler; John S Parks; Lawrence L Rudel |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-10-15 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-18 Completed Date: 2010-01-14 Revised Date: 2012-05-24 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 24-30 Citation Subset: IM |
Affiliation:
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Wake Forest University School of Medicine, Department of Pathology, Section on Lipid Sciences, Medical Center Blvd, Winston-Salem, NC 27157-1040, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoprotein B-100 / genetics, metabolism Atherosclerosis / drug therapy, immunology, prevention & control* Combined Modality Therapy Dietary Fats, Unsaturated / pharmacology* Fatty Acids / pharmacology Fatty Liver / drug therapy, prevention & control Fish Oils / pharmacology* Hyperlipidemias / drug therapy, prevention & control Insulin Resistance Macrophages / immunology Male Metabolic Syndrome X / diet therapy, immunology, prevention & control* Mice Mice, Mutant Strains Obesity / drug therapy, prevention & control Oligoribonucleotides, Antisense / pharmacology* Receptors, LDL / genetics, metabolism Stearoyl-CoA Desaturase / antagonists & inhibitors, genetics* Toll-Like Receptor 4 / immunology |
| Grant Support | |
ID/Acronym/Agency:
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1K99HL096166-01/HL/NHLBI NIH HHS; P01 HL049373-16/HL/NHLBI NIH HHS; P01 HL049373-160006/HL/NHLBI NIH HHS; P01-HL49373/HL/NHLBI NIH HHS; R00 HL096166-04/HL/NHLBI NIH HHS; R01-HL094525/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein B-100; 0/Dietary Fats, Unsaturated; 0/Fatty Acids; 0/Fish Oils; 0/Oligoribonucleotides, Antisense; 0/Receptors, LDL; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; EC 1.14.19.1/Scd1 protein, mouse; EC 1.14.19.1/Stearoyl-CoA Desaturase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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