Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 30, Issue 1, Pages 24-U63Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.109.198036
Keywords
saturated fat; fish oil; atherosclerosis; inflammation; metabolic syndrome
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Funding
- National Center for Complimentary and Alternative Medicine [NCCAM-P50AT002782]
- National Institutes of Health [NIH-P01HL49373, R01-HL094525, 1K99HL096166-01]
- American Heart Association [0625400U, 0825445E, 09POST2250225]
- Howard Hughes Medical Institute
- NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE [P50AT002782] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL094525, P01HL049373, R00HL096166, K99HL096166] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES102005] Funding Source: NIH RePORTER
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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. (Arterioscler Thromb Vasc Biol. 2010;30:24-30.)
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