Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 inhibition prevents the metabolic syndrome and atherosclerosis.

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.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 30 Issue 1 Pg. 24-30 (Jan 2010) ISSN: 1524-4636 [Electronic] United States
• PMID: 19834103 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein B-100
• Dietary Fats, Unsaturated
• Fatty Acids
• Fish Oils
• Oligoribonucleotides, Antisense
• Receptors, LDL
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Scd1 protein, mouse
• Stearoyl-CoA Desaturase

Topics

• 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 (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)