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


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.
Brown
J Mark
JM
Wake Forest University School of Medicine, Department of Pathology, Section on Lipid Sciences, Medical Center Blvd, Winston-Salem, NC 27157-1040, USA.
Chung
Soonkyu
S
Sawyer
Janet K
JK
Degirolamo
Chiara
C
Alger
Heather M
HM
Nguyen
Tam M
TM
Zhu
Xuewei
X
Duong
My-Ngan
MN
Brown
Amanda L
AL
Lord
Caleb
C
Shah
Ramesh
R
Davis
Matthew A
MA
Kelley
Kathryn
K
Wilson
Martha D
MD
Madenspacher
Jennifer
J
Fessler
Michael B
MB
Parks
John S
JS
Rudel
Lawrence L
LL
D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D003131:Combined Modality Therapy; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology; D005234:Fatty Liver / Q000188:drug therapy / Q000517:prevention & control; D005395:Fish Oils / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy / Q000517:prevention & control; D007333:Insulin Resistance; D008264:Macrophages / Q000276:immunology; D008297:Male; D024821:Metabolic Syndrome / Q000178:diet therapy / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008817:Mice, Mutant Strains; D009765:Obesity / Q000188:drug therapy / Q000517:prevention & control; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000276:immunology
D053299:Apolipoprotein B-100; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D005395:Fish Oils; D020320:Oligoribonucleotides, Antisense; D011973:Receptors, LDL; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase