title: 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.
  
  
  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.affiliation: Wake Forest University School of Medicine, Department of Pathology, Section on Lipid Sciences, Medical Center Blvd, Winston-Salem, NC 27157-1040, USA.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Brown
authors.forename: Soonkyu
authors.initials: S
authors.lastname: Chung
authors.forename: Janet K
authors.initials: JK
authors.lastname: Sawyer
authors.forename: Chiara
authors.initials: C
authors.lastname: Degirolamo
authors.forename: Heather M
authors.initials: HM
authors.lastname: Alger
authors.forename: Tam M
authors.initials: TM
authors.lastname: Nguyen
authors.forename: Xuewei
authors.initials: X
authors.lastname: Zhu
authors.forename: My-Ngan
authors.initials: MN
authors.lastname: Duong
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Brown
authors.forename: Caleb
authors.initials: C
authors.lastname: Lord
authors.forename: Ramesh
authors.initials: R
authors.lastname: Shah
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Davis
authors.forename: Kathryn
authors.initials: K
authors.lastname: Kelley
authors.forename: Martha D
authors.initials: MD
authors.lastname: Wilson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Madenspacher
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fessler
authors.forename: John S
authors.initials: JS
authors.lastname: Parks
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Rudel
mesh_terms: 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
chemical_list: 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