title: Incremental replacement of saturated fats by n-3 fatty acids in high-fat, high-cholesterol diets reduces elevated plasma lipid levels and arterial lipoprotein lipase, macrophages and atherosclerosis in LDLR-/- mice.
abstract: OBJECTIVE
  Effects of progressive substitution of dietary n-3 fatty acids (FA) for saturated FA (SAT) on modulating risk factors for atherosclerosis have not been fully defined. Our previous reports demonstrate that SAT increased, but n-3 FA decreased, arterial lipoprotein lipase (LpL) levels and arterial LDL-cholesterol deposition early in atherogenesis. We now questioned whether incremental increases in dietary n-3 FA can counteract SAT-induced pro-atherogenic effects in atherosclerosis-prone LDL-receptor knockout (LDLR-/-) mice and have identified contributing mechanisms.
  
  
  RESULTS
  Mice were fed chow or high-fat diets enriched in SAT, n-3, or a combination of both SAT and n-3 in ratios of 3:1 (S:n-3 3:1) or 1:1 (S:n-3 1:1). Each diet resulted in the expected changes in fatty acid composition in blood and aorta for each feeding group. SAT-fed mice became hyperlipidemic. By contrast, n-3 inclusion decreased plasma lipid levels, especially cholesterol. Arterial LpL and macrophage levels were increased over 2-fold in SAT-fed mice but these were decreased with incremental replacement with n-3 FA. n-3 FA partial inclusion markedly decreased expression of pro-inflammatory markers (CD68, IL-6, and VCAM-1) in aorta. SAT diets accelerated advanced atherosclerotic lesion development, whereas all n-3 FA-containing diets markedly slowed atherosclerotic progression.
  
  
  CONCLUSIONS
  Mechanisms whereby dietary n-3 FA may improve adverse cardiovascular effects of high-SAT, high-fat diets include improving plasma lipid profiles, increasing amounts of n-3 FA in plasma and the arterial wall. Even low levels of replacement of SAT by n-3 FA effectively reduce arterial lipid deposition by decreasing aortic LpL, macrophages and pro-inflammatory markers.
authors.affiliation: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Chuchun L
authors.initials: CL
authors.lastname: Chang
authors.affiliation: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Campus Norte Hospital Roberto del Río, University of Chile, Santiago, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Torrejon
authors.affiliation: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Un Ju
authors.initials: UJ
authors.lastname: Jung
authors.affiliation: Campus Norte Hospital Roberto del Río, University of Chile, Santiago, Chile.
authors.forename: Kristin
authors.initials: K
authors.lastname: Graf
authors.affiliation: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: rjd20@columbia.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Deckelbaum
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001011:Aorta / Q000201:enzymology*; D001018:Aortic Diseases / Q000097:blood / Q000178:diet therapy* / Q000209:etiology / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000178:diet therapy* / Q000209:etiology / Q000235:genetics; D001835:Body Weight; D002791:Cholesterol, Dietary; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D015536:Down-Regulation; D005395:Fish Oils / Q000008:administration & dosage* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002791:Cholesterol, Dietary; D005395:Fish Oils; D018836:Inflammation Mediators; D015850:Interleukin-6; D008055:Lipids; D008071:Lipoprotein Lipase; D011973:Receptors, LDL; D019010:Vascular Cell Adhesion Molecule-1; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C577686:interleukin-6, mouse; C033266:Menhaden oil
keywords: Atherosclerosis; Inflammation; LDLR−/−; Lipoprotein lipase; n−3 fatty acids
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