title: Dietary fat-induced alterations in atherosclerosis are abolished by ACAT2-deficiency in ApoB100 only, LDLr-/- mice.
abstract: OBJECTIVE
  The enzyme acyl-coenzymeA (CoA):cholesterol O-acyltransferase 2 (ACAT2) in the liver synthesizes cholesteryl esters (CE) from cholesterol and fatty acyl-CoA, which get incorporated into apoB-containing lipoproteins that are secreted into the bloodstream. Dietary fatty acid composition influences the amount and fatty acid composition of CE within apoB-containing lipoproteins. We hypothesized that when ACAT2 activity is removed by gene deletion, hepatic CE synthesis and secretion would be minimal and, as a result, dietary fat-related differences in atherosclerosis would be eliminated.
  
  
  RESULTS
  Groups of female apoB100 only, LDLr-/- mice with and without ACAT2 were fed diets enriched in either omega-3 or omega-6 polyunsaturated fat, saturated fat, and cis or trans monounsaturated fat. After 20 weeks on diet, mice fed diets enriched in monounsaturated or saturated fat exhibited significantly higher amounts of plasma cholesterol, larger LDL particles enriched in monounsaturated CE, and more atherosclerosis than mice fed polyunsaturated fat. The dietary fat-induced shifts in plasma cholesterol, LDL size, LDL CE composition, and atherosclerosis were not observed in ACAT2-/- mice. Regardless of the diet fed, the ACAT2-/- mice were protected from atherosclerosis.
  
  
  CONCLUSIONS
  The results indicate that in apoB100 only, LDLr-/- mice, ACAT2 plays an essential role in facilitating dietary fat type-specific atherosclerosis through its various effects on plasma lipoprotein concentration and composition.
authors: Wake Forest University School of Medicine, Department of Pathology/Lipid Sciences, Medical Center Blvd, Winston-Salem, NC 27157, USA.
authors: Thomas A
authors: TA
authors: Bell
authors: Kathryn
authors: K
authors: Kelley
authors: Martha D
authors: MD
authors: Wilson
authors: Janet K
authors: JK
authors: Sawyer
authors: Lawrence L
authors: LL
authors: Rudel
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D050197:Atherosclerosis / Q000139:chemically induced / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004036:Diet, Atherogenic; D004041:Dietary Fats; D004195:Disease Models, Animal; D005260:Female; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010316:Particle Size; D010865:Pilot Projects; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002785:Sterol O-Acyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D000097587:Sterol O-Acyltransferase 2
chemical_list: D053299:Apolipoprotein B-100; D002784:Cholesterol; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004041:Dietary Fats; D008055:Lipids; D011973:Receptors, LDL; D002785:Sterol O-Acyltransferase; D014280:Triglycerides; D000097587:Sterol O-Acyltransferase 2