on April 12, 2007
Published online before print April 12, 2007, doi: 10.1161/ATVBAHA.107.142802
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Submitted on January 9, 2007
Accepted on March 30, 2007
Dietary Fat-Induced Alterations in Atherosclerosis Are Abolished by ACAT2-Deficiency in ApoB100 Only, LDLr-/- Mice
Thomas A. Bell III ;
From the Wake Forest University School of Medicine, Department of Pathology, Section on Lipid Sciences, Winston-Salem, NC.
* To whom correspondence should be addressed. E-mail: lrudel{at}wfubmc.edu.
Objectives--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.
Methods and Results--Groups of female apoB100 only, LDLr-/- mice with and without ACAT2 were fed diets enriched in either 
-3 or -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.
Key words: ACAT2 • cholesteryl esters • lipoproteins • liver • aortic atherosclerosis
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