Dietary Fat–Induced Alterations in Atherosclerosis Are Abolished by ACAT2-Deficiency in ApoB100 Only, LDLr −/− Mice

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Abstract
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 ω-3 or ω-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 ath... When ACAT2 was removed by gene deletion in apoB100 only,LDLr−/− mice, the ability of any of several types of dietary fat to induce atherosclerosis was prevented. LDL concentration, CE composition, and particle size were modified in ACAT2−/− mice; these changes appeared to play an important role in limiting atherogenesis.

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