出版社：American Society for Biochemistry and Molecular Biology
摘要：ACAT2, the enzyme responsible for the formation of cholesterylesters incorporated into apolipoprotein B-containing lipoproteinsby the small intestine and liver, forms predominantly cholesteryloleate from acyl-CoA and free cholesterol. The accumulationof cholesteryl oleate in plasma lipoproteins has been foundto be predictive of atherosclerosis. Accordingly, a method wasdeveloped in which fatty acyl-CoA subspecies could be extractedfrom mouse liver and quantified. Analyses were performed onliver tissue from mice fed one of four diets enriched with oneparticular type of dietary fatty acid: saturated, monounsaturated,n-3 polyunsaturated, or n-6 polyunsaturated. We found that thehepatic fatty acyl-CoA pools reflected the fatty acid compositionof the diet fed. The highest percentage of fatty acyl-CoAs acrossall diet groups was in monoacyl-CoAs, and values were 36% and46% for the n-3 and n-6 polyunsaturated diet groups and 55%and 62% in the saturated and monounsaturated diet groups, respectively.The percentage of hepatic acyl-CoA as oleoyl-CoA was also highlycorrelated to liver cholesteryl ester, plasma cholesterol, LDLmolecular weight, and atherosclerosis extent. These data suggestthat replacing monounsaturated with polyunsaturated fat canbenefit coronary heart disease by reducing the availabilityof oleoyl-CoA in the substrate pool of hepatic ACAT2, therebyreducing cholesteryl oleate secretion and accumulation in plasmalipoproteins.Supplementary key words acyl-coenzyme A:cholesterol acyltransferase 2 • stearoyl-coenzyme A desaturase 1 • saturated fat • polyunsaturated fat • dietary fat • cholesterol • cholesteryl ester • low density lipoprotein receptor-deficient • apolipoprotein B-100
