n-3 and n-6 polyunsaturated fatty acids have different effects on acyl-CoA:cholesterol acyltransferase in J774 macrophages.
The effects of incubating J774 mouse macrophages with different fatty acids on cholesterol esterification were investigated. In cells incubated with n-3 polyunsaturated fatty acids, the rate of cholesterol esterification was significantly reduced compared with cells incubated with n-6 polyunsaturated fatty acids or with oleic acid. This change in cholesterol esterification appears to be the result of reductions in the activity of acyl-CoA:cholesterol acyltransferase (ACAT) in the endoplasmic reticulum of the macrophages incubated with the n-3 polyunsaturated fatty acids. No differences in microsomal cholesterol were observed among cells incubated with different fatty acids. However, cellular cholesterol levels were lower in cells incubated with n-3 polyunsaturated fatty acids. In microsomes from cells incubated with n-3 polyunsaturated fatty acids, both the Km and the Vmax of ACAT were lower than in microsomes from cells incubated with n-6 fatty acids or oleic acid. These findings may explain some of the reduction in atherosclerotic lesions that are observed with dietary fish oils that contain high levels of n-3 polyunsaturated fatty acids.
Davis
P J
PJ
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D004951:Esterification; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D002785:Sterol O-Acyltransferase / Q000378:metabolism*
D002788:Cholesterol Esters; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D002785:Sterol O-Acyltransferase