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A more recent version of this article appeared on April 1, 2003
Papers In Press, published online ahead of print January 16, 2003
J. Lipid Res., doi:10.1194/jlr.M200431-JLR200
Submitted on November 6, 2002
Revised on January 10, 2003
Accepted on January 14, 2003
Effects of LDL enriched with different dietary fatty acids on cholesteryl ester accumulation and turnover in THP-1 macrophages
Aaron T. Lada, Lawrence L. Rudel, and Richard W. St. Clair
Pathology Dept., Wake Forest University School of Medicine, Winston-Salem, NC 27157
Corresponding Author: rstclair{at}wfubmc.edu
LDL enriched in either saturated, monounsaturated, n-6 polyunsaturated, or n-3 polyunsaturated fatty acids were used to study the effects of dietary fatty acids on macrophage cholesteryl ester (CE) accumulation, physical state, hydrolysis, and cholesterol efflux. Incubation of THP-1 macrophages with acetylated LDL from each of the four diet groups resulted in both CE and TG accumulation in addition to alterations of cellular CE, TG, and phospholipid fatty acyl compositions reflective of the individual LDLs. Incubation with monounsaturated LDL resulted in significantly higher total and CE accumulation when compared with the other groups. After TG depletion, intracellular anisotropic lipid droplets were visible in all four groups with 71% of the cells incubated with monounsaturated AcLDL containing anisotropic lipid droplets, compared with 30% of cells incubated with n-3 AcLDL. These physical state differences translated into higher rates of both CE hydrolysis and cholesterol efflux in the n-3 group. These data suggest that monounsaturated fatty acids may enhance atherosclerosis by increasing both cholesterol delivery to macrophage foam cells, and the percentage of anisotropic lipid droplets, while n-3 polyunsaturated fatty acids decrease atherosclerosis by creating more fluid cellular CE droplets, which accelerates the rate of CE hydrolysis and the efflux of cholesterol from the cell.

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Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
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