Abstract
LDL enriched with 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 (AcLDL) from each of the four diet groups resulted in both CE and triglyceride (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 PUFAs decrease atherosclerosis by creating more fluid cellular CE droplets that accelerate the rate of CE hydrolysis and the efflux of cholesterol from the cell.
Highlights
LDL enriched with 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
To better understand the mechanism underlying the differential effects of dietary fatty acids on atherosclerosis, we have examined the effects of fatty acid composition on macrophage cholesteryl ester (CE) metabolism
In order to study the effects of dietary fatty acids on macrophages in vitro, we utilized LDL isolated from the plasma of African green monkeys fed diets enriched in either saturated, monounsaturated, n-6 polyunsaturated, or n-3 polyunsaturated fatty acids
Summary
LDL enriched with 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. 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. The use of animal models has provided valuable insight into this debate through the generation of more definitive endpoints than would be possible in human studies In studies with both African green monkeys and transgenic mice, despite the positive effects of monounsaturated fats on the plasma lipid profile, monounsaturated-fat fed animals developed similar levels of atherosclerosis as saturated fat-fed animals, while animals fed polyunsaturated fats developed less atherosclerosis [12, 13]. At body temperature (37ЊC), when CE fatty acids are mainly unsaturated, such as n-6 or n-3 polyunsaturated fatty acids, CE is in a liquid state, and when saturated or even monounsaturated fatty acids predominate, the physical state becomes liquid-crystalline [25, 29,30,31,32]
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