Macrophage Elovl6 Deficiency Ameliorates Foam Cell Formation and Reduces Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

Abstract

Objective— Elovl6, a long-chain fatty acid elongase, is a rate-limiting enzyme that elongates saturated and monounsaturated fatty acids and has been shown to be related to obesity-induced insulin resistance via modification of fatty acid composition. In this study, we investigated the roles of Elovl6 in foam cell formation in macrophages and atherosclerosis in mice. Methods and Results— To investigate the roles of Elovl6 in macrophages in the progression of atherosclerosis, we transplanted bone marrow cells of wild-type or Elovl6 −/− mice into irradiated LDL-R −/− mice that were fed a western diet. Aortic atherosclerotic lesion areas and infiltration of macrophages were significantly smaller in Elovl6 −/− bone marrow cells-transplanted LDL-R −/− mice than in wild-type. Accumulation of esterified cholesterol on exposure to acetylated-LDL was less severe in peritoneal macrophages from Elovl6 −/− mice than those from wild-type. Cholesterol efflux and expression of cholesterol efflux transporters were increased in Elovl6 −/− macrophages, although no difference in uptake of acetylated-LDL was found between the two groups. On analysis of fatty acid composition of the esterified cholesterol fraction in macrophages, n-6 polyunsaturated fatty acids were decreased by absence of Elovl6. Conclusion— These findings suggest that Elovl6 in macrophages may contribute to foam cell formation and progression of atherosclerosis.