Choline status modulates the development of atherosclerosis in LDL receptor knockout mice (272.7)

Abstract

Background: Phosphatidylethanolamine N‐methyltransferase (Pemt) is the only de novo pathway for phosphatidylcholine (PC) synthesis in mammals; as such, Pemt ‐/‐ mice are chronically choline‐deficient. PEMT deficiency dramatically reduces atherosclerosis development in LDL receptor (LDLR) knockout mice. This atheroprotective effect is believed to be mediated by reduction in circulating lipid levels.Purpose: to investigate the effect of altering choline status on plasma lipid profiles and atherosclerosis development in LDLR‐/‐ mice, and to test the hypothesis that choline supplementations reverse the atheroprotective effect of PEMT deletion via normalization plasma lipid profiles.Methods: LDLR‐/‐ and PEMT‐/‐/ LDLR‐/‐ male mice were given free access to high fat high cholesterol diet. Choline in diet (g/Kg) ranged from 0‐10. Atherosclerosis development was assessed by measuring plaque area in cross sectional aortic root.Results: In LDLR‐/‐ mice, choline‐deficient group gained less weight, presented higher liver TG, CE and PL compared to other groups. Excessive choline group presented significantly higher liver PC and plasma TG.Choline supplementation caused step‐wise increase in atherosclerosis development in LDLR‐/‐ mice. Significant correlations were observed between choline in diet and plasma PL (r=0.8075, P<0.0001), plasma total cholesterol (r=0.8369, P<0.0001), plasma TG (r=0.7551, P<0.0001), and aortic root atherosclerotic plaque area (r=0.6985, P<0.0001).As previously reported, PEMT‐/‐/ LDLR‐/‐ mice were protected from atherosclerosis. Increasing dietary choline from 3‐10 (g/Kg) decreased liver weight, TG, and PL. Surprisingly; it didn’t promote atherogenic plasma lipid profiles nor increased plaque formation.Conclusion: There is a positive correlation between dietary choline and the development of atherosclerosis in the LDLR‐/‐ mice. Choline deficiency cannot solely explain the atheroprotective effect of PEMT deletion in the LDLR‐/‐ mice.Grant Funding Source: Supported by Canadian Institutes of Health Research (CIHR) & Alberta Innovates Bio Solutions (AI B)