The effect of dietary sphingolipids on plasma sphingomyelin metabolism and atherosclerosis

Sphingomyelin (SM) plays a very important role in cell membrane formation and plasma lipoprotein metabolism. All these functions may have an impact on atherosclerotic development. To investigate the relationship between SM metabolism and atherosclerosis, we utilized a sphingolipid-rich diet to feed LDL receptor gene knockout (LDLr KO) mice and studied lipid metabolism and atherosclerosis in the mice. After 3 months of a sphingolipid-rich diet, we found a significant increase in SM, cholesterol, and SM/phosphatidylcholine (PC) ratio (50%, P < 0.001; 62%, P < 0.01; and 45%, P < 0.01, respectively), compared to chow fed diet. HDL-lipids were not significantly altered. Non-HDL-SM, non-HDL-C, and non-HDL-SM/non-HDL-PC ratio were significantly increased (115%, P < 0.001; 106%, P < 0.001; and 106%, P < 0.01, respectively). FPLC confirmed the results. SDS-PAGE showed an increase of apoB48 and apoB100, but no changes of apoAI. Moreover, we found that an SM-rich diet significantly increased atherosclerotic lesion area in both root assay and en face assay, compared to chow diet (58,210 ± 15,300 μm2 vs. 9670 ± 2370 μm2, P < 0.001; 5.9 ± 3.1% vs. 1.1 ± 0.9%, P < 0.001). These results indicate that the enrichment of sphingolipids in diet has proatherogenic properties.