Figure 5.

Schematic illustration of NPC1L1-mediated intestinal absorption of sphingomyelin (SM) and regulation of VLDL/LDL-apoM-sphingosine-1-phosphate (S1P). NPC1L1 would be involved in the intestinal absorption of dietary SM. It is still unclear whether SM hydrolysates such as choline, ceramide, fatty acids, and sphingosine, which are enzymatically produced from SM in the intestinal lumen, are physiological substrates of NPC1L1. After absorption, some SM is metabolized to S1P and, after several steps, S1P is exported into the blood as the apoM-bound form in VLDL/LDL. Although the (patho)physiological functions of VLDL/LDL-apoM-S1P are unclear, considering that WD-induced atherosclerotic plaques are diminished in apoM knockout mice compared to apoM wild-type mice [17], VLDL/LDL-apoM-S1P may exacerbate atherosclerosis.