Relevance of interactions between sphingomyelin and cholesterol in biliary and intestinal tract

Phosphatidylcholine and sphingomyelin are the major phospholipids of the hepatocytic canalicular membrane outer leaflet. Sphingomyelin may preferentially reside with cholesterol in liquid-ordered domains. In contrast, phosphatidylcholine is the exclusive phospholipid secreted in rat bile (enriched in hydrophilic species compared to the canalicular membrane), subsequently incorporated into bile salt-cholesterol micelles. We determined the bile lipid composition in 95 vertebrate species (Moschetta et al., J Lipid Res. 2005, 46, 2221-2232). Phospholipid was often virtually absent in bile of cartilaginous fish and reptiles, occurred in low relative amounts (compared to bile salts) in bony fish or birds and in high relative amounts in most mammals. Biles with low relative amounts of phospholipid often contained high proportions of sphingomyelin. Phosphatidylcholine was the predominant phospholipid in biles with high phospholipid contents. We then compared, in CaCo2 cells (without appreciable phospholipase A(2) activity), the effects of incorporating sphingomyelin, egg yolk phosphatidylcholine or lyso-phosphatidylcholine in apical bile salt-cholesterol micelles. Egg yolk phosphatidylcholine and (more pronounced) sphingomyelin inhibited cholesterol absorption with decreased ABC-A1 and -G1 expression. Lyso-phosphatidylcholine enhanced cholesterol absorption with increased basolateral HDL-depenclent cholesterol efflux and high expression of ABC-A1 and -G1. In conclusion, sphingomyelin plays a pivotal role in protecting hepatocytes against detergent bile salts. Dietary sphingomyelin may inhibit intestinal cholesterol absorption.