Lipid Trafficking in Hepatocytes: Relevance to Biliary Lipid Secretion

The liver contains several cell types. Parenchymal cells, or hepatocytes, are in number and in volume (60% and 80% of all liver cells, respectively) the largest group. Hepatocytes are polarized cells in which three surface domains can be distinguished: (1) the basolateral surface (sinusoidal domain) that faces the liver sinusoid and is in contact with plasma, (2) the contiguous surface in among neighboring cells, and (3) the apical surface (bile canalicular domain) where bile secretion occurs. Bile contains a variety of solutes, including a substantial amount of cholesterol and (bile-specific) phospholipids. Hepatocytes are actively involved in uptake and secretion processes. Uptake takes place at the basolateral surface, secretion both at the apical and basolateral surface. Distinct differences in lipid composition exist between the various plasma and intracellular membranes. Moreover, in spite of the continuous flow of lipids among the membranes, resulting from vesicular trafficking among intracellular membranes (organelles), these differences are maintained. Thus, machinery must be operational in the hepatocyte to ensure the maintenance of the specific lipid composition and the appropriate selection of the lipids destined for bile secretion or to prevent nonbiliary lipids from entering such a pathway. This chapter focuses on the aspects of intracellular lipid trafficking involved in bile secretory processes: the lipid composition at different sites of the hepatocyte, the origin of biliary lipids, the transport processes through the hepatocytes, and the possible mechanisms of secretion