Mechanisms of biliary lipid secretion and their role in lipid homeostasis.
Bile secretion serves different important functions. First, it is one of the main mechanisms for the disposition of many endogenous and exogenous amphipatic compounds, including drugs, toxins, and waste products. Second, it supplies bile salts to the intestine, which is of crucial importance for the emulsification of dietary lipids. In the last decade considerable progress has been achieved in the elucidation of the process of bile formation. Several key transporters in the canalicular membrane have been identified and characterized. This also holds for the mechanism of biliary lipid secretion, where the lipid translocating function of a P-glycoprotein was found to be indispensable for phospholipid secretion. Concomitantly, it became clear that bile salt-induced lipid secretion is an extremely complex process, in which several steps remain elusive. The production of mice with a specific defect in biliary lipid secretion and the identification of an analogous inherited human disease have made it possible to study the integrated function of biliary lipid secretion in whole body lipid homeostasis. In this review we discuss our current understanding of hepatocanalicular lipid secretion in this context. The pathologic consequences of defects in biliary lipid secretion are discussed in another review in this issue.
Oude Elferink
R P
RP
Lab. Exp. Hepatology, Academic Medical Center F0-116, Amsterdam, The Netherlands. r.p.oude-elferink@amc.uva.nl
Groen
A K
AK
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000502:physiology; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D001648:Bile Canaliculi / Q000378:metabolism; D002779:Cholestasis / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; C095122:multidrug resistance protein 3