Regulation of biliary cholesterol secretion is independent of hepatocyte canalicular membrane lipid composition: a study in the diosgenin-fed rat model

Background/Aims: Phosphatidylcholine (PC) and sphingomyelin (SM) are the ma jor phospholipids on the outer leaflet of the hepatocyte canalicular membra ne. Since cholesterol preferentially associates with SM in detergent-resist ant microdomains, we hypothesized that canalicular membrane lipid compositi on could modulate secretion of the sterol into bile. Methods: Male Wistar rats were fed for 10 days with a control diet with or without the plant sterol diosgenin (1% w/w) to induce biliary cholesterol h ypersecretion. Thereafter, Lipid compositions and phospholipid molecular sp ecies were determined in fistula bile and highly enriched canalicular membr ane fractions. Results. Despite four-fold higher biliary cholesterol output in diosgenin-f ed rats, no differences were observed between canalicular membranes of dios genin and control groups with respect to cholesterol/phospholipid ratios (0 .58 vs 0.62), phospholipid classes and acyl chain compositions of SMs (16:0 > 24:1 > 24:0 > 22:0 > 18:0 > 23:0 > 20:0 > 24:2), or PCs (mainly diacyl 1 6:0-18:2,16:0-20:4,18:0-20:4, and 18:0-18:2). In contrast to canalicular PC s, bile contained more hydrophilic species (mainly diacyl 16:0-18:2 and 16: 0-20:4), without differences between both groups. In vitro resistance of pu rified canalicular membrane fractions against detergents such as Triton X-1 00 and taurocholate was also similar in both groups. Conclusions: Diosgenin-induced biliary cholesterol hypersecretion occurs in the absence of changes of canalicular membrane lipids. Our data therefore do not support a major role of canalicular membrane lipid composition in re gulation of biliary cholesterol secretion. ((C)) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights r eserved.