BACKGROUND/AIMS: Phosphatidylcholine (PC) and sphingomyelin (SM) are the major phospholipids on the outer leaflet of the hepatocyte canalicular membrane. Since cholesterol preferentially associates with SM in detergent-resistant microdomains, we hypothesized that canalicular membrane lipid composition 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 hypersecretion. Thereafter, lipid compositions and phospholipid molecular species were determined in fistula bile and highly enriched canalicular membrane fractions. RESULTS: Despite four-fold higher biliary cholesterol output in diosgenin-fed rats, no differences were observed between canalicular membranes of diosgenin 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 16:0-18:2, 16:0-20:4, 18:0-20:4, and 18:0-18:2). In contrast to canalicular PCs, 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 purified canalicular membrane fractions against detergents such as Triton X-100 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 regulation of biliary cholesterol secretion.
BACKGROUND/AIMS: Phosphatidylcholine (PC) and sphingomyelin (SM) are the major phospholipids on the outer leaflet of the hepatocyte canalicular membrane. Since cholesterol preferentially associates with SM in detergent-resistant microdomains, we hypothesized that canalicular membrane lipid composition 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 hypersecretion. Thereafter, lipid compositions and phospholipid molecular species were determined in fistula bile and highly enriched canalicular membrane fractions. RESULTS: Despite four-fold higher biliary cholesterol output in diosgenin-fed rats, no differences were observed between canalicular membranes of diosgenin 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 16:0-18:2, 16:0-20:4, 18:0-20:4, and 18:0-18:2). In contrast to canalicular PCs, 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 purified canalicular membrane fractions against detergents such as Triton X-100 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 regulation of biliary cholesterol secretion.
Authors: Astrid Kosters; Cindy Kunne; Norbert Looije; Shailendra B Patel; Ronald P J Oude Elferink; Albert K Groen Journal: J Lipid Res Date: 2006-06-01 Impact factor: 5.922
Authors: Donna J Coy; Clavia R Wooton-Kee; Baoxiang Yan; Nadezhda Sabeva; Kai Su; Gregory Graf; Mary Vore Journal: Am J Physiol Gastrointest Liver Physiol Date: 2010-04-22 Impact factor: 4.052
Authors: Kamil Nosol; Rose Bang-Sørensen; Rossitza N Irobalieva; Satchal K Erramilli; Bruno Stieger; Anthony A Kossiakoff; Kaspar P Locher Journal: Proc Natl Acad Sci U S A Date: 2021-08-17 Impact factor: 11.205