Regulation of biliary cholesterol secretion is independent of hepatocyte canalicular membrane lipid composition: a study in the diosgenin-fed rat model.
OBJECTIVE
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.
Nibbering
C P
CP
Department of Gastroenterology, Gastrointestinal Research Unit, University Medical Center Utrecht, The Netherlands.
Groen
A K
AK
Ottenhoff
R
R
Brouwers
J F
JF
vanBerge-Henegouwen
G P
GP
van Erpecum
K J
KJ
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D003902:Detergents; D004032:Diet; D004144:Diosgenin / Q000008:administration & dosage*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010840:Phytosterols / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013109:Sphingomyelins / Q000378:metabolism
D003902:Detergents; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D010840:Phytosterols; D013109:Sphingomyelins; D002784:Cholesterol; D004144:Diosgenin