The role of transhepatic bile salt flux in the control of hepatic secretion of triacylglycerol-rich lipoproteins in vivo in rodents.
Bile salts (BS) have been shown to suppress the secretion of very-low-density lipoprotein-triglyceride (VLDL-TG) in rat and human hepatocytes in vitro. In the present study, we investigated whether the transhepatic BS flux affects VLDL-TG concentration and hepatic VLDL-TG secretion in vivo. In rats, the transhepatic BS flux was quantitatively manipulated by 1-week chronic bile diversion (BD), followed by intraduodenal infusion with taurocholate (TC) or saline for 6 h. In mice, the transhepatic BS flux was manipulated by a 3-week dietary supplementation with TC (0.5 wt.%) or cholestyramine (2 wt.%). In rats, BD followed by saline or TC infusion did not affect plasma triacylglycerol (TG) concentration, hepatic TG production rate or VLDL lipid composition, compared to control rats. In mice supplemented for 3 weeks with TC or cholestyramine, the transhepatic BS flux was increased by 335% and decreased by 48%, respectively, compared to controls. Among the three experimental groups of mice, an inverse relationship between transhepatic BS flux and either plasma TG concentration (R(2)=0.89) or VLDL-TG production rate (R(2)=0.87) was observed, but differences were relatively small. Present data support the concept that BS can reduce VLDL-TG concentration and inhibit hepatic TG secretion in vivo; however, this occurs only at supraphysiological transhepatic BS fluxes in mice.
Elzinga
Baukje M
BM
Groningen University Institute for Drug Exploration (GUIDE), Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, University Hospital Groningen, The Netherlands. B.M.Elzinga@med.rug.nl
Havinga
Rick
R
Baller
Julius F W
JF
Wolters
Henk
H
Bloks
Vincent
V
Mensenkamp
Arjen R
AR
Kuipers
Folkert
F
Verkade
Henkjan J
HJ
D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000097:blood; D001647:Bile Acids and Salts / Q000378:metabolism / Q000502:physiology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002792:Cholestyramine Resin / Q000008:administration & dosage; D004032:Diet; D008079:Lipoproteins, VLDL / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000008:administration & dosage; D014280:Triglycerides / Q000032:analysis / Q000096:biosynthesis / Q000097:blood
D001055:Apolipoproteins B; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D002792:Cholestyramine Resin; D013656:Taurocholic Acid