Coordinate regulation of bile acid biosynthetic and recovery pathways.
Intestinal and hepatic recovery of bile acids is principally mediated by sodium dependent bile acid transporters. Of these, the ileal sodium bile acid transporter (isbt) and the hepatic sodium bile acid cotransporting polypeptide (ntcp) may be most important in determining the efficiency of bile acid recovery within the enterohepatic circulation. We used molecular probes to explore the relationship between the bile acid recovery pathway, at the level of isbt and ntcp, and the biosynthetic pathway, at the level of cholesterol 7 alpha-hydroxylase (cyp7). Taurocholate feeding of mice suppressed ntcp, isbt, and cyp7 mRNA levels as compared to controls. Cholestyramine feeding induced both cyp7 and isbt mRNA gene expression. Cholesterol feeding induced cyp7 mRNA levels but suppressed isbt gene expression. These results suggest that in mice the bile acid recovery and biosynthetic pathways are coordinately regulated, and these pathways may be responsive to the size of the bile acid pool in the enterohepatic circulation.
Torchia
E C
EC
Lipid and Lipoprotein Research Group, University of Alberta, Edmonton, Canada.
Cheema
S K
SK
Agellon
L B
LB
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D002792:Cholestyramine Resin / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D007082:Ileum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger / Q000096:biosynthesis; D013552:Swine; D027981:Symporters; D013656:Taurocholic Acid / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D002791:Cholesterol, Dietary; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; D002792:Cholestyramine Resin; C071908:sodium-bile acid cotransporter; D013656:Taurocholic Acid; D002790:Cholesterol 7-alpha-Hydroxylase