Publikationsserver der RWTH Aachen University
Fasten-induzierte Regulation hepatischer basolateraler Gallensäuretransporter in Ratten vermittelt über PGC-1[alpha]/HNF-4[alpha]
Abstract
dc:descriptionFasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4-alpha PGC-1-alpha-pathway. Because HNF4-alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4-alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1-alpha in electrophoretic mobility shift assays remained unchanged, HNF4-alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4-alpha and PGC-1-alpha. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4-alpha/PGC-1-alpha pathway and that this signalling pathway is not just involved in the regulation of the gluconeogenesis but can be seen as a global adaptive process in the fasting situation.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2008
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Porn, Anne Christine
- Contributors dc:contributor
-
- Trautwein, Christian
Subjects
dc:subject × 13Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger