Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Lampl, F.
Structure-activity relationship of primary and secondary bile acids on different isoforms of murine and human FXR
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp. 76
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Fickert Peter
- Moustafa Tarek
- Altmetrics:
- Abstract:
- In humans and mice, the secretion of conjugated and unconjugated bile acids (BA) from the liver reaches the GIT through bile ducts and the gallbladder and later reach the liver again. BAs act as ligands for the various isoforms of the Farnesoid X Receptor (FXR), which leads to changes in the gene expression and further metabolic alterations. FXR also plays an important role in the regulation of BA synthesis and liver regeneration. The receptor isoforms are mainly expressed in the intestine and in the liver, where BAs can activate them. In comparison to humans, mice have a different BA-pool, with more hydrophilic BAs. This diploma thesis demonstrates, that human FXR isoforms have a higher affinity to chenodeoxycholic acid (CDCA) than the murine counterpart. It also clarifies, that solely in rodents appearing BAs do not cause activation of FXR. Beyond that, this thesis sinks into the importance of the BA-transporter sodium-taurocholate cotransporting polypeptide (NTCP) as a possibility to transport hydrophilic bile acids in order to reach the nuclear FXR receptors through the cell membrane. Furthermore, this thesis gives insights about novel mechanisms involving uptake and competition of different Bas via NTCP and other not well investigated mechanisms.