Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Wenzl, F.
The influence of bile acid conjugation on hepatic and intestinal metabolism
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2018. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Fickert Peter
- Moustafa Tarek
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- Abstract:
- Background Bile acids (BAs) are formed in the liver, stored in the gallbladder and secreted into the intestine. Under physiologic conditions, almost exclusively conjugated BAs are secreted into the intestine. However, unconjugated BAs are used widely in BA-feeding experiments and solely in clinical practice. Aims and Methods This study aimed to investigate the impact of taurine-conjugation on hepatic and intestinal metabolism. In an animal experiment mice were fed the unconjugated BAs cholic acid (CA) and ursodeoxycholic acid (UDCA) or the corresponding taurine-conjugated BAs taurocholic acid (TCA) and tauroursodeoxycholic acid (TUDCA) for 7 hours, 4 days and 3 weeks. Biometric measurements and liver functions tests were performed. Hepatic BA synthesis, hydroxylation and excretion were assessed by Q-PCR for cytochrome P-450 (Cyp)7a1, Cyp8b1, Cyp3a11, Cyp2b10 and organic solute transporter (Ost)-ß. Expression levels of peroxisome proliferator-activated receptor alpha (Ppar-a) and its target genes (Acox1, G0s2 and Cyp4a14) were quantified in the liver. Further, we determined insulin-like growth factor binding protein 1 (Igfbp1) mRNA levels in the liver and protein levels in serum by Western blot analysis. Ileal expression of fibroblast growth factor 15 (Fgf15), small heterodimer partner (Shp), ileal bile acid-binding protein (I-BABP) and Ost-ß was also measured. Results Taurine-conjugation of both CA and UDCA reduced liver weight after 3 weeks. TUDCA increased body weight gain compared to UDCA after 3 weeks. Conjugated BAs tended to repress Cyp7a1 and Cyp8b1 less without reaching statistical significance in most groups. TUDCA repressed Ost-ß in liver tissue stronger than UDCA. Cyp3a11 and Cyp2b10 expression tended to be lower in conjugated groups. Ppar-a and Acox1 were induced by TUDCA but not by UDCA after 4 days and 3 weeks, suggesting a conjugation-dependent modulation of Ppar-¿ signaling by BAs. Igfbp1 mRNA levels in the liver and protein levels in serum were massively elevated by TCA but hardly affected by CA. Taurine-conjugation had only minor effects on ileal expression of Fgf15, Shp, I-BABP and Ost-ß. Conclusion The observed conjugation-dependent effects on the expression of major regulatory enzymes of BA, lipid and glucose metabolism may question the transferability of experiments using unconjugated BAs to a physiologic condition.