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Bile acid flux through portal but not peripheral veins inhibits CYP7A1 expression without involvement of ileal FGF19 in rabbits
- Source :
- American Journal of Physiology-Gastrointestinal and Liver Physiology. 307:G479-G486
- Publication Year :
- 2014
- Publisher :
- American Physiological Society, 2014.
-
Abstract
- It was proposed that CYP7A1 expression is suppressed through the gut-hepatic signaling pathway fibroblast growth factor (FGF) 15/19-fibroblast growth factor receptor 4, which is initiated by activation of farnesoid X receptor in the intestine rather than in the liver. The present study tested whether portal bile acid flux alone without ileal FGF19 could downregulate CYP7A1 expression in rabbits. A rabbit model was developed by infusing glycodeoxycholic acid (GDCA) through the splenic vein to bypass ileal FGF19. Study was conducted in four groups of rabbits: control; bile fistula + bovine serum albumin solution perfusion (BF); BF + GDCA (by portal perfusion); and BF + GDCA-f (by femoral perfusion). Compared with only BF, BF + GDCA (6 h portal perfusion) suppressed CYP7A1 mRNA, whereas BF + GDCA-f (via femoral vein) with the same perfusion rate of GDCA did not show inhibitory effects. Meanwhile, there was a decrease in ileal FGF19 expression and portal FGF19 protein levels, but an equivalent increase in biliary bile acid outputs in both GDCA perfusion groups. This study demonstrated that portal bile acid flux alone downregulated CYP7A1 expression with diminished FGF19 expression and protein levels, whereas the same bile acid flux reaching the liver through the hepatic artery via femoral vein had no inhibitory effect on CYP7A1. We propose that bile acid flux through the portal venous system may be a kind of “intestinal factor” that suppresses CYP7A1 expression.
- Subjects :
- medicine.medical_specialty
Biliary Fistula
Physiology
medicine.drug_class
Down-Regulation
Cholesterol 7 alpha-hydroxylase
Fibroblast growth factor
Peripheral veins
Growth factor receptor
Ileum
Physiology (medical)
Internal medicine
Animals
Medicine
Cholesterol 7-alpha-Hydroxylase
Hepatology
Bile acid
Portal Vein
business.industry
Gastroenterology
FGF19
Fibroblast Growth Factors
Endocrinology
Glycodeoxycholic Acid
Rabbits
Signal transduction
business
Flux (metabolism)
Subjects
Details
- ISSN :
- 15221547 and 01931857
- Volume :
- 307
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Accession number :
- edsair.doi.dedup.....b23aa6158ef09ebf0798fb147f5e93fe