Helene Johansson1, Lisa-Mari Mörk1, Meng Li1, Anita L Sandblom2, Ingemar Björkhem2, Jonas Höijer3, Bo-Göran Ericzon1, Carl Jorns1, Stefan Gilg4, Ernesto Sparrelid4, Bengt Isaksson4, Greg Nowak1, Ewa Ellis1. 1. Division of Transplantation Surgery, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden. 2. Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden. 3. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 4. Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden.
Abstract
BACKGROUND: Bile acid homeostasis is essential and imbalance may lead to liver damage and liver failure. The bile acid induced intestinal factor fibroblast growth factor 19 (FGF19) has been identified as a key protein for mediating negative feedback inhibition of bile acid synthesis. The aim of the study was to define FGF19 and bile acid concentrations in portal and systemic blood in the fasted and postprandial state. We also addressed the question if physiological portal levels of FGF19 can be extrapolated from the concentration in systemic blood. METHODS: Portal and systemic blood was collected from 75 fasted patients undergoing liver surgery and from three organ donors before and after enteral nutrition. Serum concentration of FGF19 was determined with ELISA and bile acid concentration with gas chromatography-mass spectrometry. RESULTS: Concentration of bile acids was twice as high in portal compared to systemic blood in the fasted group and 3-5 times higher in the postprandial group. FGF19 increased after enteral nutrition but did not differ between portal and systemic blood, in either group. In addition, a strong, positive correlation between bile acids and FGF19 was found. CONCLUSION: Our results confirm that bile acids drive the postprandial increase of circulating FGF19 but a hepatic clearance of FGF19 is unlikely. We conclude that systemic concentrations of FGF19 reflect portal concentrations of FGF19.
BACKGROUND: Bile acid homeostasis is essential and imbalance may lead to liver damage and liver failure. The bile acid induced intestinal factor fibroblast growth factor 19 (FGF19) has been identified as a key protein for mediating negative feedback inhibition of bile acid synthesis. The aim of the study was to define FGF19 and bile acid concentrations in portal and systemic blood in the fasted and postprandial state. We also addressed the question if physiological portal levels of FGF19 can be extrapolated from the concentration in systemic blood. METHODS: Portal and systemic blood was collected from 75 fasted patients undergoing liver surgery and from three organ donors before and after enteral nutrition. Serum concentration of FGF19 was determined with ELISA and bile acid concentration with gas chromatography-mass spectrometry. RESULTS: Concentration of bile acids was twice as high in portal compared to systemic blood in the fasted group and 3-5 times higher in the postprandial group. FGF19 increased after enteral nutrition but did not differ between portal and systemic blood, in either group. In addition, a strong, positive correlation between bile acids and FGF19 was found. CONCLUSION: Our results confirm that bile acids drive the postprandial increase of circulating FGF19 but a hepatic clearance of FGF19 is unlikely. We conclude that systemic concentrations of FGF19 reflect portal concentrations of FGF19.
Entities:
Keywords:
CA, cholic acid; CDCA, chenodeoxycholic acid; CYP7A1, cholesterol 7α-hydroxylase; DCA, deoxycholic acid; FGF19, fibroblast growth factor 19; FXR, farnesoid X receptor; LCA, litocholic acid; SHP, small heterodimer partner; UDCA, ursodeoxycholic acid; bile acid synthesis; bile acids; cholesterol 7α-hydroxylase; farnesoid X receptor; liver
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