title: The portal-drained viscera release fibroblast growth factor 19 in humans.
abstract: Fibroblast growth factor 19 (FGF19) is an ileum-derived endrocrine factor that is produced in response to transepithelial bile salt flux. FGF19 represses bile salt synthesis in the liver. Despite the general assumption that FGF19 signals to the liver via portal blood, no human data are available to support this notion. The aim was to study portal FGF19 levels, and determined bile salt and FGF19 fluxes across visceral organs in humans. Bile salt and FGF19 levels were assessed in arterial, portal, and hepatic venous blood collected from fasted patients who underwent partial liver resection for colorectal liver metastases (n = 30). Fluxes across the portal-drained viscera (PDV), liver, and splanchnic area were calculated. Portal bile salt levels (7.8 [5.0-12.4] μmol/L) were higher than levels in arterial (2.7 [1.7-5.5] μmol/L, P < 0.0001) and hepatic venous blood (3.4 [2.5-6.5] μmol/L, P < 0.0001). Bile salts released by the PDV (+1.2 [+0.7-+2.0] mmol kg-1h-1, P < 0.0001) were largely taken up by the liver (-1.0 [-1.8 to -0.4] mmol kg-1h-1, P < 0.0001). Portal levels of FGF19 (161 ± 78 pg/mL) were higher than arterial levels (135 ± 65 pg/mL, P = 0.046). A net release of FGF19 by the PDV (+4.0 [+2.1 to +9.9] ng kg-1h-1, P < 0.0001) was calculated. There was no significant flux of FGF19 across the liver (-0.2 [-3.7 to +7.4] ng kg-1h-1, P = 0.93). In conclusion, FGF19 levels in human portal blood are higher than in arterial blood. FGF19 is released by the portal-drained viscera under fasted steady state conditions.
authors.affiliation: Department of Surgery, Maastricht University Medical Center and NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University, Maastricht, The Netherlands k.koelfat@maastrichtuniversity.nl.
authors.forename: Kiran V K
authors.initials: KV
authors.lastname: Koelfat
authors.affiliation: Department of Surgery, Maastricht University Medical Center and NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University, Maastricht, The Netherlands.
authors.forename: Johanne G
authors.initials: JG
authors.lastname: Bloemen
authors.affiliation: Department of Surgery, Maastricht University Medical Center and NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University, Maastricht, The Netherlands.
authors.forename: Peter L M
authors.initials: PL
authors.lastname: Jansen
authors.affiliation: Department of Surgery, Maastricht University Medical Center and NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University, Maastricht, The Netherlands.|GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
authors.affiliation: Department of Surgery, Maastricht University Medical Center and NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University, Maastricht, The Netherlands.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Schaap
authors.affiliation: Department of Surgery, Maastricht University Medical Center and NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University, Maastricht, The Netherlands.|Department of HPB Surgery & Liver Transplantation, Institute for Liver and Digestive Health University College London, London, United Kingdom.
authors.forename: Steven W M
authors.initials: SW
authors.lastname: Olde Damink
mesh_terms: D000368:Aged; D001647:Bile Acids and Salts / Q000097:blood; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011168:Portal System / Q000378:metabolism*; D014781:Viscera / Q000098:blood supply / Q000378:metabolism*
chemical_list: D001647:Bile Acids and Salts; C117476:FGF19 protein, human; D005346:Fibroblast Growth Factors
keywords: FGF19; bile salts; entero‐hepatic circulation; organ fluxes