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−1 h−1, P < 0.0001) were largely taken up by the liver (−1.0 [−1.8 to −0.4] mmol kg−1 h−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−1 h−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−1 h−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.
Highlights
Related to their role in digestion and absorption of dietary lipids, bile salts are signaling molecules engaged in regulation of postprandial nutrient handling (Kuipers et al 2014)
Portal bile salts were strongly related with bile salt levels in arterial (q = +0.80; P < 0.001) and hepatic venous blood (q = +0.65; P < 0.0001) (Fig. 2A)
No correlation was observed between bile salts and Fibroblast growth factor 19 (FGF19) in portal venous blood under fasted conditions (q = +0.26, P = 0.16) (Fig. 3A), whereas a positive association between FGF19 and bile salt levels was noted in arterial (q = +0.49, P = 0.006) and hepatic venous blood (q = +0.42, P = 0.02) (Fig. 3B & C)
Summary
Related to their role in digestion and absorption of dietary lipids, bile salts are signaling molecules engaged in regulation of postprandial nutrient handling (Kuipers et al 2014). Bile salt signaling is mediated by dedicated receptors expressed at the plasma membrane or inside the cell (e.g., Farnesoid X Receptor, FXR) (Schaap et al 2014). Besides (postprandial) control of hepatic metabolism, bile salt/FXR signaling is implicated in other processes including gut barrier integrity and liver regeneration (Gadaleta et al 2011; Zhang et al 2012). FXR plays a central role in this process by mediating negative feedback inhibition of bile salt synthesis (Schaap et al 2014). Regulation of bile salt synthesis occurs primarily at the transcriptional level by a 2016 The Authors.
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