Page 58 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 3
portal vein was considerable (i.e., enterohepatic cycle). However, after the meal transorgan fluxes doubled, in particular of the glycine-conjugated BA (Fig. 5A). Thus, the postprandial exposure to BA in the enterohepatic circulation was high. The postprandial peak in portal BA concentrations was also clearly visible in the BA fluxes, as shown in Fig. 5. For all BAs the PDV flux was always positive with a clear postprandial peak, while the liver flux was negative and mirrored the curve of the PDV flux. These fluxes show the appearance of BA from the gut into the portal vein and the efficient absorption of BA by the liver. There was no net transorgan BAs flux over the kidneys and hindquarter (Supplemental Fig. S11).
gCDCA A gHDCA 600
400 200
00 0 60 120 180 240
uptake
release
uptake release
C
0 -200 -400 -600
time (min)
Liver flux - major bile acids
0 60 120 180 240
time (min)
time (min)
D Liver flux - minor bile acids
PDV flux - major bile acids
CDCA B tCDCA 200 HDCA
tHDCA
PDV flux - minor bile acids
0 60 120 180 240
Fig. 5. BAs are released from the intestine and subsequently very efficiently absorbed by the liver. (A and B) After meal intake the BA flux over the portal drained viscera (PDV) steeply increases. A positive flux denotes net production by the organs. Data represent mean ± SEM with N = 11. (C and D) Postprandially, the liver takes up most released BAs. A negative flux reflects net uptake by the organ. CDCA: chenodeoxycholic acid, HDCA: hyodeoxycholic acid, g: glycine-conjugated form, t: taurine-conjugated form. Data represent mean ± SEM with N = 9.
Peripheral exposure to the secondary BA with the highest TGR5
affinity is low
Lithocholic acid (LCA) is a secondary BA that has a high affinity for TGR5. Therefore, LCA had our special interest. In the fasted state unconjugated LCA concentration in the portal vein was approximately two times higher than gLCA and tLCA (Fig. 4A). In general, LCA and its conjugates were detected in all portal
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150 100 50
50 0 -50 -100 -150 -200
0 60 120 180 240
time (min)