Page 57 - Human Bile Acid Metabolism: a Postprandial Perspective

Fig. 4. Lithocholic acid forms, BAs with high TGR5 affinity, are mainly found in the enterohepatic circulation and not peripherally. (A) Lithocholic acid (LCA) and its glycine- (g) and taurine- (t) conjugated forms are present in pig plasma in stable low concentrations. gLCA shows a postprandial increase in the portal vein but not in the peripheral circulation. The other forms do not show a postprandial response and conjugated forms of LCA are not even detected outside the enterohepatic circulation. Fasted state: x = 0, PDV: portal drained viscera, dotted line indicates the 50% detection limit, undetected concentrations were set to this number (0.025 mmol/L). N = 11. (B) Transorgan fluxes of LCA forms. Like the other BAs LCA and conjugates are released from the intestine and very efficiently taken up by the liver.
gCDCA A PDV flux - major bile acids CDCA B
gHDCA 600 tCDCA 200 To quantify hepatic clearance rates, we calculated the differences HbDeCtAween
PDV flux - minor b
0 60 120 time (min)
Liver flux - minor b
0 60 120 time (min)
BA concentrations proximal and distal of the liver:
[BA]portal vein aorta - [BA]hepatic vein = [BA]portal vein aorta. 200
tHDCA
100
50
400
150
Indeed, the hepatic clearance rate of gCDCA was significantly higher than that
Transhepatic bile acid kinetics
00 0 60 120 180 240
of gHDCA (t = 60 min, p < 0.0001, Fig. 3G). In general, the hepatic clearance
3
uptake
release
time (min)
rates of conjugated BA were significCantlyLihveirgfhluexr- tmhaajonr btihleeacildesarance rates of theiDr
unconjugated forms.
0 50 0
-200
Postprandial BA exposure is high in the enterohepatic cycle compared
-50
-100
-150
-200
to the peripheral circulation
-400
Transorgan flux is different from clearance, since it is calculated by multiplying
-600
concentration difference by plasma flow. In the fasted state, BA flux in the
0 60 120 180 240
time (min)
55