Page 63 - Human Bile Acid Metabolism: a Postprandial Perspective

postprandial response. Finally, animals received antimicrobial therapy peri-operatively and this may have affected BA pool composition although this has not been reported previously for the antibiotics that we used.
In conclusion, the liver selectively extracts most BAs and BAs with high TGR5
affinity are typically low in the porcine and human peripheral circulation. Our data
do not preclude a role for BAs to activate TGR5 in the periphery postprandially. 3 However, their low peripheral plasma concentrations and high interindividual
variability raise questions about the magnitude of such a signal and the ultimate
clinical application of TGR5 agonists if the liver is not passed [44].
*
Transhepatic bile acid kinetics
12 10 8 6 4 2 2
1 0
Fig. 7. Hypothetical TGR5 activating capacity is higher for the portal vein compared to the periphery, independently of food intake. This measure expresses in one number the potential amount of TGR5 activation by the total bile acid pool and is calculated for individual BAs in the pool by dividing the average concentration by their EC50, whereafter all are totalled. The value is lower in a peripheral vein (V) compared to the portal vein (P) in healthy obese humans (grey) and in pigs (black). There are no differences between the fasted and the postprandial state (fed pigs vs fasted pigs). However, when comparing the fasted state to the peak of the postprandial concentration curve (fed pigs peak) food intake caused a significant increase in the TGR5 activating potential of over 30%. Data represent mean ± SEM. Porcine outcomes fasted vs fed staged were tested with a one-way ANOVA and Tukey post-hoc test, *p < 0.05.
Funding sources
M.R.S. is funded by the Dutch Diabetes Research Foundation (grant 2011.80.1423). N.E.P.D. has a financial relationship with Abbott Nutrition for work in consulting, speakers bureau and research grants/contracts.
Supplementary data related to this article can be found at http://dx.doi. org/10.1016/j.clnu.2017.06.015
VPVPVPVP
obese fasted fed pigs fed pigs humans pigs mean peak
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"TGR5 activation capacity"