Page 119 - Human Bile Acid Metabolism: a Postprandial Perspective

the effects of DJBL and also found increased GLP-1 levels [33]. However, this study did not investigate subfractions of bile acids. Interestingly, they were able to observe an increase in FGF19 that did not result in lower plasma bile acids. Most subjects with obesity or DM2 exhibit reduced serum FGF19 levels [34]. Here, FGF19 levels were unchanged throughout the entire study. The mismatch between plasma bile acid and FGF19 levels is difficult to explain FXR sensitivity to its ligand could be decreased, either as a cause of the increased circulating bile acid pool or as a consequence of it. A recent study in healthy subjects revealed that FXR agonist-induced repression of bile salt synthesis occurred without alterations in FGF19 level [35].
Our study has a few limitations. First, we were only able to perform a short mixed-
meal test, which may have missed differences in postprandial signalling factors
that occur later (such as FGF19 that peaks between 3 and 4 h). Also, we were
not able to document the exact moment where changes in bile acid homeostasis
became apparent due to the timing of experiments at week 1 and 24. Additionally,
this was an observational uncontrolled study emphasizing the need for future 6 controlled studies. Finally, we did not quantify satiety and appetite with visual
analogue scores.
In this study, duodenal lining led to beneficial improvements in glucose metabolism and weight in patients with DM2. Surprisingly, unconjugated bile acids showed a marked increase after 24 weeks whereas the increase in GLP-1 was evident after one week. In contrast, correlations of bile acids and FGF19 were abolished immediately. Our data suggest that future studies should be comparing effects of duodenal lining and other means of weight loss on bile acids, GLP-1 and FGF19 taking into account the time course of these changes.
Grant Support
This research was supported by a Dutch Diabetes Research Foundation Ruby grant (#2011801423).
Duodenal-jejunal bypass liner
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