Page 178 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 10
Bile acid metabolism in humans: postprandial perspective
Chapter 1
An introduction in current understanding of bile acid biology. This chapter outlines the enterohepatic cycle of bile acid synthesis, secretion and reabsorption, as well as the presumed role of bile acids in metabolism through their effects on the two main bile acid receptors, Farnesoid X Receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR5). Thereafter, the research questions and experiments that form the basis of this thesis are described.
Chapter 2 (Sonne et al., 2016)
In this chapter, we investigated the effect of diabetes on postprandial bile acid levels and the gut hormone fibroblast growth factor-19 (FGF19). We describe postprandial plasma concentrations of 12 individual bile acid subspecies as well as FGF19 in fifteen patients with type 2 diabetes (DM2), compared to healthy controls with normal glucose tolerance. To this end, we used a 75-g oral glucose tolerance test and three isocaloric and isovolemic liquid meals with low, medium, and high fat content, respectively. We showed that postprandial total bile acid concentrations increased with increasing meal fat content (p<.05), peaked after 1–2 hours, and were higher in DM2 patients than in controls (oral glucose tolerance test, low and medium fat meals, p<.05; high fat meal, p=.30). The differences reflected mainly unconjugated and glycine-conjugated forms of deoxycholic acid (DCA) and to a lesser extent cholic acid (CA) and ursodeoxycholic acid (UDCA), whereas chenodeoxycholic acid (CDCA) concentrations were comparable in the two groups. FGF19 concentrations tended to be lower in patients with DM2 then in controls, but the difference was not statistically significant due to considerable variation.
Chapter 3 (Eggink et al., 2018)
Bile acids play a key role in lipid uptake and possibly in metabolic signalling in different organs including gut, liver, muscle and brown adipose tissue. Portal and peripheral plasma BA concentrations are known to increase after a meal containing fats and carbohydrates. However, the exact kinetics of postprandial bile acid metabolism have never been described in great detail. We used a porcine model to investigate postprandial plasma concentrations and transorgan fluxes of bile acids, glucose and insulin, using the para-aminohippuric acid dilution
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