Page 181 - Human Bile Acid Metabolism: a Postprandial Perspective

The increase consisted of unconjugated bile acid species. 3 hour-postprandial GLP-1 levels increased after 1 week and were sustained, whereas FGF19 levels and postprandial plasma courses were unaffected. We conclude that DJBL placement leads to profound increases in unconjugated bile acid levels after 6 months, similar to the effects of bariatric surgery. The temporal dissociation between the changes in bile acids, GLP-1 and FGF19 and other gut hormone responses suggest that the improvement in insulin sensitivity is not induced by increased bile acid signaling. This observational uncontrolled study emphasizes the need for future controlled studies.
Chapter 7 (Stenvers et al., unpublished)
Patients with type 2 diabetes have a disturbed diurnal rhythm of plasma glucose tolerance. We hypothesized that this may be due to altered diurnal regulation of plasma bile acid levels. We provided six patients with DM2 and six age-matched healthy controls with three identical meals per day, and measured plasma concentrations of primary and secondary BAs using tandem mass spectrometry. Postprandial BA responses were not affected by time of day. However, postprandial peak times were earlier for total BAs, chenodeoxycholic acid, and glycine conjugates in DM2, which may be explained by increased intestinal and/or decreased liver BA uptake. Our results suggest that while bile acid synthesis is known to vary during the day, bile acid responses to a meal do not, and are therefore not responsible for the altered diurnal rhythm of glucose tolerance seen in DM2.
Chapter 8 (van Nierop et al., 2017b)
In chapter 8 we reviewed the literature on the physiological relevance of the Takeda G protein-coupled receptor 5 (TGR5) with a focus on translating the data to clinical applications in human metabolism. We summarize the key concepts of bile acid signaling and discuss the physiological and pharmacological literature on TGR5 activation in glucagon-like receptor 1 (GLP-1) secretion and glucose homeostasis, energy expenditure and modulation of inflammatory signals. The available preclinical data suggests that TGR5 plays a role in GLP-1 secretion, insulin sensitivity and energy expenditure. However, evidence in humans is ambiguous and clinical application is still far away. Ultimately, safe and selective human TGR5 agonists are needed to further study the therapeutic potential of TGR5.
Summary
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