Page 20 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 1
low-calorie diet (VLCD) to investigate the effects of rapid weight loss on bile acid pool composition and postprandial dynamics. We performed mixed meal tests in insulin resistant obese subjects before and after the diet. We measured postprandial plasma levels of glucose, insulin, bile acids and the enterokines GLP-1 and FGF19.
In chapter 5 we describe the effect of starvation-induced insulin resistance on bile acid metabolism. We investigated the postprandial bile acid response in relation to insulin, GLP-1 and FGF19 after 40 hours of starvation. After finding a correlation between postprandial levels of insulin and glycine-conjugated deoxycholic acid (gDCA), we performed a follow-up experiment in which we administered gDCA with the meal to try to modulate postprandial glucose, insulin and GLP-1 levels.
After these dietary and pharmacological interventions, we performed bile acid measurements in a bariatric model in chapter 6. The duodenal-jejunal bypass liner (DJBL) is an intraduodenal device that leads to rapid weight loss and restoration of insulin sensitivity in a similar fashion to Roux-en-Y gastric bypass (RYGB) surgery. Analogous to findings after RYGB, increased systemic bile acid levels are candidate effectors for the beneficial effects on metabolism. We performed mixed meal testing in 17 obese patients with DM2 directly before, one week after and 6 months after DJBL placement.
Part IV - Central nervous system: Since autonomic innervation is involved in the regulation of many endocrine and metabolic processes, we speculated that bile acids metabolism could be regulated in a similar fashion. In chapter 7, we examine whether circadian rhythms influence postprandial bile acid responses. Obese patients with DM2 show a disturbed diurnal rhythm in plasma glucose tolerance. Since circulating bile acids affect glucose metabolism and bile acid synthesis is known to be regulated by the circadian clock, we hypothesized that obese patients with DM2 show an altered diurnal rhythm of postprandial bile acid plasma excursions. We studied 6 obese patients with DM2 and 6 matched controls who were provided with three equicaloric equidistant meals per day for three days. Extensive blood sampling was performed throughout the study day.
Part V - Bile acids in perspective: Finally, we reflect on the differences between animal and human studies and their consequences for the future use of bile acid targeted therapy in clinical practice. Chapter 8 details the profound interspecies differences
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