Page 179 - Human Bile Acid Metabolism: a Postprandial Perspective

method. To this end, eleven pigs with indwelling intravascular catheters received a standardized mixed meal. During and after the meal, venous blood was sampled from different veins such as the portal vein, abdominal aorta and hepatic vein to calculate fluxes of bile acids across different organ compartments. To compare the data to humans, fasted venous and portal blood was obtained from non-diabetic obese patients during gastric bypass surgery.
The majority of the circulating plasma bile acid pool and postprandial response consisted of glycine-conjugated forms of the primary bile acids CA and CDCA. Conjugated bile acids, which have higher affinity for TGR5, were more efficiently cleared by the liver than unconjugated forms. Taking into account the previously published EC50 of individual BA subtypes for TGR5, the potential TGR5-activating signal in the portal vein was ~5-10 times stronger than in the systemic circulation. The timing and size of the postprandial response showed large interindividual variability for bile acids.
Chapter 4 (van Nierop et al., 2017a)
The physiochemical properties of different bile acid subspecies affect their enterohepatic dynamics and their affinity for bile acid receptors. The composition of the bile acid pool is known to be altered in patients with type 2 diabetes and obesity, as we have again observed in Chapter 2, suggesting a causal link between bile acid metabolism and metabolic derangement. Here, we used a 2-week very- low-calorie diet to investigate the effects of acute weight loss through calorie restriction on bile acid pool composition and postprandial bile acid dynamics. We performed mixed meal tests in obese, insulin-resistant subjects before and after the weight loss period. Weight loss increased peak postprandial levels of the secondary bile acid DCA and decreased resting energy expenditure. Other BA species, glucose, insulin and FGF19 levels and postprandial excursions were not significantly affected. We hypothesize that the modestly increased postprandial DCA levels are secondary to a combination of increased intestinal uptake and increased CYP8B1 activity. Additionally, the timeframe of the intervention may have been too short to induce observable changes in the bile acid pool.
Summary
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