Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity

Abstract

Background Bile acids (BAs) are nutrient-responsive hormones that modulate energy balance through cell surface and nuclear receptors. Postprandial plasma BAs have been found to be decreased in obesity.Objective We aimed to determine whether meal-stimulated circulating BA levels are altered by Roux-en-Y gastric bypass (RYGB), an operation that modifies the neurohumoral determinants of food intake and energy expenditure to cause significant and durable weight loss.Design Longitudinal study measuring fasting and postprandial plasma BAs before and after RYGB.Subjects Five obese surgical patients and eight lean controls underwent frequent blood sampling after a standard liquid meal. Obese subjects were also tested at 1, 4 and 40 weeks after RYGB. Primary and secondary circulating BAs, as well as their glycine and taurine conjugates, were measured via reverse-phase high-performance liquid chromatography/mass spectroscopy.Results We found that postprandial excursion of conjugated BAs was 52.4% lower in obese than in lean individuals by area-under-the-curve (AUC) analysis (378 vs 793 μmol min l(-1), respectively, P<0.05). By 40 weeks after RYGB, the meal-induced rise in conjugated BAs increased by 55.5% to the level of healthy lean controls (378 pre-op vs 850 μmol min l(-) post-op by AUC analyses, P<0.05). In contrast, postprandial concentrations of unconjugated BAs were similar in lean and obese individuals and were not affected by surgery.Conclusion In light of the growing evidence that BAs have key roles in glucose, lipid and energy homeostasis, the observation that RYGB normalizes the blunted postprandial circulating BA response in obesity suggests that BAs may contribute to the improvement in meal-related physiology seen after RYGB. Further studies are warranted to examine this hypothesis and to determine the degree to which an augmented BA response to nutrient ingestion may mediate the increased incretin response, brown adipose tissue activation and thermic effect of feeding that has been observed after this operation.