1] Obesity, Metabolism and Nutrition Institute, Gastrointestinal Unit and MGH Weight Center, Massachusetts General Hospital, Boston, MA, USA [2] Department of Medicine, Harvard Medical School, Boston, MA, USA.
Int J Obes (Lond). 2013 Dec;37(12):1553-9. doi: 10.1038/ijo.2013.38. Epub 2013 Apr 9.
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.
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.
Longitudinal study measuring fasting and postprandial plasma BAs before and after RYGB.
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.
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.
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.
胆汁酸(BAs)是营养感应激素,通过细胞表面和核受体调节能量平衡。餐后血浆胆汁酸已被发现在肥胖中降低。
我们旨在确定 Roux-en-Y 胃旁路术(RYGB)是否改变了餐后循环 BA 水平,RYGB 手术改变了食物摄入和能量消耗的神经激素决定因素,导致显著和持久的体重减轻。
测量 RYGB 前后空腹和餐后血浆 BA 的纵向研究。
5 名肥胖手术患者和 8 名瘦对照者在标准液体餐后进行频繁采血。肥胖患者还在 RYGB 后 1、4 和 40 周进行了测试。通过反相高效液相色谱/质谱法测量主要和次要循环 BA 及其甘氨酸和牛磺酸缀合物。
我们发现,通过曲线下面积(AUC)分析,肥胖患者餐后共轭 BA 的偏移量比瘦个体低 52.4%(分别为 378 和 793 μmol·min·l-1,P<0.05)。在 RYGB 后 40 周时,共轭 BA 的餐后升高增加了 55.5%,达到健康瘦对照者的水平(AUC 分析为 378 术前与 850 μmol·min·l-1术后,P<0.05)。相比之下,瘦个体和肥胖个体的未结合 BA 的餐后浓度相似,并且不受手术影响。
鉴于越来越多的证据表明 BA 在葡萄糖、脂质和能量稳态中具有关键作用,RYGB 使肥胖患者餐后循环 BA 反应减弱恢复正常的观察结果表明,BA 可能有助于改善 RYGB 后与饮食相关的生理学。需要进一步研究来检验这一假设,并确定摄入营养物质后 BA 反应增强在多大程度上介导了术后观察到的肠促胰岛素反应、棕色脂肪组织激活和摄食的热效应增加。