Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery.
Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery.
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DOI：
10.1038/ncomms8715
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发表时间：
2015-07-21
影响因子：
16.6
通讯作者：
Abumrad NN
中科院分区：
文献类型：
--
作者：
Flynn CR;Albaugh VL;Cai S;Cheung-Flynn J;Williams PE;Brucker RM;Bordenstein SR;Guo Y;Wasserman DH;Abumrad NN
Roux-en-Y 胃绕道术 (RYGB) 在逆转肥胖和相关糖尿病方面非常有效。最近对人类的观察表明，循环胆汁酸的增加在调节这种效应中发挥着重要作用。在这里，我们使用饮食诱导肥胖（DIO）小鼠模型，并比较当胆汁流通过胆囊吻合术转移至空肠、回肠或十二指肠（假手术对照）时的代谢缓解情况。我们发现，只有胆汁转移到回肠才会导致类似于 RYGB 的生理变化，包括体重、葡萄糖耐量和肝脂肪变性的持续改善，尽管对肝基因表达的影响不同。循环游离脂肪酸和甘油三酯减少，而胆汁酸增加，特别是缀合牛磺-β-鼠胆酸（一种 FXR 拮抗剂）。肝脏 FXR/FGF15 信号轴的活性降低并与肠道微生物群的改变相关。因此，独立于胃肠道手术重排的胆汁改道可显着减轻体重，同时改善葡萄糖和脂质稳态，这是 RYGB 的标志。胃绕道手术是实现持久减肥的最有效的干预措施之一。在这里，弗林等人。研究表明，在小鼠中，胆汁转移至小肠可带来有益且持续的代谢改善，类似于 Roux-en-Y 胃绕道手术。
Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and associated diabetes. Recent observations in humans suggest a contributing role of increased circulating bile acids in mediating such effects. Here we use a diet-induced obesity (DIO) mouse model and compare metabolic remission when bile flow is diverted through a gallbladder anastomosis to jejunum, ileum or duodenum (sham control). We find that only bile diversion to the ileum results in physiologic changes similar to RYGB, including sustained improvements in weight, glucose tolerance and hepatic steatosis despite differential effects on hepatic gene expression. Circulating free fatty acids and triglycerides decrease while bile acids increase, particularly conjugated tauro-β-muricholic acid, an FXR antagonist. Activity of the hepatic FXR/FGF15 signalling axis is reduced and associated with altered gut microbiota. Thus bile diversion, independent of surgical rearrangement of the gastrointestinal tract, imparts significant weight loss accompanied by improved glucose and lipid homeostasis that are hallmarks of RYGB. Gastric bypass surgery is one of the most effective interventions to achieve durable weight loss. Here, Flynn et al. show that, in mice, bile diversion to the small intestine results in beneficial and sustained metabolic improvements similar to Roux-en-Y gastric bypass surgery.