Albaugh Vance L, Banan Babak, Ajouz Hana, Abumrad Naji N, Flynn Charles R
Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
American University of Beirut, Beirut, Lebanon.
Mol Aspects Med. 2017 Aug;56:75-89. doi: 10.1016/j.mam.2017.04.001. Epub 2017 Apr 17.
Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective and durable treatments for morbid obesity and potentially a viable treatment for type 2 diabetes (T2D). The resolution rate of T2D following these procedures is between 40 and 80% and far surpasses that achieved by medical management alone. The molecular basis for this improvement is not entirely understood, but has been attributed in part to the altered enterohepatic circulation of bile acids. In this review we highlight how bile acids potentially contribute to improved lipid and glucose homeostasis, insulin sensitivity and energy expenditure after these procedures. The impact of altered bile acid levels in enterohepatic circulation is also associated with changes in gut microflora, which may further contribute to some of these beneficial effects. We highlight the beneficial effects of experimental surgical procedures in rodents that alter bile secretory flow without gastric restriction or altering nutrient flow. This information suggests a role for bile acids beyond dietary fat emulsification in altering whole body glucose and lipid metabolism strongly, and also suggests emerging roles for the activation of the bile acid receptors farnesoid x receptor (FXR) and G-protein coupled bile acid receptor (TGR5) in these improvements. The limitations of rodent studies and the current state of our understanding is reviewed and the potential effects of bile acids mediating the short- and long-term metabolic improvements after bariatric surgery is critically examined.
减肥手术,特别是Roux-en-Y胃旁路术(RYGB)和垂直袖状胃切除术(VSG),是治疗病态肥胖最有效且持久的方法,对2型糖尿病(T2D)而言可能也是一种可行的治疗方法。接受这些手术后T2D的缓解率在40%至80%之间,远远超过仅通过药物治疗所达到的缓解率。这种改善的分子基础尚未完全明确,但部分原因被认为是胆汁酸的肝肠循环发生了改变。在本综述中,我们重点阐述了胆汁酸如何可能有助于改善这些手术后的脂质和葡萄糖稳态、胰岛素敏感性及能量消耗。肝肠循环中胆汁酸水平的改变所产生的影响还与肠道微生物群的变化有关,这可能会进一步促成其中一些有益效果。我们着重介绍了在啮齿动物身上进行的实验性手术程序的有益效果,这些手术改变了胆汁分泌流量,但没有限制胃部或改变营养物质流动。这些信息表明,胆汁酸在强力改变全身葡萄糖和脂质代谢方面的作用不仅仅局限于膳食脂肪乳化,还表明胆汁酸受体法尼醇X受体(FXR)和G蛋白偶联胆汁酸受体(TGR5)的激活在这些改善过程中发挥着新出现的作用。本文回顾了啮齿动物研究的局限性以及我们目前的理解状态,并对胆汁酸介导减肥手术后短期和长期代谢改善的潜在作用进行了批判性审视。