Departments of Surgery and Medicine, University of Michigan, Ann Arbor, MI.
Novo Nordisk Research Center Seattle, Inc., Seattle, WA.
Diabetes. 2018 Sep;67(9):1720-1728. doi: 10.2337/dbi17-0007.
Bariatric surgery procedures, such as Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective interventions available for sustained weight loss and improved glucose metabolism. Bariatric surgery alters the enterohepatic bile acid circulation, resulting in increased plasma bile levels as well as altered bile acid composition. While it remains unclear why both VSG and RYGB can alter bile acids, it is possible that these changes are important mediators of the effects of surgery. Moreover, a molecular target of bile acid synthesis, the bile acid-activated transcription factor FXR, is essential for the positive effects of VSG on weight loss and glycemic control. This Perspective examines the relationship and sequence of events between altered bile acid levels and composition, FXR signaling, and gut microbiota after bariatric surgery. We hypothesize that although bile acids and FXR signaling are potent mediators of metabolic function, unidentified downstream targets are the main mediators behind the benefits of weight-loss surgery. One of these targets, the gut-derived peptide FGF15/19, is a potential molecular and therapeutic marker to explain the positive metabolic effects of bariatric surgery. Focusing research efforts on identifying these complex molecular mechanisms will provide new opportunities for therapeutic strategies to treat obesity and metabolic dysfunction.
减重手术程序，如 Roux-en-Y 胃旁路术（RYGB）和垂直袖状胃切除术（VSG），是目前用于持续减肥和改善葡萄糖代谢最有效的干预措施。减重手术改变了肠肝胆汁酸循环，导致血浆胆汁水平升高和胆汁酸组成改变。虽然尚不清楚为什么 VSG 和 RYGB 都可以改变胆汁酸，但这些变化可能是手术效果的重要介导因素。此外，胆汁酸合成的分子靶标，胆汁酸激活的转录因子 FXR，是 VSG 对体重减轻和血糖控制的积极作用所必需的。本观点探讨了减重手术后胆汁酸水平和组成、FXR 信号和肠道微生物群之间的关系和事件顺序。我们假设，尽管胆汁酸和 FXR 信号是代谢功能的有效调节剂，但未识别的下游靶标是减肥手术益处的主要调节剂。其中一个靶标，肠道衍生肽 FGF15/19，是解释减重手术积极代谢作用的潜在分子和治疗标志物。集中研究这些复杂的分子机制将为治疗肥胖和代谢功能障碍的治疗策略提供新的机会。
