Targeting FXR and FGF19 to Treat Metabolic Diseases-Lessons Learned From Bariatric Surgery.
Targeting FXR and FGF19 to Treat Metabolic Diseases-Lessons Learned From Bariatric Surgery.
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DOI：
10.2337/dbi17-0007
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发表时间：
2018-09
期刊：
影响因子：
7.7
通讯作者：
Seeley RJ
中科院分区：
文献类型：
--
作者：
Bozadjieva N;Heppner KM;Seeley RJ
Roux-en-Y 胃绕道手术 (RYGB) 和垂直袖状胃切除术 (VSG) 等减肥手术是持续减肥和改善糖代谢的最有效干预措施。减肥手术改变了肠肝胆汁酸循环，导致血浆胆汁水平升高以及胆汁酸成分改变。虽然尚不清楚为什么 VSG 和 RYGB 都能改变胆汁酸，但这些变化可能是手术效果的重要介质。此外，胆汁酸合成的分子靶标，即胆汁酸激活转录因子 FXR，对于 VSG 对减肥和血糖控制的积极作用至关重要。本视角研究了减肥手术后胆汁酸水平和成分改变、FXR 信号传导和肠道微生物群之间的关系和事件顺序。我们假设，虽然胆汁酸和 FXR 信号传导是代谢功能的有效介质，但未识别的下游靶点是减肥手术益处背后的主要介质。其中一个靶点是肠道衍生肽 FGF15/19，它是一种潜在的分子和治疗标志物，可以解释减肥手术的积极代谢作用。将研究工作集中在识别这些复杂的分子机制上将为治疗肥胖和代谢功能障碍的治疗策略提供新的机会。
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.
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影响因子：
24.5
作者：
McGavigan AK;Garibay D;Henseler ZM;Chen J;Bettaieb A;Haj FG;Ley RE;Chouinard ML;Cummings BP
通讯作者：
Cummings BP
影响因子：
15.9
作者：
Morton, Gregory J.;Matsen, Miles E.;Schwartz, Michael W.
通讯作者：
Schwartz, Michael W.
影响因子：
7.7
作者：
Huang, Xinqiang;Yang, Chaofeng;McKeehan, Wallace L.
通讯作者：
McKeehan, Wallace L.
垂直套筒胃切除术减少肝脂肪变性，同时以减轻体重的方式增加血清胆汁酸。
DOI：
10.1002/oby.20548
发表时间：
2014-02
期刊：
Obesity (Silver Spring, Md.)
影响因子：
--
作者：
Myronovych A;Kirby M;Ryan KK;Zhang W;Jha P;Setchell KD;Dexheimer PJ;Aronow B;Seeley RJ;Kohli R
通讯作者：
Kohli R
肠道选择性法尼醇 X 受体抑制可改善肥胖相关的代谢功能障碍。
影响因子：
16.6
作者：
Jiang C;Xie C;Lv Y;Li J;Krausz KW;Shi J;Brocker CN;Desai D;Amin SG;Bisson WH;Liu Y;Gavrilova O;Patterson AD;Gonzalez FJ
通讯作者：
Gonzalez FJ