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来自美国辛辛那提大学及瑞典哥德堡大学 Sahlgrenska 学院等机构的研究人员研究了FXR与垂直袖状胃切除手术作用的相关性。这篇文章刊登在最新一期《NATURE》杂志上。

                                                                                                                                                                          -2014年3月26日《自然》

中文翻译


【题目】FXR是对垂直袖状胃切除手术产生效应的分子靶标

【译文】 减肥手术,如垂直袖状胃切除手术(VSG),是目前治愈肥胖症的最有效疗法。除了能达到减肥效果外,还能够有效治疗与肥胖相关的疾病,例如2型糖尿病。尽管揭示了可能存在的治疗干预的新靶点,但其大部分的分子机制都是未知的。目前已知在袖状胃切除手术后,循环胆汁酸的量会发生显著的变化。此外,胆汁酸可以通过结合核受体FXR(farsenoid-x受体,也被称为NR1H4)来调节生长代谢。因此,我们给由于过度饮食而导致肥胖且FXR靶基因缺失的小鼠做垂直袖状胃切除手术。实验结果表明了VSG的治疗价值不是因为机械性地限制了胃的大小而导致的。恰好相反,袖状胃切除手术与循环胆汁酸增加和肠道微生物群体的改变相关。此外,如果缺乏FXR基因,VSG的减肥效果和提高葡萄糖耐受度的能力明显下降。这些实验结果表明,胆汁酸和FXR信号通路作为一种重要分子基础,有利于减肥手术达到良好的治疗效果。

英文原稿


[Title]:  FXR is a molecular target for the effects of vertical sleeve gastrectomy

[Authors]Karen K.Ryan,  Valentina Tremaroli,  Christoffer Clemmensen,  Petia Kovatcheva-Datchary,  Andriy Myronovych,  Rebekah Karns,  Hilary E. Wilson-Pérez,  Darleen A. Sandoval,  Rohit Kohli,  Fredrik Bäckhed& Randy J. Seeley

[Abstract]:Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at present the most effectivetherapy for the treatment of obesity, and are associated with considerable improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering the potential to reveal new targets for therapeutic intervention. Substantial changes in circulating total bile acids are known to occur after VSG. Moreover, bile acids are known to regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor, also known as NR1H4). We therefore examined the results of VSG surgery applied to mice with diet-induced obesity and targeted genetic disruption of FXR. Here we demonstrate that the therapeutic value of VSG does not result from mechanical restriction imposed by a smaller stomach. Rather, VSG is associated with increased circulating bile acids, and associated changes to gut microbial communities. Moreover, in the absence of FXR, the ability of VSG to reduce body weight and improve glucose tolerance is substantially reduced. These results point to bile acids and FXR signalling as an important molecular underpinning for the beneficial effects of this weight-loss surgery.

原文地址:http://www.nature.com/nature/journal/v509/n7499/full/nature13135.html

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本文链接: http://www.bioku.cn/201403/nature2014-03-26-fxr-is-a-molecular-target-for-the-effects-of-vertical-sleeve-gastrectomy/
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