Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice.
Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice.
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DOI：
10.1002/hep.28689
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发表时间：
2016-09
期刊：
影响因子：
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通讯作者：
Huang W
中科院分区：
文献类型：
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作者：
Ding L;Sousa KM;Jin L;Dong B;Kim BW;Ramirez R;Xiao Z;Gu Y;Yang Q;Wang J;Yu D;Pigazzi A;Schones D;Yang L;Moore D;Wang Z;Huang W
垂直袖状胃切除术（VSG）是临床上最常用的减肥手术之一，用于缓解肥胖和糖尿病。然而，VSG发挥其有益作用的精确分子机制仍然难以捉摸。我们报告说，膜结合G蛋白偶联胆汁酸受体GPBAR-1（也称为TGR 5）是介导VSG在小鼠中的抗肥胖、抗高血糖和脂肪肝改善作用所必需的。在缺乏TGR 5的情况下，VSG在小鼠中的有益代谢作用丧失。此外，我们发现VSG后TGR 5的表达显著增加，并且VSG改变小鼠中BA水平和组成，导致回肠和棕色脂肪组织中TGR 5信号传导增强，伴随着改善的葡萄糖控制和增加的能量消耗。结论：我们的研究阐明了一种新的潜在机制，VSG通过增强TGR 5信号传导实现其术后治疗效果。（肝病学2016;64：760 - 773）
Vertical sleeve gastrectomy (VSG) is one of the most commonly performed clinical bariatric surgeries used for the remission of obesity and diabetes. However, the precise molecular mechanism by which VSG exerts its beneficial effects remains elusive. We report that the membrane‐bound G protein‐coupled bile acid receptor, GPBAR‐1 (also known as TGR5), is required to mediate the effects of anti‐obesity, anti‐hyperglycemia, and improvements of fatty liver of VSG in mice. In the absence of TGR5, the beneficial metabolic effects of VSG in mice are lost. Moreover, we found that the expression of TGR5 increased significantly after VSG, and VSG alters both BA levels and composition in mice, resulting in enhancement of TGR5 signaling in the ileum and brown adipose tissues, concomitant with improved glucose control and increased energy expenditure. Conclusion: Our study elucidates a novel underlying mechanism by which VSG achieves its postoperative therapeutic effects through enhanced TGR5 signaling. (Hepatology 2016;64:760‐773)