减重手术通过“肠-脑轴”重塑食欲的作用机制研究

减重手术是目前治疗重度肥胖最有效的方法之一，术后食欲下降是其有效降重的关键，但是胃肠重建引起中枢调控食欲改变的具体机制尚不明确。申请人通过较大肥胖样本术后随访，进行肠道宏基因组分析结合脑功能磁共振成像，建立减重术后肠道菌群、GLP-1、右壳核和食欲改变的相关性，并筛选出可能参与的细菌代谢通路－短链脂肪酸（SCFAs），从而初步提示“菌群/ SCFAs—GLP-1—中枢—食欲”的“肠-脑轴”调节关系。在此基础上，我们将基于肥胖动物减重手术模型，借助抗生素干预、粪菌移植阐明肠道菌群在术后“肠-脑轴”中的调节作用，通过SCFAs受体敲除、GLP-1受体抑制证明SCFAs和GLP-1在 “肠-脑轴”中的枢纽作用，通过尾壳核神经元凋亡证明尾壳核是响应术后“肠-脑轴”改变的关键核团。通过上述研究阐明各节点参与“肠-脑轴”调节的因果关系，阐明减重手术食欲降低机制，为寻找减重手术无创替代治疗提供理论基础。

Bariatric surgery has proved to be one of the most effective treatments for severe obesity. The key to weight loss after the surgery is the significant decrease in appetite, which is owning to the changes in feeding center caused by intestinal signal changes after gastrointestinal reconstruction. However, the role of gut-brain axis in the change of appetite after bariatric surgery awaits further study. My group found the correlation among changes in intestinal flora，plasma GLP-1 level during oral glucose tolerance test (OGTT)，the regional homogeneity (ReHo) of putamen，and the results of three-factor eating questionnaire (TFEQ) after the bariatric surgery. Some of the increased bacterial species involve in the metabolism of short-chain fatty acids (SCFAs), which have been reported to promote secretion of the appetite stimulating hormone GLP-1. Consequently, we made the scientific hypothesis of "Bariatric surgery-intestinal flora-SCFAs-GLP-1-caudate putamen-appetite performance" to explain the change in feeding behavior after bariatric surgery. In this project we aimed to provide further evidence to support the hypothesis and clarify the role of intestinal flora, SCFAs, GLP-1, and caudate putamen in the " bariatric surgery-gut-brain" axis.