OBJECTIVE It has been suggested that weight reduction and improvements in satiety after Roux-en-Y gastric bypass (RYGB) are partly mediated via postoperative neuroendocrine changes. Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted after food ingestion and is associated with appetite and weight reduction, mediated via effects on the central nervous system (CNS). Secretion of GLP-1 is greatly enhanced after RYGB. We hypothesized that postoperative elevated GLP-1 levels contribute to the improved satiety regulation after RYGB via effects on the CNS. RESEARCH DESIGN AND METHODS Effects of the GLP-1 receptor antagonist exendin 9-39 (Ex9-39) and placebo were assessed in 10 women before and after RYGB. We used functional MRI to investigate CNS activation in response to visual food cues (pictures) and gustatory food cues (consumption of chocolate milk), comparing results with Ex9-39 versus placebo before and after RYGB. RESULTS After RYGB, CNS activation was reduced in the rolandic operculum and caudate nucleus in response to viewing food pictures ( P = 0.03) and in the insula in response to consumption of palatable food ( P = 0.003). GLP-1 levels were significantly elevated postoperatively ( P < 0.001). After RYGB, GLP-1 receptor blockade resulted in a larger increase in activation in the caudate nucleus in response to food pictures ( P = 0.02) and in the insula in response to palatable food consumption ( P = 0.002). CONCLUSIONS We conclude that the effects of RYGB on CNS activation in response to visual and gustatory food cues may be mediated by central effects of GLP-1. Our findings provide further insights into the mechanisms underlying the weight-lowering effects of RYGB.

中文翻译：

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较高的术后内源性GLP-1水平介导Roux-en-Y胃旁路对食物线索的神经反应性的影响

目的研究表明，Roux-en-Y胃搭桥术（RYGB）术后体重的减轻和饱腹感的改善部分是由术后神经内分泌的改变引起的。胰高血糖素样肽1（GLP-1）是食物摄入后分泌的肠激素，与食欲和体重减轻有关，通过对中枢神经系统（CNS）的影响介导。RYGB后，GLP-1的分泌大大增强。我们假设RYGB后，通过对中枢神经系统的影响，术后GLP-1水平升高有助于改善饱腹感调节。研究设计和方法在RYGB之前和之后，对10名妇女评估了GLP-1受体拮抗剂exendin 9-39（Ex9-39）和安慰剂的作用。我们使用功能性MRI来研究对视觉食物线索（图片）和味觉食物线索（食用巧克力牛奶）的响应中枢神经系统激活，将Ex9-39与RYGB之前和之后的安慰剂进行比较。结果RYGB后，通过观看食物图片（P = 0.03）和在岛ula中食用可口食物（P = 0.003），CNS的激活在罗汉和尾状核中减少。术后GLP-1水平显着升高（P <0.001）。RYGB后，GLP-1受体阻滞导致响应食物图像的尾状核活化增加（P = 0.02）和响应食物消耗的脑岛中活化的较大增加（P = 0.002）。结论我们得出结论，RYGB对视觉和味觉食物暗示的中枢神经系统激活的影响可能是由GLP-1的中枢作用介导的。我们的发现为RYGB减肥作用的潜在机制提供了进一步的见解。