The improvement of cognitive function following bariatric surgery has been highlighted, yet its underlying mechanisms remain elusive. Finding the improved brain glucose uptake of patients after Roux-en-Y gastric bypass (RYGB), duodenum-jejunum bypass (DJB) and sham surgery (Sham) were performed on obese and diabetic Wistar rats, and intracerebroventricular (ICV) injection of glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira), antagonist exendin-(9-39) (Exe-9), and the viral-mediated GLP-1 receptor (Glp-1r) knockdown (KD) were applied on both groups to elucidate the role of GLP-1 in mediating cognitive function and brain glucose uptake assessed with the Morris water maze (MWM) and positron emission tomography (PET). Insulin and GLP-1 in serum and cerebral spinal fluid (CSF) were measured, and the expression of glucose uptake-related proteins including GLUT-1, GLUTT-4, pAS160, AS160, Rab10, Myosin-Va as well as the c-fos marker in the brain were examined. Along with augmented glucose homeostasis following DJB, central GLP-1 was correlated with the improved cognitive function and ameliorated brain glucose uptake, which was further confirmed by the enhancive role of Lira on both groups while the Exe-9 and Glp-1r KD were opposite. Known to activate insulin signaling pathways, central GLP-1 contributes to improved cognitive function and brain glucose uptake after DJB.

中文翻译：

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中枢 GLP-1 有助于改善肥胖和糖尿病大鼠十二指肠空肠旁路术后认知功能和脑葡萄糖摄取

减肥手术后认知功能的改善已经得到强调，但其潜在机制仍然难以捉摸。发现对肥胖和糖尿病 Wistar 大鼠进行 Roux-en-Y 胃旁路术 (RYGB)、十二指肠-空肠旁路术 (DJB) 和假手术 (Sham) 以及脑室内 (ICV) 注射胰高血糖素后患者脑葡萄糖摄取的改善-样肽-1 (GLP-1) 类似物利拉鲁肽 (Lira)、拮抗剂 exendin-(9-39) (Exe-9) 和病毒介导的 GLP-1 受体 (Glp-1r) 敲低 (KD)阐明 GLP-1 在介导认知功能和脑葡萄糖摄取方面的作用，通过莫里斯水迷宫 (MWM) 和正电子发射断层扫描 (PET) 进行评估。测定血清和脑脊液 (CSF) 中的胰岛素和 GLP-1，并检测了葡萄糖摄取相关蛋白的表达，包括 GLUT-1、GLUTT-4、pAS160、AS160、Rab10、Myosin-Va 以及大脑中的 c-fos 标志物。随着 DJB 后葡萄糖稳态的增强，中枢 GLP-1 与认知功能的改善和脑葡萄糖摄取的改善相关，Lira 对两组的增强作用进一步证实了这一点，而 Exe-9 和 Glp-1r KD 则相反. 已知激活胰岛素信号通路，中枢 GLP-1 有助于改善 DJB 后的认知功能和大脑葡萄糖摄取。Lira 对两组的增强作用进一步证实了这一点，而 Exe-9 和 Glp-1r KD 则相反。已知激活胰岛素信号通路，中枢 GLP-1 有助于改善 DJB 后的认知功能和大脑葡萄糖摄取。Lira 对两组的增强作用进一步证实了这一点，而 Exe-9 和 Glp-1r KD 则相反。已知激活胰岛素信号通路，中枢 GLP-1 有助于改善 DJB 后的认知功能和大脑葡萄糖摄取。