Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People's Republic of China.
Am J Physiol Endocrinol Metab. 2021 Sep 1;321(3):E392-E409. doi: 10.1152/ajpendo.00126.2021. Epub 2021 Aug 9.
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 () 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 glucose transporter 1 (GLUT-1), GLUT-4, phospho-Akt substrate of 160kDa (pAS160), AS160, Rab10, Myosin-Va as well as the 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 whereas the Exe-9 and KD were opposite. Known to activate insulin-signaling pathways, central GLP-1 contributes to improved cognitive function and brain glucose uptake after DJB. The improvement of cognitive function following bariatric surgery has been highlighted while its mechanisms remain elusive. The brain glucose uptake of patients was improved after RYGB, and the DJB and sham surgery performed on obese and diabetic Wistar rats revealed that the elevated central GLP-1 contributes to the dramatic improvement of cognitive function, brain glucose uptake, transport, glucose sensing, and neuronal activation.
减重手术后认知功能的改善已得到强调，但潜在机制仍难以捉摸。我们在肥胖和糖尿病 Wistar 大鼠上进行了 RYGB、十二指肠空肠旁路术（DJB）和假手术（Sham），并在两组大鼠中应用脑室内（ICV）注射胰高血糖素样肽-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（）敲低（KD），以阐明 GLP-1 在介导认知功能和脑葡萄糖摄取中的作用，用 Morris 水迷宫（MWM）和正电子发射断层扫描（PET）进行评估。测量了血清和脑脊髓液（CSF）中的胰岛素和 GLP-1，检查了与葡萄糖摄取相关的蛋白表达，包括葡萄糖转运蛋白 1（GLUT-1）、GLUT-4、磷酸化 Akt 底物 160kDa（pAS160）、AS160、Rab10、肌球蛋白-Va 以及大脑中的标志物。随着 DJB 后葡萄糖内稳态的增强，中枢 GLP-1 与认知功能的改善和脑葡萄糖摄取的改善相关，这进一步通过 Lira 对两组的增强作用得到证实，而 Exe-9 和 KD 则相反。已知中枢 GLP-1 可激活胰岛素信号通路，有助于 DJB 后认知功能和脑葡萄糖摄取的改善。减重手术后认知功能的改善已得到强调，但其机制仍难以捉摸。RYGB 后患者的脑葡萄糖摄取得到改善，在肥胖和糖尿病 Wistar 大鼠上进行的 DJB 和假手术显示，中枢 GLP-1 的升高有助于认知功能、脑葡萄糖摄取、转运、葡萄糖感应和神经元激活的显著改善。
