Abstract
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 glucose transporter 1 (GLUT-1), GLUT-4, phospho-Akt substrate of 160kDa (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 whereas 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.NEW & NOTEWORTHY 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.
Highlights
The rapid development of urbanization and modernization favored a booming population of obesity and type 2 diabetes mellitus (T2DM) worldwide [1, 2]
Assessed by positron emission tomography-computed tomography (PET-CT) in our clinical practice, we found that the brain glucose uptake of patients who underwent Roux-en-Y gastric bypass (RYGB) was improved after surgery, and to dissect the possible mechanism of bariatric surgery in improving brain glucose uptake, favoring a better cognitive function, duodenum-jejunum bypass (DJB) and sham surgery were performed on obese and diabetic Wistar rats and intracerebroventricular (ICV) injection of glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira) and antagonist exendin-(9–39) (Exe-9), along with the viral-mediated GLP-1 receptor (Glp-1r) knockdown (KD) were applied to elucidate the role of GLP-1 in mediating cognitive function and brain glucose uptake using the Morris water maze (MWM) test and PET
Significant differences were seen in body weight, body mass index (BMI), fasting blood glucose (FBG), insulin resistance, postprandial blood glucose (PPBG), and hemoglobin A1c (HbA1c) compared with their preoperative status (Fig. 1, B– G), which all indicated a profound amelioration in systemic metabolism and glucose homeostasis
Summary
The rapid development of urbanization and modernization favored a booming population of obesity and type 2 diabetes mellitus (T2DM) worldwide [1, 2]. For instance, elevates cerebral glucose metabolism and ameliorates insulin resistance [18] All these changes are beneficial for brain volume, blood flow, and lower the risk of possible cognitive dysfunction. Another therapeutic approach for obesity and T2DM, bariatric surgery, effectively improves cognitive function [19] though the exact underlying mechanisms remain poorly understood. It was shown that GLP-1 enhances glycogen synthesis and glucose transport by affecting various pathways [24,25,26] It improves insulin-stimulated glucose uptake by augmenting GLUT-1 and GLUT-4 expression in adipocytes [27]. The levels of insulin and GLP-1 in serum and cerebral spinal fluid (CSF) were measured, and the expression of glucose uptakerelated proteins including GLUT-1, GLUTT-4, pAS160, AS160, Rab, Myosin-Va as well as the c-fos marker in the brain were examined
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: American journal of physiology. Endocrinology and metabolism
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
