©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling
Huai-Jie Wang, Li-Bin Zhang, Si-Peng Sun, Qing-Tao Yan, Zhi-Qin Gao, Fang-Ming Fu, Mei-Hua Qu
Huai-Jie Wang, Si-Peng Sun, Mei-Hua Qu, Translational Medical Center, Weifang Second People's Hospital, Weifang 261041, Shandong Province, China
Li-Bin Zhang, Department of Endocrinology, Weifang Second People's Hospital, Weifang 261041, Shandong Province, China
Qing-Tao Yan, Department of Pediatric Surgery, Weifang People’s Hospital, Weifang 261041, Shandong Province, China
Zhi-Qin Gao, School of Bioscience and Technology, Weifang Medical University, Weifang 261053, Shandong Province, China
Fang-Ming Fu, Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
Co-corresponding authors: Fang-Ming Fu and Mei-Hua Qu.
Author contributions: Qu MH and Fu FM had equal contribution to this paper; Qu MH and Fu FM designed the research scheme and directed the relevant experimental techniques and methods; Wang HJ, Zhang LB, Sun SP, Yan QT, Gao ZQ performed the research and data analysis; Wang HJ, Qu MH analyzed the data and wrote the manuscript; All authors have read and approve the final manuscript. Qu MH and Fu FM contributed to the experimental design. Qu primarily developed the research direction and experimental hypothesis based on literature and previous research. Fu FM participated in the design of the experimental verification scheme. Qu MH and Fu FM jointly supervised the modeling and duodenal jejunal bypass surgery-related experiments. They are co-corresponding authors of this study, and there is no conflict of interest between them.
Supported by the Natural Science Foundation of China, No. 82070856; the Science and Technology Development Plan of Shandong Medical and Health Science, No. 202102040075; Scientific Research Plan of Weifang Health Commission, No. WFWSJK-2022-010 and No. WFWSJK-2022-008; and Weifang Science and Technology Development Plan, No. 2021YX071 and No. 2021YX070.
Institutional review board statement: This study was carried out following the recommendations of Weifang Medical University, China. The experimental protocol was approved by the Research Ethics Committee of Weifang Medical University, China, Approval No. 2020SDL074.
Institutional animal care and use committee statement: The experimental protocols were approved by the Institutional Animal Care and Use Committee, No. 2021SDL574.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Corresponding author: Mei-Hua Qu, PhD, Professor, Translational Medical Center, Weifang Second People's Hospital, No. 7 Yuanxiao Street, Weifang 261041, Shandong Province, China.
qumeihua2016@163.com
Received: October 10, 2023
Peer-review started: October 10, 2023
First decision: November 17, 2023
Revised: December 12, 2023
Accepted: January 12, 2024
Article in press: January 12, 2024
Published online: February 15, 2024
Processing time: 117 Days and 2.4 Hours
ARTICLE HIGHLIGHTS
Research background
Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal injury and inflammation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, but its role in brain injury and the underlying mechanisms are still unclear.
Research motivation
DJB can increase serum glucagon-like peptide 1 (GLP-1) Levels and enhance brain glucose utilization, playing a positive role in the treatment of diabetes. Therefore, GLP-1 signaling may play a significant role after DJB surgery in alleviating T2DM-related brain injury.
Research objectives
To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats.
Research methods
A T2DM rat model was induced via a high-glucose, high-fat diet, and a low-dose streptozotocin injection. T2DM rats underwent DJB surgery or Sham surgery. Differential expression of hypothalamic proteins and genes was analyzed by protein microarray, flow cytometry, quantitative real-time PCR, western blot, and immunofluorescence.
Research results
Protein microarray results showed significant differences between the T2DM-Sham rats and the T2DM-DJB rats in signaling proteins related to oxidative stress, inflammation, and neuronal injury. DJB surgery increased the serum levels of GLP-1 and upregulated the expression of GLP-1 receptor and antioxidant signaling proteins (Nrf2 and HO-1) in the hypothalamic tissue of T2DM rats. DJB also reduced the expression of hypothalamic inflammatory and nerve cell injury-related factors, playing a neuroprotective role and reducing hypothalamic injury.
Research conclusions
DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the GLP-1-mediated Nrf2/HO-1 signaling pathway.
Research perspectives
Further investigation is needed to determine the influence of enteric neural or endocrine pathways after DJB surgery on the amelioration of diabetes-induced central brain injury by GLP-1.
