Protective effect of exenatide on oxidative stress in hypothalamus of diabetes mice and its mechanism
10.3969/j.issn.1006-5725.2025.03.004
- VernacularTitle:艾塞那肽对糖尿病小鼠下丘脑氧化应激的保护作用及其机制
- Author:
Lu ZHENG
1
;
Haohao ZHANG
;
Feifei WU
;
Jiaqi GUO
;
Youqin WANG
;
Ruimin HAO
;
Lihui FENG
;
Yan LI
Author Information
1. 长治医学院附属和平医院内分泌科(山西 长治 046000)
- Publication Type:Journal Article
- Keywords:
exenatide;
diabetes mellitus;
hypothalamic oxidative stress;
melanocortin receptor-4
- From:
The Journal of Practical Medicine
2025;41(3):330-338
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of exenatide on oxidative stress in the hypothalamus of diabetes mice and its potential mechanism.Methods After one week of adaptive feeding,C57BL/6J mice were randomly divided into the CON group(normal chaw diet),the T2DM group(high-fat diet,HFD),and the T2DM+Exe group(HFD+exenatide).After 8 weeks of HFD,mice in the T2DM+Exe group were intraperitoneally injected with exenatide[24 nmol/(kg·d)]for 8 weeks.The weight and glucose and lipid metabolism levels of the mice were measured,and the levels of inflammatory and adipokine factors in mice were detected using the ELISA method.Western Blot was used to detect the expression of melanocortin receptor-4(MC4R)and proopiomelanocor-tin(POMC)in the hypothalamus.Hypothalamic mitochondria were extracted,and the content of mitochondrial reactive oxygen species(ROS)was measured using a flow cytometer.The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)in the mitochondria were detected using assay kits.Changes in the ultrastructure of mitochondria were observed using a transmission electron microscope.In vitro experiments,pal-mitic acid(PA)and exenatide were used to treat hypothalamic GT1-7 cells,and short hairpin RNA(shRNA)was used to silence the melanocortin 4 receptor(MC4R),and observe the cellular oxidative stress and lipid deposition.Results Compared with the CON group,the T2DM group mice showed a significant increase in glucose and lipid metabolism indicators,pro-inflammatory factors,and adipose factor levels(P<0.05),the expression of MC4R and POMC proteins in the hypothalamus were decreased(P<0.05),and the mitochondrial ROS and MDA content in the hypothalamus significantly were increased(P<0.05),while SOD and CAT activities were decreased(P<0.05).Mitochondrial morphology was abnormal.After intervention with exenatide,the above indicators were signifi-cantly improved.After inhibiting MC4R expression in vitro experiments,compared with the intervention group with exenatide,the ROS and MDA content was significantly increased(P<0.05),SOD activity was decreased(P<0.05),and lipid deposition occurred in the cells.Conclusions Exenatide exhibits a protective effect on hypotha-lamic oxidative stress injury in diabetic mice,and this mechanism may be associated with the upregulation of MC4R expression.
