Study on the role of aerobic exercise in regulating the CNPY2-mediated AKT/GSK3β pathway for improving non-alcoholic fatty liver
- VernacularTitle:有氧运动对CNPY2基因调控AKT/GSK3β通路改善非酒精性脂肪肝的作用研究
- Author:
Jiaqian WANG
1
;
Changjun JIANG
;
Yi PENG
;
Mi MA
;
Junhan LI
Author Information
- Publication Type:Journal Article
- Keywords: fatty liver; high-fat diet; hepatocyte apoptosis; aerobic exercise; CNPY2; AKT; GSK3β; Caspase-3
- From: Chinese Journal of Tissue Engineering Research 2025;29(30):6441-6448
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Non-alcoholic fatty liver disease is one of the common chronic liver diseases in the world.Aerobic exercise is considered to be an important means for the treatment of non-alcoholic fatty liver disease.However,the mechanism of exercise to improve non-alcoholic fatty liver disease has not been fully clarified.OBJECTIVE:To investigate the effects of aerobic exercise on the protein kinase B/glycogen synthase kinase-3β pathway mediated by Canopy FGF signaling regulator 2(CNPY2)in the liver canopy of non-alcoholic fatty liver disease mice and its mechanism.METHODS:Thirty male CNPY2 knockout mice(ko)and thirty their litters of wild-type mice(wt)were fed adaptively for one week and randomly divided into control group,model group,and model exercise group,with 10 mice in each group.The control group was fed with ordinary diet.The model group and the model exercise group were fed with high-fat diet for 17 weeks.The model exercise group received continuous aerobic exercise intervention from week 10 until the end of the experiment at week 18.Liver histopathology was observed by hematoxylin-eosin and oil red O staining.The levels of serum lipids and liver function were detected by automatic biochemical analyzer.The expression levels of CNPY2,protein kinase B/glycogen synthase kinase-3β pathway,and Caspase-3 protein in liver tissues were detected by Western Blotting.The apoptosis rate of hepatocytes was detected by TUNEL staining.RESULTS AND CONCLUSION:(1)Compared with wt control group,CNPY2 expression in liver tissues of wt model group was increased(P＜0.05),while CNPY2 expression in wt model exercise group was decreased compared with wt model group(P＜0.05).Compared with control group,wt mice and ko mice in model group showed steatosis,increased lipid droplets,abnormal blood lipids and liver function,decreased protein kinase B/glycogen synthase kinase-3β expression(P＜0.05)and increased Caspase-3 expression(P＜0.05),and increased hepatocyte apoptosis rate in liver tissue(P＜0.05).(2)Compared with the model group,wt mice and ko mice showed improvement in the above indexes in model exercise group.(3)Compared with wt mice,the above indexes of ko mice were improved.(4)These findings indicate that CNPY2 gene deletion and aerobic exercise can effectively improve non-alcoholic fatty liver disease.The mechanism may be related to aerobic exercise reducing CNPY2 expression,activating protein kinase B/glycogen synthase kinase-3β signaling pathway,and thus inhibiting hepatocyte apoptosis.
