Roles of hepatic Dishevelled/Egl-10/pleckstrin domain-containing protein 5/mammalian target of rapamycin complex 1 signaling axis on the development of non-alcoholic fatty liver disease
10.16098/j.issn.0529-1356.2024.03.006
- VernacularTitle:肝细胞DEP结构域蛋白5/哺乳动物雷帕霉素靶蛋白复合物1信号轴在非酒精性脂肪肝形成中的作用
- Author:
Lin XU
1
,
2
;
Xi-Wen XIONG
;
Zun LI
;
Rong HUANG
;
Hong-Hui MA
;
Jie MA
Author Information
1. 新乡医学院医学技术学院,河南 新乡 453003
2. 新乡医学院新乡市代谢与整合生理学重点实验室,河南 新乡 453003
- Keywords:
Dishevelled/Egl-10/pleckstrin containing protein 5;
Mammalian target of rapamycin complex 1;
High-fat-diet;
Rapamycin;
Nonalcoholic fatty liver;
Western blotting;
Mouse
- From:
Acta Anatomica Sinica
2024;55(3):295-301
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of hepatic Dishevelled/Egl-10/pleckstrin domain-containing protein 5(DEPDC5)/mammalian target of rapamycin complex 1(mTORC1)on nonalcoholic fatty liver disease by establishing a high-fat diet feeding model of Depdc5 gene hepatocyte specific knockout mice.Methods Depdc5flox/flox mice were constructed and mated with Alumin-Cre mice to obtain Depdc5flox/flox;Alb-Cre mice(LKO),Depdc5flox/flox mice were as control(Loxp).Totally 32 male mice aged 2-3 months were randomly divided into high-fat-diet LKO group,high-fat-diet Loxp control group,high-fat-diet+rapamycin LKO group,and high-fat-diet+rapamycin Loxp control group,with 8 mice in each group.Liver serum biochemistry,lipid content,protein,mRNA and pathological sections were detected;Graphpad prism 8 software was used for statistical analysis.Results High-fat-diet induced liver steatosis in Loxp mice,while LKO mice were protected from steatosis but had aggravated liver injury.Rapamycin treatment attenuated the hyperactivation of mTORC1 pathway caused by Depdc5 knockout,alleviated the liver steatosis in Loxp mice and liver injury in LKO mice.Conclusion Deletion of Depdc5 gene protects mice from high-fat-diet induced liver steatosis and rapamycin treatment might be used to improve liver injury caused by DEPDC5 loss of function.
