Sestrin1 is involved in the regulation of gluconeogenesis in mouse liver cells
10.16352/j.issn.1001-6325.2024.02.0141
- VernacularTitle:Sestrin1参与调控小鼠肝脏细胞糖异生
- Author:
Yanfang GUO
1
;
Chao GENG
;
Xianghong XIE
;
Enhui CHEN
;
Zeyu GUO
;
Minglong ZHANG
;
Xiaojun LIU
Author Information
1. 中国医学科学院基础医学研究所 北京协和医学院基础学院 重大疾病共性机制研究全国重点实验室,北京 100005
- Keywords:
hepatic gluconeogenesis;
stress-inducing protein 1(SESN1);
Sirtuin 1(SIRT1);
peroxisome proliferators-activated recep-tors gamma co-activator 1α(PGC-1α)
- From:
Basic & Clinical Medicine
2024;44(2):141-146
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and regulatory mechanism of stress-inducing protein 1(SESN1)in liver gluconeogenesis of fasting mice.Methods RT-qPCR was used to detect mRNA expression of SESN1 in liver tissues of C57BL/6J mice and primary mouse hepatocytes treated with forskolin(Fsk)and dexamethasone(Dex).HepG2 cells were transfected with plasmids and the effects of SESN1 overexpression on mRNA expression of gluconeogenesis related genes PGC-1α,PEPCK and G6Pase was detected by RT-qPCR.The effect of SESN1 on the promoter activity of PGC-1α in HepG2 cells was studied using a dual luciferase reporter system.The effect of SESN1 on PGC-1α deacetylation was detected by overexpression of SESN1 and inhibition of SIRT1 expression.By knocking down SIRT1 expression,we detected whether it mediated the changes in mRNA levels of SESN1 in-duced gluconeogenesis related genes.Results The mRNA expression of SESN1 was significantly increased in liver tissues of starved C57BL/6J mice and in primary hepatocytes treated with Fsk and Dex(P<0.001).Over-expression of SESN1 in HepG2 cells promoted mRNA expression of PGC-1α,PEPCK and G6Pase(P<0.001)and promoter activity of PGC-1α(P<0.001).Over-expression of SESN1 decreased the acetylation level of PGC-1α in primary hepatocytes.Sirt family inhibitors NAM and shRNA adenovirus interfered with SIRT1 expression respective-ly,and antagonized the deacetylation effect of SESN1 on PGC-1α.The expression of PGC-1α,PEPCK and G6Pase induced by SIRT1 was also significantly impaired(P<0.000 1).Conclusions SESN1 regulates liver gluconeogene-sis in mice with a SIRT1-dependent mechanism.
