NF- B/HDAC1/SREBP1c pathway mediates the inflammation signal in progression of hepatic steatosis.
10.1016/j.apsb.2020.02.005
- Author:
Yunwei GUO
1
;
Xiaoying ZHANG
2
;
Zhiyun ZHAO
3
;
Hongyun LU
3
;
Bilun KE
3
;
Xin YE
3
;
Bin WU
1
;
Jianping YE
2
Author Information
1. Department of Gastroenterology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
2. Shanghai Diabetes Institute, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
3. Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
- Publication Type:Journal Article
- Keywords:
HDAC1;
Hepatic steatosis;
NF-κB;
SREBP1;
Succinylation
- From:
Acta Pharmaceutica Sinica B
2020;10(5):825-836
- CountryChina
- Language:English
-
Abstract:
The transcription factor nuclear factor kappa B (NF-B) is activated in hepatocytes in the pathogenesis of hepatic steatosis. However, the action mechanism of NF-B remains to be established in the hepatic steatosis. In this study, the subunit of NF-B was found to promote the hepatic steatosis through regulation of histone deacetylase 1 (HDAC1) in hepatocytes. The activity was supported by the phenotypes of knockout (-KO) mice and knockout (-KO) mice. Hepatic steatosis was reduced in the -KO mice, but not in the -KO mice. The reduction was a result of inhibition of HDAC1 activity in the -KO cells. Knockdown of gene led to suppression of hepatocyte steatosis in HepG2 cells. A decrease in sterol-regulatory element binding protein 1c (SREBP1c) protein was observed in the liver of -KO mice and in cell with knockdown. The decrease was associated with an increase in succinylation of SREBP1c protein. The study suggests that stabilizes HDAC1 to support the SREBP1c activity in hepatic steatosis in the pathophysiological condition. Interruption of this novel pathway in the -KO, but not the -KO mice, may account for the difference in hepatic phenotypes in the two lines of transgenic mice.
