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  • NF- κ B/HDAC1/SREBP1c pathway mediates the inflammation signal in progression of hepatic steatosis.

NF- κ B/HDAC1/SREBP1c pathway mediates the inflammation signal in progression of hepatic steatosis.

Acta pharmaceutica Sinica. B (2020-06-13)
Yunwei Guo, Xiaoying Zhang, Zhiyun Zhao, Hongyun Lu, Bilun Ke, Xin Ye, Bin Wu, Jianping Ye
ABSTRACT

The transcription factor nuclear factor kappa B (NF-κB) is activated in hepatocytes in the pathogenesis of hepatic steatosis. However, the action mechanism of NF-κB remains to be established in the hepatic steatosis. In this study, the P50 subunit of NF-κB was found to promote the hepatic steatosis through regulation of histone deacetylase 1 (HDAC1) in hepatocytes. The activity was supported by the phenotypes of P50 knockout (P50-KO) mice and P65 knockout (P65-KO) mice. Hepatic steatosis was reduced in the P50-KO mice, but not in the P65-KO mice. The reduction was a result of inhibition of HDAC1 activity in the P50-KO cells. Knockdown of Hdac1 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 P50-KO mice and in cell with Hdac1 knockdown. The decrease was associated with an increase in succinylation of SREBP1c protein. The study suggests that P50 stabilizes HDAC1 to support the SREBP1c activity in hepatic steatosis in the pathophysiological condition. Interruption of this novel pathway in the P50-KO, but not the P65-KO mice, may account for the difference in hepatic phenotypes in the two lines of transgenic mice.

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