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.

转录因子核因子κB（NF- κ B）是在肝细胞中激活肝脂肪变性的发病机理。然而，NF-κB的作用机制κ B能保持在肝脂肪变性建立。在这项研究中，P50 NF-的亚基κ乙发现通过组蛋白的调节，以促进脂肪肝的肝细胞中脱乙酰酶1（HDAC1）。该活性由P50基因敲除（P50 -KO）小鼠和P65基因敲除（P65 -KO）小鼠的表型支持。肝脂肪变性在P50 -KO小鼠中减少，但在P65中没有减少-KO小鼠。减少是由于抑制了P50 -KO细胞中HDAC1活性。击倒Hdac1基因可抑制HepG2细胞中的肝细胞脂肪变性。在P50 -KO小鼠的肝脏和Hdac1基因敲低的细胞中观察到固醇调节元件结合蛋白1c（SREBP1c）蛋白的减少。减少与SREBP1c蛋白的琥珀酰化增加有关。研究表明，P50可以在病理生理状况下稳定HDAC1以支持肝脂肪变性中的SREBP1c活性。在P50 -KO而非P65中中断该新途径-KO小鼠可能解释了转基因小鼠两系中肝表型的差异。