HK4 counteracts lipotoxicity-induced gene expression changes in hepatocytes

A novel positive allosteric modulator of the GABAA receptor, HK4, was reported to exhibit hepatoprotective effects against lipotoxicity-induced apoptosis, DNA damage, inflammation and ER stress in vitro. This might be mediated by downregulated phosphorylation of the transcription factors NF-kB and STAT3. The current study aimed to investigate the effect of HK4 on lipotoxicity-induced hepatocyte injury at the transcriptional level. Therefore, HepG2 cells were treated with palmitate in the presence or absence of HK4 for 7 h. Total RNA was isolated and the expression profiles of mRNAs were assessed. We conclude that HK4 specifically targets mitochondrial respiration, protein ubiquitination, apoptosis and cell cycle. These findings suggest that HK4 has a great potential for the treatment of non-alcoholic fatty liver disease