Deleting Gata4 in hepatocytes promoted the progression of NAFLD via increasing steatosis and apoptosis, and desensitizing insulin signaling. Academic Article uri icon


  • Gata4 is a member of the zinc finger GATA transcription factor family and is required for liver development during the embryonic stage. Gata4 expression is repressed during NAFLD progression, however how it functions in this situation remains unclear. Here, Gata4 was deleted specifically in hepatocytes via Cre recombinase driven by the Alb promoter region. Under a high-fat diet (HFD) or methionine and choline deficient diet (MCD), Gata4 knockout (KO) male, but not female, mice displayed more severe NAFLD or NASH, evidenced by increased steatosis, fibrosis, as well as a higher NAS score and serum ALT level. The Gata4KO male liver exposed to a HFD or MCD had a reduced ratio of pACC/ACC, similar to the Gata4KO hepatocytes treated with palmitic acid. More cell apoptosis, which is associated with activated JNK signaling and inhibited NFB signaling, was observed in the Gata4KO male liver and isolated hepatocytes. However, the inflammatory status in the Gata4KO male liver was similar to the control liver. Importantly, lower activation of AKT signaling in the liver, which is consistent with de-sensitized insulin signaling in isolated hepatocytes, was found in the Gata4KO male. In summary, our data demonstrated that loss of Gata4 in hepatocytes promoted NAFLD progression in male mice.

published proceedings

  • J Nutr Biochem

author list (cited authors)

  • He, L., Wang, X., Ding, Z., Liu, L., Cheng, H., Bily, D., ... Xie, L.

citation count

  • 1

complete list of authors

  • He, Leya||Wang, Xian||Ding, Zehuan||Liu, Lin||Cheng, Henghui||Bily, Donalyn||Wu, Chaodong||Zhang, Ke||Xie, Linglin

publication date

  • January 2023