Figure 6.

Schematic model of ROS mediated liver protection from hepatic steatosis. Inhibiting de novo GMP synthesis by MPA-treatment or the GMP synthetase^s850 mutation induced hepatic steatosis. Supplying GMP rescued the hepatic steatosis phenotype in GMP synthetase^s850 mutant larva. De novo GMP synthesis influenced the activation of Rac1 and inhibiting Rac1 activity in hepatocytes by overexpressing dominant negative Rac1 (DN-Rac1) also induced hepatic steatosis. Rac1 regulates the activity of NADPH oxidases (Nox1, 2) and inhibiting NADPH oxidases mediated ROS production by DPI or quenching ROS by N-acetyl cysteine (NAC) also induced hepatic steatosis. Supplying hydrogen peroxide (H₂O₂) rescued the hepatic steatosis phenotype in GMP synthetase^s850 mutant, Rac1 inhibitor-treated, and DN-Rac1 expressing larvae. ROS levels influenced triglyceride hydrolase gene expression. The small molecule inhibitor for Triglyceride hydrolase (E600) treatment also induced hepatic steatosis.