Effect of Depdc5 deficiency on the development of alcohol-induced hepatic steatosis in mice

Hyperactivation of mTORC1 signaling has been observed in the livers of ALD mouse models or patients, but the in vivo role of sustained mTORC1 activity in ALD still remains unclear. DEPDC5, a component of GATOR1 complex, is a repressor of amino acid-sensing branch of the mTORC1 pathway. To define the in vivo role of DEPDC5 in ALD development, we generated Depdc5 hepatocyte-specific knockout mouse model (Depdc5-LKO) in which mTORC1 pathway was constitutively activated through loss of the inhibitory effect of GATOR1. Ethanol-fed Depdc5-LKO mice developed severe hepatic steatosis and inflammation. To determine the underlying molecular mechanisms, we performed RNA sequencing of liver tissues of chronic-plus-binge ethanol fed WT and Depdc5-LKO mice.