Deficiency of mTORC1 accelerates, while deficiency of mTORC2 blocks the development and progression of steatosis to steatohepatitis and hepatocellular carcinoma induced by PTEN-deletion in hepatocytes

Nonalcoholic fatty liver disease (NAFLD) is a group of liver diseases that includes from a simple steatosis up to nonalcoholic steatohepatitis (NASH), which may eventually progress to cirrhosis and hepatocellular carcinoma (HCC). Interestingly, constitutive activation of the PI3K-mTORC2-Akt-mTORC1 pathway induced by PTEN deletion in hepatocytes promotes the development of severe hepatic steatosis that later progresses to NASH and HCC. The molecular mechanisms underlying this progression have not been fully elucidated yet.