The down regulation of ubiquitin‐proteasome proteolysis system in response to amino acids and insulin involves AMPK and mTOR pathways in rat liver hepatocytes

Abstract

The purpose of this work was to examine whether changes in dietary protein level could elicit differential responses of tissue proteolysis and the pathway involved in this response. In rats fed a high protein diet (55%, HP) for 14 days, the liver is the main organ where adaptations occur, characterized by an increased protein pool and a strong meal‐induced inhibition of protein breakdown rate (−42%) as compared to the NP diet (14%). This was associated with a decrease of key‐proteins involved in ubiquitin‐proteasome and autophagy pathway gene expression and a decrease of hepatic ubiquitinated protein level. In hepatocytes, we demonstrated that the increase of amino acid (AA) concentration was sufficient to down regulate ubiquitin proteasome pathway but the inhibition was stronger in the presence of insulin. Interestingly, our results highlights that the inhibition of AMPK and the activation of mTOR transduction pathways are requested for the down regulation of protein ubiquitination in response to high amino acid and insulin concentration.