LAUSR

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease that ranges from benign steatosis to nonalcoholic steatohepatitis (NASH) . The role of cholesterol alterations in NAFLD progression have been shown in various studies. Additionally, activation of ER stress, induces inflammation, insulin resistance and apoptotic cell death which results in NAFLD/NASH transition. UPR is mediated by the activation of three ER proteins: IRE1, PERK and ATF-6 . These proteins are inactivated by binding to the ER chaperone GRP78 under normal conditions. Following disassociation of GRP78, each of these sensor proteins (PERK, ATF6 and IRE1) use a unique mechanism to induce transcription factors. If the stress is too severe and excess the capacity of defense mechanisms, cells switch to apoptotic cell death pathways which is mainly driven by CHOP. The aim of this study is to identify the effect of ER stress on the molecular mechanisms of apoptosis in hypercholesterolemia induced NAFLD. In this direction, lipid accumulation and protein expressions of GRP78, GRP94, IRE1, PERK, Bax, CHOP, Caspase 3 has been investigated in the liver tissues of NAFLD rabbit model. Our model demostrated that high cholesterol diet increase ER stress, that triggers apoptosis in the progresion of NAFLD.