To die or not to die: death signaling in nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is an emerging liver disease worldwide. In subset of patients, NAFLD progresses to its advanced form, nonalcoholic steatohepatitis (NASH), which is accompanied with inflammation and fibrosis. Saturated free fatty acid-induced hepatocyte apoptosis is a feature of NASH. Death signaling in NASH does not always result in apoptosis, but can alternatively lead to the survival of cells presenting signs of pro-inflammatory and pro-fibrotic signals. With the current lack of established treatments for NASH, it is important to understand the molecular mechanisms responsible for disease development and progression. This review focuses on the latest findings in hepatocyte death signaling and discusses possible targets for intervention, including caspases, death receptor and c-Jun N-terminal kinase 1 signaling, oxidative stress, and endoplasmic reticulum stress, as well as epigenomic factors.