Endoplasmic Reticulum Stress and Autophagy in the Pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD): Current Evidence and Perspectives

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease with rising prevalence worldwide. Herein, we provide a comprehensive overview of the current knowledge supporting the role of ER stress and autophagy processes in NAFLD pathogenesis and progression. We also highlight the interrelation between these two pathways and the impact of ER stress and autophagy modulators on NAFLD treatment. The pathophysiological mechanisms involved in NAFLD progression are currently under investigation. The endoplasmic reticulum (ER) stress and the concomitant unfolded protein response (UPR) seem to contribute to its pathogenesis mainly due to high ER content in the liver which exerts significant metabolic functions and can be dysregulated. Furthermore, disruption of autophagy processes has also been identified in NAFLD. The crucial role of these two pathways in NAFLD is underlined by the fact that they have recently emerged as promising targets of therapeutic interventions. There is a greater need for finding the natural/chemical compounds and drugs which can modulate the ER stress pathway and autophagy for the treatment of NAFLD. Clarifying the inter-relation between these two pathways and their interaction with inflammatory and apoptotic mechanisms will allow the development of additional therapeutic options which can better target and reprogram the underlying pathophysiological pathways, aiming to attenuate NAFLD progression.