Endoplasmic reticulum stress and Oxidative stress in the pathogenesis of Non-alcoholic fatty liver disease

Free Radic Res. 2015;49(12):1405-18. doi: 10.3109/10715762.2015.1078461. Epub 2015 Aug 25.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. The underlying causes of the disease progression in NAFLD are unclear. Recent evidences suggest endoplasmic reticulum stress in the development of lipid droplets (steatosis) and subsequent generation of reactive oxygen species (ROS) in the progression to non-alcoholic steatohepatitis (NASH). The signalling pathway activated by disruption of endoplasmic reticulum (ER) homoeostasis, called as unfolded protein response, is linked with membrane biosynthesis, insulin action, inflammation and apoptosis. ROS are important mediators of inflammation. Protein folding in ER is linked to ROS. Therefore understanding the basic mechanisms that lead to ER stress and ROS in NAFLD have become the topics of immense interest. The present review focuses on the role of ER stress and ROS in the pathogenesis of NAFLD. We also highlight the cross talk between ER stress and oxidative stress which suggest and encourage the development of therapeutics for NAFLD. Further we have reviewed various strategies used for the management of NAFLD/NASH and limitations of such strategies. Our review therefore highlights the need for newer strategies with regards to ER stress and oxidative stress.

Keywords: ER stress; Non-alcoholic Fatty liver disease; Oxidative stress; cell death.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Endoplasmic Reticulum Stress / physiology*
  • Humans
  • Non-alcoholic Fatty Liver Disease / physiopathology*
  • Oxidative Stress / physiology*