Mechanism lipotoxicity in the progression from fatty liver to non-alcoholic steatohepatitis

Abstract

Non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease worldwide. A subset of these individuals develops hepatocyte damage, inflammation and fibrosis, a syndrome referral as nonalcoholic steatohepatitis (NASH). Although much progress has been made since NASH was first documented, the pathogenesis of NASH is not fully elucidated. Recent studies suggest that free fatty acids (FFA) induced lipotoxicity contributes to the pathogenesis of NAFLD and NASH. Currently there are no clinically effective treatments for NASH, understanding the pathomechanisms responsible for disease development and progression could give the clue to a beneficial therapeutic approach. The purpose of this chapter is to discuss the pathophysiology involving hepatocyte injury by lipotoxicity, focuses on the known mechanisms of cellular toxicity secondary the network between lipid metabolism, autophagy, oxidative stress, ER-stress, JNK activation, death receptors and BCL-2 family proteins. A more comprehensive understanding of the molecular mechanism that triggers lipotoxicity-related pathways could likely create potential therapeutic opportunities for NASH.