Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic which affects up to 30 % of the American population. Nonalcoholic steatohepatitis (NASH), the more severe form of NAFLD, is associated with increased risk of cardiovascular morbidity and mortality, insulin resistance (IR), type 2 diabetes mellitus (T2DM), hepatic steatosis, elevated circulating levels of free fatty acids (FFAs) and hepatocyte apoptosis. Because lipid-induced toxicity, or lipoapoptosis, represents a key pathogenic factor for NAFLD, we will focus on the evidence connecting the accumulation of certain lipid types in the liver with the progressive induction of hepatocyte injury and secondary inflammation/fibrosis during the disease. A better understanding of the molecular and cellular pathway of lipotoxicity has both diagnostic and therapeutic implication for the treatment of NAFLD.