Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder
characterized by an ectopic accumulation of lipids in at least 5% of hepatocytes. The
first phase of the disease, called hepatic steatosis, progresses over time to chronic
conditions, such as steatohepatitis, cirrhosis, and finally, hepatic insufficiency and
cancer. The accumulation of free fatty acids in hepatocytes, particularly saturated fatty
acids, is a key process in the development and progression of NAFLD. Furthermore, the
accumulation of oxidative stress markers in NAFLD is closely linked to lipotoxicity due to
impaired lipid metabolism and increased generation of reactive oxygen species (ROS).
However, endogenous mechanisms are activated early in the liver to protect against
lipotoxicity and oxidative stress, thus preventing liver mass loss and disease
progression. Thus, in order to develop appropriate therapies, the purpose of this review
is to discuss recent data from the literature regarding the importance of intrinsic
mechanisms deployed by the liver in protecting itself against the adverse effects related
to chronic lipid accumulation and ROS generation.