Abstract
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) probably represent the most common chronic liver diseases in western countries with a substantial risk of liver cirrhosis and high cardiovascular morbidity and mortality. The pathogenic mechanism involved in the development of fatty liver remains unclear.
It is known that severity of steatosis is well correlated with progression to NASH in humans, and several recent reports gave suggested that accumulation of lipids in the liver, and especially disturbances in the composition of hepatic fatty acids, might play a causal role in the development of NASH. Intricacies of the molecular and cellular mechanisms responsible for progression from simple steatosis to NASH have not been fully elucidated.
Excessive accumulation of lipid substrates in the liver has serious adverse effects on cell functions and especially saturated free fatty acids are directly hepatotoxic, perhaps by mediating an endoplasmic reticulum stress response and inducing hepatocyte apoptosis referred to as lipoapoptosis or lipotoxicity. Recent studies suggest that excess fat accumulation in the liver associated with depletion of n-3 polyunsaturated fatty acids and disturbances in the ratio of saturated/unsaturated fatty acids may play a causal role in the pathophysiology of NASH.