Molecular mechanism of hepatic steatosis: pathophysiological role of autophagy

Steatosis is an early characteristic in the pathogenesis of fatty liver disease (FLD). Mechanisms of hepatic steatosis are aetiology-dependent. Activation of autophagy in liver ameliorates hepatic steatosis. A modulation of hepatic autophagy affects the degree of hepatocyte steatosis and the progression of FLD as demonstrated by pre-clinical models and clinical trials. This review summarises recent advances on pathophysiological roles of autophagy in hepatic lipid metabolism. A comprehensive regulation of autophagic networks holds promise for the improvement of hepatic steatosis. Autophagic signalling pathway may be a novel therapeutic target against FLD.

• Hepatic steatosis is a pathological condition wherein vacuoles of triglyceride (TG) fat are overaccumulated in liver because of abnormal metabolism of lipids. • Hepatic autophagy regulates lipid metabolism as demonstrated by macrolipophagy in response to starvation and hepatic overabundance of TG in obesity. • Autophagic signals are closely associated with apoptotic pathways. There is distinctive relationship between hepatic autophagy and apoptosis, which affects the progression of fatty liver. • Regulation of autophagic process can be a novel therapeutic strategy for fatty liver disease.