Figure 3.

Cellular cross-talks in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The increase of free-fatty acid (FFA) afflux to the liver determinates hepatocyte steatosis (non-alcoholic fatty liver - NAFL); subsequently, the accumulation of abnormal lipid compounds in the hepatocytes causes lipotoxicity, leading to hepatocyte damage, apoptosis and death. Hepatocyte lipotoxicity triggers M1 macrophage recruitment and lobular inflammation (i.e., steatohepatitis: NASH) and, then, pro-fibrogenetic pathways. In pericentral zone, the activation of hepatic stellate cells (HSCs) and the M1 macrophage polarization trigger perisinusoidal fibrosis. At periportal location, ductular reaction emerges and drives the activation of local myofibroblast pools together with M1 macrophage recruitment. The main molecular factors implied in local cellular cross-talks are summarized in the scheme.