Translational approaches: From fatty liver to non-alcoholic steatohepatitis

Figure 1 Estimation of the main etiological incidence of past, present and future chronic liver diseases according to the available data from the United States[130] and Europe[131,132].

Figure 2 Extrahepatic factors involved in the pathogenesis of non-alcoholic fatty liver disease. The affected organs and their response are represented in a dynamic circle; in the center are indicated the main factors that contribute to the initiation/perpetuation of the hepatic injury (insulin resistance and chronic inflammatory state). The light blue arrows represent the organ-specific effects of each response. TNF-α: Tumor necrosis factor-α; MCP-1: Monocyte chemotactic protein 1; IL-6: Interleukin-6; FFA: Free fatty acids; LPS: Lipopolysaccharides; TLR: Toll-like receptor; GIP: Glucose-dependent insulinotropic peptide; GLP: Glucagon-like-peptide.

Figure 3 Effect of intracellular fat accumulation within the liver. Liver sensitization induces an alteration of the normal hepatic liver metabolism leading to simple steatosis with neutral triglyceride (TG) accumulation or in the more severe cases, to the production of intermediate products (DG and phospholipids) responsible for lipotoxicity. Alteration of several mediators of signaling pathways leads to the events observed during the progression from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) (hepatic insulin resistance, oxidative stress, inflammation, and fibrosis). IKKb: Protein Kinase-1-mediated IB Kinase; ROS: Reactive oxygen species; IL-6: Interleukin-6; TNFα: Tumor necrosis factor-α; IGF-1: Insulin-like growth factor-1; PDGF: Platelet-derivedgrowth factor; ECM: Extracellular matrix; MAPK: Mitogen-activated protein kinases; ERKs: Extracellular signal-regulated kinases; NF-κB: Nuclear factor κB.