Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies

Figure 3 Proposed model for toxic advanced glycation end-products-mediated responses in the liver. HFCS/sucrose and dietary AGEs, which are normally found in sweetened beverages and commercial food products, are taken into the body, where they enhance the production/accumulation of TAGE, upregulate RAGE mRNA expression, and increase serum TAGE concentrations, leading to TAGE-RAGE interactions. The interaction between TAGE and RAGE alters intracellular signaling, gene expression, and the release of pro-inflammatory molecules and also induces oxidative stress in hepatocytes and hepatic stellate cells, which might contribute to the pathological changes observed in NAFLD/NASH. The formation of intracellular TAGE is associated with protein dysfunction followed by inflammation and cell death. Extracellular TAGE induce inflammation and fibrosis/cancer malignancy via RAGE signaling. AGEs: Advanced glycation end-products; TAGE: Toxic AGEs; RAGE: Receptor for AGEs; Hsc70: Heat shock cognate 70; ROS: Reactive oxygen species; VEGF: Vascular endothelial growth factor; HFCS: High-fructose corn syrup; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis.