Hypoxic Signaling and Cholesterol Lipotoxicity in Fatty Liver Disease Progression

Figure 3

FC may directly or indirectly contribute to the development of hepatocyte lipotoxicity through different signaling pathways. Hydrolyzing cholesteryl ester (CE) to free cholesterol in the endosomes of Kupffer cells may lead to inflammation, oxidative stress, immune activation, and cell death. However, dietary FC can directly induce cell death in hepatocytes by different pathways, for example, activation of the Cyps pathway and induction of toxic bile acid production, mitochondrial dysfunction, and ER stress. CE: cholesteryl ester; Cyps: cytochrome P 450 enzymes; CHOP: C/EBP homologous protein; pyroptosis: type of cell death that involves caspase 1 activation and cell swelling [83]; UPR: unfolded protein response.