Metabolic dysfunction‐associated fatty liver disease: mechanisms and targets for intervention

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is a complex disease ranging from simple steatosis to steatohepatitis, fibrosis, cirrhosis and eventually hepatocellular carcinoma. One of the hallmarks of MAFLD is exposure to excessive amounts of (toxic) lipids, leading to lipid accumulation in hepatocytes, mitochondrial dysfunction, oxidative stress, ER stress and eventually hepatocyte injury and death. Damaged hepatocytes also impact on non-parenchymal liver cells like Kupffer cells and stellate cells leading to inflammation and fibrosis. The general aim of this thesis is to investigate the mechanisms of lipotoxicity in non-alcoholic fatty liver disease in different cell types of the liver in vitro and to
explore the possibilities to intervene in these mechanisms.