Metabolic Activation of Dendritic Cells in Non-Alcoholic Steatohepatitis – DeCodeNASH

Non-alcoholic fatty liver disease (NAFLD) is a major global health problem for which there are no effective treatments. Early stages of NAFLD are described by isolated hepatic lipid accumulation, which, over time, can lead to inflammation and fibrosis, called Non-alcoholic steatohepatitis (NASH). NAFLD and especially NASH are closely associated to dysfunction in hepatic glucose and lipid homeostasis. However, the mechanisms driving activation of the hepatic immune system and progression from steatosis to NASH, remain poorly understood. We recently identified hepatic dendritic cells (DC) as a key immune population that is associated with NASH in humans. We hypothesize that the altered metabolic environment, including excess circulating lipids, alters the hepatic DC population triggering progression to NASH. The present proposal aims to dissect the key intracellular metabolic pathways of hepatic DC that are affected by activation during NASH pathogenesis.