Microscopy, cell culture, animal models
PhD Projekt: Fatty acid species-dependent hepatic cellular lipotoxicity
In periods of high fatty acid load in the plasma, when either a fat rich diet is consumed or when fatty acids are released from adipose tissue to compensate for starvation, the liver acts as buffer by storing fatty acids as triacylglycerol in lipid droplets. These fatty acids can be remobilized for lipoprotein synthesis to provide fatty acids to other organs, burned in mitochondria as energy substrates, used for cellular membrane biosynthesis or as lipid signaling molecules. However, in this perpetual cycle of fat accumulation and release in the liver, hepatocytes are stressed and damaged, starting the pathogenic progress of inflammation and fibrosis. Employing a human hepatocyte cell line (HepG2), we mimicked the environmental conditions of elevated fatty acid levels and observed the morphological and physiological changes of the cells. In addition, we performed label free quantitative proteomics as well as a Nano-LC-NSI-MS/MS lipidomics analysis to investigate the specific fatty acid-dependent cellular effects and determine their metabolic fate uncovering distinct effects for each individual fatty acid.