Proteomic and lipidomic profiling of retinol ester lipid droplets in hepatic stellate cells

• Applicant: Dr. Natalie Krahmer
• Subject Area: Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 538651361

Due to the obesity epidemic, the prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and its severe form, Metabolic Dysfunction-Associated Steatohepatitis (MASH) has dramatically increased. MASLD stems from an imbalance in liver energy metabolism, causing triglyceride and toxic lipid buildup in hepatocytes. This leads to hepatocyte damage and activates hepatic stellate cells (HSCs), which typically store vitamin A as retinyl esters (RE) in lipid droplets (LDs). When activated, HSCs release retinol and transform into myofibroblasts, contributing to fibrosis. The precise mechanisms of RE LD formation and breakdown in HSCs are not well understood. We plan to use advanced organelle proteomic and lipidomic tools to study these processes in cell models and in vivo, aiming to identify factors involved in RE LD formation and mobilization, which could be promising drug targets to prevent MASH progression.

• DFG Programme: Research Units
• Subproject of: FOR 5815: Structural and functional lipid droplet heterogeneity