CRC/TR 412

Hepatic-MBOAT7 downregulation in obese humans and mice is associated with the development of liver fibrosis. We hypothesise that bioactive lipids secreted by MBOAT7-deficient hepatocytes mediate pro-fibrotic crosstalk with hepatic stellate cells (HSCs) via specific lipid signalling pathways. Using in vitro experiments with mouse/human primary cells and mass spectrometry based lipidomics we will identify molecular players of the proposed signalling mechanism and validate it in vivo using various transgenic mouse models and pharmacological inhibitors. Our findings will identify druggable pathways that drive the MBOAT7-dependent cellular crosstalk and fibrosis.