Lipid mobilization, interorgan transport and absorption within the body provide a functional readout of systemic lipid metabolism. The clinical lipid panel reports concertation of triglycerides, cholesterol, and phospholipids in different lipoprotein fractions to support diagnosis and prognosis of metabolic risks and disorders. Despite the clear significance of lipoprotein lipid component to systemic lipid metabolism, the lipoprotein lipidome and its remodelling in metabolic pathologies remain poorly characterized.
Hepatocytes represent an excellent system to study the cross talk between cellular and systemic lipid metabolism, as they do not only store lipids in lipid droplets but also export them into the circulation in the form of very‑low density lipoproteins (VLDLs). By using mass spectrometry based lipidomic approaches in a model system consisting of healthy and steatotic hepatocytes, this project aims to obtain a detailed molecular description of metabolic and bioactive lipids secreted in VLDLs under physiological and pathological conditions. This will enhance our current understanding on the liver and the whole body metabolic crosstalk in physiological and pathological conditions.
Involved LMAI members:
Understanding dynamics of lipid metabolism and oxidation in ferroptotic cell death programme
Ferroptosis as a common underlying pathomechanism in tissue ischemia/reperfusion injury
Dysregulated systemic release of metabolic and bioactive lipids along hepatocyte-VLDL axis
Extension of the Lipidomics technology platform to include targeted high-throughput phenotyping of lipid metabolism and its remodelling