Simplified Abstract

The aim of my thesis was to investigate the role of two enzymes in a process called lipotoxicity. Lipotoxicity is a metabolic syndrome in which high concentrations of free fatty acids lead to cell dysfunction and subsequent cell death. However, how these free fatty acids trigger this cytotoxicity is not yet fully understood

One of the enzymes studied in this thesis (SCD1) is necessary for the conversion of saturated to unsaturated fatty acids, the other (GPX8) is thought to play a role in maintaining a healthy environment in the cell. To understand the role of these enzymes in lipotoxicity in more detail, they were made non-functional in cultured mouse cells by a so-called “knockout”. The subsequent treatment of these cells with fatty acids and the analysis of the following cell reactions should provide information about their role in lipotoxicity.

This work demonstrated that both GPX8 and SCD1 play a major role in protection against lipotoxicity. It could be shown that cell death in mouse cells could be induced by the addition of elevated concentrations of saturated fatty acids but could be prevented by the simultaneous addition of unsaturated fatty acids. The “knockout” of the two enzymes led to cell death at significantly lower concentrations of saturated fatty acids. By analyzing different cellular pathways, answers could be found how this lipotoxicity protection is ensured by the enzymes.