Dissertation submitted to the Combined Faculties for Natural Sciences and for Mathematics of the Ruperto-Carola University of Heidelberg, Germany for the degree of Doctor of Natural Sciences Presented by Ulrike Lemke Diploma: Biochemistry, University of Leipzig, Germany Date and Place of Birth: 14.03.1978 in Salzwedel, Germany The role of transcriptional repressor Hes-1 in glucocorticoid-mediated fatty liver development Referees: Prof. Dr. Lutz Gissmann (University of Heidelberg/ DKFZ) PD Dr. Ursula Klingmüller (University of Heidelberg/DKFZ) Science is organized knowledge. Immanuel Kant (German Philosopher, 1724 – 1804) IVAbstract Aberrant hepatic fat accumulation (“fatty liver”) represents a pathophysiological hallmark of obesity and is associated with extended glucocorticoid therapy, obesity, Type II diabetes, and starvation. Elevated glucocorticoid levels under these conditions are causative for the fatty liver phenotype, although the molecular mechanisms of their action remain largely unclear. This study demonstrates that glucocorticoids (GCs) promote fatty liver development through facilitated fat transport into the liver and not due to increased de novo fat synthesis.