Molekulare Stoffwechselkontrolle durch hormonelle Gegenregulation
Final Report Abstract
This project has aimed to determine the role of glucocorticoid hormone signaling in the control of metabolic pathways and the pathogenesis of metabolic disorders, including obesity, fatty liver disease and other components of the Metabolic Syndrome. In this context, our studies identified a novel glucorticoid receptor-Hes1 transcriptional axis in the control of hepatic triglycerid metabolism and highlighted the importance of this pathway for fatty liver development. Furthermore, additional studies demonstrated a role of the hypothalamic-pituitary axis in the endocrine regulation of bile acid homeostasis through the liver GR by controlling essential steps in hepatic bile acid uptake and further implications for cholesterol gallstone susceptibility. Together, these studies have highlighted the importance of transcriptional regulators for the maintenance of systemic energy homeostasis and have provided novel targets for alternative therapeutic approaches in cholesterol gallstone disease and the Metabolic Syndrome.
Publications
- 2008. The glucocorticoid receptor controls hepatic dyslipidemia through Hes1. Cell Metab. 8: 212-223
Lemke, U., Krones-Herzig, A., Berriel Diaz, M., Narvekar, P., Ziegler, A., Vegiopoulos, A., Kirilov, M., Maier, J., Cato, A., Kersten, S., Screaton, R., and Herzig, S.
- 2011. Molecular control of systemic bile acid homeostasis by the liver glucocorticoid receptor. Cell Metab. 14: 123-130
Rose, A.J., Berriel Díaz, M., Reimann, A., Klement, J., Walcher, T., Krones-Herzig, A., Strobel, O., Werner, J., Peters, A., Kleyman, A., Tuckermann, J.P., Vegiopoulos, A., and Herzig, S.