Matz-Soja, Madlen and Rennert, Christiane and Schoenefeld, Kristin and Aleithe, Susanne and Boettger, Jan and Schmidt-Heck, Wolfgang and Weiss, Thomas S. and Hovhannisyan, Amalya and Zellmer, Sebastian and Kloeting, Nora and Schulz, Angela and Kratzsch, Juergen and Guthke, Reinhardt and Gebhardt, Rolf (2016) Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis. ELIFE, 5: e13308. ISSN 2050-084X,
Full text not available from this repository. (Request a copy)Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries and is increasing in prevalence. The pathomechanisms, however, are poorly understood. This study assessed the unexpected role of the Hedgehog pathway in adult liver lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion of Smoothened in adult mice, we showed that hepatocellular inhibition of Hedgehog signaling leads to steatosis by altering the abundance of the transcription factors GLI1 and GLI3. This steatotic 'Gli-code' caused the modulation of a complex network of lipogenic transcription factors and enzymes, including SREBP1 and PNPLA3, as demonstrated by microarray analysis and siRNA experiments and could be confirmed in other steatotic mouse models as well as in steatotic human livers. Conversely, activation of the Hedgehog pathway reversed the "Gli-code" and mitigated hepatic steatosis. Collectively, our results reveal that dysfunctions in the Hedgehog pathway play an important role in hepatic steatosis and beyond.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN INTERACTION NETWORKS; HEPATIC STEATOSIS; BETA-CATENIN; NONALCOHOLIC STEATOHEPATITIS; MITOCHONDRIAL DYSFUNCTION; TRANSCRIPTION FACTORS; MOUSE HEPATOCYTES; MICE; ZONATION; DISEASE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Mar 2019 08:19 |
| Last Modified: | 21 Mar 2019 08:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2930 |
Actions (login required)
 |
View Item |
