The role of Cdc-like kinase 2 (Clk2) in hepatic glucose and lipid metabolism

• Applicant: Dr. Maximilian Hatting
• Subject Area: Gastroenterology
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 253002145

Insulin resistance (IR) plays a crucial role in the pathophysiology of the metabolic syndrome. Non- alcoholic fatty liver disease (NAFLD) is an early and prominent hallmark of this disease. As a consequence, IR triggers changes in signal transduction pathways, including glucose and lipid metabolism and the development of liver injury to chronic end-stage cirrhosis and HCC. In our previous work, we have dissected the molecular pathways involved in liver inflammation, NAFLD, liver cirrhosis and HCC development. My current aim is to deepen in the intrahepatic signaling pathways which lead to metabolic disorders such as diabetes and metabolic syndrome.The host institution possesses an outstanding expertise in the field of molecular metabolism, systems biology and related metabolites. Recently, the role of the Cdc-like Kinase 2 (Clk2) in hepatic glucose metabolism was described and published. Clk2 is highly regulated depending on the cellular energy state. PGC1-alpha , a transcription coactivator, is phosphorylated by Clk2 leading to a decrease of hepatic gluconeogenesis. Changes in the conformational state of PGC1- alpha affect its interaction with PPAR-alpha. Thus PGC1-alpha might have a potential role in fatty acid oxidation and lipid metabolism. However, the precise mechanism of this regulation remains elusive. The host institution will provide a wide variety of technical solutions and transgene mouse models allowing the modulation of Clk2 activity and its substrate PGC1-alpha, respectively.The final aim of the present proposal is to elucidate the role of Clk2 and its interaction with PGC1-alpha in different metabolic conditions such as Fasting, Feeding and Diabetes. The host institution will provide broad knowledge in this field of research. The project will help the applicant to further develop his skills in the field of Signal Transduction and metabolism, transferring this knowledge to the RWTH Aachen.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Pere Puigserver, Ph.D.