Whole-Organism Screening for Modulators of Fasting Metabolism Using Transgenic Zebrafish
Organismal energy homeostasis is maintained by complex interorgan communications making the discovery of novel drugs against metabolic diseases challenging using traditional high-throughput approaches in vitro. Here, we describe a method that rapidly identifies small molecules with an impact on organismal energy balance in vivo. Specifically, we developed a whole-organism screen for modulators of fasting metabolism using transgenic bioluminescence-reporter zebrafish for the gluconeogenic gene phosphoenolpyruvate-carboxykinase 1 (pck1).
Key wordsZebrafish Gluconeogenesis Diabetes Metabolic disease Fasting metabolism Small-molecule screening Bioluminescence Phosphoenolpyruvate-carboxykinase pck1 Transgenesis
This study was supported in part by a postdoctoral fellowship DFG GU 1082/101 from the German Research Foundation to P.G., NIH grant RO1 DK60322, a pilot and feasibility award from the University of California—San Francisco diabetes center funded by NIH U01 DK089541 and the Packard Foundation to D.Y.R.S.