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Whole-Organism Screening for Modulators of Fasting Metabolism Using Transgenic Zebrafish

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Chemical Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1263))

Abstract

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).

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References

  1. Baur JA et al (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342

    Article  CAS  PubMed  Google Scholar 

  2. Le Couteur DG et al (2012) Aging biology and novel targets for drug discovery. J Gerontol A Biol Sci Med Sci 67:168–174

    Article  PubMed  Google Scholar 

  3. Guarente LL (2006) Sirtuins as potential targets for metabolic syndrome. Nature 444:868–874

    Article  CAS  PubMed  Google Scholar 

  4. Anson RM et al (2003) Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A 100:6216–6220

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Moller DE (2012) Metabolic disease drug discovery- “hitting the target” is easier said than done. Cell Metab 15:19–24

    Article  CAS  PubMed  Google Scholar 

  6. Lemieux GA et al (2011) A whole-organism screen identifies new regulators of fat storage. Nat Chem Biol 7:206–213

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Gut P et al (2013) Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism. Nat Chem Biol 9:97–104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Andersson O et al (2012) Adenosine signaling promotes regeneration of pancreatic β cells in vivo. Cell Metab 15:885–894

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Zon LI, Peterson RT (2005) In vivo drug discovery in the zebrafish. Nat Rev Drug Discov 4:35–44

    Article  CAS  PubMed  Google Scholar 

  10. Lin HV, Accili D (2011) Hormonal regulation of hepatic glucose production in health and disease. Cell Metab 14:9–19

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Rena G, Pearson ER, Sakamoto K (2013) Molecular mechanism of action of metformin: old or new insights? Diabetologia 56:1898–1906

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgements

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.

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Correspondence to Philipp Gut or Didier Y. R. Stainier .

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© 2015 Springer Science+Business Media New York

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Gut, P., Stainier, D.Y.R. (2015). Whole-Organism Screening for Modulators of Fasting Metabolism Using Transgenic Zebrafish. In: Hempel, J., Williams, C., Hong, C. (eds) Chemical Biology. Methods in Molecular Biology, vol 1263. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2269-7_12

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  • DOI: https://doi.org/10.1007/978-1-4939-2269-7_12

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2268-0

  • Online ISBN: 978-1-4939-2269-7

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