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Regulation of adaptive behaviour during fasting by hypothalamic Foxa2

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  • Jose P. Silva

    (The Rockefeller University, Laboratory of Metabolic Diseases, 1230 York Avenue, New York, New York 10021, USA
    Present address: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, Jupiter, Florida 33458, USA.)

  • Ferdinand von Meyenn

    (Swiss Federal Institute of Technology, ETH Zürich, Institute for Molecular Systems Biology, Wolfgang Pauli Strasse 16, 8093 Zürich, Switzerland)

  • Jessica Howell

    (The Rockefeller University, Laboratory of Metabolic Diseases, 1230 York Avenue, New York, New York 10021, USA
    Swiss Federal Institute of Technology, ETH Zürich, Institute for Molecular Systems Biology, Wolfgang Pauli Strasse 16, 8093 Zürich, Switzerland)

  • Bernard Thorens

    (Center of Integrative Genomics, University of Lausanne)

  • Christian Wolfrum

    (Swiss Federal Institute of Technology, ETH Zürich, Institute for Molecular Systems Biology, Wolfgang Pauli Strasse 16, 8093 Zürich, Switzerland)

  • Markus Stoffel

    (The Rockefeller University, Laboratory of Metabolic Diseases, 1230 York Avenue, New York, New York 10021, USA
    Swiss Federal Institute of Technology, ETH Zürich, Institute for Molecular Systems Biology, Wolfgang Pauli Strasse 16, 8093 Zürich, Switzerland)

Abstract

Foxa2 shows antiobesity potential A novel mechanism by which insulin regulates metabolic and behavioural responses to fasting and feeding has been discovered. During fasting, the neuropeptides orexin and MCH (melanin-concentrating hormone) are released in the lateral hypothalamic area — the classic 'feeding centre' of the brain — where they induce motivated behaviour and stimulate food intake. Work in mice shows that expression of orexin and MCH is regulated by the transcription factor Foxa2. After a meal, insulin signalling renders Foxa2 ineffective and orexin and MCH production ceases. Mice with Foxa2 permanently 'on' have more orexin and MCH, eat more and are more physically active and have improved insulin sensitivity. Turning on Foxa2 in obese mice increases lean body mass and reduces their fat content. Pharmacological blockade of Foxa2 phosphorylation may therefore increase levels of physical activity and improve overall health.

Suggested Citation

  • Jose P. Silva & Ferdinand von Meyenn & Jessica Howell & Bernard Thorens & Christian Wolfrum & Markus Stoffel, 2009. "Regulation of adaptive behaviour during fasting by hypothalamic Foxa2," Nature, Nature, vol. 462(7273), pages 646-650, December.
    • Handle: RePEc:nat:nature:v:462:y:2009:i:7273:d:10.1038_nature08589
    DOI: 10.1038/nature08589
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    Cited by:

    1. Joram D Mul & Susanne E la Fleur & Pim W Toonen & Anthonieke Afrasiab-Middelman & Rob Binnekade & Dustin Schetters & Michel M M Verheij & Robert M Sears & Judith R Homberg & Anton N M Schoffelmeer & R, 2011. "Chronic Loss of Melanin-Concentrating Hormone Affects Motivational Aspects of Feeding in the Rat," PLOS ONE, Public Library of Science, vol. 6(5), pages 1-13, May.

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