Oxyntomodulin regulates resetting of the liver circadian clock by food

  1. Dominic Landgraf
  2. Anthony H Tsang
  3. Alexei Leliavski
  4. Christiane E Koch
  5. Johanna L Barclay
  6. Daniel J Drucker
  7. Henrik Oster  Is a corresponding author
  1. University of California, San Diego, United States
  2. Max Planck Institute for Biophysical Chemistry, Germany
  3. University of Lübeck, Germany
  4. University of Toronto, Canada

Abstract

Circadian clocks coordinate 24-hr rhythms of behavior and physiology. In mammals, a master clock residing in the suprachiasmatic nucleus (SCN) is reset by the light-dark cycle, while timed food intake is a potent synchronizer of peripheral clocks such as the liver. Alterations in food intake rhythms can uncouple peripheral clocks from the SCN, resulting in internal desynchrony, which promotes obesity and metabolic disorders. Pancreas-derived hormones such as insulin and glucagon have been implicated in signaling mealtime to peripheral clocks. Here we identify a novel, more direct pathway of food-driven liver clock resetting involving oxyntomodulin (OXM). In mice, food intake stimulates OXM secretion from the gut, which resets liver transcription rhythms via induction of the core clock genes Per1 and 2. Inhibition of OXM signaling blocks food-mediated resetting of hepatocyte clocks. These data reveal a direct link between gastric filling with food and circadian rhythm phasing in metabolic tissues.

Article and author information

Author details

  1. Dominic Landgraf

    Department of Psychiatry, University of California, San Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Anthony H Tsang

    Circadian Rhythms Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Alexei Leliavski

    Circadian Rhythms Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Christiane E Koch

    Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Johanna L Barclay

    Circadian Rhythms Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniel J Drucker

    Department of Medicine, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Henrik Oster

    Circadian Rhythms Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    For correspondence
    henrik.oster@uksh.de
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Louis Ptáček, University of California, San Francisco, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the German law for animal welfare (TierschGes). All animals were handled according to approved institutional animal care and use committee protocols of the Max Planck Institutes Göttingen and the University of Lübeck. The protocol was approved by the ethical committees of the Niedersächsisches Amt für Verbraucherschutz und Lebensmittelsicherheit (LAVES) and the Ministerium für Energiewende, Landwirtschaft, Umwelt und ländliche Räume (MELUR; license numbers V312-7224.122-4 and 33.12-42502-04-12/0893). Every effort was made to minimize suffering

Version history

  1. Received: December 23, 2014
  2. Accepted: March 27, 2015
  3. Accepted Manuscript published: March 30, 2015 (version 1)
  4. Version of Record published: May 11, 2015 (version 2)

Copyright

© 2015, Landgraf et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Dominic Landgraf
  2. Anthony H Tsang
  3. Alexei Leliavski
  4. Christiane E Koch
  5. Johanna L Barclay
  6. Daniel J Drucker
  7. Henrik Oster
(2015)
Oxyntomodulin regulates resetting of the liver circadian clock by food
eLife 4:e06253.
https://doi.org/10.7554/eLife.06253

Share this article

https://doi.org/10.7554/eLife.06253

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