Oxyntomodulin regulates resetting of the liver circadian clock by food
- University of California, San Diego, United States
- Max Planck Institute for Biophysical Chemistry, Germany
- University of Lübeck, Germany
- 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.
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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
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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Oxyntomodulin regulates resetting of the liver circadian clock by food
eLife 4:e06253.
https://doi.org/10.7554/eLife.06253
