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Liver-derived ketone bodies are necessary for food anticipation

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Albrecht Urs ,
Project Clock synchronization: From brain to periphery or periphery to brain?
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Original article (peer-reviewed)

Journal Nature Communications
Volume (Issue) 7
Page(s) 10580
Title of proceedings Nature Communications
DOI 10.1038/ncomms10580

Open Access

Type of Open Access Publisher (Gold Open Access)


The circadian system has endowed animals with the ability to anticipate recurring food availability at particular times of day. As daily food anticipation (FA) is independent of the suprachiasmatic nuclei, the central pacemaker of the circadian system, questions arise of where FA signals originate and what role components of the circadian clock might play. Here we show that liver-specific deletion of Per2 in mice abolishes FA, an effect that is rescued by viral overexpression of Per2 in the liver. RNA sequencing indicates that Per2 regulates β-hydroxybutyrate (βOHB) production to induce FA leading to the conclusion that liver Per2 is important for this process. Unexpectedly, we show that FA originates in the liver and not in the brain. However, manifestation of FA involves processing of the liver-derived βOHB signal in the brain, indicating that the food-entrainable oscillator is not located in a single tissue but is of systemic nature.