Abstract
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.
Highlights
The circadian system has endowed animals with the ability to anticipate recurring food availability at particular times of day
The deletion leads to a truncated PER2 protein consisting of the first 188 N-terminal amino acids plus 23 unrelated amino acids containing no structural elements involved in interaction with other clock proteins
Resetting in L Per[2] À / À animals was not affected (Supplementary Fig. 2g). These results indicate that light- and food-entrainable circadian rhythms can be functionally separated and that Per[2] in the liver is specific for food anticipation (FA)
Summary
The circadian system has endowed animals with the ability to anticipate recurring food availability at particular times of day. The circadian (B24 h) timing system is a network of brain clocks and peripheral oscillators that enable mammals to adapt to daily recurring events such as light/dark (LD) changes and availability of food[1]. While the SCN remains coupled to the LD cycle, peripheral oscillators such as the liver align with the daily feeding time This is associated with the emergence of a daily bout of activity, rise in body temperature and increase in corticosteroids that precede meal time by 1–3 h (refs 5,6). This so-called food anticipation (FA) exhibits the formal properties of a circadian clock, but persists robustly after removal of the SCN7,8. We find that liver-specific deletion of Per[2] can inhibit FA by interfering with b-hydroxybutyrate (bOHB) production and its subsequent processing in the brain
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
