The Mysterious Food-Entrainable Oscillator: Insights from Mutant and Engineered Mouse Models

Julie S. Pendergast, Shin Yamazaki

Research output: Contribution to journalReview articlepeer-review

57 Scopus citations


The food-entrainable oscillator (FEO) is a mysterious circadian clock because its anatomical location(s) and molecular timekeeping mechanism are unknown. Food anticipatory activity (FAA), which is defined as the output of the FEO, emerges during temporally restricted feeding. FAA disappears immediately during ad libitum feeding and reappears during subsequent fasting. A free-running FAA rhythm has been observed only in rare circumstances when food was provided with a period outside the range of entrainment. Therefore, it is difficult to study the circadian properties of the FEO. Numerous studies have attempted to identify the critical molecular components of the FEO using mutant and genetically engineered mouse models. Herein we critically review the experimental protocols and findings of these studies in mouse models. Several themes emerge from these studies. First, there is little consistency in restricted feeding protocols between studies. Moreover, the protocols were sometimes not optimal, resulting in erroneous conclusions that FAA was absent in some mouse models. Second, circadian genes are not necessary for FEO timekeeping. Thus, another noncanonical timekeeping mechanism must exist in the FEO. Third, studies of mouse models have shown that signaling pathways involved in circadian timekeeping, reward (dopaminergic), and feeding and energy homeostasis can modulate, but are not necessary for, the expression of FAA. In sum, the approaches to date have been largely unsuccessful in discovering the timekeeping mechanism of the FEO. Moving forward, we propose the use of standardized and optimized experimental protocols that focus on identifying genes that alter the period of FAA in mutant and engineered mouse models. This approach is likely to permit discovery of molecular components of the FEO timekeeping mechanism.

Original languageEnglish
Pages (from-to)458-474
Number of pages17
JournalJournal of Biological Rhythms
Issue number5
StatePublished - Oct 1 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).


  • FEO
  • circadian
  • food anticipatory activity
  • food entrainment
  • restricted feeding

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


Dive into the research topics of 'The Mysterious Food-Entrainable Oscillator: Insights from Mutant and Engineered Mouse Models'. Together they form a unique fingerprint.

Cite this