Rhythmic oxygen levels reset circadian clocks through HIF1α

Yaarit Adamovich, Benjamin Ladeuix, Marina Golik, Maarten Koeners, Gad Asher

Research output: Contribution to journalArticle (Academic Journal)peer-review

82 Citations (Scopus)
350 Downloads (Pure)

Abstract

The mammalian circadian system consists of a master clock in the brain that synchronizes subsidiary oscillators in peripheral tissues. The master clock maintains phase coherence in peripheral cells through systemic cues such as feeding-fasting and temperature cycles. Here, we examined the role of oxygen as a resetting cue for circadian clocks. We continuously measured oxygen levels in living animals and detected daily rhythms in tissue oxygenation. Oxygen cycles, within the physiological range, were sufficient to synchronize cellular clocks in a HIF1α-dependent manner. Furthermore, several clock genes responded to changes in oxygen levels through HIF1α. Finally, we found that a moderate reduction in oxygen levels for a short period accelerates the adaptation of wild-type but not of HIF1α-deficient mice to the new time in a jet lag protocol. We conclude that oxygen, via HIF1α activation, is a resetting cue for circadian clocks and propose oxygen modulation as therapy for jet lag.
Original languageEnglish
Pages (from-to)93-101
Number of pages9
JournalCell Metabolism
Volume25
Issue number1
Early online date20 Oct 2016
DOIs
Publication statusPublished - 10 Jan 2017

Keywords

  • circadian rhythms
  • clock
  • oxygen
  • HIF1
  • jetlag
  • metabolism
  • entrainment
  • Cry2
  • Rorα

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