title: Rhythmic Oxygen Levels Reset Circadian Clocks through HIF1α.
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.
authors: Department of Biomolecular Sciences, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors: Yaarit
authors: Y
authors: Adamovich
authors: Department of Biomolecular Sciences, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors: Benjamin
authors: B
authors: Ladeuix
authors: Department of Biomolecular Sciences, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors: Marina
authors: M
authors: Golik
authors: School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol BS8 1TH, UK.
authors: Maarten P
authors: MP
authors: Koeners
authors: Department of Biomolecular Sciences, Weizmann Institute of Science, 7610001 Rehovot, Israel. Electronic address: gad.asher@weizmann.ac.il.
authors: Gad
authors: G
authors: Asher
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D057906:Circadian Clocks / Q000187:drug effects / Q000235:genetics; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D020179:Jet Lag Syndrome / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D010100:Oxygen / Q000494:pharmacology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen
keywords: Cry2; HIF1; Rorα; circadian rhythms; clock; entrainment; jetlag; metabolism; oxygen