Oxygen and Carbon Dioxide Rhythms Are Circadian Clock Controlled and Differentially Directed by Behavioral Signals

Cell Metab. 2019 May 7;29(5):1092-1103.e3. doi: 10.1016/j.cmet.2019.01.007. Epub 2019 Feb 14.


Daily rhythms in animal physiology are driven by endogenous circadian clocks in part through rest-activity and feeding-fasting cycles. Here, we examined principles that govern daily respiration. We monitored oxygen consumption and carbon dioxide release, as well as tissue oxygenation in freely moving animals to specifically dissect the role of circadian clocks and feeding time on daily respiration. We found that daily rhythms in oxygen and carbon dioxide are clock controlled and that time-restricted feeding restores their rhythmicity in clock-deficient mice. Remarkably, day-time feeding dissociated oxygen rhythms from carbon dioxide oscillations, whereby oxygen followed activity, and carbon dioxide was shifted and aligned with food intake. In addition, changes in carbon dioxide levels altered clock gene expression and phase shifted the clock. Collectively, our findings indicate that oxygen and carbon dioxide rhythms are clock controlled and feeding regulated and support a potential role for carbon dioxide in phase resetting peripheral clocks upon feeding.

Keywords: carbon dioxide; circadian clocks; metabolic cages; metabolism; oxygen; phase resetting; respiration; time restricted feeding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • Animals
  • Carbon Dioxide / metabolism*
  • Circadian Clocks / physiology*
  • Circadian Rhythm / physiology*
  • Eating
  • Feeding Behavior / physiology*
  • Gene Expression / genetics
  • Gene Knockout Techniques
  • Locomotion / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NIH 3T3 Cells
  • Oxygen / metabolism*
  • Oxygen Consumption / genetics
  • Period Circadian Proteins / genetics
  • Rats
  • Rats, Wistar
  • Respiration


  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Per1 protein, mouse
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Carbon Dioxide
  • Oxygen