Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis.
Level 5 - mechanism / opinion, no new human data
Preclinical bench and animal mechanism study in mice
PubMed 19299583 · doi:10.1126/science.1171641
What was done
Investigated the circadian oscillation of nicotinamide phosphoribosyltransferase (NAMPT) and NAD+ levels in mice, and evaluated the mechanistic feedback loop between NAMPT, SIRT1, and the circadian transcription factors CLOCK, BMAL1, and Per2.
What was found
The abstract reports no quantitative values or statistical metrics. It reports that NAMPT and NAD+ levels oscillate under circadian regulation in mice; NAMPT inhibition promoted Per2 oscillation by relieving SIRT1 suppression of CLOCK:BMAL1; and CLOCK bound to and upregulated Nampt expression, completing a feedback loop.
Why it matters
Identifies a direct bidirectional molecular link connecting cellular NAD+ energy metabolism to the mammalian circadian transcriptional clock.
Limits
Conducted entirely in preclinical mouse models with no human data. The abstract omits sample sizes, quantitative effect estimates, and tissue-specific details.
Cited by
- supports NAD+ levels rise during fasting and exercise, and fluctuate with circadian rhythms.
- contradicts The circadian clock is regulated by NAD+ levels.