Circadian clock feedback cycle through NAMPT-Mediated NAD+ biosynthesis

Kathryn Moynihan Ramsey, Jun Yoshino, Cynthia S. Brace, Dana Abrassart, Yumiko Kobayashi, Biliana Marcheva, Hee Kyung Hong, Jason L. Chong, Ethan D. Buhr, Choogon Lee, Joseph S. Takahashi, Shin Ichiro Imai, Joseph Bass

Research output: Contribution to journalArticlepeer-review

785 Scopus citations


The circadian clock is encoded by a transcription-translation feedback loop that synchronizes behavior and metabolism with the light-dark cycle. Here we report that both the rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD+) biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT), and levels of NAD+ display circadian oscillations that are regulated by the core clock machinery in mice. Inhibition of NAMPT promotes oscillation of the clock gene Per2 by releasing CLOCK:BMAL1 from suppression by SIRT1. In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1.

Original languageEnglish (US)
Pages (from-to)651-654
Number of pages4
Issue number5927
StatePublished - May 1 2009

ASJC Scopus subject areas

  • General


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