Circadian Clock Feedback Cycle Through NAMPT-Mediated NAD + Biosynthesis
Top Cited Papers
- 1 May 2009
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 324 (5927) , 651-654
- https://doi.org/10.1126/science.1171641
Abstract
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.Keywords
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