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. Author manuscript; available in PMC: 2012 Jun 6.
Published in final edited form as: FEBS Lett. 2011 May 6;585(11):1657–1662. doi: 10.1016/j.febslet.2011.04.060

Figure 2.

Figure 2

A circadian oscillatory feedback loop regulated by NAMPT, SIRT1, and CLOCK/BMAL1 and a possible functional interplay between adipose tissue and two frailty tissues in the NAD World, pancreatic β cells and neurons. NAMPT and NAD levels display circadian oscillations that are regulated by CLOCK/BMAL1 in peripheral tissues, such as the liver and WAT. This NAD oscillation periodically activates SIRT1, which represses CLOCK/BMAL1-mediated transcription of clock target genes, including Nampt itself, completing an interlocked transcriptional-enzymatic feedback loop involving NAMPT-NAD and SIRT1-CLOCK/BMAL1. In pancreatic β cells and central neurons, intracellular NAMPT (iNAMPT) levels are so low [45] that they may not be able to drive the NAMPT-NAD-SIRT1-dependent circadian feedback loop. However, their NAD oscillation might be generated by incorporating NMN that is likely synthesized from nicotinamide (Nic) by extracellular NAMPT (eNAMPT) that could be periodically secreted from adipose tissue.