Figure 2.

Circadian rhythms are regulated by the availability of NAD+. NAMPT is a SIRT1/CLOCK/BMAL1-regulated circadian gene. SIRT1 and NAMPT and NMNAT form part of a circadian regulatory feedback loop, regulating the availability of NAD+. NAD+ regulates SIRT1, SIRT3 and SIRT6 activities. SIRT1 also regulates CLOCK/BMAL1 expression in the suprachiasmatic nucleus. SIRT6 regulates chromatin recruitment of CLOCK/BMAL1. SIRT3 regulates oxidative phosphorylation and fatty acid oxidation in the mitochondria via circadian deacetylation of mitochondrial enzymes. Abbreviations: NAD+, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyltransferase; NMNAT, nicotinamide mononucleotide adenyltransferase; SIRT, sirtuins.