LAUSR

Significance We evaluate the role of NAD+ circadian control by comparing diurnal gene expression across brown adipose tissue (BAT), white adipose tissue (WAT), and skeletal muscle of mice with tissue-specific deletion of the NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT). Despite a substantial reduction in NAD+ levels across all three tissues, the outcomes on the clock are markedly different. We observe profound attenuation of core clock oscillation in response to Nampt deletion in BAT, moderate attenuation in WAT, and no changes in skeletal muscle. Furthermore, Nampt deletion reduced the number of rhythmic transcripts and metabolites in BAT. Our study underscores the importance of investigating in vitro clock mechanisms across different organs to determine their ubiquitous versus cell-specific contributions to circadian biology in vivo.