A systemic circadian nicotinic acid riboside (NaR) signal engages the unfolded protein response and adipogenesis via the prefoldin complex.

Daily light-dark cycles impose environmental fluctuations that require coordinated regulation of physiology. This coordination is mediated by the circadian clock, which operates as a network of tissue oscillators; however, the signals that convey circadian information between organs remain incompletely defined. We identify nicotinic acid riboside (NaR) as a circulating metabolite whose rhythmicity depends on the liver clock. In adipocytes and neuronal cells, NaR engages the unfolded protein response (UPR). Proteome-wide stability profiling implicates the prefoldin complex as a target of NaR, linking NaR exposure to altered proteostasis. In adipocytes, NaR-induced UPR signaling converges on the transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). Sustained NaR exposure suppresses adipocyte lipid deposition, whereas temporally restricted NaR stimulation enhances adipogenesis. Together, these findings identify NaR as a liver clock-controlled circulating metabolite that couples systemic circadian metabolism to proteostasis and tissue remodeling, revealing a mechanism by which temporal metabolic signals shape tissue-specific physiological outcomes.