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

Nicotinic acid riboside (NaR) is a liver clock-controlled circulating metabolite that modulates proteostasis and adipogenesis through the unfolded protein response.

• Why it matters: Understanding how circadian signals coordinate systemic physiology remains incomplete, especially the molecular mediators linking the liver clock to other tissues and metabolic processes.
• What they did: The study identified NaR as a rhythmic metabolite dependent on the liver clock and used proteome-wide stability profiling to implicate the prefoldin complex as a NaR target, examining its effects on UPR and adipogenesis.
• The result: NaR exposure influences proteostasis and adipocyte function by modulating UPR signaling and CEBPA activity, with sustained NaR suppressing lipid deposition and transient stimulation promoting adipogenesis, revealing a mechanism for circadian regulation of tissue remodeling.