Daily nicotinic acid riboside signals may activate protein stress response and fat cell formation through the prefoldin complex

Nicotinic acid riboside (NaR) is identified as a circulating metabolite whose rhythmicity is dependent on the liver clock.

• NaR engages the unfolded protein response (UPR) in adipocytes and neuronal cells.
• The prefoldin complex is implicated as a target of NaR, linking it to changes in protein stability.
• NaR-induced UPR signaling affects the transcription factor CCAAT/enhancer-binding protein alpha (CEBPA) in adipocytes.
• Sustained exposure to NaR suppresses lipid accumulation in adipocytes, while limited exposure promotes fat cell formation.
• These findings suggest that NaR connects liver circadian rhythms to metabolic processes and tissue changes.

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