Nature Communications · 12 authors, 4 centres
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This preclinical study in obese mice shows that the metabolic benefits of NAD+ administration depend on the time of day. Treatment given at the onset of the active phase (ZT11) improved metabolic parameters and aligned the hepatic clock, while treatment at the opposite phase (ZT23) was less effective and caused circadian misalignment.
The study found that NAD+ injection at the onset of the active phase (ZT11) improved metabolic parameters including glucose tolerance, insulin sensitivity, and hepatic steatosis, and restored daily rhythms in hepatic insulin and nutrient signaling. In contrast, NAD+ administration at the opposite circadian phase (ZT23) did not fully improve glucose tolerance or insulin sensitivity and inverted the phase of the hepatic molecular clock, demonstrating that efficacy is time-dependent. The findings suggest that the hepatic clock is a key interface for timing-specific metabolic modulation by NAD+, highlighting the importance of considering circadian rhythms in therapeutic approaches for metabolic diseases.
