Nicotinamide Riboside Improves Cardiac Function and Prolongs Survival After Disruption of the Cardiomyocyte Clock
Pieterjan Dierickx1,2, Bryce J Carpenter1,2, Isaac Celwyn1,2
1Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States.
Abstract:
The REV-ERB nuclear receptors are key components of the circadian clock. Loss of REV-ERBs in the mouse heart causes dilated cardiomyopathy and premature lethality. This is associated with a marked reduction in NAD+ production, but whether this plays a role in the pathophysiology of this heart failure model is not known. Here, we show that supplementation with the NAD+ precursor NR as a dietary supplement improves heart function and extends the lifespan of female mice lacking cardiac REV-ERBs. Thus, boosting NAD+ levels can improve cardiac function in a setting of heart failure caused by disruption of circadian clock factors, providing new insights into the links between the circadian clock, energy metabolism, and cardiac function.
Insights
Supplementing with NR, a NAD+ precursor, improved heart function and lifespan in female mice lacking cardiac REV-ERBs. This highlights the link between circadian clock factors, NAD+ metabolism, and heart health.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Chronobiology
Background:
- REV-ERB nuclear receptors are crucial for the circadian clock.
- Loss of cardiac REV-ERBs in mice leads to dilated cardiomyopathy and reduced lifespan.
- This condition is linked to decreased NAD+ production, but its role is unclear.
Purpose of the Study:
- To investigate the therapeutic potential of boosting NAD+ levels in a mouse model of heart failure.
- To explore the connection between circadian clock disruption, NAD+ metabolism, and cardiac function.
Main Methods:
- Utilized a mouse model with genetic disruption of cardiac REV-ERBs.
- Administered nicotinamide riboside (NR) as a dietary supplement.
- Assessed cardiac function and lifespan.
Main Results:
- NR supplementation significantly improved heart function in affected mice.
- Lifespan was extended in female mice treated with NR.
- Demonstrated that boosting NAD+ levels can ameliorate cardiac dysfunction.
Conclusions:
- NAD+ precursor supplementation is a viable strategy to improve cardiac function in the context of circadian clock disruption.
- This study provides novel insights into the interplay between the circadian clock, energy metabolism, and heart health.
- Targeting NAD+ metabolism may offer therapeutic benefits for certain types of heart failure.
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