Nicotinamide Riboside Restores Metabolic Balance in Muscle Cells by Reversing NAD+ Depletion: Preclinical Findings

Synopsis

Skeletal muscle plays a key role in overall body metabolism, but aging and disease can reduce its ability to function properly. Researchers studied how changes in NAD+ levels affect muscle cell metabolism because NAD+ is essential for energy production. Using muscle cell models, they controlled NAD+ levels by depleting, restoring, or increasing them with nicotinamide riboside (NR) and measured how carbon metabolism was affected. They found that increasing NAD+ with NR helped clear nicotinamide but didn’t change overall energy metabolism. In contrast, reducing NAD+ by blocking the enzyme NAMPT caused a buildup of certain metabolites before the enzyme GAPDH, and increased production of aspartate through glycolysis and the TCA cycle. These changes were quickly reversed when NAD+ was restored with NR. NAD+ depletion lowered GAPDH activity in the cytosol but did not affect mitochondrial metabolism, indicating different effects within cell compartments. While NR supplementation reversed these effects, the role of increased aspartate after NAD+ loss remains unclear and needs more study. This work shows that when studying NAD+ precursors in muscle health, it’s important to consider how carbon metabolism and clearance pathways are involved.

Journal

Wellcome Open Research