Nicotinamide Riboside Kinases Mediate NMN and NR Metabolism in Muscle Cells: Preclinical Findings

Synopsis

Increasing NAD+ levels may help protect muscles from age-related decline. This study examined how skeletal muscle cells make NAD+ from precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR). Using gene expression analysis and mice lacking the enzymes nicotinamide riboside kinase 1 and 2 (NRK1/2), researchers found that muscle cells mainly rely on NAMPT, NRK1, and NRK2 to recycle NAD+. Blocking NAMPT lowers NAD+ in muscle, but this can be restored by NR and NMN, which depend on NRK1 and NRK2. Mice missing NRK2 alone develop normally, but loss of both NRK1 and NRK2 shows that these enzymes compensate for each other in processing NR and NMN. The study reveals that both NR and NMN require NRK activity to boost muscle NAD+ levels, highlighting key pathways for maintaining muscle metabolism.

Journal

Molecular Metabolism