[HTML][HTML] The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity

C Cantó, RH Houtkooper, E Pirinen, DY Youn… - Cell metabolism, 2012 - cell.com
C Cantó, RH Houtkooper, E Pirinen, DY Youn, MH Oosterveer, Y Cen
Cell metabolism, 2012cell.com
As NAD+ is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as
a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line
with this premise, decreased activity of PARP-1 or CD38—both NAD+ consumers—
increases NAD+ bioavailability, resulting in SIRT1 activation and protection against
metabolic disease. Here we evaluated whether similar effects could be achieved by
increasing the supply of nicotinamide riboside (NR), a recently described natural NAD+ …
Summary
As NAD+ is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38—both NAD+ consumers—increases NAD+ bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD+ precursor with the ability to increase NAD+ levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD+ levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function.
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