Journal
CELL METABOLISM
Volume 15, Issue 6, Pages 838-847Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2012.04.022
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Funding
- Ecole Polytechnique Federate de Lausanne
- Swiss National Science Foundation
- European Research Council Ideas program (Sirtuins) [ERC-2008-AdG231-118]
- Velux foundation
- Rubicon fellowship of the Netherlands Organization for Scientific Research
- AMC postdoc fellowship
- Academy of Finland
- Ellison Medical Foundation New Scholar Award
- NY State Spinal Cord Injury Board [C023832]
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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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