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

Carles Cantó, Riekelt H. Houtkooper, Eija Pirinen, Dou Y. Youn, Maaike H. Oosterveer, Yana Cen, Pablo J. Fernandez-Marcos, Hiroyasu Yamamoto, Pénélope A. Andreux, Philippe Cettour-Rose, Karl Gademann, Chris Rinsch, Kristina Schoonjans, Anthony A. Sauve, Johan Auwerx

Research output: Contribution to journalArticle

512 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)838-847
Number of pages10
JournalCell metabolism
Volume15
Issue number6
DOIs
StatePublished - Jun 6 2012
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., Gademann, K., Rinsch, C., Schoonjans, K., Sauve, A. A., & Auwerx, J. (2012). The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell metabolism, 15(6), 838-847. https://doi.org/10.1016/j.cmet.2012.04.022