Cantó, CarlesHoutkooper, Riekelt H.Pirinen, EijaYoun, Dou Y.Oosterveer, Maaike H.Cen, YanaFernandez-Marcos, Pablo J.Yamamoto, HiroyasuAndreux, Pénélope A.Cettour-Rose, PhilippeGademann, KarlRinsch, ChrisSchoonjans, KristinaSauve, Anthony A.Auwerx, Johan2012-06-102012-06-102012-06-10201210.1016/j.cmet.2012.04.022https://infoscience.epfl.ch/handle/20.500.14299/81476WOS:000305502000009As 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.Dependent Histone DeacetylaseRegulates Insulin-SecretionEnergy-ExpenditureBeta-CellsSirt1AcidPgc-1-AlphaBiosynthesisReceptorPathwaystext::journal::journal article::research article