TY - JOUR
T1 - The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity
AU - Cantó, Carles
AU - Houtkooper, Riekelt H.
AU - Pirinen, Eija
AU - Youn, Dou Y.
AU - Oosterveer, Maaike H.
AU - Cen, Yana
AU - Fernandez-Marcos, Pablo J.
AU - Yamamoto, Hiroyasu
AU - Andreux, Pénélope A.
AU - Cettour-Rose, Philippe
AU - Gademann, Karl
AU - Rinsch, Chris
AU - Schoonjans, Kristina
AU - Sauve, Anthony A.
AU - Auwerx, Johan
N1 - Funding Information:
This work was supported by grants of the École Polytechnique Fédérale de Lausanne, Swiss National Science Foundation, the European Research Council Ideas program (Sirtuins; ERC-2008-AdG231-118), and the Velux foundation. R.H.H. has been supported by a Rubicon fellowship of the Netherlands Organization for Scientific Research and by an AMC postdoc fellowship. E.P. is funded by the Academy of Finland. J.A. is the Nestle chair in energy metabolism. A.A.S. received grants to support this research from the Ellison Medical Foundation New Scholar Award 2007 and contract C023832 from NY State Spinal Cord Injury Board. The authors thank Robert Myers, Peter Meinke, and Thomas Vogt at Merck Research Laboratories, Rahway, and Charles Thomas at Amazentis, Lausanne, for the kind gift of NR; all the members of the Auwerx lab for inspiring discussions; and Graham Knott of the BioEM facility at EPFL for EM imaging.
PY - 2012/6/6
Y1 - 2012/6/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84862022077&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862022077&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2012.04.022
DO - 10.1016/j.cmet.2012.04.022
M3 - Article
C2 - 22682224
AN - SCOPUS:84862022077
SN - 1550-4131
VL - 15
SP - 838
EP - 847
JO - Cell Metabolism
JF - Cell Metabolism
IS - 6
ER -
