The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity

• DOI: 10.1016/j.cmet.2012.04.022
• Publication Date: 2012-06-05T17:26:44Z
• Authors: Carles Cantó; Riekelt H. Houtko...; Eija Pirinen; Dou Y. Youn; Maaike H. Oosterveer; Yana Cen; Pablo J. Fernande...; Hiroyasu Yamamoto; Pénélope A. Andreux; Philippe Cettour-...; Karl Gademann; Chris Rinsch; Kristina Schoonjans; Anthony A. Sauve; Johan Auwerx
• Keywords: Oxidative metabolism

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.