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

• Published in: Cell metabolism Vol. 15; no. 6; pp. 838 - 847
• Main Authors: Cantó, Carles, Houtkooper, Riekelt H., Pirinen, Eija, Youn, Dou Y., Oosterveer, Maaike H., Cen, Yana, Fernandez-Marcos, Pablo J., Yamamoto, Hiroyasu, Andreux, Pénélope A., Cettour-Rose, Philippe, Gademann, Karl, Rinsch, Chris, Schoonjans, Kristina, Sauve, Anthony A., Auwerx, Johan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06-06-2012
• Subjects: Acetylation; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Adipose Tissue, Brown - pathology; Animals; Brain - metabolism; Diet, High-Fat - adverse effects; Dietary Supplements; Electron Transport Complex I - metabolism; Energy Metabolism; HEK293 Cells; Humans; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Mitochondria - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; NAD - blood; NAD - metabolism; Niacinamide - administration & dosage; Niacinamide - analogs & derivatives; Niacinamide - pharmacology; Obesity - etiology; Obesity - prevention & control; Organ Specificity; Oxidation-Reduction; Oxygen Consumption; Protein Processing, Post-Translational; Pyridinium Compounds; Receptors, G-Protein-Coupled - metabolism; Receptors, Nicotinic - metabolism; Sirtuin 1 - metabolism; Sirtuin 3 - metabolism; Superoxide Dismutase - metabolism; Weight Gain - drug effects
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2012.04.022

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.
► NR efficiently increases NAD+ levels in mammalian cells and tissues ► NR supplementation increases SIRT1 and SIRT3 activities ► NR largely prevents the detrimental metabolic effects of high-fat feeding ► NR enhances mitochondrial function and endurance performance