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

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.

• Authors: 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
• Journal: Cell metabolism (Cell Metab) Vol. 15 Issue 6 Pg. 838-47 (Jun 06 2012) ISSN: 1932-7420 [Electronic] United States
• PMID: 22682224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• HCAR2 protein, human
• Pyridinium Compounds
• Receptors, G-Protein-Coupled
• Receptors, Nicotinic
• nicotinamide-beta-riboside
• NAD
• Niacinamide
• Superoxide Dismutase
• superoxide dismutase 2
• SIRT1 protein, human
• SIRT3 protein, human
• Sirtuin 1
• Sirtuin 3
• Electron Transport Complex I
• NDUFA9 protein, human

Topics

• Acetylation
• Adipose Tissue, Brown (drug effects, metabolism, 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, metabolism)
• NAD (blood, metabolism)
• Niacinamide (administration & dosage, analogs & derivatives, pharmacology)
• Obesity (etiology, 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)