Cell Metabolism
Volume 15, Issue 6, 6 June 2012, Pages 838-847
Journal home page for Cell Metabolism

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

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Summary

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.

Highlights

► 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

Cited by (0)

6

These authors contributed equally to this work

7

Present address: Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland

8

Present address: Laboratory Genetic Metabolic Diseases, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands