The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity
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, 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
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.
Copyright © 2012 Elsevier Inc. All rights reserved.
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Source: PubMed