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

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• 作者：Carles Cantó ; ¹ ; ⁶ ; ⁷ ; Riekelt  ; H. Houtkooper¹ ; ⁶ ; ⁸ ; Eija Pirinen¹ ; ² ; Dou  ; Y. Youn³ ; Maaike  ; H. Oosterveer¹ ; Yana Cen³ ; Pablo  ; J. Fernandez-Marcos¹ ; Hiroyasu Yamamoto¹ ; Pé ; né ; lope  ; A. Andreux¹ ; Philippe Cettour-Rose¹ ; Karl Gademann⁴ ; Chris Rinsch⁵ ; Kristina Schoonjans¹ ; Anthony  ; A. Sauve³ ; Johan Auwerx¹ ; ^{admin.auwerx@epfl.ch}
• 刊名：Cell Metabolism
• 出版年：2012
• 期刊代码：46_15504131
• 类别：med
• 出版时间：6 June, 2012
• 卷：15
• 期：6
• 页码：838-847
• 文件大小：898 K

摘要

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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鈥攂oth NAD⁺ consumers鈥攊ncreases 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.