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

By C. Cantó, R. Houtkooper, E. Pirinen, D. Y. Youn, M. Oosterveer, Yana Cen, P. Fernandez-Marcos, Hiroyasu Yamamoto, P. Andreux, P. Cettour-Rose and 5 more. Cell Metabolism, 2012

1,193 citations recorded by the source corpus.

SUMMARY As NAD+ is a rate-limiting co-substrate 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 lifespan 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.

Subfields: Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/71fcf3f22ad639add77fc2dc31364cd2f3ab8dbd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Geriatrics and Gerontology

In Physiology

Citations in the corpus

Defective Mitophagy in XPA via PARP1 Hyperactivation and NAD+/SIRT1 Reduction (2014, background): “…Rescue the Mitochondrial Phenotype In Vivo Recent work has suggested that supplementation with the NAD+ precursors nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN)may attenuate the effect of the age-associated activation of PARP (Cantó et al., 2012; Mouchiroud et al., 2013).”
CD38 dictates age-related NAD decline and mitochondrial dysfunction through a SIRT3-dependent mechanism (2016, positive): “NAD+ precursors such as NMN and NR (nicotinamide riboside) have been proposed as NAD+-replacement therapy for ageand diet-induced metabolic dysfunction (Cantó et al., 2012; Gomes et al., 2013; Imai and Guarente, 2014; Prolla and Denu, 2014; Yoshino et al., 2011).”
The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling (2013, background): “In line with our previous results in mice (Bai et al., 2011b; Cantó et al., 2012), both PARP inhibition and supplying NAD precursors for 48 hr in the hepatocyte cell line AML12 increased the mtDNA/nDNA ratio (Figures 6A and 6B, upper), demonstrating mitochondrial biogenesis.”
Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice (2016, neutral): “NR is also able to ameliorate mitochondrial dysfunction in obese mouse models (Cantó et al., 2012; Gariani et al., 2015; Lee et al., 2015) and various mitochondrial disease models (Cerutti et al., 2014; Khan et al., 2014), attenuate cognitive deterioration in Alzheimer’s diseasemodel mice (Gong et…”
SIRT1 and other sirtuins in Metabolism (2013, background): “More recently, supplementation with NAD precursors has been shown to restore NAD+ levels and prevent diet- or aging-induced diabetes in wild type mice [113,114].”
Circadian Clock NAD+ Cycle Drives Mitochondrial Oxidative Metabolism in Mice (2013, background): “Clock Regulates Acetylation and Activity of Mitochondrial Oxidative Enzymes NAD is an important cofactor in oxidative metabolism, and NAD-dependent deacetylase activity affects protein acetylation in mitochondria (17, 25, 26).”
Therapeutic potential of NAD-boosting molecules: the in vivo evidence (2018, neutral): “, Danesi, P., Pompucci, G., and Preti, A. (2001). Metabolic fate of extracellular NAD in human skin fibroblasts.”