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

Cantó, Carles; Houtkooper, Riekelt H.; Pirinen, Eija; Youn, Dou Yeon; Oosterveer, Maaike H.; Cen, Yana; Fernández-Marcos, Pablo J.; Yamamoto, Hiroyasu; Andreux, Pénélope; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A.; Auwerx, Johan

doi:10.1016/j.cmet.2012.04.022

Cited by 1,010 publications

(1,311 citation statements)

References 41 publications

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“…Enhancing NAD + biosynthesis with NAD + precursors such as NMN and nicotinamide riboside increases the activity of the NAD + ‐dependent deacetylase SIRT1 (Imai, 2010; Satoh et al ., 2011; Yoshino et al ., 2011; Canto et al ., 2012). In the present study, short‐term (48‐h) incubation of NMN resulted in a threefold increase in aortic NAD + levels (Fig.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

et al. 2016

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SummaryWe tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD + intermediate, increases arterial SIRT1 activity and reverses age‐associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid artery endothelium‐dependent dilation (EDD) (60 ± 5% vs. 84 ± 2%), a measure of endothelial function, and nitric oxide (NO)‐mediated EDD (37 ± 4% vs. 66 ± 6%), compared with young mice (YC). This age‐associated impairment in EDD was restored in OC by the superoxide (O2−) scavenger TEMPOL (82 ± 7%). OC also had increased aortic pulse wave velocity (aPWV, 464 ± 31 cm s−1 vs. 337 ± 3 cm s−1) and elastic modulus (EM, 6407 ± 876 kPa vs. 3119 ± 471 kPa), measures of large elastic artery stiffness, compared with YC. OC had greater aortic O2− production (2.0 ± 0.1 vs. 1.0 ± 0.1 AU), nitrotyrosine abundance (a marker of oxidative stress), and collagen‐I, and reduced elastin and vascular SIRT1 activity, measured by the acetylation status of the p65 subunit of NFκB, compared with YC. Supplementation with NMN in old mice restored EDD (86 ± 2%) and NO‐mediated EDD (61 ± 5%), reduced aPWV (359 ± 14 cm s−1) and EM (3694 ± 315 kPa), normalized O2− production (0.9 ± 0.1 AU), decreased nitrotyrosine, reversed collagen‐I, increased elastin, and restored vascular SIRT1 activity. Acute NMN incubation in isolated aortas increased NAD + threefold and manganese superoxide dismutase (MnSOD) by 50%. NMN supplementation may represent a novel therapy to restore SIRT1 activity and reverse age‐related arterial dysfunction by decreasing oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

et al. 2016

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“…Recently, Canto et al (2012) who showed that NR supplementation in C2C12 myotubes increased NAD + content, whilst NR feeding to mice (400 mg/kg/day) resulted in modest increases in skeletal muscle NAD + (~5%) following 1-week supplementation [171]. The authors proposed that the metabolic action of NR supplementation was mediated through SIRT1, as the adaptive response of C2C12 myotubes to NR supplementation was lost following SIRT1 siRNA mediated knockdown.…”

Section: Nicotinamide Riboside (Nr)mentioning

confidence: 99%

New strategies in sport nutrition to increase exercise performance

Hamilton

Philp

et al. 2016

Free Radical Biology and Medicine

171

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Despite over 50 years of research, the field of sports nutrition continues to grow at a rapid rate. Whilst the traditional research focus was one that centred on strategies to maximize competition performance, emerging data in the last decade has demonstrated how both macronutrient and micronutrient availability can play a prominent role in regulating those cell signalling pathways that modulate skeletal muscle adaptations to endurance and resistance training. Nonetheless, in the context of exercise performance, it is clear that carbohydrate (but not fat) still remains king and that carefully chosen ergogenic aids (e.g. caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates) can all promote performance in the correct exercise setting. In relation to exercise training, however, it is now thought that strategic periods of reduced carbohydrate and elevated dietary protein intake may enhance training adaptations whereas high carbohydrate availability and antioxidant supplementation may actually attenuate training adaptation. Emerging evidence also suggests that vitamin D may play a regulatory role in muscle regeneration and subsequent hypertrophy following damaging forms of exercise. Finally, novel compounds (albeit largely examined in rodent models) such as epicatechins, nicotinamide riboside, resveratrol, β-hydroxy β-methylbutyrate, phosphatidic acid and ursolic acid may also promote or attenuate skeletal muscle adaptations to endurance and strength training. When taken together, it is clear that sports nutrition is very much at the heart of the Olympic motto, Citius, Altius, Fortius (faster, higher, stronger).

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“…In previous reports, administration of NAD precursors, such as NMN and NR, increased NAD levels in various murine tissues (Canto et al., 2012; Yoshino et al., 2011). In these models, increased NAD levels activated the SIRT1–PGC1α axis and prevented the metabolic disorders that are associated with aging and obesity.…”

Section: Resultsmentioning

confidence: 99%

“…Previously, dietary interventions with the NAD precursors NMN and NR have been shown to increase NAD levels and ameliorate diet‐induced obesity and diabetes (Canto et al., 2012; Yoshino et al., 2017). In these models, increased NAD levels induced deacetylation of PGC1α and subsequently stimulated mitochondrial biogenesis and activity.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, increases in intracellular NAD levels may combat with aging‐associated diseases. Accordingly, several studies have demonstrated that dietary supplementation with NAD precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), efficiently increases NAD levels in certain tissues and prevents aging‐ and diet‐associated obesity and insulin resistance in mice (Canto et al., 2012; Yoshino, Mills, Yoon, & Imai, 2011). …”

Section: Introductionmentioning

confidence: 99%

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Overexpression of Nmnat3 efficiently increases NAD and NGD levels and ameliorates age‐associated insulin resistance

et al. 2018

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SummaryNicotinamide adenine dinucleotide (NAD) is an important cofactor that regulates various biological processes, including metabolism and gene expression. As a coenzyme, NAD controls mitochondrial respiration through enzymes of the tricarboxylic acid (TCA) cycle, β‐oxidation, and oxidative phosphorylation and also serves as a substrate for posttranslational protein modifications, such as deacetylation and ADP‐ribosylation by sirtuins and poly(ADP‐ribose) polymerase (PARP), respectively. Many studies have demonstrated that NAD levels decrease with aging and that these declines cause various aging‐associated diseases. In contrast, activation of NAD metabolism prevents declines in NAD levels during aging. In particular, dietary supplementation with NAD precursors has been associated with protection against age‐associated insulin resistance. However, it remains unclear which NAD synthesis pathway is important and/or efficient at increasing NAD levels in vivo. In this study, Nmnat3 overexpression in mice efficiently increased NAD levels in various tissues and prevented aging‐related declines in NAD levels. We also demonstrated that Nmnat3‐overexpressing (Nmnat3 Tg) mice were protected against diet‐induced and aging‐associated insulin resistance. Moreover, in skeletal muscles of Nmnat3 Tg mice, TCA cycle activity was significantly enhanced, and the energy source for oxidative phosphorylation was shifted toward fatty acid oxidation. Furthermore, reactive oxygen species (ROS) generation was significantly suppressed in aged Nmnat3 Tg mice. Interestingly, we also found that concentrations of the NAD analog nicotinamide guanine dinucleotide (NGD) were dramatically increased in Nmnat3 Tg mice. These results suggest that Nmnat3 overexpression improves metabolic health and that Nmnat3 is an attractive therapeutic target for metabolic disorders that are caused by aging.

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

Cited by 1,010 publications

References 41 publications

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

New strategies in sport nutrition to increase exercise performance

Overexpression of Nmnat3 efficiently increases NAD and NGD levels and ameliorates age‐associated insulin resistance

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