NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus

Cantó, Carles; Menzies, Keir J.; Auwerx, Johan

doi:10.1016/j.cmet.2015.05.023

Cited by 1,193 publications

(1,223 citation statements)

References 284 publications

(468 reference statements)

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“…This metabolic shift in substrate utilization was coupled with a strengthening in redox control and tissue NAD + homeostasis, as evidenced by greater accumulation of NAD + (in muscle) and nicotinamide (in liver) in RedTg vs. Wt mice. Endogenous formation of nicotinamide can occur directly by cleavage of NAD + by NAD + ‐consuming enzymes such as sirtuins (SIRTs), CD38, and PARPs (Canto, Menzies & Auwerx, 2015; Verdin, 2015). The significant accumulation of SIRT1 protein in muscle and liver extracts of RedTg mice was accompanied by weaker global protein acetylation signal, possibly because of higher SIRT1 activity as compared to Wt mice.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

et al. 2018

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SummaryCalorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b 5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age‐associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through upregulation of these NADH‐dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and, importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD +/sirtuin pathway. The results highlight the importance of these NAD + producers for the promotion of health and extended lifespan.

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Section: Discussionmentioning

confidence: 99%

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

et al. 2018

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“…NR has garnered recent attention, as it is a direct precursor for NAD + synthesis in skeletal muscle through the Nicotinamide Riboside Kinase 1/2 (NRK1/2) pathway [169]. As a dietary derived NAD + donor in skeletal muscle, NR is thought to impact skeletal muscle mitochondrial function through the NAD + /SIRT1/PGC-1α signaling cascade [170] (Figure 1).…”

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

156

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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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“…These protective effects require activation of the Akt1 signalling pathway while alterations in mitochondrial potential and inhibition of FOX03a phosphorylation are also involved (Chong, et al, 2004). The role of NAD + , for which nicotinamide is a precursor, in both pathways is recently and thoroughly reviewed by Canto, et al (2015).…”

Section: Resultsmentioning

confidence: 99%

Relative efficacy of nicotinamide treatment of a mouse model of infantile Niemann-Pick C1 disease

2016

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Nicotinamide delivered in drinking water at about 2g/kg/day significantly prolonged survival and showed a suggestive improvement on memory in the Npc1 nih / Npc1 nih mouse model of infantile NPC1 disease. It is likely that this role is due to its function as a histone deacetylase (HDAC) inhibitor although another HDAC inhibitor, valproic acid, was without effect. Nicotinamide could also work by preventing/reversing oxidative stress. Statement of author's contributionsCAM and IAB performed the experiments which were devised by RPE who also authored the ms. with CAM.2

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NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus

Cited by 1,193 publications

References 284 publications

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

New strategies in sport nutrition to increase exercise performance

Relative efficacy of nicotinamide treatment of a mouse model of infantile Niemann-Pick C1 disease

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NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus

Cited by 1,193 publications

References 284 publications

Overexpression of CYB5R3 and NQO1, two NAD+‐producing enzymes, mimics aspects of caloric restriction

Overexpression of CYB5R3 and NQO1, two NAD+‐producing enzymes, mimics aspects of caloric restriction

New strategies in sport nutrition to increase exercise performance

Relative efficacy of nicotinamide treatment of a mouse model of infantile Niemann-Pick C1 disease

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Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction