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Review
. 2017 May 15;1(7):816-835.
doi: 10.1210/js.2017-00092. eCollection 2017 Jul 1.

Targeting NAD+ in Metabolic Disease: New Insights Into an Old Molecule

Yasir S Elhassan  1   2 , Andrew A Philp  3 , Gareth G Lavery  1   2
Affiliations
Review

Targeting NAD+ in Metabolic Disease: New Insights Into an Old Molecule

Yasir S Elhassan et al. J Endocr Soc. .

Abstract

Nicotinamide adenine dinucleotide (NAD+) is an established cofactor for enzymes serving cellular metabolic reactions. More recent research identified NAD+ as a signaling molecule and substrate for sirtuins and poly-adenosine 5'-diphosphate polymerases; enzymes that regulate protein deacetylation and DNA repair, and translate changes in energy status into metabolic adaptations. Deranged NAD+ homeostasis and concurrent alterations in mitochondrial function are intrinsic in metabolic disorders, such as type 2 diabetes, nonalcoholic fatty liver, and age-related diseases. Contemporary NAD+ precursors show promise as nutraceuticals to restore target tissue NAD+ and have demonstrated the ability to improve mitochondrial function and sirtuin-dependent signaling. This review discusses the accumulating evidence for targeting NAD+ metabolism in metabolic disease, maps the different strategies for NAD+ boosting, and addresses the challenges and open questions in the field. The health potential of targeting NAD+ homeostasis will inform clinical study design to identify nutraceutical approaches for combating metabolic disease and the unwanted effects of aging.

Keywords: aging; diabetes; mitochondria; nicotinamide mononucleotide; nicotinamide riboside; nonalcoholic fatty liver disease.

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Figures

Figure 1.
Figure 1.
NAD+ as a redox cofactor and a consumed substrate.
Figure 2.
Figure 2.
Schematic overview of human NAD+ biosynthesis. NAAD, nicotinic acid adenine dinucleotide; NADS, NAD+ synthase; NAPT, nicotinic acid phosphoribosyltransferase; NMNAT, nicotinamide mononucleotide adenylyltransferase; QAPT, quinolinic acid phosphoribosyltransferase. *NAMPT is the rate limiting step in NAD+ biosynthesis.
See this image and copyright information in PMC

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