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

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


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.

Publication types

  • Review