Elhassan Yasir S, Philp Andrew A, Lavery Gareth G
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham B15 2TT, United Kingdom.
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.
烟酰胺腺嘌呤二核苷酸（NAD+）是参与细胞代谢反应的酶的一种既定辅助因子。最近的研究将NAD+确定为去乙酰化酶和聚腺苷5'-二磷酸聚合酶的信号分子和底物；这些酶调节蛋白质去乙酰化和DNA修复，并将能量状态的变化转化为代谢适应。NAD+稳态紊乱以及线粒体功能的同时改变是代谢性疾病（如2型糖尿病、非酒精性脂肪肝和与年龄相关的疾病）的内在特征。当代NAD+前体有望作为营养保健品来恢复靶组织中的NAD+，并已证明具有改善线粒体功能和去乙酰化酶依赖性信号传导的能力。本文综述讨论了针对代谢性疾病中NAD+代谢的越来越多的证据，梳理了提高NAD+水平的不同策略，并探讨了该领域的挑战和悬而未决的问题。针对NAD+稳态的健康潜力将为临床研究设计提供参考，以确定对抗代谢性疾病和衰老不良影响所需的营养保健方法。
