Adipose tissue NAD(+) biology in obesity and insulin resistance: From mechanism to therapy.
Adipose tissue NAD(+) biology in obesity and insulin resistance: From mechanism to therapy.
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DOI：
10.1002/bies.201600227
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Yoshino J
中科院分区：
文献类型：
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作者：
Yamaguchi S;Yoshino J
烟酰胺腺嘌呤二核苷酸（Nicotinamide adenine dinucleotide，NAD+）生物合成途径由烟酰胺磷酸核糖转移酶（nicotinamide phosphoribosyltransferase，NAMPT）介导，在代谢、昼夜节律、炎症和衰老等生物学过程中起着关键作用。在过去的十年中，NAMPT介导的NAD+生物合成及其关键下游介质，即NAD+依赖性蛋白脱乙酰酶SIRT1，已被证明以组织依赖性方式调节葡萄糖和脂质代谢。这些发现为肥胖及其代谢并发症提供了新的机制和治疗见解，如胰岛素抵抗，这是发展2型糖尿病和心血管疾病的重要风险因素。本文综述了脂肪组织NAMPT介导的NAD+生物合成和SIRT1在肥胖和胰岛素抵抗的病理生理学中的重要性。我们还将严格探索脂肪组织NAD+生物学的转化和临床方面。
Nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD+ biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT-mediated NAD+ biosynthesis, together with its key downstream mediator, namely the NAD+-dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue-dependent manner. These discoveries have provided novel mechanistic and therapeutic insights into obesity and its metabolic complications, such as insulin resistance, an important risk factor for developing type 2 diabetes and cardiovascular disease. This review will focus on the importance of adipose tissue NAMPT-mediated NAD+ biosynthesis and SIRT1 in the pathophysiology of obesity and insulin resistance. We will also critically explore translational and clinical aspects of adipose tissue NAD+ biology.