Hypothalamic NAD+-Sirtuin Axis: Function and Regulation.

IF 4.8 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomolecules Pub Date : 2020-03-04 DOI:10.3390/biom10030396
Eun Roh, Min-Seon Kim
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引用次数: 9

Abstract

The rapidly expanding elderly population and obesity endemic have become part of continuing global health care problems. The hypothalamus is a critical center for the homeostatic regulation of energy and glucose metabolism, circadian rhythm, and aging-related physiology. Nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase sirtuins are referred to as master metabolic regulators that link the cellular energy status to adaptive transcriptional responses. Mounting evidence now indicates that hypothalamic sirtuins are essential for adequate hypothalamic neuronal functions. Owing to the NAD+-dependence of sirtuin activity, adequate hypothalamic NAD+ contents are pivotal for maintaining energy homeostasis and circadian physiology. Here, we comprehensively review the regulatory roles of the hypothalamic neuronal NAD+-sirtuin axis in a normal physiological context and their changes in obesity and the aging process. We also discuss the therapeutic potential of NAD+ biology-targeting drugs in aging/obesity-related metabolic and circadian disorders.

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下丘脑NAD+-Sirtuin轴:功能与调控。
迅速扩大的老年人口和肥胖流行病已成为持续的全球卫生保健问题的一部分。下丘脑是能量和葡萄糖代谢、昼夜节律和衰老相关生理的稳态调节的关键中心。烟酰胺腺嘌呤二核苷酸(NAD+)依赖的去乙酰化酶sirtuins被认为是连接细胞能量状态和适应性转录反应的主要代谢调节因子。越来越多的证据表明,下丘脑的sirtuins对于下丘脑神经元的充分功能是必不可少的。由于sirtuin活性依赖NAD+,足够的下丘脑NAD+含量对于维持能量稳态和昼夜生理至关重要。在这里,我们全面回顾了下丘脑神经元NAD+-sirtuin轴在正常生理背景下的调节作用及其在肥胖和衰老过程中的变化。我们还讨论了NAD+生物靶向药物在衰老/肥胖相关代谢和昼夜节律紊乱中的治疗潜力。
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来源期刊
Biomolecules
Biomolecules Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
3.60%
发文量
1640
审稿时长
18.28 days
期刊介绍: Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications.  Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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