Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation.

Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation.
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NAD+ 振荡被破坏的小鼠的行为和代谢昼夜节律发生改变。

DOI:
10.18632/aging.100368
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发表时间:
2011-08
期刊:
Aging
影响因子:
--
通讯作者:
Sassone-Corsi P
Sassone-Corsi P
中科院分区:
其他
文献类型:
--
作者:
Sahar S;Nin V;Barbosa MT;Chini EN;Sassone-Corsi P

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烟酰胺腺嘌呤二核苷酸 (NAD+) 的细胞内水平是有节律的,并受生物钟控制。然而,NAD+振荡是否反过来有助于昼夜节律生理学尚不完全清楚。为了解决这个问题,我们分析了 NAD+ 水解酶 CD38 突变的小鼠。我们发现 CD38 缺陷小鼠中 NAD+ 的节律性发生了改变。 NAD+ 的长期高水平会导致昼夜节律行为和新陈代谢的多种异常。 CD38 缺失小鼠表现出运动活动周期缩短和休息活动节律改变。一些时钟基因,有趣的是,参与氨基酸代谢的基因在 CD38 缺失的肝脏中失调。代谢组学分析发现,CD38 缺失小鼠中几种氨基酸的昼夜节律水平发生变化,特别是色氨酸水平在与 NAD+ 水平升高的昼夜节律时间内降低。因此,CD38 有助于行为和代谢昼夜节律,而改变的 NAD+ 水平会影响生物钟。
The Intracellular levels of nicotinamide adenine dinucleotide (NAD+) are rhythmic and controlled by the circadian clock. However, whether NAD+ oscillation in turn contributes to circadian physiology is not fully understood. To address this question we analyzed mice mutated for the NAD+ hydrolase CD38. We found that rhythmicity of NAD+ was altered in the CD38-deficient mice. The high, chronic levels of NAD+ results in several anomalies in circadian behavior and metabolism. CD38-null mice display a shortened period length of locomotor activity and alteration in the rest-activity rhythm. Several clock genes and, interestingly, genes involved in amino acid metabolism were deregulated in CD38-null livers. Metabolomic analysis identified alterations in the circadian levels of several amino acids, specifically tryptophan levels were reduced in the CD38-null mice at a circadian time paralleling with elevated NAD+ levels. Thus, CD38 contributes to behavioral and metabolic circadian rhythms and altered NAD+ levels influence the circadian clock.
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