Food anticipatory activity on a calorie-restricted diet is independent of Sirt1.

Food anticipatory activity on a calorie-restricted diet is independent of Sirt1.
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DOI:
10.1371/journal.pone.0199586
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Steele AD
Steele AD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Assali DR;Hsu CT;Gunapala KM;Aguayo A;McBurney M;Steele AD

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许多研究表明Sirtuin家族成员Sirt1是生长、代谢和寿命的关键整合者。Sirt1直接与昼夜节律时钟的关键调节因子相互作用并使其去乙酰化,使其成为喂养和昼夜节律之间的重要联系。事实上,一项研究表明,Sirt1是对有限的每日食物供应的行为预期所必需的,这一昼夜节律过程被称为食物预期活动(FAA)。在他们的研究中,过表达Sirt1的小鼠具有增强的FAA,而缺乏Sirt1的小鼠几乎没有FAA。基于Sirt1确实是FAA所必需的假设,我们试图使用Sirt1缺失来绘制负责FAA的神经回路。我们开始使用细胞类型特异性Cre驱动系proopiomelocortin灭活Sirt1,但在观察到对体重减轻或FAA没有影响后,我们转向更广泛的神经元Cre驱动系Ca2+/钙调素依赖性蛋白激酶II和巢蛋白。由于这些Sirt1的神经元缺失都没有损害FAA,我们随后测试了1)出生后他莫昔芬诱导的广泛缺失,2)Sirt1的完全发育性敲除,以及3)Sirt1的基因替代,催化活性不强;但所有这些老鼠的FAA与对照组相似。因此,我们的研究结果表明,FAA完全独立于Sirt1。
A number of studies have demonstrated that the Sirtuin family member, Sirt1, is a key integrator of growth, metabolism, and lifespan. Sirt1 directly interacts with and deacetylates key regulators of the circadian clock, positioning it to be an important link between feeding and circadian rhythms. In fact, one study suggests that Sirt1 is necessary for behavioral anticipation of limited daily food availability, a circadian process termed food anticipatory activity (FAA). In their study, mice overexpressing Sirt1 had enhanced FAA, while mice lacking Sirt1 had little to no FAA. Based on the supposition that Sirt1 was indeed required for FAA, we sought to use Sirt1 deletion to map the neural circuitry responsible for FAA. We began by inactivating Sirt1 using the cell-type specific Cre-driver lines proopiomelanocortin, but after observing no effect on body weight loss or FAA we then moved on to more broadly neuronal Cre drivers Ca2+/calmodulin-dependent protein kinase II and nestin. As neither of these neuronal deletions of Sirt1 had impaired FAA, we then tested 1) a broad postnatal tamoxifen-inducible deletion, 2) a complete, developmental knockout of Sirt1, and 3) a gene replacement, catalytically inactive, form of Sirt1; but all of these mice had FAA similar to controls. Therefore, our findings suggest that FAA is completely independent of Sirt1.
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