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Central and Peripheral Clock Control of Circadian Feeding Rhythms
Journal of Biological Rhythms ( IF 3.5 ) Pub Date : 2021-09-22 , DOI: 10.1177/07487304211045835
Carson V Fulgham 1 , Austin P Dreyer 1 , Anita Nasseri 1 , Asia N Miller 1 , Jacob Love 1 , Madison M Martin 1 , Daniel A Jabr 1 , Sumit Saurabh 1 , Daniel J Cavanaugh 1
Affiliation  

Many behaviors exhibit ~24-h oscillations under control of an endogenous circadian timing system that tracks time of day via a molecular circadian clock. In the fruit fly, Drosophila melanogaster, most circadian research has focused on the generation of locomotor activity rhythms, but a fundamental question is how the circadian clock orchestrates multiple distinct behavioral outputs. Here, we have investigated the cells and circuits mediating circadian control of feeding behavior. Using an array of genetic tools, we show that, as is the case for locomotor activity rhythms, the presence of feeding rhythms requires molecular clock function in the ventrolateral clock neurons of the central brain. We further demonstrate that the speed of molecular clock oscillations in these neurons dictates the free-running period length of feeding rhythms. In contrast to the effects observed with central clock cell manipulations, we show that genetic abrogation of the molecular clock in the fat body, a peripheral metabolic tissue, is without effect on feeding behavior. Interestingly, we find that molecular clocks in the brain and fat body of control flies gradually grow out of phase with one another under free-running conditions, likely due to a long endogenous period of the fat body clock. Under these conditions, the period of feeding rhythms tracks with molecular oscillations in central brain clock cells, consistent with a primary role of the brain clock in dictating the timing of feeding behavior. Finally, despite a lack of effect of fat body selective manipulations, we find that flies with simultaneous disruption of molecular clocks in multiple peripheral tissues (but with intact central clocks) exhibit decreased feeding rhythm strength and reduced overall food intake. We conclude that both central and peripheral clocks contribute to the regulation of feeding rhythms, with a particularly dominant, pacemaker role for specific populations of central brain clock cells.



中文翻译:

昼夜节律的中央和外围时钟控制

许多行为在内源性昼夜节律计时系统的控制下表现出约 24 小时的振荡,该系统通过分子生物钟跟踪一天中的时间。在果蝇中,黑腹果蝇, 大多数昼夜节律研究都集中在运动活动节律的产生上,但一个基本问题是生物钟如何协调多种不同的行为输出。在这里,我们研究了介导摄食行为昼夜节律控制的细胞和电路。使用一系列遗传工具,我们表明,与运动活动节律一样,进食节律的存在需要中脑腹外侧时钟神经元中的分子时钟功能。我们进一步证明,这些神经元中分子时钟振荡的速度决定了进食节律的自由运行期长度。与中央时钟细胞操作观察到的效果相反,我们表明脂肪体(一种外周代谢组织)中分子时钟的遗传消除,对进食行为没有影响。有趣的是,我们发现对照果蝇大脑和脂肪体中的分子时钟在自由运行条件下逐渐异相生长,这可能是由于脂肪体时钟的内源性周期较长。在这些条件下,进食节律的周期与中央脑时钟细胞中的分子振荡相一致,这与脑时钟在决定进食行为时间的主要作用一致。最后,尽管脂肪体选择性操作缺乏效果,我们发现在多个外周组织(但具有完整的中央时钟)中同时破坏分子时钟的果蝇表现出进食节律强度降低和整体食物摄入减少。我们得出结论,中央和外围时钟都有助于调节进食节奏,

更新日期:2021-09-22
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