Kolbe Isa, Husse Jana, Salinas Gabriela, Lingner Thomas, Astiz Mariana, Oster Henrik
Chronophysiology Group, Medical Department 1, University of Lübeck, Lübeck, Germany.
Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada.
J Biol Rhythms. 2016 Dec;31(6):577-587. doi: 10.1177/0748730416666170. Epub 2016 Sep 21.
The circadian master pacemaker in the suprachiasmatic nucleus (SCN) orchestrates peripheral clocks in various organs and synchronizes them with external time, including those in adipose tissue, which displays circadian oscillations in various metabolic and endocrine outputs. Because our knowledge about the instructive role of the SCN clock on peripheral tissue function is based mainly on SCN lesion studies, we here used an alternative strategy employing the Cre/ loxP system to functionally delete the SCN clock in mice. We performed whole-genome microarray hybridizations of murine epididymal white adipose tissue (eWAT) RNA preparations to characterize the role of the SCN clock in eWAT circadian transcriptome regulation. Most of the rhythmic transcripts in control animals were not rhythmic in SCN mutants, but a significant number of transcripts were rhythmic only in mutant eWAT. Core clock genes were rhythmic in both groups, but as was reported before for other tissues, rhythms were dampened and phase advanced in mutant animals. In SCN-mutant mice, eWAT lost the rhythm of metabolic pathway-related transcripts, while transcripts gaining rhythms in SCN-mutant mice were associated with various immune functions. These data reveal a complex interaction of SCN-derived and local circadian signals in the regulation of adipose transcriptome programs.
视交叉上核(SCN)中的昼夜节律主起搏器协调着各个器官中的外周生物钟,并使其与外部时间同步,包括脂肪组织中的生物钟,脂肪组织在各种代谢和内分泌输出中表现出昼夜节律振荡。由于我们关于SCN生物钟对外周组织功能的指导作用的认识主要基于SCN损伤研究,因此我们在这里采用了一种替代策略,即利用Cre/loxP系统在功能上删除小鼠的SCN生物钟。我们对小鼠附睾白色脂肪组织(eWAT)RNA制剂进行了全基因组微阵列杂交,以表征SCN生物钟在eWAT昼夜转录组调控中的作用。对照动物中大多数有节律的转录本在SCN突变体中没有节律,但有相当数量的转录本仅在突变体eWAT中有节律。核心生物钟基因在两组中均有节律,但正如之前在其他组织中所报道的那样,突变动物中的节律减弱且相位提前。在SCN突变小鼠中,eWAT失去了与代谢途径相关转录本的节律,而在SCN突变小鼠中获得节律的转录本与各种免疫功能相关。这些数据揭示了SCN衍生的昼夜节律信号与局部昼夜节律信号在脂肪转录组程序调控中的复杂相互作用。