Rudl Kulhava Lucie, Houdek Pavel, Novakova Michaela, Hricko Jiri, Paucova Michaela, Kuda Ondrej, Sladek Martin, Fiehn Oliver, Sumova Alena, Cajka Tomas
Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, Prague, 14200, Czech Republic.
University of California, Davis, 451 Health Sciences Drive, Davis, CA, 95616, USA.
Cell Mol Life Sci. 2025 Jun 28;82(1):264. doi: 10.1007/s00018-025-05783-w.
Circadian rhythms regulate key physiological processes through clock genes in central and peripheral tissues. While circadian gene expression during development has been well studied, the temporal dynamics of metabolism across tissues remain less understood. Here, we present the Circadian Ontogenetic Metabolomics Atlas (COMA), which maps circadian metabolic rhythms across 16 rat anatomical structures. The brain (suprachiasmatic nuclei, medial prefrontal cortex) and periphery (liver, plasma) span developmental stages from embryonic E19 to postnatal P2, P10, P20, and P28. Fecal samples include all four postnatal stages, while additional peripheral tissues were analyzed at P20 and P28. Using a multiplatform liquid chromatography-mass spectrometry approach, we annotated 851 metabolites from 1610 samples. We identified distinct circadian shifts, particularly during the transition from nursing to solid food intake (P10-P20), with an average of 24% of metabolites exhibiting circadian oscillations across sample types, as determined by JTK_CYCLE. Our study also underscores the importance of standardized sampling, as metabolite intensities fluctuate with both circadian rhythms and development. COMA serves as an open-access resource ( https://coma.metabolomics.fgu.cas.cz ) for exploring circadian metabolic regulation and its role in developmental biology.
昼夜节律通过中枢和外周组织中的时钟基因调节关键的生理过程。虽然发育过程中的昼夜节律基因表达已得到充分研究，但跨组织代谢的时间动态仍不太清楚。在这里，我们展示了昼夜个体发育代谢组学图谱（COMA），它绘制了16种大鼠解剖结构的昼夜代谢节律。大脑（视交叉上核、内侧前额叶皮质）和外周（肝脏、血浆）涵盖了从胚胎期E19到出生后P2、P10、P20和P28的发育阶段。粪便样本包括所有四个出生后的阶段，而其他外周组织在P20和P28进行分析。使用多平台液相色谱 - 质谱方法，我们从1610个样本中注释了851种代谢物。我们确定了明显的昼夜变化，特别是在从哺乳到固体食物摄入的过渡期间（P10 - P20），通过JTK_CYCLE确定，平均24%的代谢物在不同样本类型中表现出昼夜振荡。我们的研究还强调了标准化采样的重要性，因为代谢物强度会随昼夜节律和发育而波动。COMA作为一个开放获取资源（https://coma.metabolomics.fgu.cas.cz），用于探索昼夜代谢调节及其在发育生物学中的作用。
