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.

• Klíčová slova
• Atlas, Circadian rhythm, Lipidomics, Metabolomics, Resource,
• MeSH
• chromatografie kapalinová MeSH
• cirkadiánní rytmus * fyziologie   MeSH
• feces * chemie   MeSH
• játra metabolismus   MeSH
• krysa rodu Rattus MeSH
• metabolom * MeSH
• metabolomika * metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND/OBJECTIVE: Adaptation to the extrauterine environment depends on a switch from glycolysis to catabolism of fatty acids (FA) provided as milk lipids. We sought to learn whether the postnatal induction of muscle FA oxidation in mice could reflect propensity to obesity and to characterize the mechanisms controlling this induction. METHODS: Experiments were conducted using obesity-resistant A/J and obesity-prone C57BL/6J (B6) mice maintained at 30 °C, from 5 to 28 days after birth. At day 10, both A/J and B6 mice with genetic ablation (KO) of α2 subunit of AMP-activated protein kinase (AMPK) were also used. In skeletal muscle, expression of selected genes was determined using quantitative real-time PCR, and AMPK subunits content was evaluated using Western blotting. Activities of both AMPK and pyruvate dehydrogenase (PDH), as well as acylcarnitine levels in the muscle were measured. RESULTS: Acylcarnitine levels and gene expression indicated transient increase in FA oxidation during the first 2 weeks after birth, with a stronger increase in A/J mice. These data correlated with (i) the surge in plasma leptin levels, which peaked at day 10 and was higher in A/J mice, and (ii) relatively low activity of PDH linked with up-regulation of PDH kinase 4 gene (Pdk4) expression in the 10-day-old A/J mice. In contrast with the Pdk4 expression, transient up-regulation of uncoupling protein 3 gene was observed in B6 but not A/J mice. AMPK activity changed during the development, without major differences between A/J and B6 mice. Expression of neither Pdk4 nor other muscle genes was affected by AMPK-KO. CONCLUSIONS: Our results indicate a relatively strong postnatal induction of FA oxidation in skeletal muscle of the obesity-resistant A/J mice. This induction is transient and probably results from suppression of PDH activity, linked with a postnatal surge in plasma leptin levels, independent of AMPK.

• MeSH
• kosterní svaly metabolismus   MeSH
• mastné kyseliny metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• novorozená zvířata MeSH
• obezita metabolismus   MeSH
• oxidace-redukce MeSH
• proteinkinasy aktivované AMP * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mastné kyseliny MeSH
• Prkaa2 protein, mouse MeSH Prohlížeč
• proteinkinasy aktivované AMP * MeSH