DEVELOPMENTAL AND CIRCADIAN METABOLIC LANDSCAPE: AN INTERACTIVE ATLAS DERIVED FROM RAT PLASMA, TISSUE, AND FECAL METABOLOMICS

• Dr. Leila P. Mendes

  Department of Physiology, University of Cape Town, South Africa

  Author

• Dr. Farid A. Khan

  Department of Biochemistry, Cairo University, Egypt

  Author

Imagine your body running on a finely tuned internal clock, guiding everything from when you feel sleepy to how your cells process energy. These are circadian rhythms, and they're deeply connected to your metabolism. While we've learned a lot about how these internal clocks develop, we still don't fully understand how the vast network of tiny molecules in our bodies – our metabolome – changes as we grow up and throughout each day. This study set out to fill that gap. We built a groundbreaking interactive atlas using rats, looking at their development from early life (P7, P14, P21, P35, P70) and tracking their metabolic changes every four hours over a full 24-hour cycle. We examined plasma, various tissues (like the liver, kidney, muscles, fat, and different brain areas), and even their feces. Using advanced liquid chromatography-mass spectrometry (LC-MS) techniques, we identified over 1,500 unique metabolites. Our findings show that a significant part of the metabolome truly dances to a circadian beat, but how these rhythms emerge and mature changes distinctly with age and across different body parts. For instance, rhythms in peripheral tissues were quieter in early life, growing stronger as the rats got older, much like how our own internal clocks mature. We also saw age-related shifts in the timing and strength of plasma fat rhythms and discovered major developmental changes in metabolites that weren't tied to daily cycles, especially in fecal samples. Crucially, our atlas highlights specific metabolites whose daily rhythms are directly influenced by the rat's age, showing a fascinating interplay between growing up and our internal timing. We've also created an interactive website, following "FAIR" principles (making data Findable, Accessible, Interoperable, and Reusable), giving researchers an easy-to-use platform to explore this rich dataset. This includes dynamic graphs, heatmaps, powerful search tools, and integrated pathway analysis. This atlas is a unique resource, offering vital insights into how our bodies maintain metabolic balance throughout life and setting the stage for future research into how our biological clocks impact health and disease.

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