Nejvíce citovaný článek - PubMed ID 39801395
Chronodisruption that dampens output of the central clock abolishes rhythms in metabolome profiles and elevates acylcarnitine levels in the liver of female rats
The ontogenesis of the circadian clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and its sensitivity to maternal signals are not fully understood. Here, we investigated the development of the clock in the rat SCN from the fetal to the postweaning period and identified rhythmic metabolic signals from the mother to the fetal SCN. We determined daily expression profiles of clock genes (Per2, Nr1d1, Bmal1) and clock- and metabolism-related genes (Dbp, E4bp4) and performed time-resolved analysis of the metabolome and lipidome in the SCN and plasma of 19-day-old embryos (E19) and 2-, 10-, 20-, and 28-day-old pups (P02-28). Our data show that rhythms in the expression of canonical clock genes are absent at E19 and develop gradually until P10, but the Dbp rhythm was still developing between P20 and P28. Expression of the metabolism-sensitive gene E4bp4 and levels of essential amino acids and other metabolites supplied by maternal food are rhythmic in the fetal SCN, which is lost after birth at P02 and reappears later in the postnatal period. Maternal food-derived metabolites were also rhythmic in fetal plasma. The temporal coherence of the fetal SCN metabolome and lipidome declines markedly and its rhythmicity disappears immediately after birth. The results revealed previously unforeseen pathways by which the fetal SCN may receive rhythmic information from the mother before its clock develops.
- MeSH
- cirkadiánní hodiny * fyziologie genetika MeSH
- cirkadiánní proteiny Period genetika metabolismus MeSH
- cirkadiánní rytmus fyziologie MeSH
- krysa rodu Rattus MeSH
- metabolom MeSH
- nucleus suprachiasmaticus * metabolismus embryologie fyziologie MeSH
- proteiny CLOCK genetika metabolismus MeSH
- těhotenství MeSH
- transkripční faktory ARNTL genetika metabolismus MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cirkadiánní proteiny Period MeSH
- proteiny CLOCK MeSH
- transkripční faktory ARNTL MeSH