Influence of feeding time on daily rhythms of locomotor activity, clock genes, and epigenetic mechanisms in the liver and hypothalamus of the European sea bass (Dicentrarchus labrax).

The circadian system plays a crucial role in most physiological processes. The molecular clock is linked to epigenetic mechanisms, both of which are influenced by nutrient status and, consequently, to feeding. This research investigated how feeding times (mid-light, ML, vs. mid-dark, MD) synchronize daily rhythms of behavior, clock genes, and epigenetic mechanisms in the European sea bass (Dicentrarchus labrax), focusing on hypothalamus and liver to assess the impact on central and peripheral pacemakers. Feeding at MD influenced the molecular clock of the hypothalamus, causing shifts in acrophases (peaks) for genes of the negative loop (per1b, per2, cry1a). In the liver, the ML fed group showed rhythmic expression for all clock genes, whereas only per2 maintained the rhythms in the MD group. Epigenetic genes related to methylation (dnmt1, dnmt3a) and demethylation (tet2, gadd45aa, mbd4) in the liver displayed rhythmic expression in the ML group, but only dnmt3a maintained the rhythm in the MD group. Nutrient-related factors (SAM and SAH) showed differences between day and night, suggesting a different utilization based on feeding times. Finally, sirt1, a gene involved in deacetylation, displayed a clear daily rhythm in the ML group. All epigenetic genes peaked during the night (resting phase). Overall, these findings indicated feeding time serves as a potent zeitgeber, synchronizing circadian clock and epigenetic rhythms in the liver, with peaks during the resting phase, suggesting this phase represents the adequate time for epigenetic modifications.