The clock is running Effects of timed exercise and food intake on the circadian timing system in the rat

Circadian misalignment, a condition in which internal biological rhythms fall out of sync with the external 24-hour cycle, disrupts metabolic homeostasis and increases the risk of metabolic disorders such as obesity and type 2 diabetes. In this thesis, we investigated how the timing of feeding and physical activity influences daily rhythms of peripheral clock gene expression and systemic metabolism, using melatonin-proficient Wistar rats. Using time-restricted feeding (TRF) and/or time-restricted running (TRR), we explored strategies to realign tissue-specific clocks, particularly in the liver and skeletal muscle, and improve metabolic health.
Initial findings showed that while TRF during the rest phase shifted liver clock rhythms, it disrupted skeletal muscle rhythms, suggesting tissue desynchrony contributes to impaired glucose metabolism. TRR during the rest phase did not shift the liver or muscle clock, but combining TRR with TRF successfully shifter and aligned liver and muscle clocks. Notably, dark-phase TRR and TRF produced the most favourable metabolic outcomes, while misaligned activity (light-phase TRR) had detrimental effects.
Subsequent experiments revealed that high-fat diets (HFD) disrupted clock synchrony and attenuated TRRxTRF benefits, emphasizing the importance of dietary context. TRR also improved insulin action without significantly altering glucose tolerance or the daily rhythm of body temperature. Moreover, voluntary wheel running influenced ΔFOSB expression in the suprachiasmatic nucleus (SCN), with sex differences and estradiol modulation suggesting hormonal effects on central clock plasticity.
In conclusion, optimal circadian alignment of feeding and activity behaviors, alongside dietary considerations, is critical for maintaining metabolic health and guiding circadian-based interventions for metabolic disorders.