Daily meal timing is not necessary for resetting the main circadian clock by calorie restriction

In rodents, entrainment and/or resetting by feeding of the central circadian clock, the suprachiasmatic nucleus (SCN), is more efficient when food cues arise from a timed calorie restriction. Because timed calorie restriction is associated with a single meal each day at the same time, its resetting properties on the SCN possibly depend on a combination of meal time-giving cues and hypocaloric conditions per se. To exclude any effect of daily meal timing in resetting by calorie restriction, the present study employed a model of ultradian feeding schedules, divided into six meals with different durations of food access (6 x 8-min versus 6 x 12-min meal schedule) every 4 h over the 24-h cycle. The effects of such an ultradian calorie restriction were evaluated on the rhythms of wheel-running activity (WRA) and body temperature (Tb) in rats. The results indicate that daily/circadian rhythms of WRA and Tb were shifted by a hypocaloric feeding distributed in six ultradian short meals (i.e. 6 x 8-min meal schedule), showing both phase advances and delays. The magnitude of phase shifts was positively correlated with body weight loss and level of day-time behavioural activity. By contrast, rats fed daily with six ultradian meals long enough (i.e. 6 x 12-min meal schedule) to prevent body weight loss, showed only small, if any, phase shifts in WRA and Tb rhythms. The results obtained reveal the potency of calorie restriction to reset the SCN clock without synchronisation to daily meal timing, highlighting functional links between metabolism, calorie restriction and the circadian timing system.