Entrainment in calorie-restricted mice: conflicting zeitgebers and free-running conditions

Phase-shifting effects of timed calorie restriction were investigated in mice during exposure to a 12:12-h light-dark cycle. Food-anticipatory activity (FAA), the output of a food-entrainable pacemaker, was expressed before the time of feeding whether mice received daily hypocaloric food (3.3 g of chow/day) or normocaloric food (5 g of chow/day) at zeitgeber time (ZT) 2 (ZT12 = lights off). Subsequently, mice were placed in constant darkness and fed ad libitum. The onset of the nocturnal period of locomotor activity was phase advanced by 1 h in calorie-restricted mice compared with normocalorie-fed controls. The phase advance still occurred when FAA was prevented by restraining calorie-restricted mice. Giving hypocaloric food at ZT2, ZT10, ZT14, or ZT22 phase advanced the nocturnal pattern of activity by 1, 3, 1, and 1 h, respectively. After transfer to constant darkness, FAA free ran in parallel with the normal nocturnal period of locomotor activity. A light pulse during the early subjective night phase delayed both components. These results indicate that 1) timed calorie restriction under a light-dark cycle can phase advance the light-entrainable pacemaker with a phase-dependent magnitude, 2) FAA feedback is not crucial for the observed phase advance, and 3) the light-entrainable pacemaker may control the period of the food-entrainable pacemaker in mice fed ad libitum.