Lesions of glucose-responsive neurons impair synchronizing effects of calorie restriction in mice

Calorie restriction can induce phase-advances of daily rhythms in rodents exposed to light-dark cycles. To test whether glucose-responsive neurons are involved in the synchronizing effects of calorie restriction, C57BL/6J mice were injected with gold-thioglucose (GTG; 0.6 g/kg) which damages glucose-responsive neurons, primarily located in the ventromedial hypothalamus. From the day of injection, GTG-treated and control mice received a hypocaloric diet (66% of ad libitum food intake) 2 h after lights on. When mice were transferred to constant darkness after 4 weeks and fed ad libitum, the onset of circadian rhythm of locomotor activity was phase-advanced by 1 h in control but not in GTG-treated mice. Therefore, glucose-responsive neurons in the ventromedial hypothalamus may play a role in the synchronizing effects of calorie restriction on circadian rhythmicity.