An obligatory role for AgRP neurons in maintaining body temperature during time-restricted feeding

Homeotherms maintain a steady body temperature through thermoregulation, a process critical for survival during fasting, in which the brain has to defend energy-costly body temperature while reducing energy expenditure to conserve energy reserve; however, the neural basis for defending body temperature remains unclear. Here, we demonstrated that AgRP neuron lesion led to lethality during time-restricted feeding on chow but not on HFD, and caused no obvious impact on HFD-induced obesity or obesity-reducing responses to glucagon-like peptide-1 receptor agonism. The lesion disrupted adaptive feeding behaviors during time-restricted feeding and reduced motivational feeding on chow. Notably, the lethality was caused by hypothermia instead of reduced food intake. The lesion also caused failure in body temperature maintenance during acute fasting in cold. Fasting-induced activation in AgRP neurons was abrogated when mice were placed in a warm environment. Our results identify the physiological role for AgRP neurons in defending body temperature during restricted availability of low-calorie diets but dispensable for body weight regulation with food ad libitum.