Feeding-State-Dependent Modulation of Temperature Preference Requires Insulin Signaling in Drosophila Warm-Sensing...

Starvation is life-threatening and therefore strongly modulates many aspects of animal behavior and physiology [1]. In mammals, hunger causes a reduction in body temperature and metabolism [2], resulting in conservation of energy for survival. However, the molecular basis of the modulation of thermoregulation by starvation remains largely unclear. Whereas mammals control their body temperature internally, small ectotherms, such as Drosophila, set their body temperature by selecting an ideal environmental temperature through temperature preference behaviors [3, 4]. Here, we demonstrate in Drosophila that starvation results in a lower preferred temperature, which parallels the reduction in body temperature in mammals. The insulin/insulin-like growth factor (IGF) signaling (IIS) pathway is involved in starvation-induced behaviors and physiology and is well conserved in vertebrates and invertebrates [5-7]. We show that insulin-like peptide 6 (Ilp6) in the fat body (fly liver and adipose tissues) is responsible for the starvation-induced reduction in preferred temperature (T_p). Temperature preference behavior is controlled by the anterior cells (ACs), which respond to warm temperatures via transient receptor potential A1 (TrpA1) [4]. We demonstrate that starvation decreases the responding temperature of ACs via insulin signaling, resulting in a lower T_p than in nutrient-rich conditions. Thus, we show that hunger information is conveyed from fat tissues via Ilp6 and influences the sensitivity of warm-sensing neurons in the brain, resulting in a lower temperature set point. Because starvation commonly results in a lower body temperature in both flies and mammals, we propose that insulin signaling is an ancient mediator of starvation-induced thermoregulation.