Orexin neurons are indispensable for prostaglandin E2‐induced fever and defence against environmental cooling in mice

• We recently showed that orexin neurons in the hypothalamus are indispensable for stress-induced thermogenesis. • In this study we examined whether the orexin neurons are also important for other forms of thermogenic processes, including brain prostaglandin E2 (PGE2) injection that mimics inflammatory fever and environmental cold exposure. • As was the case with stress-induced thermogenesis, orexin neuron-ablated (ORX-AB) mice exhibited a blunted PGE2-induced fever and intolerance to cold (5 ◦ C) exposure. • Injection of retrograde tracer into the medullary raphe nucleus, where sympathetic premotor neurons regulating thermogenesis by the brown adipose tissue are located, revealed direct and indirect projection from the orexin neurons, of which the latter seemed to be preserved in the ORX-AB mice. • These results suggest that orexin neurons are important in general thermogenic processes, and their importance is not restricted to stress-induced thermogenesis.