Functional characterization of an orexin neuropeptide in amphioxus reveals an ancient origin of orexin/orexin receptor system in chordate.

Amphioxus belongs to the subphylum cephalochordata, an extant representative of the most basal chordates, whose regulation of endocrine system remains ambiguous. Here we clearly demonstrated the existence of a functional orexin neuropeptide in amphioxus, which is able to interact with orexin receptor, activate both PKC and PKA pathways, decrease leptin expression, and stimulate lipogenesis. We also showed the transcription level of amphioxus orexin was affected by fasting or temperature, indicating a role of this gene in the regulation of energy balance. In addition, the expression of the amphioxus orexin was detected at cerebral vesicle, which has been proposed to be a homolog of the vertebrate brain. These data collectively suggest that a functional orexin neuropeptide has already emerged in amphioxus, which provide insights into the evolutionary origin of orexin in chordate and the functional homology between the cerebral vesicle and vertebrate brain.