Octopamine enhances oxidative stress resistance through the fasting-responsive transcription factor DAF-16/FOXO in C. elegans

Dietary restriction regimens lead to enhanced stress resistance and extended life span in many species through the regulation of fasting and/or diet-responsive mechanisms. The fasting stimulus is perceived by sensory neurons and causes behavioral and metabolic adaptations. Octopamine (OA), one of the Caenorhabditis elegans neurotransmitters, is involved in behavioral adaptations, and its levels are increased under fasting conditions. However, it remains largely unknown how OA contributes to the fasting responses. In this study, we found that OA administration enhanced organismal resistance to oxidative stress. This enhanced resistance was suppressed by a mutation of the OA receptors, SER-3 and SER-6. Moreover, we found that OA administration promoted the nuclear translocation of DAF-16, the key transcription factor in fasting responses, and that the OA-induced enhancement of stress resistance required DAF-16. Altogether, our results suggest that OA signaling, which is triggered by the absence of food, shifts the organismal state to a more protective one to prepare for environmental stresses.