Role of the non-opioid dynorphin peptide des-Tyr-dynorphin (DYN-A2−17) in food intake and physical activity, and its interaction with orexin-A.

• des-Tyr-dynorphin (DYN-A2−17) is a non-opioid dynorphin peptide.
• Whether DYN-A2−17 has a role in energy balance is unknown.
• DYN-A2−17 injected into PVN increases food intake and locomotor activity.
• Co-injection of orexin-A and DYN-A2−17 increased food intake further compared to each peptide alone.
• This study shows a novel function of DYN-A2−17 in regulating behaviors related to energy balance.

Food intake and physical activity are regulated by multiple neuropeptides, including orexin and dynorphin (DYN). Orexin-A (OXA) is one of two orexin peptides with robust roles in regulation of food intake and spontaneous physical activity (SPA). DYN collectively refers to several peptides, some of which act through opioid receptors (opioid DYN) and some whose biological effects are not mediated by opioid receptors (non-opioid DYN). While opioid DYN is known to increase food intake, the effects of non-opioid DYN peptides on food intake and SPA are unknown. Neurons that co-express and release OXA and DYN are located within the lateral hypothalamus. Limited evidence suggests that OXA and opioid DYN peptides can interact to modulate some aspects of behaviors classically related to orexin peptide function. The paraventricular hypothalamic nucleus (PVN) is a brain area where OXA and DYN peptides might interact to modulate food intake and SPA. We demonstrate that injection of des-Tyr-dynorphin (DYN-A2−17, a non opioid DYN peptide) into the PVN increases food intake and SPA in adult mice. Co-injection of DYN-A2−17 and OXA in the PVN further increases food intake compared to DYN-A2−17 or OXA alone. This is the first report describing the effects of non-opioid DYN-A2−17 on food intake and SPA, and suggests that DYN-A2−17 interacts with OXA in the PVN to modulate food intake. Our data suggest a novel function for non-opioid DYN-A2−17 on food intake, supporting the concept that some behavioral effects of the orexin neurons result from combined actions of the orexin and DYN peptides.