Effects on Hedonic Feeding, Energy Expenditure and Balance of the Non-opioid Peptide DYN-A_2-17

The dynorphin (DYN) peptide family includes opioid and non-opioid peptides, yet the physiological role of the non-opioid DYN peptides remains poorly understood. Recent evidence shows that administering the non-opioid peptide DYN-A_2-17 into the paraventricular hypothalamic nucleus (PVN) simultaneously increased short-term intake of standard rodent chow and spontaneous physical activity (SPA). The present studies aimed to expand upon the mechanisms and role of DYN-A_2-17 on food intake and energy expenditure. Injection of DYN-A_2-17 in PVN increased SPA, energy expenditure and wheel running in the absence of food. Repeated DYN-A_2-17 injection in PVN increased short-term chow intake, but this effect habituated over time and failed to alter cumulative food intake, body weight or adiposity. Pre-treatment with a CRF receptor antagonist into PVN blocked the effects of DYN-A_2-17 on food intake while injection of DYN-A_2-17 in PVN increased plasma ACTH. Finally, as DYN peptides are co-released with orexin peptides, we compared the effects of DYN-A_2-17 to orexin-A and the opioid peptide DYN-A_1-13 on food choice and intake in PVN when palatable snacks and chow were available. DYN-A_1-13 selectively increased intake of palatable snacks. DYN-A_2-17 and orexin-A decreased palatable snack intake while orexin-A also increased chow intake. These findings demonstrate that the non-opioid peptide DYN-A_2-17 acutely regulates physical activity, energy expenditure and food intake without long-term effects on energy balance. These data also propose different roles of opioid, non-opioid DYN and orexin peptides on food choice and intake when palatable and non-palatable food options are available.