Effects on Hedonic Feeding, Energy Expenditure and Balance of the Non-opioid Peptide DYN-A 2-17

Neuroscience. 2018 Feb 10;371:337-345. doi: 10.1016/j.neuroscience.2017.11.044. Epub 2017 Dec 2.

Abstract

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-A2-17 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-A2-17 on food intake and energy expenditure. Injection of DYN-A2-17 in PVN increased SPA, energy expenditure and wheel running in the absence of food. Repeated DYN-A2-17 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-A2-17 on food intake while injection of DYN-A2-17 in PVN increased plasma ACTH. Finally, as DYN peptides are co-released with orexin peptides, we compared the effects of DYN-A2-17 to orexin-A and the opioid peptide DYN-A1-13 on food choice and intake in PVN when palatable snacks and chow were available. DYN-A1-13 selectively increased intake of palatable snacks. DYN-A2-17 and orexin-A decreased palatable snack intake while orexin-A also increased chow intake. These findings demonstrate that the non-opioid peptide DYN-A2-17 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.

Keywords: dynorphin; energy expenditure; exercise; food intake; hedonic food intake; orexin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / drug effects
  • Adiposity / physiology
  • Adrenocorticotropic Hormone / blood
  • Animals
  • Body Weight / drug effects
  • Body Weight / physiology
  • Central Nervous System Agents / pharmacology*
  • Choice Behavior / drug effects
  • Choice Behavior / physiology
  • Dynorphins / pharmacology*
  • Energy Metabolism / drug effects*
  • Energy Metabolism / physiology
  • Feeding Behavior / drug effects*
  • Feeding Behavior / physiology
  • Male
  • Mice, Inbred BALB C
  • Orexins / metabolism
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Peptide Fragments / pharmacology*
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • Running* / physiology

Substances

  • Central Nervous System Agents
  • Orexins
  • Peptide Fragments
  • Receptors, Corticotropin-Releasing Hormone
  • Dynorphins
  • dynorphin (2-17)
  • Adrenocorticotropic Hormone