Orexin-A signaling in the paraventricular nucleus modulates spontaneous firing of glucose-sensitive neurons and promotes food intake via the NPY pathway in rats

Biochem Biophys Res Commun. 2018 Oct 20;505(1):162-167. doi: 10.1016/j.bbrc.2018.09.091. Epub 2018 Sep 20.

Abstract

Understanding the mechanisms regulating feeding is crucial to unraveling the pathogenesis of obesity. The study primary explored the effects of orexin-A and neuropeptide Y (NPY) signaling in the hypothalamic paraventricular nucleus (PVN) on feeding and glucose-sensitive (GS) neuron activity in rats. Microinjection of orexin-A into the PVN promoted feeding and modulated the spontaneous firing of GS neurons. Those effects were eliminated by pre-injection of the orexin-A receptor-1 (OX1R) antagonist SB-334867 and weaken by the NPY-1 receptor (NPY-1R) antagonist BMS-193885. After orexin-A administration into the PVN, the number of c-fos cells in the arcuate nucleus (ARC) was significantly higher than that in the group receiving normal saline. Furthermore, most cells exhibited co-expression of NPY and c-fos, indicating activation of NPY neurons in the ARC by PVN-administered orexin-A, which might be involved in feeding regulation. These findings indicate that orexin-A and NPY signaling in the PVN are essential to regulating GS neuronal excitability and feeding in rats.

Keywords: Food intake; Glucose-sensitive neurons; Hypothalamus paraventricular nucleus; NPY-1 receptor; Orexin-A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazoles / pharmacology
  • Dihydropyridines / pharmacology
  • Eating / drug effects*
  • Glucose / pharmacology*
  • Male
  • Naphthyridines
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / physiology
  • Neuropeptide Y / metabolism*
  • Orexin Receptors / genetics
  • Orexin Receptors / metabolism
  • Orexins / administration & dosage
  • Orexins / pharmacology*
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Phenylurea Compounds / pharmacology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats, Sprague-Dawley
  • Receptors, Neuropeptide Y / antagonists & inhibitors
  • Receptors, Neuropeptide Y / metabolism
  • Signal Transduction / drug effects
  • Urea / analogs & derivatives
  • Urea / pharmacology

Substances

  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • BMS 193885
  • Benzoxazoles
  • Dihydropyridines
  • Naphthyridines
  • Neuropeptide Y
  • Orexin Receptors
  • Orexins
  • Phenylurea Compounds
  • Proto-Oncogene Proteins c-fos
  • Receptors, Neuropeptide Y
  • Urea
  • Glucose