Dorsomedial hypothalamic NPY affects cholecystokinin-induced satiety via modulation of brain stem catecholamine neuronal signaling.

Abstract

Increased neuropeptide Y (NPY) gene expression in the dorsomedial hypothalamus (DMH) has been shown to cause hyperphagia, but the pathway underlying this effect remains less clear. Hypothalamic neural systems play a key role in the control of food intake, in part, by modulating the effects of meal-related signals, such as cholecystokinin (CCK). An increase in DMH NPY gene expression decreases CCK-induced satiety. Since activation of catecholaminergic neurons within the nucleus of solitary tract (NTS) contributes to the feeding effects of CCK, we hypothesized that DMH NPY modulates NTS neural catecholaminergic signaling to affect food intake. We used an adeno-associated virus system to manipulate DMH NPY gene expression in rats to examine this pathway. Viral-mediated hrGFP anterograde tracing revealed that DMH NPY neurons project to the NTS; the projections were in close proximity to catecholaminergic neurons, and some contained NPY. Viral-mediated DMH NPY overexpression resulted in an increase in NPY content in the NTS, a decrease in NTS tyrosine hydroxylase (TH) expression, and reduced exogenous CCK-induced satiety. Knockdown of DMH NPY produced the opposite effects. Direct NPY administration into the fourth ventricle of intact rats limited CCK-induced satiety and overall TH phosphorylation. Taken together, these results demonstrate that DMH NPY descending signals affect CCK-induced satiety, at least in part, via modulation of NTS catecholaminergic neuronal signaling.

• Authors: Claire B de La Serre, Yonwook J Kim, Timothy H Moran, Sheng Bi
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 311 Issue 5 Pg. R930-R939 (11 01 2016) ISSN: 1522-1490 [Electronic] United States
• PMID: 27534875 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2016 the American Physiological Society.

Chemical References

• Catecholamines
• Cholagogues and Choleretics
• Neuropeptide Y
• Cholecystokinin

Topics

• Animals
• Brain Stem (drug effects, physiology)
• Catecholamines (metabolism)
• Cholagogues and Choleretics (administration & dosage, pharmacology)
• Cholecystokinin (administration & dosage, pharmacology)
• Dorsomedial Hypothalamic Nucleus (drug effects, physiology)
• Dose-Response Relationship, Drug
• Eating (drug effects, physiology)
• Male
• Neurons (drug effects, physiology)
• Neuropeptide Y (metabolism)
• Rats
• Rats, Sprague-Dawley
• Satiety Response (drug effects, physiology)
• Synaptic Transmission (physiology)