Faculty Collaboration Database

Acute Blockade of PACAP-Dependent Activity in the Ventromedial Nucleus of the Hypothalamus Disrupts Leptin-Induced Behavioral and Molecular Changes in Rats. Neuroendocrinology 2020;110(3-4):271-281

Date

06/06/2019

Pubmed ID

31167202

Pubmed Central ID

PMC6895395

DOI

10.1159/000501337

Scopus ID

2-s2.0-85081162094 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

Leptin signaling pathways, stemming primarily from the hypothalamus, are necessary for maintaining normal energy homeostasis and body weight. In both rodents and humans, dysregulation of leptin signaling leads to morbid obesity and diabetes. Since leptin resistance is considered a primary factor underlying obesity, understanding the regulation of leptin signaling could lead to therapeutic tools and provide insights into the causality of obesity. While leptin actions in some hypothalamic regions such as the arcuate nuclei have been characterized, less is known about leptin activity in the hypothalamic ventromedial nuclei (VMN). Recently, pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to reduce feeding behavior and alter metabolism when administered into the VMN in a pattern similar to that of leptin. In the current study, we examined whether leptin and PACAP actions in the VMN share overlapping pathways in the regulation of energy balance. Interestingly, PACAP administration into the VMN increased STAT3 phosphorylation and SOCS3 mRNA expression, both of which are hallmarks of leptin receptor activation. In addition, BDNF mRNA expression in the VMN was increased by both leptin and PACAP administration. Moreover, antagonizing PACAP receptors fully reversed the behavioral and cellular effects of leptin injections into the VMN. Electrophysiological studies further illustrated that leptin-induced effects on VMN neurons were blocked by antagonizing PACAP receptors. We conclude that leptin dependency on PACAP signaling in the VMN suggests a potential common signaling cascade, allowing a tonically and systemically secreted neuropeptide to be more precisely regulated by central neuropeptides.

Author List

Hurley MM, Anderson EM, Chen C, Maunze B, Hess EM, Block ME, Patel N, Cooper Z, McCoy R, Dabra T, Conley W, Reilly MJ, Hearing M, Choi S

Author

Sujean Choi PhD in the School of Allied Health department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Behavior, Animal
Body Temperature Regulation
Brain-Derived Neurotrophic Factor
Eating
Leptin
Male
Pituitary Adenylate Cyclase-Activating Polypeptide
Rats
Rats, Sprague-Dawley
STAT3 Transcription Factor
Signal Transduction
Ventromedial Hypothalamic Nucleus