Endogenous Glucagon-like Peptide-1 Receptor Signaling in the Nucleus Tractus Solitarius is Required for Food Intake Control

Alhough the glucagon-like peptide-1 (GLP-1) system is critical to energy balance control and is a target for obesity pharmacotherapies, the receptor-population-mediating effects of endogenous GLP-1 signaling are not fully understood. To address this, we developed a novel adeno-associated virus (AAV-...

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Published inNeuropsychopharmacology (New York, N.Y.) Vol. 42; no. 7; pp. 1471 - 1479
Main Authors Alhadeff, Amber L, Mergler, Blake D, Zimmer, Derek J, Turner, Christopher A, Reiner, David J, Schmidt, Heath D, Grill, Harvey J, Hayes, Matthew R
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.06.2017
Subjects
Adenoviridae
Animals
Conditioning, Operant - physiology
Eating - physiology
Energy
Food
Glucagon
Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors
Glucagon-Like Peptide-1 Receptor - biosynthesis
Laboratories
Male
Motivation - physiology
Original
Peptides
Rats
Rats, Sprague-Dawley
Self Administration
Signal Transduction - physiology
Solitary Nucleus - metabolism
Weight control
United States > US
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Summary:Alhough the glucagon-like peptide-1 (GLP-1) system is critical to energy balance control and is a target for obesity pharmacotherapies, the receptor-population-mediating effects of endogenous GLP-1 signaling are not fully understood. To address this, we developed a novel adeno-associated virus (AAV-GLP-1R) that utilizes short hairpin RNA to chronically knock down GLP-1 receptors (GLP-1R) in rats. As pharmacological studies highlight the hindbrain nucleus tractus solitarius (NTS) as a brain region important for GLP-1R-mediated effects on energy balance, AAV-GLP-1R was injected into the NTS to examine the role of endogenous NTS GLP-1R signaling in energy balance control. Chow intake and meal size were significantly increased following chronic NTS GLP-1R knockdown. In addition, NTS GLP-1R knockdown significantly increased self-administration of palatable food under both fixed and progressive ratio schedules of reinforcement. Collectively, these data demonstrate that endogenous NTS GLP-1R signaling is required for the control of food intake and motivation to feed, and provide a new strategy to investigate the importance of distinct GLP-1R populations in the control of a variety of functions.
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ISSN:0893-133X
1740-634X
DOI:10.1038/npp.2016.246