title: Endogenous Glucagon-like Peptide-1 Receptor Signaling in the Nucleus Tractus Solitarius is Required for Food Intake Control.
abstract: 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.
authors: Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.|Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.|Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors: Amber L
authors: AL
authors: Alhadeff
authors: Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
authors: Blake D
authors: BD
authors: Mergler
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors: Derek J
authors: DJ
authors: Zimmer
authors: Department of Biobehavioral Health Sciences, University of Pennsylvania, Philadelphia, PA, USA.
authors: Christopher A
authors: CA
authors: Turner
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors: David J
authors: DJ
authors: Reiner
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.|Department of Biobehavioral Health Sciences, University of Pennsylvania, Philadelphia, PA, USA.
authors: Heath D
authors: HD
authors: Schmidt
authors: Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
authors: Harvey J
authors: HJ
authors: Grill
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors: Matthew R
authors: MR
authors: Hayes
mesh_terms: D000256:Adenoviridae; D000818:Animals; D003216:Conditioning, Operant / Q000502:physiology; D004435:Eating / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008297:Male; D009042:Motivation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D015398:Signal Transduction / Q000502:physiology*; D017552:Solitary Nucleus / Q000378:metabolism*
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor