title: GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake.
abstract: Central glucagon-like-peptide-1 (GLP-1) receptor activation reduces food intake; however, brain nuclei and mechanism(s) mediating this effect remain poorly understood. Although central nervous system GLP-1 is produced almost exclusively in the nucleus of the solitary tract in the hindbrain, GLP-1 receptors (GLP-1R) are expressed throughout the brain, including nuclei in the mesolimbic reward system (MRS), e.g. the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Here, we examine the MRS as a potential site of action for GLP-1-mediated control of food intake and body weight. Double immunohistochemistry for Fluorogold (monosynaptic retrograde tracer) and GLP-1 neuron immunoreactivity indicated that GLP-1-producing nucleus tractus solitarius neurons project directly to the VTA, the NAc core, and the NAc shell. Pharmacological data showed that GLP-1R activation in the VTA, NAc core, and NAc shell decreased food intake, especially of highly-palatable foods, and body weight. Moreover, blockade of endogenous GLP-1R signaling in the VTA and NAc core resulted in a significant increase in food intake, establishing a physiological relevance for GLP-1 signaling in the MRS. Current data highlight these nuclei within the MRS as novel sites for GLP-1R-mediated control of food intake and body weight.
authors: Department of Psychiatry, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors: Amber L
authors: AL
authors: Alhadeff
authors: Laura E
authors: LE
authors: Rupprecht
authors: Matthew R
authors: MR
authors: Hayes
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000502:physiology*; D000077270:Exenatide; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D017552:Solitary Nucleus / Q000166:cytology*; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000166:cytology*
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide