title: Endogenous Glucagon-like Peptide-1 Suppresses High-Fat Food Intake by Reducing Synaptic Drive onto Mesolimbic Dopamine Neurons.
abstract: Glucagon-like peptide-1 (GLP-1) and its analogs act as appetite suppressants and have been proven to be clinically efficacious in reducing body weight in obese individuals. Central GLP-1 is expressed in a small population of brainstem cells located in the nucleus tractus solitarius (NTS), which project to a wide range of brain areas. However, it remains unclear how endogenous GLP-1 released in the brain contributes to appetite regulation. Using chemogenetic tools, we discovered that central GLP-1 acts on the midbrain ventral tegmental area (VTA) and suppresses high-fat food intake. We used integrated pathway tracing and synaptic physiology to further demonstrate that activation of GLP-1 receptors specifically reduces the excitatory synaptic strength of dopamine (DA) neurons within the VTA that project to the nucleus accumbens (NAc) medial shell. These data suggest that GLP-1 released from NTS neurons can reduce highly palatable food intake by suppressing mesolimbic DA signaling.
authors.affiliation: Child Health Institute of New Jersey, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Child Health Institute of New Jersey, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: Child Health Institute of New Jersey, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Xia
authors.affiliation: Child Health Institute of New Jersey, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
authors.affiliation: Child Health Institute of New Jersey, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mirabella
authors.affiliation: Child Health Institute of New Jersey, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA; Department of Neuroscience and Cell Biology, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA; Department of Pediatrics, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA. Electronic address: zhiping.pang@rutgers.edu.
authors.forename: Zhiping P
authors.initials: ZP
authors.lastname: Pang
mesh_terms: D000818:Animals; D004041:Dietary Fats; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D052216:Glucagon-Like Peptide 1