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Cell Rep. 2015 Aug 4;12(5):726-33. doi: 10.1016/j.celrep.2015.06.062. Epub 2015 Jul 23.

Endogenous Glucagon-like Peptide-1 Suppresses High-Fat Food Intake by Reducing Synaptic Drive onto Mesolimbic Dopamine Neurons.

Author information

1
Child Health Institute of New Jersey, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
2
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.

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.

PMID:
26212334
PMCID:
PMC4860285
DOI:
10.1016/j.celrep.2015.06.062
[Indexed for MEDLINE]
Free PMC Article

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