| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2041051 | Cell Reports | 2015 | 8 Pages |
•NTS GLP-1 neuron activation suppresses food intake•Activation of GLP-1 terminals in the VTA suppresses high-fat diet intake•GLP-1 specifically decreases excitatory synaptic input in mesolimbic DA neurons
SummaryGlucagon-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.
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