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

• DOI: 10.1016/j.celrep.2015.06.062
• Publication Date: 2015-07-23T16:30:29Z
• Authors: Xue-Feng Wang; Jing-Jing Liu; Julia Xia; Ji Liu; Vincent Mirabella; Zhiping P. Pang
• Keywords: 2. Zero hunger; 0301 basic medicine; QH301-705.5; Dopaminergic Neurons; Ventral Tegmental Area; Mice, Transgenic; Dietary Fats; Nucleus Accumbens; Eating; Mice; 03 medical and health sciences; Glucagon-Like Peptide 1; Synapses; Animals; Biology (General); Signal Transduction

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.