| First Author | Martinez de Morentin PB | Year | 2024 |
| Journal | Curr Biol | Volume | 34 |
| Issue | 8 | Pages | 1646-1656.e4 |
| PubMed ID | 38518777 | Mgi Jnum | J:349706 |
| Mgi Id | MGI:7627828 | Doi | 10.1016/j.cub.2024.02.074 |
| Citation | Martinez de Morentin PB, et al. (2024) A brainstem to hypothalamic arcuate nucleus GABAergic circuit drives feeding. Curr Biol 34(8):1646-1656.e4 |
| abstractText | The obesity epidemic is principally driven by the consumption of more calories than the body requires. It is therefore essential that the mechanisms underpinning feeding behavior are defined. Neurons within the brainstem dorsal vagal complex (DVC) receive direct information from the digestive system and project to second-order regions in the brain to regulate food intake. Although gamma-aminobutyric acid is expressed in the DVC (GABA(DVC)), its function in this region has not been defined. In order to discover the unique gene expression signature of GABA(DVC) cells, we used single-nucleus RNA sequencing (Nuc-seq), and this revealed 19 separate clusters. We next probed the function of GABA(DVC) cells and discovered that the selective activation of GABA(DVC) neurons significantly controls food intake and body weight. Optogenetic interrogation of GABA(DVC) circuitry identified GABA(DVC) --> hypothalamic arcuate nucleus (ARC) projections as appetite suppressive without creating aversion. Electrophysiological analysis revealed that GABA(DVC) --> ARC stimulation inhibits hunger-promoting neuropeptide Y (NPY) neurons via GABA release. Adopting an intersectional genetics strategy, we clarify that the GABA(DVC) --> ARC circuit curbs food intake. These data identify GABA(DVC) as a new modulator of feeding behavior and body weight and a controller of orexigenic NPY neuron activity, thereby providing insight into the neural underpinnings of obesity. |
