Martinez de Morentin, P.B. orcid.org/0000-0002-0684-3215, Gonzalez, J.A. orcid.org/0000-0001-7045-4831, Dowsett, G.K.C. orcid.org/0000-0002-2134-8554 et al. (4 more authors) (2024) A brainstem to hypothalamic arcuate nucleus GABAergic circuit drives feeding. Current Biology, 34. ISSN 0960-9822
Abstract
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 γ-aminobutyric acid is expressed in the DVC (GABADVC), its function in this region has not been defined. In order to discover the unique gene expression signature of GABADVC cells, we used single-nucleus RNA sequencing (Nuc-seq), and this revealed 19 separate clusters. We next probed the function of GABADVC cells and discovered that the selective activation of GABADVC neurons significantly controls food intake and body weight. Optogenetic interrogation of GABADVC circuitry identified GABADVC → hypothalamic arcuate nucleus (ARC) projections as appetite suppressive without creating aversion. Electrophysiological analysis revealed that GABADVC → ARC stimulation inhibits hunger-promoting neuropeptide Y (NPY) neurons via GABA release. Adopting an intersectional genetics strategy, we clarify that the GABADVC → ARC circuit curbs food intake. These data identify GABADVC 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). Published by Elsevier. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | hunger; body weight; gamma-aminobutyric acid; neuropeptide Y; nucleus of the solitary tract; dorsal vagal complex; hypothalamus; food intake; obesity |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Apr 2024 14:01 |
Last Modified: | 05 Apr 2024 14:01 |
Status: | Published |
Publisher: | Elsevier BV |
Identification Number: | 10.1016/j.cub.2024.02.074 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:211194 |