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. The brainstem nucleus of the solitary tract (NTS) receives direct information from the digestive system and projects to second order regions including the arcuate nucleus of the hypothalamus (ARC). Here we reveal that selective activation of NTS γ-Aminobutyric acid (GABANTS) neurons is sufficient to significantly control food intake and body weight. Optogenetic interrogation of GABANTS circuitry identified GABANTS→ARC projections as appetite suppressive without creating aversion. Electrophysiological analysis revealed GABANTS→ARC stimulation inhibits hunger promoting agouti-related protein/neuropeptide Y (AgRP/NPY) neurons via GABA release. Adopting an intersectional genetics strategy, we clarify that the GABANTS→ARC circuit induces satiety. These data identify GABANTS as a new modulator of feeding behavior, body weight and controller of orexigenic AgRP/NPY activity, thereby providing insight into the neural underpinnings of obesity.
| Original language | English |
|---|---|
| Publisher | bioRxiv |
| DOIs | |
| Publication status | Published - 3 May 2023 |
Bibliographical note
We gratefully acknowledge Dr F. Naneix for advice on optogenetics and editorial advice, and staff within the University of Aberdeen Medical Research Facility and the Microscopy Facility for their technical assistance. This work was supported by the ERC (MSCA-IF-NeuroEE538 660219) to PBM, Wellcome Trust Institutional Strategic Support Fund (204815/Z/16/Z) to PBM and LKH, and the Biotechnology and Biological Sciences Research Council (BB/V010557/1) to JAG and (BB/V016849/1) to LKH and SS. GKCD is funded by a BBSRC CASE 4-year PhD studentship, co-funded by Novo Nordisk. GSHY is funded by the UK Medical Research Council (MC_UU_00014/1).
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