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Sotelo-Hitschfeld, T.* ; Minère, M.* ; Klemm, P.* ; Borgmann, D.* ; Wnuk-Lipinski, D.* ; Jais, A. ; Jia, X.* ; Corneliussen, S.* ; Kloppenburg, P.* ; Fenselau, H.* ; Brüning, J.C.*

GABAergic disinhibition from the BNST to PNOCARC neurons promotes HFD-induced hyperphagia.

Cell Rep. 43:114343 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Activation of prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus (ARC) promotes high-fat-diet (HFD)-induced hyperphagia. In turn, PNOCARC neurons can inhibit the anorexic response of proopiomelanocortin (POMC) neurons. Here, we validate the necessity of PNOCARC activity for HFD-induced inhibition of POMC neurons in mice and find that PNOCARC-neuron-dependent inhibition of POMC neurons is mediated by gamma-aminobutyric acid (GABA) release. When monitoring individual PNOCARC neuron activity via Ca2+ imaging, we find a subpopulation of PNOCARC neurons that is inhibited upon gastrointestinal calorie sensing and disinhibited upon HFD feeding. Combining retrograde rabies tracing and circuit mapping, we find that PNOC neurons from the bed nucleus of the stria terminalis (PNOCBNST) provide inhibitory input to PNOCARC neurons, and this inhibitory input is blunted upon HFD feeding. This work sheds light on how an increase in caloric content of the diet can rewire a neuronal circuit, paving the way to overconsumption and obesity development.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cp: Metabolism ; Cp: Neuroscience
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 43, Issue: 6, Pages: , Article Number: 114343 Supplement: ,
Publisher Cell Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)