PNOCARC neurons promote hyperphagia and obesity upon high-fat-diet feeding

Jais, Alexander; Paeger, Lars; Sotelo-Hitschfeld, Tamara; Bremser, Stephan; Prinzensteiner, Melanie; Klemm, Paul; Mykytiuk, Vasyl; Widdershooven, Pia J.M.; Vesting, Anna Juliane; Grzelka, Katarzyna; Minère, Marielle; Cremer, Anna Lena; Xu, Jie; Korotkova, Tatiana; Lowell, Bradford B.; Zeilhofer, Hanns Ulrich; Fenselau, Henning; Backes, Heiko; Wunderlich, Frank Thomas; Kloppenburg, Peter; Brüning, Jens Claus

doi:10.1016/j.neuron.2020.03.022

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

PNOCARC neurons promote hyperphagia and obesity upon high-fat-diet feeding

MPS-Authors

/persons/resource/persons288267

Sotelo-Hitschfeld, Tamara
Max Planck Institute for Metabolism Research, Brüning Group, Max Planck Society;

/persons/resource/persons233068

Grzelka, Katarzyna
Fenselau - Synaptic Transmission in Energy Homeostasis, Max Planck Institute for Metabolism Research, Managing Director: Jens Brüning, Max Planck Society;

/persons/resource/persons210944

Korotkova, Tatiana
Neuronal Circuits and Behavior, Department Jens Brüning, Max Planck Institute for Metabolism Research, Managing Director: Jens Brüning, Max Planck Society;

/persons/resource/persons220250

Fenselau, Henning
Fenselau – Synaptic Transmission in Energy Homeostasis, Research Groups, Max Planck Institute for Metabolism Research, Max Planck Society;

/persons/resource/persons147126

Backes, Heiko
Backes, Wiedermann – Multimodal Imaging, Scientific Services and Development, Max Planck Institute for Metabolism Research, Max Planck Society;

/persons/resource/persons147349

Wunderlich, Frank Thomas
Wunderlich – Obesity and Cancer, Department Brüning, Max Planck Institute for Metabolism Research, Max Planck Society;

/persons/resource/persons288285

Kloppenburg, Peter
Brüning Group, Max Planck Institute for Metabolism Research, Max Planck Society;

/persons/resource/persons147140

Brüning, Jens Claus
Brüning – Neuronal Control of Metabolism, Department Brüning, Max Planck Institute for Metabolism Research, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Jais, A., Paeger, L., Sotelo-Hitschfeld, T., Bremser, S., Prinzensteiner, M., Klemm, P., et al. (2020). PNOCARC neurons promote hyperphagia and obesity upon high-fat-diet feeding. Neuron, 106(6), 1009-1025.e10. doi:10.1016/j.neuron.2020.03.022.

Cite as: https://hdl.handle.net/21.11116/0000-0006-3FE9-E

Abstract

Calorie-rich diets induce hyperphagia and promote obesity, although the underlying mechanisms remain poorly defined. We find that short-term high-fat-diet (HFD) feeding of mice activates prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus of the hypothalamus (ARC). PNOCARC neurons represent a previously unrecognized GABAergic population of ARC neurons distinct from well-defined feeding regulatory AgRP or POMC neurons. PNOCARC neurons arborize densely in the ARC and provide inhibitory synaptic input to nearby anorexigenic POMC neurons. Optogenetic activation of PNOCARC neurons in the ARC and their projections to the bed nucleus of the stria terminalis promotes feeding. Selective ablation of these cells promotes the activation of POMC neurons upon HFD exposure, reduces feeding, and protects from obesity, but it does not affect food intake or body weight under normal chow consumption. We characterize PNOCARC neurons as a novel ARC neuron population activated upon palatable food consumption to promote hyperphagia.