Neuron
Volume 106, Issue 6, 17 June 2020, Pages 1009-1025.e10
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Article
PNOCARC Neurons Promote Hyperphagia and Obesity upon High-Fat-Diet Feeding

https://doi.org/10.1016/j.neuron.2020.03.022Get rights and content
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Highlights

  • Acute high-fat-diet feeding activates PNOC neurons in the arcuate nucleus (ARC)

  • GABAergic PNOCARC neurons inhibit anorexigenic POMC neurons

  • Optogenetic activation of PNOCARC neurons promotes feeding

  • Ablation of PNOCARC neurons protects from obesity

Summary

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.

Keywords

prepronociceptin
nociceptin
orphanin FQ
food intake
acute high-fat-diet feeding
neuropeptide
PNOC neurons
arcuate nucleus
hypothalamus
obesity

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These authors contributed equally

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