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Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively.

Abstract
POMC-derived melanocortins inhibit food intake. In the adult rodent brain, POMC-expressing neurons are located in the arcuate nucleus (ARC) and the nucleus tractus solitarius (NTS), but it remains unclear how POMC neurons in these two brain nuclei regulate feeding behavior and metabolism differentially. Using pharmacogenetic methods to activate or deplete neuron groups in separate brain areas, in the present study, we show that POMC neurons in the ARC and NTS suppress feeding behavior at different time scales. Neurons were activated using the DREADD (designer receptors exclusively activated by designer drugs) method. The evolved human M3-muscarinic receptor was expressed in a selective population of POMC neurons by stereotaxic infusion of Cre-recombinase-dependent, adeno-associated virus vectors into the ARC or NTS of POMC-Cre mice. After injection of the human M3-muscarinic receptor ligand clozapine-N-oxide (1 mg/kg, i.p.), acute activation of NTS POMC neurons produced an immediate inhibition of feeding behavior. In contrast, chronic stimulation was required for ARC POMC neurons to suppress food intake. Using adeno-associated virus delivery of the diphtheria toxin receptor gene, we found that diphtheria toxin-induced ablation of POMC neurons in the ARC but not the NTS, increased food intake, reduced energy expenditure, and ultimately resulted in obesity and metabolic and endocrine disorders. Our results reveal different behavioral functions of POMC neurons in the ARC and NTS, suggesting that POMC neurons regulate feeding and energy homeostasis by integrating long-term adiposity signals from the hypothalamus and short-term satiety signals from the brainstem.
AuthorsCheng Zhan, Jingfeng Zhou, Qiru Feng, Ju-En Zhang, Shuailiang Lin, Junhong Bao, Ping Wu, Minmin Luo
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 33 Issue 8 Pg. 3624-32 (Feb 20 2013) ISSN: 1529-2401 [Electronic] United States
PMID23426689 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Pro-Opiomelanocortin
Topics
  • Adiposity (genetics)
  • Animals
  • Brain Stem (physiology, virology)
  • Dependovirus (genetics)
  • Feeding Behavior (physiology)
  • Female
  • Genetic Vectors (administration & dosage)
  • HEK293 Cells
  • Homeostasis (genetics)
  • Humans
  • Hypothalamus (physiology)
  • Male
  • Mice
  • Mice, Transgenic
  • Neural Inhibition (genetics, physiology)
  • Neural Pathways (physiopathology)
  • Neurons (physiology, virology)
  • Pro-Opiomelanocortin (antagonists & inhibitors, physiology)

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