Hypothalamic POMC neurons promote cannabinoid-induced feeding

Marco Koch, Luis Varela, Jae Geun Kim, Jung Dae Kim, Francisco Hernández-Nuño, Stephanie E. Simonds, Carlos M. Castorena, Claudia R. Vianna, Joel K. Elmquist, Yury M. Morozov, Pasko Rakic, Ingo Bechmann, Michael A. Cowley, Klara Szigeti-Buck, Marcelo O. Dietrich, Xiao Bing Gao, Sabrina Diano, Tamas L. Horvath

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety. Cannabinoid receptor 1 (CB 1 R) is critical for the central regulation of food intake. Here we test whether CB 1 R-controlled feeding in sated mice is paralleled by decreased activity of POMC neurons. We show that chemical promotion of CB 1 R activity increases feeding, and notably, CB 1 R activation also promotes neuronal activity of POMC cells. This paradoxical increase in POMC activity was crucial for CB 1 R-induced feeding, because designer-receptors-exclusively-activated-by-designer-drugs (DREADD)-mediated inhibition of POMC neurons diminishes, whereas DREADD-mediated activation of POMC neurons enhances CB 1 R-driven feeding. The Pomc gene encodes both the anorexigenic peptide α-melanocyte-stimulating hormone, and the opioid peptide β-endorphin. CB 1 R activation selectively increases β-endorphin but not α-melanocyte-stimulating hormone release in the hypothalamus, and systemic or hypothalamic administration of the opioid receptor antagonist naloxone blocks acute CB 1 R-induced feeding. These processes involve mitochondrial adaptations that, when blocked, abolish CB 1 R-induced cellular responses and feeding. Together, these results uncover a previously unsuspected role of POMC neurons in the promotion of feeding by cannabinoids.

Original languageEnglish (US)
Pages (from-to)45-50
Number of pages6
JournalNature
Volume519
Issue number7541
DOIs
StatePublished - Mar 5 2015

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Pro-Opiomelanocortin
Cannabinoids
Neurons
Designer Drugs
Endorphins
Melanocyte-Stimulating Hormones
Appetite Regulation
Cannabinoid Receptors
Opioid Peptides
Narcotic Antagonists
Naloxone
Hypothalamus
Genes

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Koch, M., Varela, L., Kim, J. G., Kim, J. D., Hernández-Nuño, F., Simonds, S. E., ... Horvath, T. L. (2015). Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature, 519(7541), 45-50. https://doi.org/10.1038/nature14260

Hypothalamic POMC neurons promote cannabinoid-induced feeding. / Koch, Marco; Varela, Luis; Kim, Jae Geun; Kim, Jung Dae; Hernández-Nuño, Francisco; Simonds, Stephanie E.; Castorena, Carlos M.; Vianna, Claudia R.; Elmquist, Joel K.; Morozov, Yury M.; Rakic, Pasko; Bechmann, Ingo; Cowley, Michael A.; Szigeti-Buck, Klara; Dietrich, Marcelo O.; Gao, Xiao Bing; Diano, Sabrina; Horvath, Tamas L.

In: Nature, Vol. 519, No. 7541, 05.03.2015, p. 45-50.

Research output: Contribution to journalArticle

Koch, M, Varela, L, Kim, JG, Kim, JD, Hernández-Nuño, F, Simonds, SE, Castorena, CM, Vianna, CR, Elmquist, JK, Morozov, YM, Rakic, P, Bechmann, I, Cowley, MA, Szigeti-Buck, K, Dietrich, MO, Gao, XB, Diano, S & Horvath, TL 2015, 'Hypothalamic POMC neurons promote cannabinoid-induced feeding', Nature, vol. 519, no. 7541, pp. 45-50. https://doi.org/10.1038/nature14260
Koch M, Varela L, Kim JG, Kim JD, Hernández-Nuño F, Simonds SE et al. Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature. 2015 Mar 5;519(7541):45-50. https://doi.org/10.1038/nature14260
Koch, Marco ; Varela, Luis ; Kim, Jae Geun ; Kim, Jung Dae ; Hernández-Nuño, Francisco ; Simonds, Stephanie E. ; Castorena, Carlos M. ; Vianna, Claudia R. ; Elmquist, Joel K. ; Morozov, Yury M. ; Rakic, Pasko ; Bechmann, Ingo ; Cowley, Michael A. ; Szigeti-Buck, Klara ; Dietrich, Marcelo O. ; Gao, Xiao Bing ; Diano, Sabrina ; Horvath, Tamas L. / Hypothalamic POMC neurons promote cannabinoid-induced feeding. In: Nature. 2015 ; Vol. 519, No. 7541. pp. 45-50.
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