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

187 Scopus citations

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

ASJC Scopus subject areas

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    Koch, M., Varela, L., Kim, J. G., Kim, J. D., Hernández-Nuño, F., Simonds, S. E., Castorena, C. M., Vianna, C. R., Elmquist, J. K., Morozov, Y. M., Rakic, P., Bechmann, I., Cowley, M. A., Szigeti-Buck, K., Dietrich, M. O., Gao, X. B., Diano, S., & Horvath, T. L. (2015). Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature, 519(7541), 45-50. https://doi.org/10.1038/nature14260