Hypothalamic POMC neurons promote cannabinoid-induced feeding

Marco Koch, Luis Varela, Jae Geun Kim, Jung Dae Kim, Francisco Hernandez-Nuno, 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 de Oliveira Dietrich, Xiao-Bing Gao, Sabrina Diano, Tamas L Horvath

Research output: Contribution to journalArticleResearchpeer-review

217 Citations (Scopus)

Abstract

Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety. Cannabinoid receptor 1 (CB1R) is critical for the central regulation of food intake. Here we test whether CB1R-controlled feeding in sated mice is paralleled by decreased activity of POMC neurons. We show that chemical promotion of CB1R activity increases feeding, and notably, CB1R activation also promotes neuronal activity of POMC cells. This paradoxical increase in POMC activity was crucial for CB1R-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 CB1R-driven feeding. The Pomc gene encodes both the anorexigenic peptide alpha-melanocyte-stimulating hormone, and the opioid peptide beta-endorphin. CB1R activation selectively increases beta-endorphin but not alpha-melanocyte-stimulating hormone release in the hypothalamus, and systemic or hypothalamic administration of the opioid receptor antagonist naloxone blocks acute CB1R-induced feeding. These processes involve mitochondrial adaptations that, when blocked, abolish CB1R-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
Pages (from-to)45 - 50
Number of pages6
JournalNature
Volume519
DOIs
Publication statusPublished - 2015

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