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 and Tamas L. Horvath ()
Additional contact information
Marco Koch: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
Luis Varela: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
Jae Geun Kim: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
Jung Dae Kim: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
Francisco Hernández-Nuño: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
Stephanie E. Simonds: Obesity & Diabetes Institute, Monash University
Carlos M. Castorena: The University of Texas Southwestern Medical Center
Claudia R. Vianna: The University of Texas Southwestern Medical Center
Joel K. Elmquist: The University of Texas Southwestern Medical Center
Yury M. Morozov: Yale University School of Medicine
Pasko Rakic: Yale University School of Medicine
Ingo Bechmann: Institute of Anatomy, University of Leipzig, 04103 Leipzig, Germany
Michael A. Cowley: Obesity & Diabetes Institute, Monash University
Klara Szigeti-Buck: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
Marcelo O. Dietrich: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
Xiao-Bing Gao: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
Sabrina Diano: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
Tamas L. Horvath: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine

Nature, 2015, vol. 519, issue 7541, 45-50

Abstract: 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 α-melanocyte-stimulating hormone, and the opioid peptide β-endorphin. CB1R 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 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.

Date: 2015
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DOI: 10.1038/nature14260

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