Hypothalamic POMC neurons promote cannabinoid-induced feeding
| Autor: | Jae Geun Kim, Pasko Rakic, Tamas L. Horvath, Francisco Hernandez-Nuno, Xiao-Bing Gao, Luis Varela, Sabrina Diano, Joel K. Elmquist, Stephanie E. Simonds, Claudia R. Vianna, Carlos M. Castorena, Yury M. Morozov, Klara Szigeti-Buck, Michael A. Cowley, Ingo Bechmann, Marcelo O. Dietrich, Jung Dae Kim, Marco Koch |
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| Přispěvatelé: | Koch, Marco, Varela, Lui, 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 |
| Rok vydání: | 2015 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Pro-Opiomelanocortin medicine.drug_class medicine.medical_treatment Hypothalamus (+)-Naloxone Biology Satiety Response Ion Channels Mitochondrial Proteins Eating Mice chemistry.chemical_compound Receptor Cannabinoid CB1 Ion Channel Opioid receptor Internal medicine Hypothalamu medicine Mitochondrial Protein Animals Premovement neuronal activity Uncoupling Protein 2 Opioid peptide Receptor Cannabinoid Neurons Multidisciplinary Animal Cannabinoids Naloxone beta-Endorphin digestive oral and skin physiology Neuron Mitochondria Mice Inbred C57BL Endocrinology nervous system chemistry alpha-MSH Energy Metabolism hormones hormone substitutes and hormone antagonists |
| Zdroj: | Nature. 519:45-50 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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