Publication Date:
2015-02-25
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496586/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496586/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koch, Marco -- Varela, Luis -- Kim, Jae Geun -- Kim, Jung Dae -- Hernandez-Nuno, 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 -- DP1 DK098058/DK/NIDDK NIH HHS/ -- DP1DK098058/DK/NIDDK NIH HHS/ -- P01 NS062686/NS/NINDS NIH HHS/ -- R01 AG040236/AG/NIA NIH HHS/ -- R01 DA023999/DA/NIDA NIH HHS/ -- R01AG040236/AG/NIA NIH HHS/ -- R01DK097566/DK/NIDDK NIH HHS/ -- R37 DK053301/DK/NIDDK NIH HHS/ -- England -- Nature. 2015 Mar 5;519(7541):45-50. doi: 10.1038/nature14260. Epub 2015 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA [2] Institute of Anatomy, University of Leipzig, 04103 Leipzig, Germany. ; Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; 1] Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA [2] Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; Obesity &Diabetes Institute, Department of Physiology, Monash University, Clayton, Victoria 3800, Australia. ; Division of Endocrinology &Metabolism, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; 1] Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA [2] Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; Institute of Anatomy, University of Leipzig, 04103 Leipzig, Germany. ; 1] Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA [2] Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; 1] Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA [2] Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA [3] Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; 1] Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA [2] Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA [3] Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA [4] Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25707796" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cannabinoids/*pharmacology
;
Eating/*drug effects/*physiology
;
Energy Metabolism/drug effects
;
Hypothalamus/*cytology/drug effects/physiology
;
Ion Channels/metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mitochondria/drug effects/metabolism
;
Mitochondrial Proteins/metabolism
;
Naloxone/pharmacology
;
Neurons/*drug effects/*metabolism
;
Pro-Opiomelanocortin/*metabolism
;
Receptor, Cannabinoid, CB1/agonists/metabolism
;
Satiety Response/drug effects/physiology
;
alpha-MSH/secretion
;
beta-Endorphin/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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