Hypothalamic POMC neurons promote cannabinoid-induced feeding

M Koch, L Varela, JG Kim, JD Kim, F Hernández-Nuño… - Nature, 2015 - nature.com
M Koch, L Varela, JG Kim, JD Kim, F Hernández-Nuño, SE Simonds, CM Castorena
Nature, 2015nature.com
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 …
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.
nature.com