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Hypothalamic POMC neurons promote cannabinoid-induced feeding

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  • Marco Koch

    (Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
    Institute of Anatomy, University of Leipzig, 04103 Leipzig, Germany)

  • 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
    Present address: Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 406-772, South Korea.)

  • Jung Dae Kim

    (Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine
    Gynecology and Reproductive Sciences, 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
    Kavli Institute for Neuroscience, 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
    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
    Gynecology and Reproductive Sciences, Yale University School of 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
    Gynecology and Reproductive Sciences, Yale University School of Medicine
    Yale University School of Medicine
    Kavli Institute for Neuroscience, Yale University School of Medicine)

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.

Suggested Citation

  • 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 & , 2015. "Hypothalamic POMC neurons promote cannabinoid-induced feeding," Nature, Nature, vol. 519(7541), pages 45-50, March.
    • Handle: RePEc:nat:nature:v:519:y:2015:i:7541:d:10.1038_nature14260
    DOI: 10.1038/nature14260
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    Cited by:

    1. Weihua Ding & Liuyue Yang & Eleanor Shi & Bowon Kim & Sarah Low & Kun Hu & Lei Gao & Ping Chen & Wei Ding & David Borsook & Andrew Luo & Jee Hyun Choi & Changning Wang & Oluwaseun Akeju & Jun Yang & C, 2023. "The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Albert Stuart Reece & Gary Kenneth Hulse, 2023. "Clinical Epigenomic Explanation of the Epidemiology of Cannabinoid Genotoxicity Manifesting as Transgenerational Teratogenesis, Cancerogenesis and Aging Acceleration," IJERPH, MDPI, vol. 20(4), pages 1-24, February.
    3. Nathan Fearby & Samantha Penman & Panayotis Thanos, 2022. "Effects of Δ9-Tetrahydrocannibinol (THC) on Obesity at Different Stages of Life: A Literature Review," IJERPH, MDPI, vol. 19(6), pages 1-28, March.
    4. Albert Stuart Reece & Gary Kenneth Hulse, 2022. "Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis," IJERPH, MDPI, vol. 19(24), pages 1-57, December.
    5. Timothy R. Hodge & Cooper Hazel, 2022. "The munchies: Marijuana legalization and food sales in Washington," Southern Economic Journal, John Wiley & Sons, vol. 89(1), pages 112-137, July.
    6. Albert Stuart Reece & Gary Kenneth Hulse, 2022. "State Trends of Cannabis Liberalization as a Causal Driver of Increasing Testicular Cancer Rates across the USA," IJERPH, MDPI, vol. 19(19), pages 1-37, October.
    7. Hongli Li & Yuanzhong Xu & Yanyan Jiang & Zhiying Jiang & Joshua Otiz-Guzman & Jessie C. Morrill & Jing Cai & Zhengmei Mao & Yong Xu & Benjamin R. Arenkiel & Cheng Huang & Qingchun Tong, 2023. "The melanocortin action is biased toward protection from weight loss in mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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