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Sustained NPY signaling enables AgRP neurons to drive feeding

  1. Yiming Chen
  2. Rachel A Essner
  3. Seher Kosar
  4. Oliver H Miller
  5. Yen-Chu Lin
  6. Sheyda Mesgarzadeh
  7. Zachary A Knight  Is a corresponding author
  1. University of California, San Francisco, United States
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Cite this article as: eLife 2019;8:e46348 doi: 10.7554/eLife.46348

Abstract

Artificial stimulation of Agouti-Related Peptide (AgRP) neurons promotes intense food consumption, yet paradoxically during natural behavior these cells are inhibited before feeding begins. To reconcile these observations, we showed in a previous paper (Chen et al., 2016) that brief stimulation of AgRP neurons can generate hunger that persists for tens of minutes, but the mechanisms underlying this sustained hunger drive remain unknown. Here we show that Neuropeptide Y (NPY) is uniquely required for the long-lasting effects of AgRP neurons on feeding behavior. We blocked the ability of AgRP neurons to signal through AgRP, NPY, or GABA, and then stimulated these cells using a paradigm that mimics their natural regulation. Deletion of NPY, but not AgRP or GABA, abolished optically-stimulated feeding, and this was rescued by NPY re-expression selectively in AgRP neurons. These findings reveal a unique role for NPY in sustaining hunger in the interval between food discovery and consumption.

Article and author information

Author details

  1. Yiming Chen

    Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Rachel A Essner

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Seher Kosar

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Oliver H Miller

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yen-Chu Lin

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Sheyda Mesgarzadeh

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Zachary A Knight

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    For correspondence
    zachary.knight@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7621-1478

Funding

National Institutes of Health (R01DK106399)

  • Zachary A Knight

National Institutes of Health (R01NS094781)

  • Zachary A Knight

Howard Hughes Medical Institute

  • Zachary A Knight

American Diabetes Association (ADA Accelerator Grant)

  • Zachary A Knight

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States

Publication history

  1. Received: February 26, 2019
  2. Accepted: April 26, 2019
  3. Accepted Manuscript published: April 29, 2019 (version 1)
  4. Version of Record published: May 13, 2019 (version 2)

Copyright

© 2019, Chen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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