Cold-induced hyperphagia requires AgRP-neuron activation in mice

  1. Jennifer Deem
  2. Chelsea L Faber
  3. Christian Pedersen
  4. Bao Anh Phan
  5. Sarah A Larsen
  6. Kayoko Ogimoto
  7. Jarrell T Nelson
  8. Vincent Damian
  9. Megan A Tran
  10. Richard D Palmiter
  11. Karl J Kaiyala
  12. Jarrad M Scarlett
  13. Michael Bruchas
  14. Michael W Schwartz
  15. Gregory J Morton  Is a corresponding author
  1. University of Washington, United States
  2. Howard Hughes Medical Institute, University of Washington, United States
  3. Seattle Children's Hospital, United States

Abstract

To maintain energy homeostasis during cold exposure, the increased energy demands of thermogenesis must be counterbalanced by increased energy intake. To investigate the neurobiological mechanisms underlying this cold-induced hyperphagia, we asked whether agouti-related peptide (AgRP) neurons are activated when animals are placed in a cold environment and, if so, whether this response is required for the associated hyperphagia. We report that AgRP-neuron activation occurs rapidly upon acute cold exposure, as do increases of both energy expenditure and energy intake, suggesting the mere perception of cold is sufficient to engage each of these responses. We further report that silencing of AgRP neurons selectively blocks the effect of cold exposure to increase food intake but has no effect on energy expenditure. Together, these findings establish a physiologically important role for AgRP neurons in the hyperphagic response to cold exposure.

Data availability

Photometry data has been deposited in DryadDOI: https://doi.org/10.5061/dryad.0p2ngf208Individual source data files are associated with individual figures.

Article and author information

Author details

  1. Jennifer Deem

    Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8865-5145
  2. Chelsea L Faber

    Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4812-8164
  3. Christian Pedersen

    Bioengineering, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Bao Anh Phan

    Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sarah A Larsen

    Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kayoko Ogimoto

    Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jarrell T Nelson

    Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Vincent Damian

    Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Megan A Tran

    Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Richard D Palmiter

    Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6587-0582
  11. Karl J Kaiyala

    Oral Health Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Jarrad M Scarlett

    Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Michael Bruchas

    Anesthesiology and Pain Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4713-7816
  14. Michael W Schwartz

    Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1619-0331
  15. Gregory J Morton

    Medicine, University of Washington, Seattle, United States
    For correspondence
    gjmorton@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8106-8386

Funding

National Institutes of Health (DK089056)

  • Gregory J Morton

National Institutes of Health (T32 GM095421)

  • Chelsea L Faber

National Institutes of Health (T32 HL007028)

  • Jennifer Deem

Diabetes Research Center

  • Jennifer Deem

American Diabetes Association (ADA 1-19-PDF-103)

  • Jennifer Deem

National Institutes of Health (DK083042)

  • Michael W Schwartz

National Institutes of Health (DK101997)

  • Michael W Schwartz

National Institutes of Health (R37 DA033396)

  • Michael Bruchas

National Institutes of Health (R01DA24908)

  • Richard D Palmiter

National Institutes of Health (P30 DA048736)

  • Michael Bruchas

National Institutes of Health (DK035816)

  • Gregory J Morton

Diabetes Research Center (DK17047)

  • Gregory J Morton

National Institutes of Health (F31 DK113673)

  • Chelsea L Faber

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to a protocol approved by the institutional animal care and use committee (IACUC) of the University of Washington (#2456-06). All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Stephen Liberles, Harvard Medical School, United States

Publication history

  1. Received: May 10, 2020
  2. Accepted: December 14, 2020
  3. Accepted Manuscript published: December 15, 2020 (version 1)
  4. Version of Record published: January 26, 2021 (version 2)

Copyright

© 2020, Deem 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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  1. Jennifer Deem
  2. Chelsea L Faber
  3. Christian Pedersen
  4. Bao Anh Phan
  5. Sarah A Larsen
  6. Kayoko Ogimoto
  7. Jarrell T Nelson
  8. Vincent Damian
  9. Megan A Tran
  10. Richard D Palmiter
  11. Karl J Kaiyala
  12. Jarrad M Scarlett
  13. Michael Bruchas
  14. Michael W Schwartz
  15. Gregory J Morton
(2020)
Cold-induced hyperphagia requires AgRP-neuron activation in mice
eLife 9:e58764.
https://doi.org/10.7554/eLife.58764

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