The p75 neurotrophin receptor in AgRP neurons is necessary for homeostatic feeding and food anticipation

Abstract

Networks of neurons control feeding and activity patterns by integrating internal metabolic signals of energy balance with external environmental cues such as time-of-day. Proper circadian alignment of feeding behavior is necessary to prevent metabolic disease, and thus it is imperative that molecular players that maintain neuronal coordination of energy homeostasis are identified. Here, we demonstrate that mice lacking the p75 neurotrophin receptor, p75NTR, decrease their feeding and food anticipatory behavior (FAA) in response to daytime, but not nighttime, restricted feeding. These effects lead to increased weight loss, but do not require p75NTR during development. Instead, p75NTR is required for fasting-induced activation of neurons within the arcuate hypothalamus. Indeed, p75NTR specifically in AgRP neurons is required for FAA in response to daytime restricted feeding. These findings establish p75NTR as a novel regulator gating behavioral response to food scarcity and time-of-day dependence of circadian food anticipation.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Brandon Podyma

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Dove-Anna Johnson

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Laura Sipe

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Thomas Parks Remcho

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Katherine Battin

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Yuxi Liu

    Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Sung Ok Yoon

    The Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Christopher D Deppmann

    Department of Biology, University of Virginia, Charlottesville, United States
    For correspondence
    deppmann@virginia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6591-1767
  9. Ali Deniz Güler

    Department of Biology, University of Virginia, Charlottesville, United States
    For correspondence
    aguler@virginia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8218-850X

Funding

Hartwell Foundation

  • Christopher D Deppmann

National Institutes of Health (T32-GM7267-39)

  • Brandon Podyma

National Institutes of Health (T32-GM7055-45)

  • Brandon Podyma

National Institutes of Health (R01-GM121937)

  • Ali Deniz Güler

National Institutes of Health (RO1-AG055059)

  • Sung Ok Yoon

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 approved institutional animal care and use committee (IACUC) protocols (#3795, 3975, 4183, 4191, 4200) of the University of Virginia.

Reviewing Editor

  1. Moses V Chao, New York University Langone Medical Center, United States

Version history

  1. Received: October 10, 2019
  2. Accepted: January 27, 2020
  3. Accepted Manuscript published: January 29, 2020 (version 1)
  4. Version of Record published: March 4, 2020 (version 2)

Copyright

© 2020, Podyma 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. Brandon Podyma
  2. Dove-Anna Johnson
  3. Laura Sipe
  4. Thomas Parks Remcho
  5. Katherine Battin
  6. Yuxi Liu
  7. Sung Ok Yoon
  8. Christopher D Deppmann
  9. Ali Deniz Güler
(2020)
The p75 neurotrophin receptor in AgRP neurons is necessary for homeostatic feeding and food anticipation
eLife 9:e52623.
https://doi.org/10.7554/eLife.52623

Share this article

https://doi.org/10.7554/eLife.52623

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