Leptin-receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism

  1. Chelsea L Faber  Is a corresponding author
  2. Jennifer D Deem
  3. Bao Anh Phan
  4. Tammy P Doan
  5. Kayoko Ogimoto
  6. Zaman Mirzadeh
  7. Michael W Schwartz
  8. Gregory J Morton  Is a corresponding author
  1. University of Washington, United States
  2. Barrow Neurological Institute, United States

Abstract

Animal behavior and metabolism are tightly coordinated with sleep-wake cycles governed by the brain in harmony with environmental light:dark cycles. Within the brain, the dorsomedial hypothalamic nucleus (DMH) has been implicated in the integrative control of feeding, energy homeostasis, and circadian rhythms,1 but the underlying cell types are unknown. Here, we identify a role for DMH leptin receptor-expressing neurons (DMHLepR) in this integrative control. Using a viral approach, we show that silencing neurotransmission in DMHLepR neurons in adult mice not only increases body weight and adiposity, but also phase-advances diurnal rhythms of feeding and metabolism into the light-cycle and abolishes the normal increase in dark-cycle locomotor activity (LMA) characteristic of nocturnal rodents. Finally, DMHLepR-silenced mice fail to entrain to a restrictive change in food availability. Together, these findings identify DMHLepR neurons as critical determinants of the daily time of feeding and associated metabolic rhythms.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-4.

Article and author information

Author details

  1. Chelsea L Faber

    Medicine, University of Washington, Seattle, United States
    For correspondence
    kasperc@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4812-8164
  2. Jennifer D 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
  3. Bao Anh Phan

    Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Tammy P Doan

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

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

    Department of Neurosurgery, Barrow Neurological Institute, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. 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
  8. 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 (F31-DK113673)

  • Chelsea L Faber

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

  • Jennifer D Deem

U.S. Department of Defense (W81XWH2010250)

  • Zaman Mirzadeh

National Institutes of Health (DK128802)

  • Zaman Mirzadeh

National Institutes of Health (T32-GM095421)

  • Chelsea L Faber

National Institutes of Health (DK089056)

  • Gregory J Morton

National Institutes of Health (DK124238)

  • Gregory J Morton

National Institutes of Health (DK083042)

  • Michael W Schwartz

National Institutes of Health (DK101997)

  • Michael W Schwartz

National Institutes of Health (T32 DK007247)

  • Chelsea L Faber

National Institutes of Health (T32 HL007028)

  • Jennifer D Deem

American Diabetes Association (ADA 1-19-IBS-192)

  • Gregory J Morton

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

Ethics

Animal experimentation: All procedures were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Animal Care Committee at the University of Washington. (Jackson Laboratory no. 008320)

Reviewing Editor

  1. Joel K Elmquist, University of Texas Southwestern Medical Center, United States

Publication history

  1. Received: October 2, 2020
  2. Accepted: February 1, 2021
  3. Accepted Manuscript published: February 2, 2021 (version 1)
  4. Version of Record published: February 12, 2021 (version 2)

Copyright

© 2021, Faber 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. Chelsea L Faber
  2. Jennifer D Deem
  3. Bao Anh Phan
  4. Tammy P Doan
  5. Kayoko Ogimoto
  6. Zaman Mirzadeh
  7. Michael W Schwartz
  8. Gregory J Morton
(2021)
Leptin-receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism
eLife 10:e63671.
https://doi.org/10.7554/eLife.63671

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