1. Developmental Biology
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Early postnatal interactions between beige adipocytes and sympathetic neurites regulate innervation of subcutaneous fat

  1. Jingyi Chi
  2. Zeran Lin
  3. William Barr
  4. Audrey Crane
  5. Xiphias Ge Zhu
  6. Paul Cohen  Is a corresponding author
  1. The Rockefeller University, United States
Research Article
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Cite this article as: eLife 2021;10:e64693 doi: 10.7554/eLife.64693

Abstract

While beige adipocytes have been found to associate with dense sympathetic neurites in mouse inguinal subcutaneous white fat (iWAT), little is known about when and how this patterning is established. Here, we applied whole-tissue imaging to examine the development of sympathetic innervation in iWAT. We found that parenchymal neurites actively grow between postnatal day 6 (P6) and P28, overlapping with early postnatal beige adipogenesis. Constitutive deletion of Prdm16 in adipocytes led to a significant reduction in early postnatal beige adipocytes and sympathetic density within this window. Using an inducible, adipocyte-specific Prdm16 knockout model, we found that Prdm16 is required for guiding sympathetic growth during early development. Deleting Prdm16 in adult animals, however, did not affect sympathetic structure in iWAT. Together, these findings highlight that beige adipocyte-sympathetic neurite communication is crucial to establish sympathetic structure during the early postnatal period but may be dispensable for its maintenance in mature animals.

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. Jingyi Chi

    Laboratory of Molecular Metabolism, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Zeran Lin

    Laboratory of Molecular Metabolism, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. William Barr

    Laboratory of Molecular Metabolism, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Audrey Crane

    Laboratory of Molecular Metabolism, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Xiphias Ge Zhu

    Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Paul Cohen

    Laboratory of Molecular Metabolism, The Rockefeller University, New York, United States
    For correspondence
    pcohen@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2786-8585

Funding

Leona M. and Harry B. Helmsley Charitable Trust (Center for Basic and Translational Research on Disorders of the Digestive System Pilot Award)

  • Jingyi Chi

National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK120649)

  • Paul Cohen

American Diabetes Association (Grant # 1-17-ACE-17)

  • Paul Cohen

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 (#18016-H) of The Rockefeller University.

Reviewing Editor

  1. Peter Tontonoz, University of California, Los Angeles, United States

Publication history

  1. Received: November 7, 2020
  2. Accepted: February 15, 2021
  3. Accepted Manuscript published: February 16, 2021 (version 1)
  4. Version of Record published: March 24, 2021 (version 2)

Copyright

© 2021, Chi 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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