Early postnatal interactions between beige adipocytes and sympathetic neurites regulate innervation of subcutaneous fat

Abstract
Data availability
Article and author information
Metrics

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

Jingyi Chi

Laboratory of Molecular Metabolism, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Zeran Lin

Laboratory of Molecular Metabolism, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
William Barr

Laboratory of Molecular Metabolism, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Audrey Crane

Laboratory of Molecular Metabolism, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
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.
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.

"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.

Copyright

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.