A neurogenic signature involving monoamine oxidase-a controls human thermogenic adipose tissue development

Abstract

Mechanisms that control 'beige/brite' thermogenic adipose tissue development may be harnessed to improve human metabolic health. To define these mechanisms, we developed a species-hybrid model in which human mesenchymal progenitor cells were used to develop white or thermogenic/beige adipose tissue in mice. The hybrid adipose tissue developed distinctive features of human adipose tissue, such as larger adipocyte size, despite its neurovascular architecture being entirely of murine origin. Thermogenic adipose tissue recruited a denser, qualitatively distinct vascular network, differing in genes mapping to circadian rhythm pathways, and denser sympathetic innervation. The enhanced thermogenic neurovascular network was associated with human adipocyte expression of THBS4, TNC, NTRK3 and SPARCL1, which enhance neurogenesis, and decreased expression of MAOA and ACHE, which control neurotransmitter tone. Systemic inhibition of MAOA, which is present in human but absent in mouse adipocytes, induced browning of human but not mouse adipose tissue, revealing the physiological relevance of this pathway. Our results reveal species-specific cell type dependencies controlling the development of thermogenic adipose tissue and point to human adipocyte MAOA as a potential target for metabolic disease therapy.

Data availability

RNASeq data has been deposited in the Gene Expression Omnibus under the accession number GSE200141.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Javier Solivan-Rivera

    Morningside Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Zinger Yang Loureiro

    Morningside Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8543-4841
  3. Tiffany DeSouza

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Anand Desai

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sabine Pallat

    Morningside Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Qin Yang

    Morningside Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Raziel Rojas-Rodriguez

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Rachel Ziegler

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Pantos Skritakis

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Shannon Joyce

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Denise Zhong

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Tammy Nguyen

    Department of Surgery, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Silvia Corvera

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    silvia.corvera@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0009-4129

Funding

National Institutes of Health (DK089101)

  • Silvia Corvera

National Institutes of Health (DK123028)

  • Silvia Corvera

National Institutes of Health (GM135751)

  • Javier Solivan-Rivera

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 University of Massachusetts Medical School's Institutional Animal Care and use Committee protocol PROTO202100015.

Reviewing Editor

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

Publication history

  1. Preprint posted: December 30, 2021 (view preprint)
  2. Received: March 25, 2022
  3. Accepted: September 9, 2022
  4. Accepted Manuscript published: September 15, 2022 (version 1)
  5. Accepted Manuscript updated: September 20, 2022 (version 2)
  6. Version of Record published: September 28, 2022 (version 3)
  7. Version of Record updated: September 30, 2022 (version 4)

Copyright

© 2022, Solivan-Rivera 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. Javier Solivan-Rivera
  2. Zinger Yang Loureiro
  3. Tiffany DeSouza
  4. Anand Desai
  5. Sabine Pallat
  6. Qin Yang
  7. Raziel Rojas-Rodriguez
  8. Rachel Ziegler
  9. Pantos Skritakis
  10. Shannon Joyce
  11. Denise Zhong
  12. Tammy Nguyen
  13. Silvia Corvera
(2022)
A neurogenic signature involving monoamine oxidase-a controls human thermogenic adipose tissue development
eLife 11:e78945.
https://doi.org/10.7554/eLife.78945

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