Abstract

During obesity and high fat-diet (HFD) feeding in mice, sustained low-grade inflammation includes not only increased pro-inflammatory macrophages in the expanding adipose tissue, but also bone marrow (BM) production of invasive Ly6Chigh monocytes. As BM adiposity also accrues with HFD, we explored the relationship between the gains in BM white adipocytes and invasive Ly6Chigh monocytes in vivo and through ex vivo paradigms. We find a temporal and causal link between BM adipocyte whitening and the Ly6Chigh monocyte surge, preceding the adipose tissue macrophage rise during HFD. Phenocopying this, ex vivo treatment of BM cells with conditioned media from BM adipocytes or from bona fide white adipocytes favoured Ly6Chigh monocyte preponderance. Notably, Ly6Chigh skewing was preceded by monocyte metabolic reprogramming towards glycolysis, reduced oxidative potential and increased mitochondrial fission. In sum, short-term HFD changes BM cellularity, resulting in local adipocyte whitening driving a gradual increase and activation of invasive Ly6Chigh monocytes.

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

Article and author information

Author details

  1. Parastoo Boroumand

    Cell Biology Program, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. David C Prescott

    Department of Immunology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Tapas Mukherjee

    Department of Immunology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Philip J Bilan

    Cell Biology Program, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Michael Wong

    Cell Biology Program, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Jeff Shen

    Cell Biology Program, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Ivan Tattoli

    Department of Laboratory Medicine and Pathopysiology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Yuhuan Zhou

    Cell Biology Program, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Angela Li

    Research Institute, Toronto General Hospital, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Tharini Sivasubramaniyam

    Research Institute, Toronto General Hospital, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  11. Nan Shi

    Cell Biology Program, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  12. Lucie Y Zhu

    Cell Biology Program, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1048-5377
  13. Zhi Liu

    Cell Biology Program, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  14. Clinton Robbins

    Department of Laboratory Medicine and Pathophysiology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  15. Dana J Philpott

    Department of Immunology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  16. Stephen E Girardin

    Department of Immunology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  17. Amira Klip

    Cell Biology Program, Hospital for Sick Children, Toronto, Canada
    For correspondence
    amira@sickkids.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7906-0302

Funding

Canadian Institutes of Health Research FDN-143203 (FDN-143203)

  • Amira Klip

Canadian Institutes of Health Research FDN-14333 (FDN-14333)

  • Dana J Philpott

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

Ethics

Animal experimentation: Mouse protocols followed the strictest protocols dictated by the Canadian Institutes of Health Research guidelines and were approved by the animal care committee (Protocol #20011850 to S.E.G. and 483 D.J.P., University of Toronto; and #1000047074 to A.K., The Hospital for Sick Children).

Copyright

© 2022, Boroumand 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. Parastoo Boroumand
  2. David C Prescott
  3. Tapas Mukherjee
  4. Philip J Bilan
  5. Michael Wong
  6. Jeff Shen
  7. Ivan Tattoli
  8. Yuhuan Zhou
  9. Angela Li
  10. Tharini Sivasubramaniyam
  11. Nan Shi
  12. Lucie Y Zhu
  13. Zhi Liu
  14. Clinton Robbins
  15. Dana J Philpott
  16. Stephen E Girardin
  17. Amira Klip
(2022)
Bone marrow adipocytes drive the development of tissue invasive Ly6Chigh monocytes during obesity
eLife 11:e65553.
https://doi.org/10.7554/eLife.65553

Share this article

https://doi.org/10.7554/eLife.65553

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