1. Cell Biology

Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits

  1. Ziru Li
  2. Emily Bowers
  3. Junxiong Zhu
  4. Hui Yu
  5. Julie Hardij
  6. Devika P Bagchi
  7. Hiroyuki Mori
  8. Kenneth T Lewis
  9. Katrina Granger
  10. Rebecca L Schill
  11. Steven M Romanelli
  12. Simin Abrishami
  13. Kurt D Hankenson
  14. Kanakadurga Singer
  15. Clifford J Rosen
  16. Ormond MacDougald  Is a corresponding author
  1. University of Michigan-Ann Arbor, United States
  2. Maine Medical Center Research Institute, United States
https://doi.org/10.7554/eLife.78496
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Cite this article
  1. Ziru Li
  2. Emily Bowers
  3. Junxiong Zhu
  4. Hui Yu
  5. Julie Hardij
  6. Devika P Bagchi
  7. Hiroyuki Mori
  8. Kenneth T Lewis
  9. Katrina Granger
  10. Rebecca L Schill
  11. Steven M Romanelli
  12. Simin Abrishami
  13. Kurt D Hankenson
  14. Kanakadurga Singer
  15. Clifford J Rosen
  16. Ormond MacDougald
(2022)
Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits
eLife 11:e78496.
https://doi.org/10.7554/eLife.78496
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  3. Download .RIS

Abstract

To investigate roles for bone marrow adipocyte (BMAd) lipolysis in bone homeostasis, we created a BMAd-specific Cre mouse model in which we knocked out adipose triglyceride lipase (ATGL, Pnpla2 gene). BMAd-Pnpla2-/- mice have impaired BMAd lipolysis, and increased size and number of BMAds at baseline. Although energy from BMAd lipid stores is largely dispensable when mice are fed ad libitum, BMAd lipolysis is necessary to maintain myelopoiesis and bone mass under caloric restriction. BMAd-specific Pnpla2 deficiency compounds the effects of caloric restriction on loss of trabecular bone in male mice, likely due to impaired osteoblast expression of collagen genes and reduced osteoid synthesis. RNA sequencing analysis of bone marrow adipose tissue reveals that caloric restriction induces dramatic elevations in extracellular matrix organization and skeletal development genes, and energy from BMAd is required for these adaptations. BMAd-derived energy supply is also required for bone regeneration upon injury, and maintenance of bone mass with cold exposure.

Data availability

The accession number for the BMAT bulk RNA seq data reported in this paper is GEO: GSE183784.

The following data sets were generated

Article and author information

Author details

  1. Ziru Li

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Emily Bowers

    Department of Pediatrics, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Junxiong Zhu

    Department of Orthopedic Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Hui Yu

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5249-0193

  5. Julie Hardij

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Devika P Bagchi

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Hiroyuki Mori

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Kenneth T Lewis

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Katrina Granger

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Rebecca L Schill

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Steven M Romanelli

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  12. Simin Abrishami

    Department of Pediatrics, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  13. Kurt D Hankenson

    Department of Orthopedic Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  14. Kanakadurga Singer

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8278-3800

  15. Clifford J Rosen

    Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3436-8199

  16. Ormond MacDougald

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    For correspondence
    macdouga@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6907-7960

Funding

National Institutes of Health (R01 DK62876)

  • Ormond MacDougald

National Institutes of Health (T32 DK071212)

  • Kenneth T Lewis

National Institutes of Health (F32 DK122654)

  • Kenneth T Lewis

National Institutes of Health (T32 DK101357)

  • Rebecca L Schill

National Institutes of Health (F32 DK123887)

  • Rebecca L Schill

National Institutes of Health (R01AR066028)

  • Kurt D Hankenson

National Institutes of Health (R24DK092759)

  • Clifford J Rosen

American Diabetes Association (1-18-PDF-087)

  • Ziru Li

American Heart Association (20-PAF00361)

  • Emily Bowers

National Institutes of Health (R24 DK092759)

  • Ormond MacDougald

National Institutes of Health (R01 DK126230)

  • Ormond MacDougald

National Institutes of Health (R01 AG069795)

  • Ormond MacDougald

National Institutes of Health (T32 GM835326)

  • Steven M Romanelli

National Institutes of Health (F31 DK12272301)

  • Steven M Romanelli

National Institutes of Health (T32 HD007505)

  • Devika P Bagchi

National Institutes of Health (T32 GM007863)

  • Devika P Bagchi

National Institutes of Health (R01DK115583)

  • Kanakadurga Singer

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 approved by the University of Michigan Committee on the Use and Care of Animals with the protocol number as PRO00009687.

Copyright

© 2022, Li 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. Ziru Li
  2. Emily Bowers
  3. Junxiong Zhu
  4. Hui Yu
  5. Julie Hardij
  6. Devika P Bagchi
  7. Hiroyuki Mori
  8. Kenneth T Lewis
  9. Katrina Granger
  10. Rebecca L Schill
  11. Steven M Romanelli
  12. Simin Abrishami
  13. Kurt D Hankenson
  14. Kanakadurga Singer
  15. Clifford J Rosen
  16. Ormond MacDougald
(2022)
Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits
eLife 11:e78496.
https://doi.org/10.7554/eLife.78496

Share this article

https://doi.org/10.7554/eLife.78496

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