A bone-specific adipogenesis pathway in fat-free mice defines key origins and adaptations of bone marrow adipocytes with age and disease

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Abstract

Bone marrow adipocytes accumulate with age and in diverse disease states. However, their origins and adaptations in these conditions remain unclear, impairing our understanding of their context-specific endocrine functions and relationship with surrounding tissues. In this study, by analyzing bone and adipose tissues in the lipodystrophic 'fat-free' mouse, we define a novel, secondary adipogenesis pathway that relies on the recruitment of adiponectin-negative stromal progenitors. This pathway is unique to the bone marrow and is activated with age and in states of metabolic stress in the fat-free mouse model, resulting in the expansion of bone marrow adipocytes specialized for lipid storage with compromised lipid mobilization and cytokine expression within regions traditionally devoted to hematopoiesis. This finding further distinguishes bone marrow from peripheral adipocytes and contributes to our understanding of bone marrow adipocyte origins, adaptation, and relationships with surrounding tissues with age and disease.

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All applicable source data are included with publication.

Article and author information

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Xiao Zhang

Department of Medicine; Department of Biomedical Engineering, Washington University, Saint Louis, United States

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

Department of Medicine, Washington University, Saint Louis, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6439-1309
Kristann L Magee

Department of Medicine, Washington University, Saint Louis, United States

Competing interests
The authors declare that no competing interests exist.
Madelyn R Lorenz

Department of Medicine, Washington University, Saint Louis, United States

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

Department of Medicine: Department of Orthopaedic Surgery, Washington University, Saint Louis, United States

Competing interests
The authors declare that no competing interests exist.
Charles A Harris

Department of Medicine, Washington University, Saint Louis, United States

Competing interests
The authors declare that no competing interests exist.
Clarissa S Craft

Department of Medicine, Washington University, Saint Louis, United States

Competing interests
The authors declare that no competing interests exist.
Erica L Scheller

Department of Medicine; Department of Biomedical Engineering, Washington University, Saint Louis, United States

For correspondence
scheller@wustl.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1551-3816

Funding

National Institutes of Health (R00-DE02417)

Erica L Scheller

National Institutes of Health (P30-AR074992)

Erica L Scheller

Children's Discovery Institute (CDI-CORE-2015-505 and CDI-CORE-2019-813)

Erica L Scheller

Foundation for Barnes-Jewish Hospital (3770 and 4642)

Erica L Scheller

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 work was performed as approved by the Institutional Animal Care and Use Committee (IACUC) at Washington University (Saint Louis, MO, USA; Protocol IDs 20160183 and 20180282). Animal facilities at Washington University meet federal, state, and local guidelines for laboratory animal care and are accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC).

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.