A bone-specific adipogenesis pathway in fat-free mice defines key origins and adaptations of bone marrow adipocytes with age and disease
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
Author details
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
© 2021, Zhang 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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