Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis

Karla J. Suchacki, Adriana A. S. Tavares, Domenico Mattiucci, Erica L. Scheller, Giorgos Papanastasiou, Calum Gray, Matthew C. Sinton, Lynne E. Ramage, Wendy A. McDougald, Andrea Lovdel, Richard J. Sulston, Benjamin J. Thomas, Bonnie M. Nicholson, Amanda J. Drake, Carlos J. Alcaide-Corral, Diana Said, Antonella Poloni, Saverio Cinti, Gavin J. Macpherson, Marc R. Dweck, Jack P. M. Andrews, Michelle C. Williams, Robert J. Wallace, Edwin J. R. Beek, Ormond A. MacDougald, Nicholas M. Morton, Roland H. Stimson and William P. Cawthorn ()
Additional contact information
Karla J. Suchacki: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Adriana A. S. Tavares: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Domenico Mattiucci: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Erica L. Scheller: Washington University
Giorgos Papanastasiou: Edinburgh Imaging, University of Edinburgh
Calum Gray: Edinburgh Imaging, University of Edinburgh
Matthew C. Sinton: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Lynne E. Ramage: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Wendy A. McDougald: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Andrea Lovdel: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Richard J. Sulston: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Benjamin J. Thomas: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Bonnie M. Nicholson: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Amanda J. Drake: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Carlos J. Alcaide-Corral: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Diana Said: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Antonella Poloni: Università Politecnica delle Marche
Saverio Cinti: Università Politecnica delle Marche
Gavin J. Macpherson: Royal Infirmary of Edinburgh
Marc R. Dweck: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Jack P. M. Andrews: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Michelle C. Williams: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Robert J. Wallace: The University of Edinburgh
Edwin J. R. Beek: Edinburgh Imaging, University of Edinburgh
Ormond A. MacDougald: University of Michigan
Nicholas M. Morton: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
Roland H. Stimson: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter
William P. Cawthorn: University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass, yet unlike white or brown adipose tissues (WAT or BAT) its metabolic functions remain unclear. Herein, we address this critical gap in knowledge. Our transcriptomic analyses revealed that BMAT is distinct from WAT and BAT, with altered glucose metabolism and decreased insulin responsiveness. We therefore tested these functions in mice and humans using positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose. This revealed that BMAT resists insulin- and cold-stimulated glucose uptake, while further in vivo studies showed that, compared to WAT, BMAT resists insulin-stimulated Akt phosphorylation. Thus, BMAT is functionally distinct from WAT and BAT. However, in humans basal glucose uptake in BMAT is greater than in axial bones or subcutaneous WAT and can be greater than that in skeletal muscle, underscoring the potential of BMAT to influence systemic glucose homeostasis. These PET/CT studies characterise BMAT function in vivo, establish new methods for BMAT analysis, and identify BMAT as a distinct, major adipose tissue subtype.

Date: 2020
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DOI: 10.1038/s41467-020-16878-2

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