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

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作者
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. van Beek
Ormond A. MacDougald
Nicholas M. Morton
Roland H. Stimson
William P. Cawthorn
机构
[1] University/BHF Centre for Cardiovascular Science,Dipartimento di Scienze Cliniche e Molecolari, Clinica di Ematologia
[2] University of Edinburgh,Division of Bone and Mineral Diseases, Department of Medicine
[3] The Queen’s Medical Research Institute,Dipartimento di Medicina Sperimentale e Clinica, Center of Obesity
[4] Edinburgh BioQuarter,Department of Orthopaedic Surgery
[5] Università Politecnica delle Marche,Department of Orthopaedics
[6] Washington University,Department of Molecular & Integrative Physiology
[7] Edinburgh Imaging,undefined
[8] University of Edinburgh,undefined
[9] Università Politecnica delle Marche,undefined
[10] Royal Infirmary of Edinburgh,undefined
[11] The University of Edinburgh,undefined
[12] University of Michigan,undefined
来源
Nature Communications | / 11卷
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摘要
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.
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