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. van Beek; Ormond A. MacDougald; Nicholas M. Morton; Roland H. Stimson; William P. Cawthorn

doi:10.1038/s41467-020-16878-2

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. DweckJack 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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	3097
Journal	Nature Communications
Volume	11
DOIs	https://doi.org/10.1038/s41467-020-16878-2
Publication status	Published - 18 Jun 2020

Keywords / Materials (for Non-textual outputs)

Bone marrow adipose tissue
Adipose tissue
metabolism
PET-CT
Imaging

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10.1038/s41467-020-16878-2

s41467-020-16878-2Final published version, 6.42 MBLicence: Creative Commons: Attribution (CC-BY)

Combined magnetic resonance coronary angiography and positron emission tomography in patients with coronary artery disease
Williams, M. (Principal Investigator)
UK central government bodies/local authorities, health and hospital authorities
1/08/18 → 31/07/19
Project: Research
Regulation of brown adipose tissue and cold induced thermogenesis in humans
Stimson, R. (Principal Investigator)
UK central government bodies/local authorities, health and hospital authorities
1/03/18 → 30/06/23
Project: Research
Early clinical development of a thrombus 18F-radiotracer
Andrews, J. (Principal Investigator)
UK-based charities
1/10/17 → 30/09/20
Project: Research

Adipocytes and Bone
Cawthorn, W. (Invited speaker)
24 Jun 2020
Activity: Academic talk or presentation types › Invited talk

Edinburgh Imaging Facility
Grant, A. (Manager), van Beek, E. (Manager) & Semple, S. (Manager)
School of Neurological and Cardiovascular Sciences
Facility/equipment: Facility
Edinburgh Preclinical Imaging
Moran, C. (Manager), Thomson, A. (Manager), Lennen, R. J. (Manager), Tavares, A. (Manager), Alcaide-Corral, C. J. (Manager), Morgan, T. (Other), Cranston, I. (Other) & O'Rourke, K. (Other)
School of Neurological and Cardiovascular Sciences
Facility/equipment: Facility
Image Analysis Core
MacGillivray, T. (Manager) & Gray, C. (Other)
Work Enabled by Edinburgh Clinical Research Facility
Facility/equipment: Facility

William Cawthorn
- Centre for Cardiovascular Science
- School of Neurological and Cardiovascular Sciences - Reader
Person: Academic: Research Active

Cite this

Suchacki, K. J., Tavares, A. A. S., Mattiucci, D., Scheller, E. L., Papanastasiou, G., Gray, C., Sinton, M. C., Ramage, L. E., McDougald, W. A., Lovdel, A., Sulston, R. J., Thomas, B. J., Nicholson, B. M., Drake, A. J., Alcaide-Corral, C. J., Said, D., Poloni, A., Cinti, S., Macpherson, G. J., ... Cawthorn, W. P. (2020). Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis. Nature Communications, 11, Article 3097. https://doi.org/10.1038/s41467-020-16878-2

@article{830b082c99f34131849e659a640ea53d,

title = "Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis",

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.",

keywords = "Bone marrow adipose tissue, Adipose tissue, metabolism, PET-CT, Imaging",

author = "Suchacki, \{Karla J.\} and Tavares, \{Adriana A. S.\} and Domenico Mattiucci and Scheller, \{Erica L\} and Giorgos Papanastasiou and Calum Gray and Sinton, \{Matthew C.\} and Ramage, \{Lynne E.\} and McDougald, \{Wendy A.\} and Andrea Lovdel and Sulston, \{Richard J.\} and Thomas, \{Benjamin J.\} and Nicholson, \{Bonnie M.\} and Drake, \{Amanda J.\} and Alcaide-Corral, \{Carlos J.\} and Diana Said and Antonella Poloni and Saverio Cinti and Macpherson, \{Gavin J.\} and Dweck, \{Marc R.\} and Andrews, \{Jack P. M.\} and Williams, \{Michelle C.\} and Wallace, \{Robert J.\} and \{van Beek\}, \{Edwin J. R.\} and MacDougald, \{Ormond A.\} and Morton, \{Nicholas M.\} and Stimson, \{Roland H.\} and Cawthorn, \{William P.\}",

year = "2020",

month = jun,

day = "18",

doi = "10.1038/s41467-020-16878-2",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Suchacki, KJ, Tavares, AAS, Mattiucci, D, Scheller, EL, Papanastasiou, G, Gray, C, Sinton, MC, Ramage, LE, McDougald, WA, Lovdel, A, Sulston, RJ, Thomas, BJ, Nicholson, BM, Drake, AJ, Alcaide-Corral, CJ, Said, D, Poloni, A, Cinti, S, Macpherson, GJ, Dweck, MR, Andrews, JPM, Williams, MC, Wallace, RJ, van Beek, EJR, MacDougald, OA, Morton, NM, Stimson, RH & Cawthorn, WP 2020, 'Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis', Nature Communications, vol. 11, 3097. https://doi.org/10.1038/s41467-020-16878-2

TY - JOUR

T1 - Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis

AU - Suchacki, Karla J.

AU - Tavares, Adriana A. S.

AU - Mattiucci, Domenico

AU - Scheller, Erica L

AU - Papanastasiou, Giorgos

AU - Gray, Calum

AU - Sinton, Matthew C.

AU - Ramage, Lynne E.

AU - McDougald, Wendy A.

AU - Lovdel, Andrea

AU - Sulston, Richard J.

AU - Thomas, Benjamin J.

AU - Nicholson, Bonnie M.

AU - Drake, Amanda J.

AU - Alcaide-Corral, Carlos J.

AU - Said, Diana

AU - Poloni, Antonella

AU - Cinti, Saverio

AU - Macpherson, Gavin J.

AU - Dweck, Marc R.

AU - Andrews, Jack P. M.

AU - Williams, Michelle C.

AU - Wallace, Robert J.

AU - van Beek, Edwin J. R.

AU - MacDougald, Ormond A.

AU - Morton, Nicholas M.

AU - Stimson, Roland H.

AU - Cawthorn, William P.

PY - 2020/6/18

Y1 - 2020/6/18

N2 - 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.

AB - 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.

KW - Bone marrow adipose tissue

KW - Adipose tissue

KW - metabolism

KW - PET-CT

KW - Imaging

U2 - 10.1038/s41467-020-16878-2

DO - 10.1038/s41467-020-16878-2

M3 - Article

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

M1 - 3097

ER -

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

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