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

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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
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-16878-2
State	Published - Dec 1 2020

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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(1), [3097]. https://doi.org/10.1038/s41467-020-16878-2

Suchacki, Karla J. ; Tavares, Adriana A.S. ; Mattiucci, Domenico ; Scheller, Erica L. ; Papanastasiou, Giorgos ; Gray, Calum ; Sinton, Matthew C. ; Ramage, Lynne E. ; McDougald, Wendy A. ; Lovdel, Andrea ; Sulston, Richard J. ; Thomas, Benjamin J. ; Nicholson, Bonnie M. ; Drake, Amanda J. ; Alcaide-Corral, Carlos J. ; Said, Diana ; Poloni, Antonella ; Cinti, Saverio ; Macpherson, Gavin J. ; Dweck, Marc R. ; Andrews, Jack P.M. ; Williams, Michelle C. ; Wallace, Robert J. ; van Beek, Edwin J.R. ; MacDougald, Ormond A. ; Morton, Nicholas M. ; Stimson, Roland H. ; Cawthorn, William P. / Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis. In: Nature communications. 2020 ; Vol. 11, No. 1.

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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.",

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.}",

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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, no. 1, 3097. https://doi.org/10.1038/s41467-020-16878-2

Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis. / Suchacki, Karla J.; Tavares, Adriana A.S.; Mattiucci, Domenico; Scheller, Erica L.; Papanastasiou, Giorgos; Gray, Calum; Sinton, Matthew C.; Ramage, Lynne E.; McDougald, Wendy A.; Lovdel, Andrea; Sulston, Richard J.; Thomas, Benjamin J.; Nicholson, Bonnie M.; Drake, Amanda J.; Alcaide-Corral, Carlos J.; Said, Diana; Poloni, Antonella; Cinti, Saverio; Macpherson, Gavin J.; Dweck, Marc R.; Andrews, Jack P.M.; Williams, Michelle C.; Wallace, Robert J.; van Beek, Edwin J.R.; MacDougald, Ormond A.; Morton, Nicholas M.; Stimson, Roland H.; Cawthorn, William P.

In: Nature communications, Vol. 11, No. 1, 3097, 01.12.2020.

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

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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 - 2020/12/1

Y1 - 2020/12/1

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.

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