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.
N1 - Funding Information:
This work was supported by grants from the Medical Research Council (MR/M021394/1 to W.P.C.; MR/K010271/1 to R.H.S.), the National Institutes of Health (R01 DK62876 and R24 DK092759 to O.A.M.; K99-DE024178 to E.L.S.; and P30 DK089503 to the Michigan Nutrition Obesity Research Center), the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund (to W.P.C. and K.J.S.), and the British Heart Foundation (4-year BHF PhD Studentship to R.J.S., B.J.T., M.C.S. and B.M.N; BHF CoRE Bioinformatics Grant to W.P.C.; BHF CoRE grant to A.J.D.). W.P.C. is further supported by a Chancellor’s Fellowship from the University of Edinburgh. A.A.S.T was funded by the British Heart Foundation (RG/16/10/32375). E.J.R.v.B is supported by SINAPSE (the Scottish Imaging Network). We are grateful to the British Heart Foundation for providing funding towards establishment of the Edinburgh Preclinical PET/CT laboratory (RE/13/3/30183), and to NHS Research Scotland (NRS) for financial support of the Edinburgh Clinical Research Facility. R.H.S and M.C.W. are supported by The Chief Scientist Office of the Scottish Government (SCAF/17/02 to R.H.S.; PCL/17/04 to M.C.W.). J.P.M.A is supported by BHF Clinical Research Training Fellowship no. FS/17/ 51/33096. We are grateful to John Henderson (BVS, University of Edinburgh) for support with mouse husbandry; Anish K. Amin (Department of Orthopaedic Surgery, Royal Infirmary Edinburgh), Beena Polouse and Frank Morrow (Edinburgh Clinical Research Facility,) for help with human studies; Tashfeen Walton and Christophe Lucatelli (Edinburgh Imaging, University of Edinburgh) for radiotracer production; Robert K. Semple (Centre for Cardiovascular Science, University of Edinburgh) for critical feedback on this paper; and to staff at the University of Michigan microarray core facility for processing of rabbit microarray data.
Publisher Copyright:
© 2020, The Author(s).
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.
UR - http://www.scopus.com/inward/record.url?scp=85086693645&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-16878-2
DO - 10.1038/s41467-020-16878-2
M3 - Article
C2 - 32555194
AN - SCOPUS:85086693645
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3097
ER -