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

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.; Said, D.; Poloni, A.; Cinti, S.; MacPherson, G. J.; Dweck, M. R.; Andrews, J. P. M.; Williams, M. C.; Wallace, R. J.; van Beek, E. J. R.; MacDougald, O. A.; Morton, N. M.; Stimson, R. H.; Cawthorn, W. P.

doi:10.1101/673129

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bioRxiv · 10.1101/673129

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

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Abstract

Bone marrow adipose tissue (BMAT) represents >10% of total adipose mass, yet unlike white or brown adipose tissues (WAT or BAT), its role in systemic metabolism remains unclear. Using transcriptomics, we reveal that BMAT is molecularly distinct to WAT but is not enriched for brown or beige adipocyte markers. Instead, pathway analysis indicated altered glucose metabolism and decreased insulin responsiveness in BMAT. We therefore tested these functions in mice and humans using positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose, including establishing a new method for BMAT identification from clinical CT scans. This revealed that BMAT resists insulin- and cold-stimulated glucose uptake and is thus functionally distinct to WAT and BAT. However, BMAT displayed greater basal glucose uptake than axial bones or subcutaneous WAT, underscoring its potential to influence systemic glucose homeostasis. These PET/CT studies are the first to characterise BMAT function in vivo and identify BMAT as a distinct, major subtype of adipose tissue.\n\nHIGHLIGHTSO_LIBone marrow adipose tissue (BMAT) is molecularly distinct to other adipose subtypes.\nC_LIO_LIBMAT is less insulin responsive than WAT and, unlike BAT, is not cold-responsive.\nC_LIO_LIHuman BMAT has greater basal glucose uptake than axial bone or subcutaneous WAT.\nC_LIO_LIWe establish a PET/CT method for BMAT localisation and functional analysis in vivo.\nC_LI

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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., Said, D., Poloni, A., Cinti, S., MacPherson, G. J., Dweck, M. R., Andrews, J. P. M., Williams, M. C., Wallace, R. J., van Beek, E. J. R., MacDougald, O. A., Morton, N. M., Stimson, R. H., Cawthorn, W. P.. 2019-06-18. Bone marrow adipose tissue is a unique adipose subtype with distinct roles in systemic glucose homeostasis. https://doi.org/10.1101/673129

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