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Evidence for two types of brown adipose tissue in humans

Abstract

The previously observed supraclavicular depot of brown adipose tissue (BAT) in adult humans was commonly believed to be the equivalent of the interscapular thermogenic organ of small mammals. This view was recently disputed1 on the basis of the demonstration that this depot consists of beige (also called brite) brown adipocytes, a newly identified type of brown adipocyte that is distinct from the classical brown adipocytes that make up the interscapular thermogenic organs of other mammals. A combination of high-resolution imaging techniques and histological and biochemical analyses showed evidence for an anatomically distinguishable interscapular BAT (iBAT) depot in human infants that consists of classical brown adipocytes, a cell type that has so far not been shown to exist in humans. On the basis of these findings, we conclude that infants, similarly to rodents, have the bona fide iBAT thermogenic organ consisting of classical brown adipocytes that is essential for the survival of small mammals in a cold environment.

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Figure 1: Three-dimensional reconstruction of iBAT in a human infant.
Figure 2: BAT depots identified by MRI represent bona fide BAT containing classical brown adipocytes.
Figure 3: Gene expression profiling of human BAT depots.

References

  1. 1

    Wu, J. et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150, 366–376 (2012).

    CAS  Article  Google Scholar 

  2. 2

    Nedergaard, J., Bengtsson, T. & Cannon, B. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab. 293, E444–E452 (2007).

    CAS  Article  Google Scholar 

  3. 3

    Cypess, A.M. et al. Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360, 1509–1517 (2009).

    CAS  Article  Google Scholar 

  4. 4

    van Marken Lichtenbelt, W.D. et al. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 360, 1500–1508 (2009).

    CAS  Article  Google Scholar 

  5. 5

    Virtanen, K.A. et al. Functional brown adipose tissue in healthy adults. N. Engl. J. Med. 360, 1518–1525 (2009).

    CAS  Article  Google Scholar 

  6. 6

    Lee, P., Greenfield, J.R., Ho, K.K. & Fulham, M.J. A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab. 299, E601–E606 (2010).

    CAS  Article  Google Scholar 

  7. 7

    Ouellet, V. et al. Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG–detected BAT in humans. J. Clin. Endocrinol. Metab. 96, 192–199 (2011).

    CAS  Article  Google Scholar 

  8. 8

    Pfannenberg, C. et al. Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans. Diabetes 59, 1789–1793 (2010).

    CAS  Article  Google Scholar 

  9. 9

    Cousin, B. et al. Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J. Cell Sci. 103, 931–942 (1992).

    CAS  PubMed  Google Scholar 

  10. 10

    Guerra, C., Koza, R.A., Yamashita, H., Walsh, K. & Kozak, L.P. Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J. Clin. Invest. 102, 412–420 (1998).

    CAS  Article  Google Scholar 

  11. 11

    Seale, P. et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature 454, 961–967 (2008).

    CAS  Article  Google Scholar 

  12. 12

    Atit, R. et al. β-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse. Dev. Biol. 296, 164–176 (2006).

    CAS  Article  Google Scholar 

  13. 13

    Gupta, R.K. et al. Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells. Cell Metab. 15, 230–239 (2012).

    CAS  Article  Google Scholar 

  14. 14

    Lee, Y.H., Petkova, A.P., Mottillo, E.P. & Granneman, J.G. In vivo identification of bipotential adipocyte progenitors recruited by βa3-adrenoceptor activation and high-fat feeding. Cell Metab. 15, 480–491 (2012).

    CAS  Article  Google Scholar 

  15. 15

    Tran, K.V. et al. The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Metab. 15, 222–229 (2012).

    CAS  Article  Google Scholar 

  16. 16

    Cannon, B. & Nedergaard, J. Cell biology: neither brown nor white. Nature 488, 286–287 (2012).

    CAS  Article  Google Scholar 

  17. 17

    Aherne, W. & Hull, D. Brown adipose tissue and heat production in the newborn infant. J. Pathol. Bacteriol. 91, 223–234 (1966).

    CAS  Article  Google Scholar 

  18. 18

    Heaton, J.M. The distribution of brown adipose tissue in the human. J. Anat. 112, 35–39 (1972).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Hu, H.H., Tovar, J.P., Pavlova, Z., Smith, M.L. & Gilsanz, V. Unequivocal identification of brown adipose tissue in a human infant. J. Magn. Reson. Imaging 35, 938–942 (2012).

    Article  Google Scholar 

  20. 20

    Waldén, T.B., Hansen, I.R., Timmons, J.A., Cannon, B. & Nedergaard, J. Recruited vs. nonrecruited molecular signatures of brown, “brite,” and white adipose tissues. Am. J. Physiol. Endocrinol. Metab. 302, E19–E31 (2012).

    Article  Google Scholar 

  21. 21

    Houstěk, J. et al. Type II iodothyronine 5′-deiodinase and uncoupling protein in brown adipose tissue of human newborns. J. Clin. Endocrinol. Metab. 77, 382–387 (1993).

    PubMed  Google Scholar 

  22. 22

    Orava, J. et al. Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab. 14, 272–279 (2011).

    CAS  Article  Google Scholar 

  23. 23

    Dixon, W.T. Simple proton spectroscopic imaging. Radiology 153, 189–194 (1984).

    CAS  Article  Google Scholar 

  24. 24

    Rydell, J. et al. Phase sensitive reconstruction for water/fat separation in MR imaging using inverse gradient. Med. Image Comput. Comput. Assist. Interv. 10, 210–218 (2007).

    PubMed  Google Scholar 

  25. 25

    Dahlqvist Leinhard, O. et al. Quantitative abdominal fat estimation using MRI. Proc. Int. Conf. Pattern Recognition 1–4 (2008).

  26. 26

    Romu, T., Borga, M. & Dahlqvist Leinhard, O. MANA—multi scale adaptive normalized averaging. Proc. Int. Symp. Biomedical Imaging 361–364 (2011).

  27. 27

    Malmberg, F., Lindblad, J. & Nyström, I. Sub-pixel segmentation with the Image Foresting transform. Combinatorial Image Analysis: Proc. 13th Int. Workshop, IWCIA'09, Playa del Carmen, Mexico, November 24–27, 2009 5852, 201–211 (2009).

    Article  Google Scholar 

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Acknowledgements

This work was supported by grants to S.E. from the Swedish Research Council (grant numbers 2009-2590 and 2010-3281), The Knut and Alice Wallenberg Foundation, Sahlgrenska's University Hospital (LUA-ALF), EU grants (HEALTH-F2-2011-278373; DIABAT), The IngaBritt and Arne Lundgren Foundation, The Söderberg Foundation, The King Gustaf V and Queen Victoria Freemason Foundation and the Swedish Foundation for Strategic Research through the Center for Cardiovascular and Metabolic Research. M.J.B. was supported by a postdoctoral fellowship from the Fritz Thyssen Stiftung. We thank B. Mauracher (Medizinische Klinik und Poliklinik IV, Klinikum der LMU) for excellent technical assistance and acknowledge the Centre for Cellular Imaging and the Genomics Core Facility at Sahlgrenska Academy for technical assistance and use of equipment. We also acknowledge assistance from J. Kilberg and P. Quick (radiology technicians at CMIV) and J. Berge, E. Edston and H. Bengtsson (forensic pathologists) at the National Board of Forensic Medicine, Linköping Division, Department of Forensic Medicine, Linköping.

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A.P., M.B., M.E.L., M.J.B. and S.E. conceived and designed the experiments. D.N., L.E., M.E.L., M.H., M.J.B., O.D.L. and T.R. performed the experiments. A.P., D.N., L.E., M.B., M.E.L., M.H., M.J.B., O.D.L., S.E. and T.R. analyzed the data. F.B., K.A.V., M.S., T.M. and P.N. provided samples. M.E.L., M.J.B. and S.E. wrote the manuscript.

Corresponding author

Correspondence to Sven Enerbäck.

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Competing interests

S.E. is shareholder and consultant to Ember Therapeutics.

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Supplementary Figure 1 and Supplementary Table 1 (PDF 558 kb)

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Lidell, M., Betz, M., Leinhard, O. et al. Evidence for two types of brown adipose tissue in humans. Nat Med 19, 631–634 (2013). https://doi.org/10.1038/nm.3017

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