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Brown adipose tissue—a new role in humans?

Abstract

New targets for pharmacological interventions are of great importance to combat the epidemic of obesity. Brown adipose tissue could potentially represent one such target. Unlike white adipose tissue, brown adipose tissue has the ability to dissipate energy by producing heat rather than storing it as triglycerides. In small mammals, the presence of active brown adipose tissue is pivotal for the maintenance of body temperature and possibly to protect against the detrimental effects of surplus energy intake. Animal studies have shown that expansion and/or activation of brown adipose tissue counteracts diet-induced weight gain and related disorders such as type 2 diabetes mellitus. Several independent studies have now confirmed the presence of functional brown adipose tissue in adult humans, for whom this tissue is probably metabolically beneficial given its association with both low BMI and low total adipose tissue content. Over the past few years, knowledge of the transcriptional control and development of brown adipose tissue has increased substantially. Thus, several possible targets that may be useful for the expansion and/or activation of this tissue by pharmacological means have been identified. Whether or not brown adipose tissue will be useful in the battle against obesity remains to be seen. However, this possibility is certainly well worth exploring.

Key Points

  • The brown adipose organ has the capacity to consume energy by producing heat to defend an organism against a cold environment

  • Several studies have shown that metabolically active brown adipose tissue is present in notable amounts in healthy adults

  • The presence of brown adipose tissue in adults is inversely correlated with both BMI and percentage of body adipose tissue

  • Drugs aimed at expanding and/or activating brown adipose tissue are of possible interest for the treatment of obesity and obesity-related diseases like type 2 diabetes mellitus

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Figure 1: The energy balance.
Figure 2: Origin of brown adipocytes.
Figure 3: FDG-PET-CT images from the neck and upper thoracic region of a healthy adult subjected to cold and warm conditions.

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References

  1. Hossain, P., Kawar, B. & El Nahas, M. Obesity and diabetes in the developing world--a growing challenge. N. Engl. J. Med. 356, 213–215 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Shulman, G. I. Cellular mechanisms of insulin resistance. J. Clin. Invest. 106, 171–176 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Qatanani, M. & Lazar, M. A. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev. 21, 1443–1455 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Fruhbeck, G., Becerril, S., Sainz, N., Garrastachu, P. & Garcia-Velloso, M. J. BAT: a new target for human obesity? Trends Pharmacol. Sci. 30, 387–396 (2009).

    Article  PubMed  Google Scholar 

  5. Gesta, S., Tseng, Y. H. & Kahn, C. R. Developmental origin of fat: tracking obesity to its source. Cell 131, 242–256 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Timmons, J. A. et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc. Natl Acad. Sci. USA 104, 4401–4406 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Seale, P. et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab. 6, 38–54 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kajimura, S. et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev. 22, 1397–1409 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kajimura, S. et al. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature 460, 1154–1158 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tseng, Y. H. et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454, 1000–1004 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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 

  14. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Himms-Hagen, J. et al. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. Am. J. Physiol. Cell Physiol. 279, C670–C681 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Xue, B. et al. Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J. Lipid Res. 48, 41–51 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Tang, W. et al. White fat progenitor cells reside in the adipose vasculature. Science 322, 583–586 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Seale, P., Kajimura, S. & Spiegelman, B. M. Transcriptional control of brown adipocyte development and physiological function—of mice and men. Genes Dev. 23, 788–797 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vernochet, C., Peres, S. B. & Farmer, S. R. Mechanisms of obesity and related pathologies: transcriptional control of adipose tissue development. FEBS J. 276, 5729–5737 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Farmer, S. R. Molecular determinants of brown adipocyte formation and function. Genes Dev. 22, 1269–1275 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Smith, R. E. & Horwitz, B. A. Brown fat and thermogenesis. Physiol. Rev. 49, 330–425 (1969).

    Article  CAS  PubMed  Google Scholar 

  22. Lowell, B. B. & Spiegelman, B. M. Towards a molecular understanding of adaptive thermogenesis. Nature 404, 652–660 (2000).

    Article  CAS  PubMed  Google Scholar 

  23. Cannon, B. & Nedergaard, J. Brown adipose tissue: function and physiological significance. Physiol. Rev. 84, 277–359 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Davis, T. R., Johnston, D. R., Bell, F. C. & Cremer, B. J. Regulation of shivering and non-shivering heat production during acclimation of rats. Am. J. Physiol. 198, 471–475 (1960).

    Article  CAS  PubMed  Google Scholar 

  25. Davis, T. R. Chamber cold acclimatization in man. J. Appl. Physiol. 16, 1011–1015 (1961).

    Article  CAS  PubMed  Google Scholar 

  26. Golozoubova, V. et al. Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold. FASEB J. 15, 2048–2050 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Jacobsson, A., Stadler, U., Glotzer, M. A. & Kozak, L. P. Mitochondrial uncoupling protein from mouse brown fat. Molecular cloning, genetic mapping, and mRNA expression. J. Biol. Chem. 260, 16250–16254 (1985).

    CAS  PubMed  Google Scholar 

  28. Krauss, S., Zhang, C. Y. & Lowell, B. B. The mitochondrial uncoupling-protein homologs. Nat. Rev. Mol. Cell Biol. 6, 248–261 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Puigserver, P. et al. A cold-inducible co-activator of nuclear receptors linked to adaptive thermogenesis. Cell 92, 829–839 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Silva, J. E. & Larsen, P. R. Adrenergic activation of triiodothyronine production in brown adipose tissue. Nature 305, 712–713 (1983).

    Article  CAS  PubMed  Google Scholar 

  31. Puigserver, P. & Spiegelman, B. M. Peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1 alpha): transcriptional co-activator and metabolic regulator. Endocr. Rev. 24, 78–90 (2003).

    Article  CAS  PubMed  Google Scholar 

  32. Bukowiecki, L., Collet, A. J., Follea, N., Guay, G. & Jahjah, L. Brown adipose tissue hyperplasia: a fundamental mechanism of adaptation to cold and hyperphagia. Am. J. Physiol. 242, E353–E359 (1982).

    Article  CAS  PubMed  Google Scholar 

  33. Lowell, B. B. et al. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366, 740–742 (1993).

    Article  CAS  PubMed  Google Scholar 

  34. Enerback, S. et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387, 90–94 (1997).

    Article  CAS  PubMed  Google Scholar 

  35. Thomas, S. A. & Palmiter, R. D. Thermoregulatory and metabolic phenotypes of mice lacking norepinephrine and epinephrine. Nature 387, 94–97 (1997).

    Article  CAS  PubMed  Google Scholar 

  36. Bachman, E. S. et al. BetaAR signaling required for diet-induced thermogenesis and obesity resistance. Science 297, 843–845 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Lowell, B. B. & Bachman, E. S. Beta-adrenergic receptors, diet-induced thermogenesis, and obesity. J. Biol. Chem. 278, 29385–29388 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Rothwell, N. J. & Stock, M. J. A role for brown adipose tissue in diet-induced thermogenesis. Nature 281, 31–35 (1979).

    Article  CAS  PubMed  Google Scholar 

  39. Hamann, A., Flier, J. S. & Lowell, B. B. Decreased brown fat markedly enhances susceptibility to diet-induced obesity, diabetes, and hyperlipidemia. Endocrinology 137, 21–29 (1996).

    Article  CAS  PubMed  Google Scholar 

  40. Cederberg, A. et al. FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell 106, 563–573 (2001).

    Article  CAS  PubMed  Google Scholar 

  41. Kim, J. K. et al. Adipocyte-specific overexpression of FOXC2 prevents diet-induced increases in intramuscular fatty acyl CoA and insulin resistance. Diabetes 54, 1657–1663 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Zhou, Z. et al. Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat. Genet. 35, 49–56 (2003).

    Article  PubMed  Google Scholar 

  43. Strosberg, A. D. & Pietri-Rouxel, F. Function and regulation of the beta 3-adrenoceptor. Trends Pharmacol. Sci. 17, 373–381 (1996).

    Article  CAS  PubMed  Google Scholar 

  44. Ursino, M. G., Vasina, V., Raschi, E., Crema, F. & De Ponti, F. The beta3-adrenoceptor as a therapeutic target: current perspectives. Pharmacol. Res. 59, 221–234 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Friedman, J. M. & Halaas, J. L. Leptin and the regulation of body weight in mammals. Nature 395, 763–770 (1998).

    Article  CAS  PubMed  Google Scholar 

  46. Knehans, A. W. & Romsos, D. R. Reduced norepinephrine turnover in brown adipose tissue of ob/ob mice. Am. J. Physiol. 242, E253–E261 (1982).

    CAS  PubMed  Google Scholar 

  47. Collins, S. et al. Role of leptin in fat regulation. Nature 380, 677 (1996).

    Article  CAS  PubMed  Google Scholar 

  48. Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L. & Sivitz, W. I. Receptor-mediated regional sympathetic nerve activation by leptin. J. Clin. Invest. 100, 270–278 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Rothwell, N. J., Stock, M. J. & Tyzbir, R. S. Energy balance and mitochondrial function in liver and brown fat of rats fed “cafeteria” diets of varying protein content. J. Nutr. 112, 1663–1672 (1982).

    Article  CAS  PubMed  Google Scholar 

  50. Rothwell, N. J., Stock, M. J. & Tyzbir, R. S. Mechanisms of thermogenesis induced by low protein diets. Metabolism 32, 257–261 (1983).

    Article  CAS  PubMed  Google Scholar 

  51. Lean, M. E. J. & James, W. P. T. in Brown Adipose Tissue (eds Trayhurn, P. & Nicholls, D. G.) 339–365 (Arnold, London, 1986).

    Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Huttunen, P., Hirvonen, J. & Kinnula, V. The occurrence of brown adipose tissue in outdoor workers. Eur. J. Appl. Physiol. Occup. Physiol. 46, 339–345 (1981).

    Article  CAS  PubMed  Google Scholar 

  54. English, J. T., Patel, S. K. & Flanagan, M. J. Association of pheochromocytomas with brown fat tumors. Radiology 107, 279–281 (1973).

    Article  CAS  PubMed  Google Scholar 

  55. Sutherland, J. C., Callahan, W. P. Jr & Campbell, G. L. Hibernoma: a tumor of brown fat. Cancer 5, 364–368 (1952).

    Article  CAS  PubMed  Google Scholar 

  56. 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).

    Article  CAS  PubMed  Google Scholar 

  57. Soderlund, V., Larsson, S. A. & Jacobsson, H. Reduction of FDG uptake in brown adipose tissue in clinical patients by a single dose of propranolol. Eur. J. Nucl. Med. Mol. Imaging 34, 1018–1022 (2007).

    Article  PubMed  Google Scholar 

  58. Christensen, C. R., Clark, P. B. & Morton, K. A. Reversal of hypermetabolic brown adipose tissue in F-18 FDG PET imaging. Clin. Nucl. Med. 31, 193–196 (2006).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  60. Zingaretti, M. C. et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 23, 3113–3120 (2009).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  63. Saito, M. et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58, 1526–1531 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Au-Yong, I. T., Thorn, N., Ganatra, R., Perkins, A. C. & Symonds, M. E. Brown adipose tissue and seasonal variation in humans. Diabetes 58, 2583–2587 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Cohade, C., Mourtzikos, K. A. & Wahl, R. L. “USA-Fat”: prevalence is related to ambient outdoor temperature-evaluation with 18F-FDG PET/CT. J. Nucl. Med. 44, 1267–1270 (2003).

    PubMed  Google Scholar 

  66. Rothwell, N. J. & Stock, M. J. Luxuskonsumption, diet-induced thermogenesis and brown fat: the case in favor. Clin. Sci. (Lond.) 64, 19–23 (1983).

    Article  CAS  Google Scholar 

  67. Ma, S. W. & Foster, D. O. Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo. Can. J. Physiol. Pharmacol. 64, 609–614 (1986).

    Article  CAS  PubMed  Google Scholar 

  68. Sramkova, D. et al. The UCP1 gene polymorphism A-3826G in relation to DM2 and body composition in Czech population. Exp. Clin. Endocrinol. Diabetes 115, 303–307 (2007).

    Article  CAS  PubMed  Google Scholar 

  69. Fujisawa, T., Ikegami, H., Kawaguchi, Y. & Ogihara, T. Meta-analysis of the association of Trp64Arg polymorphism of beta 3-adrenergic receptor gene with body mass index. J. Clin. Endocrinol. Metab. 83, 2441–2444 (1998).

    CAS  PubMed  Google Scholar 

  70. Kurokawa, N. et al. The ADRB3 Trp64Arg variant and BMI: a meta-analysis of 44 833 individuals. Int. J. Obes. (Lond.) 32, 1240–1249 (2008).

    Article  CAS  Google Scholar 

  71. Feldmann, H. M., Golozoubova, V., Cannon, B. & Nedergaard, J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 9, 203–209 (2009).

    Article  CAS  PubMed  Google Scholar 

  72. Allegra, S. R., Gmuer, C. & O'Leary, G. P. Jr. Endocrine activity in a large hibernoma. Hum. Pathol. 14, 1044–1052 (1983).

    Article  CAS  PubMed  Google Scholar 

  73. Arch, J. R. et al. Atypical beta-adrenoceptor on brown adipocytes as target for anti-obesity drugs. Nature 309, 163–165 (1984).

    Article  CAS  PubMed  Google Scholar 

  74. Bousquet-Melou, A., Galitzky, J., Carpene, C., Lafontan, M. & Berlan, M. Beta-adrenergic control of lipolysis in primate white fat cells: a comparative study with nonprimate mammals. Am. J. Physiol. 267, R115–R123 (1994).

    Article  CAS  PubMed  Google Scholar 

  75. Langin, D. Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. Pharmacol. Res. 53, 482–491 (2006).

    Article  CAS  PubMed  Google Scholar 

  76. Spiegelman, B. M. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 47, 507–514 (1998).

    Article  CAS  PubMed  Google Scholar 

  77. Wilson-Fritch, L. et al. Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J. Clin. Invest. 114, 1281–1289 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Tran, T. T. & Kahn, C. R. Transplantation of adipose tissue and stem cells: role in metabolism and disease. Nat. Rev. Endocrinol. 6, 195–213 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We apologize to all colleagues who have been cited only cursorily, or have not been cited due to space constraints. M. E. Lidell and S. Enerbäck are supported by grants from the Söderberg Foundation, the Swedish Research Council (grant K2005-32BI-15,324-01A), the Arne and IngaBritt Lundberg Foundation, the Knut and Alice Wallenberg Foundation and the Swedish Foundation for Strategic Research through the Center for Cardiovascular and Metabolic Research.

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Lidell, M., Enerbäck, S. Brown adipose tissue—a new role in humans?. Nat Rev Endocrinol 6, 319–325 (2010). https://doi.org/10.1038/nrendo.2010.64

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