Ann. N.Y. Acad. Sci. ISSN 0077-8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: The Year in Diabetes and Obesity Three years with adult human brown adipose tissue Jan Nedergaard, Tore Bengtsson, and Barbara Cannon The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden Address for correspondence: Jan Nedergaard, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden. jan@metabol.su.se The presence of active brown adipose tissue in adult humans has been recognized in general physiology only since 2007. The intervening three years established that the depots originally observed by 18 F-fluoro-deoxy-glucose positron emission tomography (FDG PET) scanning techniques really are brown adipose tissue depots because they are enriched for uncoupling protein 1 (UCP1). Reports of low apparent prevalence of brown adipose tissue based on retrospective studies of hospital records of FDG PET scans markedly underestimate true prevalence because such studies only reflect acute activity state; consequently, such retrospective studies cannot be conclusively analysed for factors influencing activity and amount of brown adipose tissue. Dedicated studies show that the true prevalence is 30–100%, depending on cohort. Warm temperature during the investigation—as well as adrenergic antagonists— inhibit tissue activity. There is probably no sexual dimorphism in the prevalence of brown adipose tissue. Outdoor temperature may affect the amount of brown adipose tissue, and the amount is negatively correlated with age and obesity. The presence of brown adipose tissue is associated with cold-induced nonshivering thermogenesis, and the tissue may be a major organ for glucose disposal. The decline in brown adipose tissue amount with increasing age may account for or aggravate middle-age obesity. Maintained activation of brown adipose tissue throughout life may thus protect against obesity and diabetes. Keywords: FDG PET; prevalence; age; obesity; sexual dimorphism; nonshivering thermogenesis The novel realization that adult humans possess ac- tive brown adipose tissue came unexpectedly from problems arising with the use of new techniques in a clinical discipline: radiology. In the 1990s, the appli- cation of 18 F-fluoro-deoxy-glucose positron emis- sion tomography (PET) for the detection of tumors and particularly tumor metastases gained increased routine use. In principle, with this method, highly active glucose-utilizing tissues are visualized. Thus, tissues showing high uptake always included the brain and often the heart. Naturally, in some cases, metastasis or tumors were detected, as was the in- tention of the 18 F-fluoro-deoxy-glucose PET exam- inations. However, in a few cases, the interpretation of the scans was disturbed by the occurrence of ar- eas of high 18 F-fluoro-deoxy-glucose uptake in sym- metrical regions in the neck and chest region, and lower symmetrical uptakes in the kidney area, prin- cipally as illustrated in Figure 1. As it is unlikely that tumors manifest themselves in a symmetrical pat- tern, the uptake areas could hardly be tumors. They disturbed the interpretation of the PET scans but their nature remained unknown for nearly a decade. By combining 18 F-fluoro-deoxy-glucose PET with computer-assisted tomography (CT that gives in- formation about the characteristics of the tissue), it became clear that the uptake areas resembled adi- pose tissue. As early as 2002, Hany et al . 1 formulated that the indices implied that the areas represented brown adipose tissue. As this paper was published in the European Journal of Nuclear Medicine and Molecular Imaging , it was not observed by metabolic physiologists; however, the notion that the areas rep- resented brown adipose tissue gradually gained ac- ceptance among radiologists, and a series of reports and studies were successively published within the field. In 2007, we identified this radiological literature and found that by analyzing it from a physiological point of view the evidence was overwhelming that the collected data represented, unexpectedly, evi- dence for the presence of active brown adipose tissue doi: 10.1111/j.1749-6632.2010.05905.x E20 Ann. N.Y. Acad. Sci. 1212 (2011) E20–E36 c  2011 New York Academy of Sciences.