The preceding steps
In the 1990s, enigmatic symmetrical areas of unidentified tissues showing high glucose uptake were observed in routine PET scans of cancer patients (3). As early as 2002, it was suggested that such areas could represent brown adipose tissue (4), but this realization was buried in journals of radiology and went unrecognized in the metabolic world for half a decade. Even when the radiological treasure of unexpected evidence for the presence of active brown adipose tissue in adult humans was dug out (5), the data suggested that brown adipose tissue was only relevant for a small fraction (perhaps some 2%–5%) of adults. This apparent low prevalence was, however, due to all studies being “retrospective,” in that they were based on hospital records where patients were only unintentionally cold stressed. Later dedicated studies show that at least 30% of all adults — and probably close to 100% of young adults — possess brown adipose tissue (6, 7).
Acceptance that areas of glucose uptake were depots of brown adipose tissue required demonstration that the tissues contained the brown fat–specific UCP1. Indeed, concordant studies have demonstrated UCP1 mRNA and UCP1 protein in the clavicular and neck areas that show a high glucose uptake (refs. 8, 9, and Figure Figure1). 1).
However, is this brown adipose tissue really metabolically active: is brown fat on fire even in humans? After all, the indications of activity have until now been based solely on glucose uptake. One indication of increased metabolic activity could be an increased blood flow to the tissue, implying an increased oxygen requirement. Such an increased blood flow has recently been observed in humans in the cold, in parallel with an increase in glucose uptake (10). However, blood flow could increase without a concomitant increase in metabolism.
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The present step