Since one of the typical methods to activate BAT in rodents is cold exposure, we first examined the acute effects of cold exposure on FDG uptake. For this, healthy subjects were overnight fasted and kept in a room at 28°C (warm condition) or at 19°C with light clothes and intermittent application of an ice-cooled footrest (cold condition). Two hours later, they underwent FDG-PET/CT examination. Under the warm condition, a clear FDG uptake was detected in the brain, heart, and the oropharengeal region, while no FDG signal in adipose tissue (B). When the same subjects were kept under the 2-h cold condition, a clear and intense FDG uptake was found in adipose tissue at the supraclavicular and paraspinal regions (A).
FIG. 1. Whole-body FDG-PET images under cold or warm condition. A: A 25-year-old male subject fasted for 12 h and was kept in an air-conditioned room at 19°C with light clothing and put his legs on an ice block intermittently (for ~4 min at every (more ...)
During a 7-month period from August of 2006 to the following March, we performed a total of 71 FDG-PET/CT examinations under the 2-h cold condition for 56 healthy volunteers aged 23–65 years. As summarized in , cold-activated FDG uptake in the supraclavicular region was detected in 18 of 55 subjects (33%) in winter from January to March. Although the incidence of such FDG uptake seemed not to show apparent sex difference, it changed with age (P < 0.01 by χ2 test), being 52% (16 of 31) and 8% (2 of 24) in younger (aged 23–35 years) and elderly (aged 38–65 years) subjects, respectively. confirms again the stimulatory effect of acute cold exposure on FDG uptake as typically shown in ; that is, eight subjects who showed clear FDG uptake under the cold condition were tested again under the warm condition at 28°C in 2 weeks, but none of them showed detectable FDG uptake in the adipose tissue, including supraclavicular and paraspinal regions, regardless of the test seasons.
Prevalence of cold-activated BAT in adult humans
also suggests some seasonal variations of the total prevalence, being low in summer from August to September. This was clearly demonstrated from the results of some individual subjects; that is, in summer, the FDG uptake was detected in two of eight subjects. When the same subjects were examined again in winter, it was found in six subjects, four of which showed no FDG uptake in summer and the other two showed lower uptake in summer (B). Moreover, FDG uptake was sometimes detected both at the supraclavicular and paraspinal regions in winter but only in the supraclalvicular region in summer (A). Thus, the incidence and intensity of cold-activated FDG uptake showed seasonal variations, being higher in winter.
FIG. 2. FDG uptake into BAT in summer and winter. A: A 30-year-old female subject underwent FDG-PET/CT examination under the cold condition as in on 29 August 2006 (summer) and again on 22 February 2007 (winter). B: Eight subjects (five male and three (more ...)
In small rodents, BAT thermogenesis is recognized as a significant component of whole-body energy expenditure and thereby contributes to the regulation of body fat content (1
). To examine whether this is also the case in humans, we first analyzed the relationship between the cold-activated FDG uptake into BAT and adiposity in a total of 19 subjects bearing detectable BAT. As shown in , FDG uptake into the supraclavicular adipose tissue showed significant inverse relations to BMI (r
= −0.674, P
< 0.001), total fat (r
= −0.564, P
< 0.01), and visceral fat (r
= −0.681, P
< 0.001). Weaker but significant inverse relationships were also found to subcutaneous fat (r
= −0.492, P
< 0.05) and plasma insulin level (r
= −0.473, P
< 0.05) but not to plasma levels of leptin, adiponectin, and T3 (data not shown).
FIG. 3. Cold-activated BAT and adiposity. Cold-activated FDG uptake into the supraclavicular region of 19 subjects was quantified as in and plotted against BMI and total and visceral fat areas estimated from CT images at the umbilical (L4 and L5) level. (more ...)
We also compared the similar parameters in subjects bearing detectable and undetectable amounts of cold-activated BAT (). As expected from the results in , the mean age was significantly lower in the group bearing detectable BAT than that without BAT. Body weight, BMI, and visceral and subcutaneous fat areas estimated from CT tended to be lower in the group bearing detectable BAT, but the difference was not statistically significant. Since these parameters of adiposity are much influenced by aging, being higher in elderly subjects, next, we compared the two groups of 32 younger subjects (aged 23–35 years) (). The mean age was comparable in the two groups (aged 27.3 vs. 29.1 years in male subjects, aged 30.3 vs. 29.5 years in female subjects); the effects of aging may be canceled. There was no difference in height, body weight, and blood parameters examined between the two groups in both male and female subjects. The group bearing detectable BAT tended to show decreased BMI, body fat content, and visceral fat area compared with that without BAT, but again the difference was not statistically significant (data not shown). In a separate study, we examined histologically an autopsy sample of fat depots obtained from the supraclavicular region and found numerous multilocular adipocytes expressing UCP1 protein ().
Comparison between subjects bearing detectable (+) and undetectable (−) amounts of BAT
FIG. 4. Histological identification of UCP1-positive brown adipocytes in fat depots obtained from the supraclavicular region. Tissue sections were stained with hematoxylin and eosin (A) or anti-serum against rat UCP1 (B). (A high-quality representation of this (more ...)