High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity

Masayuki Saito, Yuko Okamatsu-Ogura, Mami Matsushita, Kumiko Watanabe, Takeshi Yoneshiro, Junko Nio-Kobayashi, Toshihiko Iwanaga, Masao Miyagawa, Toshimitsu Kameya, Kunihiro Nakada, Yuko Kawai, Masayuki Tsujisaki, Masayuki Saito, Yuko Okamatsu-Ogura, Mami Matsushita, Kumiko Watanabe, Takeshi Yoneshiro, Junko Nio-Kobayashi, Toshihiko Iwanaga, Masao Miyagawa, Toshimitsu Kameya, Kunihiro Nakada, Yuko Kawai, Masayuki Tsujisaki

Abstract

Objective: The significant roles of brown adipose tissue (BAT) in the regulation of energy expenditure and adiposity are established in small rodents but have been controversial in humans. The objective is to examine the prevalence of metabolically active BAT in healthy adult humans and to clarify the effects of cold exposure and adiposity.

Research design and methods: In vivo 2-[(18)F]fluoro-2-deoxyglucose (FDG) uptake into adipose tissue was measured in 56 healthy volunteers (31 male and 25 female subjects) aged 23-65 years by positron emission tomography (PET) combined with X-ray computed tomography (CT).

Results: When exposed to cold (19 degrees C) for 2 h, 17 of 32 younger subjects (aged 23-35 years) and 2 of 24 elderly subjects (aged 38-65 years) showed a substantial FDG uptake into adipose tissue of the supraclavicular and paraspinal regions, whereas they showed no detectable uptake when kept warm (27 degrees C). Histological examinations confirmed the presence of brown adipocytes in these regions. The cold-activated FDG uptake was increased in winter compared with summer (P < 0.001) and was inversely related to BMI (P < 0.001) and total (P < 0.01) and visceral (P < 0.001) fat areas estimated from CT image at the umbilical level.

Conclusions: Our findings, being against the conventional view, indicate the high incidence of metabolically active BAT in adult humans and suggest a role in the control of body temperature and adiposity.

Figures

FIG. 1.
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 5 min). After 1 h under this cold condition, he was given an intravenous injection of 18F-FDG and kept under the same cold condition. One hour after the 18F-FDG injection, whole-body PET/CT scans were performed in a room at 24°C. B: Two weeks after the first examination in the cold condition (A), the same subject underwent FDG-PET/CT examination as previously, but he was kept at 27°C with standard clothing and without leg icing (warm condition) for 2 h before the examination.
FIG. 2.
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 Fig. 1 on 29 August 2006 (summer) and again on 22 February 2007 (winter). B: Eight subjects (five male and three female subjects) underwent FDG-PET/CT examination under the cold condition in summer (29 August to 28 September 2006) and again in winter (29 January to 6 March 2007). FDG uptake into the supraclavicular region was densitometrically quantified, normalized, and expressed as relative to that in the brain. Thick bars are means ± SD.
FIG. 3.
FIG. 3.
Cold-activated BAT and adiposity. Cold-activated FDG uptake into the supraclavicular region of 19 subjects was quantified as in Fig. 2 and plotted against BMI and total and visceral fat areas estimated from CT images at the umbilical (L4 and L5) level.
FIG. 4.
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 figure is available in the online issue.)

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