¹⁵O PET Measurement of Blood Flow and Oxygen Consumption in Cold-Activated Human Brown Fat

Representative images showing BAT ¹⁸F-FDG uptake in subjects belonging to high-BAT and low-BAT groups. Presence of cold-activated BAT was derived on basis of combined conditions of HU range (−250 to −50) and SUV > 2. ROIs were defined at location of shoulder muscle (broken line) and WAT (not shown). (A) Nine of 25 subjects showed spatially extensive cold-activated BAT (high-BAT group, mass > 10 g). (B). The remaining 16 subjects showed either no cold-activated BAT or only small depots (low-BAT group, mass < 10 g).

Distribution of amount of BAT mass, maximal SUV, and lean body mass in high-BAT group (●, n = 9, 8 women and 1 man) and in low-BAT group (○, n = 16, 7 women and 9 men). Error bars represent SD of measurements. (A) Amount of BAT mass was highly variable, displaying bimodal distribution. Accordingly, subjects were stratified into high-BAT and low-BAT groups. (B) Maximal SUV in BAT was significantly higher in high-BAT group than in low-BAT group (P < 0.01). (C) Because of higher male-to-female ratio in low-BAT group, lean body mass showed tendency toward higher values in low-BAT group.

Absolute blood flow during rest and cold stress in BAT and WAT in high-BAT and low-BAT groups. (A) Blood flow in activated BAT (high-BAT) is about 50% higher than in nonactivated BAT (low-BAT). Increase in blood flow was significantly higher in high-BAT group than in low-BAT group, although both increases were significant between rest and cold stress. (B) Blood flow in WAT was significantly higher in high-BAT group at both rest and cold stress than in low-BAT group. However, no significant differences were observed between rest and cold stress in either group.

MRO₂ in BAT, muscle, and WAT observed in high-BAT and low-BAT groups. Error bars represent SEM. (A) In high-BAT group, MRO₂ in BAT at rest was about twice as high as that in low-BAT group. After cold exposure, MRO₂ increased by about 50% in high-BAT group but remained at same level in low-BAT group. In contrast, MRO₂ in WAT was higher in low-BAT group both at rest and at cold exposure. Finally, MRO₂ in muscle was similar for both groups at rest and after cold exposure. (B) Highly significant correlation (P = 0.01) was observed between MRO₂ in BAT (●), WAT (○), and muscle (×) tissue, indicating that tissue perfusion is main determinant of oxidative metabolism in all 3 types of tissue.

(A) Relationship between blood flow in BAT (both at rest and during stress) and BAT DEE (●), as well as estimates of upper limit for BAT DEE (○), calculated using almost complete oxygen extraction (OEF = 0.95) and generous estimate of activated BAT mass (SUV threshold of 1.5). Maximal contribution of activated BAT to DEE is in range of 15–25 kcal/d. We determined significant correlation (P = 0.03), indicating that tissue perfusion is an important determinant of DEE in activated BAT. (B) Correlation between maximal SUV in BAT and DEE in those subjects who had SUV > 2.0 (indicative of activated BAT). We found significant correlation between glucose uptake and DEE (P = 0.02).