Association of Heat Production with ¹⁸F-FDG Accumulation in Murine Brown Adipose Tissue After Stress

Abstract

Previous studies have demonstrated that cold stress results in increased accumulation of 18FDG in brown adipose tissue (BAT). Although it has been assumed that this effect is associated with increased thermogenesis by BAT, direct measurements of this phenomenon have not been reported. In the current investigation we evaluated the relationship between stimulation of 18FDG accumulation in BAT by three stressors and heat production measured in vivo by thermal imaging. Male SKH-1 hairless mice were subjected to full-thickness thermal injury (30% total body surface area), cold stress (4°C for 24 hours), or cutaneous wounds. Groups of 6 animals with each treatment were fasted over night and injected with 18FDG. Sixty minutes after injection the mice were sacrificed and biodistribution was measured. Other groups of six animals subjected to the three stressors were studied by thermal imaging and the difference in temperature between BAT and adjacent tissue was recorded (ΔT). Additional groups of 6 animals were studied by both thermal imaging and 18FDG biodistribution in the same animals. Accumulation of 18FDG by BAT was significantly (p <0.0001) increased by all 3 treatments (burn ~5 fold, cold: ~15 fold, and cutaneous wound ~15 fold) whereas accumulation by adjacent white adipose tissue (WAT) was unchanged. Compared with sham control mice; ΔTs in animals exposed to all three stressors showed significant (p<0.001) increases in temperature between BAT and adjacent tissue. The difference in ΔT between stressor groups was not significant, however, there was a highly significant linear correlation (r2=0.835, p<0.0001) between the ΔT measured in BAT vs. adjacent tissue and 18FDG accumulation. These results establish, for the first time, that changes in BAT temperature determined in vivo by thermal imaging parallel increases in 18FDG accumulation.

CPEB 2‐dependent translation of long 3′‐ UTR Ucp1 mRNA promotes thermogenesis in brown adipose tissue

“…Reduced UCP1 level in CPEB2‐KO and Ucp1ΔL BAT should cause inefficient non‐shivering thermogenesis and a possible decrease in glucose utilization and metabolism, as indicated by deoxyglucose uptake in UCP1‐KO mice (Inokuma et al , ) and rodents with altered thermogenic activity (Carter et al , ; Tomilov et al , ). Moreover, CPEB2 may regulate translation of other mRNAs besides Ucp1 to affect BAT activity.…”

In Vivo Noninvasive Characterization of Brown Adipose Tissue Blood Flow by Contrast Ultrasound in Mice

“…34–36 In addition, Virtanen et al reported a 15-fold increase in uptake of FDG into supraclavicular BAT after cold exposure in humans, 5 and Carter et al observed a 15- to 16-fold activation of BAT in mice exposed to cold. 34,35 These data indicate that, irrespective of species and mode of BAT activation, the degree of metabolic activation appears to be of similar magnitude as the blood flow increase of BAT.…”

Insights into Brown Adipose Tissue Physiology as Revealed by Imaging Studies

“…This was significantly different from the 0.9 C difference between skin temperature overlying BAT and adjacent skin temperature that was not overlying BAT seen in the control group. 82 Also, there was a strong linear correlation between 18 F-FDG accumulation in BAT and the increase in skin temperature detected by the thermal imaging camera (r 2 D 0.835, P<0 .0001). 82 Several human studies using thermal imaging have been reported.…”

“…82 Also, there was a strong linear correlation between 18 F-FDG accumulation in BAT and the increase in skin temperature detected by the thermal imaging camera (r 2 D 0.835, P<0 .0001). 82 Several human studies using thermal imaging have been reported. In one study, volunteers sat in a room (with the temperature maintained at 19-21 C) and were asked to place one hand in water (maintained at a temperature of [19][20] C) for 5 minutes and thermal images were recorded during the 5 minutes immediately preceding the cold stimulus as well as throughout cold stimulation.…”

“…82 The temperature of skin overlying interscapular BAT (in comparison to adjacent non-BAT tissue), measured with a thermal imaging camera, was on average 1.7 C higher in the cold stress group, 1.5 C higher in the skin wound group, and 1.5 C higher in the skin burn group. This was significantly different from the 0.9 C difference between skin temperature overlying BAT and adjacent skin temperature that was not overlying BAT seen in the control group.…”