Daniel Winter

Effects of burn injury, cold stress and cutaneous wound injury on the morphology and energy metabolism of murine brown adipose tissue (BAT) in vivo.

AIMS Cold stress has been shown to produce dramatic increases in 2-fluoro-2-deoxy-D-Glucose ((18)FDG) accumulation by brown adipose tissue (BAT) in rodents. However, neither the effects of other types of stress on (18)FDG accumulation nor the effects of stressors on the accumulation of tracers of other aspects of energy metabolism have been evaluated. In this report we studied the effects of cold stress, burn injury and cutaneous wounds on murine BAT at the macroscopic, microscopic and metabolic level. MAIN METHODS Glucose metabolism was studied with (18)FDG, fatty acid accumulation was evaluated with trans-9(RS)-(18)F-fluoro-3,4(RS,RS)-methyleneheptadecanoic acid (FCPHA) and tricarboxcylic acid cycle (TCA) activity was evaluated with (3)H acetate. KEY FINDINGS All three stressors produced dramatic changes in BAT at the macroscopic and microscopic level. Macroscopically, BAT from the stressed animals appeared to be a much darker brown in color. Microscopically BAT of stressed animals demonstrated significantly fewer lipid droplets and an overall decrease in lipid content. Accumulation of (18)FDG by BAT was significantly (p<0.01) increased by all 3 treatments (Cold: ~16 fold, burn ~7 Fold and cutaneous wound ~14 fold) whereas uptake of FDG by white fat was unchanged. This effect was also demonstrated non invasively by μPET imaging. Although less prominent than with (18)FDG, BAT uptake of FCPHA and acetate were also significantly increased by all three treatments. These findings suggest that in addition to cold stress, burn injury and cutaneous wounds produce BAT activation in mice. SIGNIFICANCE This study demonstrates brown fat activated by several stressors leads to increased uptake of various substrates.

Combination of Radiation and Burn Injury Alters [18F] 2-Fluoro-2-Deoxy-D-Glucose Uptake in Mice

Radiation exposure and burn injury have both been shown to alter glucose utilization in vivo. The present study was designed to study the effect of burn injury combined with radiation exposure on glucose metabolism in mice using [18F] 2-fluoro-2-deoxy-D-glucose (18FDG). Groups of male mice weighing approximately 30 g were studied. Group 1 was irradiated with a 137Cs source (9 Gy). Group 2 received full thickness burn injury on 25% TBSA followed by resuscitation with saline (2 ml, IP). Group 3 received radiation followed 10 minutes later by burn injury. Group 4 were sham-treated controls. After treatment, the mice were fasted for 23 hours and then injected (IV) with 50 µCi of 18FDG. One hour postinjection, the mice were sacrificed, and biodistribution was measured. Positive blood cultures were observed in all groups of animals compared to the shams. Increased mortality was observed after 6 days in the burn plus radiated group as compared to the other groups. Radiation and burn treatments separately or in combination produced major changes in 18FDG uptake by many tissues. In the heart, brown adipose tissue, and spleen, radiation plus burn produced a much greater increase (P < .0001) in 18FDG accumulation than either treatment separately. All three treatments produced moderate decreases in 18FDG accumulation (P < .01) in the brain and gonads. Burn injury, but not irradiation, increased 18FDG accumulation in skeletal muscle; however, the combination of burn plus radiation decreased 18FDG accumulation in skeletal muscle. This model may be useful for understanding the effects of burns plus irradiation injury on glucose metabolism and in developing treatments for victims of injuries produced by the combination of burn plus irradiation.