Brown Fat Deposit PhysioImaging- Dr. Rao Papineni.

Presentation at September 21, 2013 from 2:45 PM to 4:15 PM

Noninvasive Imaging of Cold Stress Responsive Reactive Oxygen Species.

Dr. Rao Papineni

PACT & Health Branford, USA
Email: papineni@graduate.hku.hk Brown adipose tissue (BAT) thermogenesis is used by small mammals like mice to maintain core body temperature in response to cold temperature exposure. While in clinics, non-malignant 18 FDG uptake by BAT clearly poses a challenge in PET interpretations. Pharmacological or physiological interventions to regulate thermogenesis may allow in development of strategies in obesity management and also in cogent PET diagnostics. Richly innervated by sympathetic nerves, the BAT contains high number of mitochondria. Thermogenesis is primarily mediated by uncoupling proteins (UCP) that directly convert the protons into heat. Vascular perfusion is however the ultimate event in this cold stress response. It allows the cold blood to enter and the warm blood to exit from BAT. This whole circuit during thermogenesis has the potential and the necessity in the rapid mobilization and activation of neutrophils and macrophages aiding in generation of reactive oxygen species (ROS) and the successive signaling cycles that include gene activation processes. Here, we evaluated the early changes in the ROS activity as a response to cold stress. The ROS activity was monitored real-time in vivo using L-012 (8-amino-5-chloro-7phenylpyridol [3,4-d]pyridazine-1,4(2H,3H) dione), a chemiluminescence reporter, using planar multimodal imaging system. Athymic nude mice were subjected to cold stress for 10 min (40C),

with the lower limbs directly exposed to cold. 0.1 ml of 1 mg/ml L-012 probe was injected (i.p.) to determine the initial changes in ROS activity. Noninvasive luminescence and X-ray images obtained show robust increase in ROS activity at BAT sites which is generally accumulated at the regions between the scapulae. Apart from the brown fat depot sites, increase in ROS activity was also observed at additional sites that include eyes. These real-time monitoring methodologies of ROS activity detection by in vivo imaging will greatly enhance the understanding of the early phase response to cold stress and aid in development of intervention strategies in several physiological and pathological processes.