The differential response of fluorobenzyl triphenyl phosphonium (FBnTP) and FDG upon activation of brown adipose tissue (BAT) thermogenesis

444 Objectives The thermogenic response of BAT has been implicated in energy balance and obesity. The mitochondrial uncoupling protein 1 (UCP1) is responsible for BAT thermogenesis and its activity is correlated linearly with decline of the organelle’s membrane potential (ΔΨm). Targeting ΔΨm may enable a direct and more accurate estimate of BAT thermogenesis than that afforded by FDG. Here we characterize the voltage sensor FBnTP as marker of BAT thermogensis and investigate its relationship with FDG. Methods C-14-FBnTP, F-18-FDG and Tc-99m-MIBI biodistribution in BAT was quantified by direct tissue counting and autoradiography in Lewis rats (n = 16) under cold (40C) and room temperature (RT, 220C) with and without IP administration (5 mg/kg) of the adrenergic agonist propranolol (PROP). Results At RT, FBnTP demonstrated intense uptake in BAT, greater than in heart. Four hours of cold resulted in a significant decrease (>75%) of FBnTP uptake in BAT, but a marked increase (3 to 5-fold) of FDG uptake. There was no change in MIBI uptake after exposure to cold. Inhibition of the adrenergic system, using PROP prevented the cold-induced decrease of FBnTP and increase of FDG uptake in BAT. The cold also affected FBnTP and FDG uptake in organs other than BAT. Conclusions This study provides evidence that it is feasible to use FBnTP as a marker to explore thermodynamic mechanisms of brown adipocytes. For the first time, FBnTP makes it possible to unravel, in the intact organ, the UCP1-mediated dynamic inverse relationship of mitochondria bioenergetics and glucose metabolism as the underlying mechanism of BAT thermogensis. The combined use of FBnTP and FDG in BAT may serve as a model for studying relationship of glucose metabolism and mitochondrial oxidative activity relevant to cancer. PET imaging studies are in progress