Profound morphological changes are associated with high FDG uptake in brown adipose tissue as observed in TEM images

1133 Objectives Brown adipose tissue can confound interpretation of FDG PET scans. Lower levels of BAT have been identified in the elderly, the obese, and those with poor glucose regulation suggesting BAT activity may impact blood glucose levels and obesity. Cold stimulation of BAT can result in markedly different levels of FDG uptake into stimulated BAT. We examined the morphological appearance, via transmission electron microscopy (TEM), of stimulated and non-stimulated BAT to determine whether specific morphological characteristics are seen that might be expected to be linked to the degree of radiotracer uptake. Methods Female Lewis rats were divided into two groups: room temperature or cold-exposed at 4 degrees for four hours. To determine FDG uptake, rats received 100uCi of FDG i.v. one-hour prior to sacrifice and uptake was determined with a gamma counter. Non-radioactive rats were used, but under the same temperature conditions, for the TEM tissues. Results Cold-stimulated BAT showed evidence of loss of BAT lipid content with profound alterations in the nuclear/cytoplasmic ratios (i.e. increased) vs. the control animals. BAT from stimulated animals also had a markedly different appearance of the mitochondria, with evidence for irregularity of the mitochondrial surfaces consistent with volume loss or altered permeability vs. control animals. The ultrastructural changes are consistent with imaging changes we have described in which the CT HU decline in activated BAT, presumably due to consumption of the lipid from the BAT cell cytoplasm. Conclusions Ultrastructural anatomy of BAT cells is markedly different between the control and cold-stimulated states. Loss of intracellular lipid and alterations of mitochondrial membrane morphology are likely the structural results of the profound lipid and glucose consumption seen in stimulated BAT. Loss of the lipid also suggests BAT activation may not be sustainable due to consumption of lipid substrate