2-[18F]fluoro-2-desoxy-glucose (FDG) uptake in brown fat cells. Both FDG and glucose are taken up by members of the glucose transporter family, most likely glucose transporter (GLUT)1 and GLUT4. After phosphorylation by hexokinase (HK) tracer, FDG cannot be further metabolized and is trapped in the cell. Glucose phosphate is, however, further metabolized by several processes in the cell; the 3 arrows symbolize resynthesis of lipid, anaplerotic reactions in the mitochondria, and cytosolic ATP production. Physiologically, the brown fat cell is stimulated by norepinephrine (NE) released from sympathetic nerves [note that the tracer compound metaiodobenzylguanidine (MIBG) is accumulated in the transmitter vesicles of the nerve], and this stimulation with NE leads to triglyceride (TG) breakdown The resulting free fatty acids (FFA) are probably involved in activation of the brown fat-specific uncoupling protein-1 (UCP1). FFA are also the main source for substrate combustion in the mitochondria. The further metabolism of glucose is linked to the ongoing thermogenesis, but the exact mechanism(s) is not known [for general overview concerning brown adipose tissue function and significance we refer to our recent review (11), to which we also refer, for space reasons, in the running text for general statements].
Sites of FDG uptake corresponding to brown adipose tissue in adult humans. The black areas are those that are most frequently described; the gray areas are not always found, even in humans positive in the black areas. (A 3-dimensional representation of the distribution of brown adipose tissue FDG uptake in adult man is presently available at www.med.harvard.edu/JPNM/chetan/normals/brown_fat/case.html).
Cold-induced brown adipose tissue activation in adult man. The same patient was investigated by fluorodeoxyglucose positron emission tomography (FDG PET) twice a few days apart. A: efforts had been made to keep the patient under warm conditions before injection and during the time from injection to imaging. The only uptake visible is that into the brain, heart, kidneys, and bladder. B: the patient had been examined under routine conditions, i.e., in comparatively cold conditions. Note that the characteristic symmetrical pattern of uptake into the supraclavicular, neck, paravertebral areas, etc., i.e., into brown adipose tissue, is now visible. Reproduced from Christensen et al. (17) with permission.
Sympathetic control of brown adipose tissue activity in adult man. The same patient was examined by FDG PET twice, once at baseline (standard conditions) and then 6 days later when the patient had received 80 mg of propranolol orally 2 h before the examination. Note the total elimination of the brown fat-related uptake by propranolol. The arrow points to a lung metastasis. Reproduced from Soderlund et al. (63) with kind permission of Springer Science and Business Media.