Brown adipose tissue (BAT) is an insulin sensitive organ having a very high uptake of glucose per gram of tissue. The role of insulin on glucose uptake in BAT is still poorly understood, moreover, it is not clear whether BAT insulin function is compromised with obesity. We used a small animal PET/CT imaging approach to analyse insulin function in vivo in lean and obese mice using a glucose analogue PET tracer (18F-FDG). Three groups of mice were analysed after administration of different diet regimens leading to progressive obesity levels: standard chow diet (SD), high fat diet (HFD, 40% fat content), super high fat diet (SHFD, 60% fat content). Each group of animals underwent two repeated PET/CT scans: the first in fasting state (basal state), the second after insulin administration (0.7 U/kg). Glucose levels, analysed during PET/CT procedures with a glucometer, revealed a slight and a severe compromise of insulin sensitivity in HFD and SHFD groups, respectively. Accordingly, PET/CT image analysis of 18F-FDG uptake in the BAT revealed that insulin strongly increased PET signal in BAT of SD mice, whereas insulin induced 18F-FDG uptake was lower in HFD group, and completely absent in SHFD group. To confirm the data, and to analyse whether counter-regulatory mechanisms originated by insulin-induced hypoglycemia influenced PET/CT analysis, we repeated the imaging procedure described above in a new cohort of SD, HFD and SHFD mice in which euglycemia was maintained by external glucose infusion through a jugular catheter. Image analysis of 18F-FDG uptake in the BAT of mice analysed in euglycemic conditions was indistinguishable from the previous approach in all the three groups, confirming the presence of an altered insulin function in the BAT of obese mice. These findings, which reveal that obesity is associated with an altered insulin function of BAT, highlight small animal PET/CT as a powerful new tool for non-invasive analysis of insulin sensitivity.
30 Apr - 04 May 2011
European Society of Endocrinology