The Young Investigator Winner
C. Quarta1, R. Mazza1, P. Iozzo3, S. Obici2, R. Pasquali1 & U. Pagotto1
Increasing evidences indicate that brown adipose tissue (BAT) functional activity is reduced during obesity. The nature of this deficit in BAT function, however, is still poorly understood. To analyze whether insulin function in the BAT is altered during obesity, we studied the in vivo metabolic activity of BAT by PET/CT imaging and euglycaemic hyperinsulinemic clamp in lean and diet-induced obese mice. Three groups of mice were analyzed after administration of different diet regimens leading to progressive obesity levels: standard chow diet (SD), high fat diet (HFD, 40% fat), super high fat diet (SHFD, 60% fat). Glucose uptake in the BAT was assessed analyzing 18F-FDG accumulation (a PET tracer glucose analogue) on PET/CT images. 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 analyze whether insulin exerts a role on BAT thermogenesis, we recorded BAT temperature during euglycaemic hyperinsulinemic clamp studies by the means of telemetric probes surgically implanted in the tissue. Insulin was able to reduce BAT thermogenesis in lean mice, whereas obese mice were not able to respond to insulin-induced modifications in BAT activity. To analyze the effect of insulin on glucose storage; glycogen accumulation into the BAT was studied analyzing glycogen content in the tissue at the end of the clamp procedure. Insulin-induced glycogen accumulation was impaired in BAT of obese mice. QT-PCR and Western blot analysis of the protein PTG (protein targeting to glycogen) confirmed the presence of a compromised glycogen metabolism in the BAT of obese mice. These data show that during diet-induced obesity, BAT is not able to correctly respond to insulin with respect to glucose uptake, glycogen accumulation and thermogenesis modifications thus indicating that obesity leads to metabolic inflexibility in BAT.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.