Brown Adipose Tissue In Nonshivering Thermogenesis

Brown adipose tissue (BAT) is vital for proper thermogenesis during cold exposure in rodents, but until recently its presence in adult humans and its contribution to human metabolism were thought to be minimal or insignificant. Recent studies using PET with 18F-fluorodeoxyglucose (18FDG) have shown the presence of BAT in adult humans. However, whether BAT contributes to cold-induced nonshivering thermogenesis in humans has not been proven. Using PET with 11C-acetate, 18FDG, and 18F-fluoro-thiaheptadecanoic acid (18FTHA), a fatty acid tracer, we have quantified BAT oxidative metabolism and glucose and nonesterified fatty acid (NEFA) turnover in 6 healthy men under controlled cold exposure conditions. All subjects displayed substantial NEFA and glucose uptake upon cold exposure. Furthermore, we demonstrated cold-induced activation of oxidative metabolism in BAT, but not in adjoining skeletal muscles and subcutaneous adipose tissue. This activation was associated with an increase in total energy expenditure. We found an inverse relationship between BAT activity and shivering. We also observed an increase in BAT radio density upon cold exposure, indicating reduced BAT triglyceride content. In sum, our study provides evidence that BAT acts as a nonshivering thermogenesis effector in humans.

The present findings support a role of BAT for nonshivering thermogenesis in humans with intracellular triglycerides as the main source of energy for this process, as observed in rodents. However, it remains to be demonstrated whether chronic and frequent bouts of cold exposure may contribute to increase BAT capacity and/or activity and may be a viable adjunct therapeutic strategy to other lifestyle interventions to prevent or treat obesity and its metabolic complications. It is also possible that energy substrate uptake by BAT could be substantially increased once intracellular triglyceride stores are depleted and/or BAT is fully cold adapted, as recently shown in rodents (22). Quantitative assessment of the contribution of intracellular triglyceride oxidation in BAT thermogenesis awaits further methodological developments.

In summary, the present study demonstrates that a cold-exposure stimulus designed to minimize muscle-mediated shivering thermogenesis enhances BAT oxidative metabolism as well as glucose and NEFA uptake in adult humans. The enhanced BAT activity was associated with a 1.8-fold increase in whole-body energy expenditure. We found a significant inverse relationship between BAT volume of activity and shivering and a significant increase in BAT radio density within 3 hours of cold exposure, indicating rapid reduction in BAT triglyceride content. The present results demonstrate that BAT is undoubtedly involved in nonshivering thermogenesis in humans.