Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults

Recent work in rodents has demonstrated that basal activity of the local sympathetic nervous system is critical for maintaining brown adipocyte phenotypes in classic brown adipose tissue (BAT) and white adipose tissue (WAT). Accordingly, we sought to assess the relationship between sympathetic innervation and cold-induced activation of BAT and WAT in lean young adults. Methods: Twenty adult lean normal subjects (10 women and 10 men; mean age +/- SD, 23.3 +/- 3.8 y; body mass index, 23.7 +/- 2.5 kg/m(2)) underwent C-11-meta-hydroxyephedrin (C-11-HED) and O-15-water PET imaging at rest and after exposure to mild cold (16 degrees C) temperature. In addition, F-18-FDG images were obtained during the cold stress condition to assess cold-activated BAT mass. Subjects were divided into 2 groups (high BAT and low BAT) based on the presence of F-18-FDG tracer uptake. Blood flow and C-11-HED retention index (RI, an indirect measure of sympathetic innervation) were calculated from dynamic PET scans at the location of BAT and WAT. Whole-body daily energy expenditure (DEE) during rest and cold stress was measured by indirect calorimetry. Tissue level oxygen consumption (MRO2) was determined and used to calculate the contribution of cold-activated BAT and WAT to daily DEE. Results: F-18-FDG uptake identified subjects with high and low levels of cold-activated BAT mass (high BAT, 96 +/- 37 g; low BAT, 16 4 g). C-11-HED RI under thermoneutral conditions significantly predicted F-18-FDG uptake during cold stress (R-2 = 0.68, P < 0.01). In contrast to the significant increase of C-11-HED RI during cold in BAT (2.42 +/- 0.85 vs. 3.43 +/- 0.93, P = 0.02), cold exposure decreased the C-11-HED RI in WAT (0.44 +/- 0.22 vs. 0.41 +/- 0.18) as a consequence of decreased perfusion (1.22 +/- 0.20 vs. 1.12 +/- 0.16 mL/100 g/min). The contribution of WAT to whole-body DEE was approximately 150 kcal/d at rest (149 +/- 52 kcal/d), which decreased to approximately 100 kcal/d during cold (102 +/- 47 kcaVd). Conclusion: The level of sympathetic innervation, as determined by C-11-HED RI, can predict levels of functional BAT. Overall, blood flow is the best independent predictor of C-11-HED RI and F-18-FDG uptake across thermoneutral and cold conditions. In contrast to BAT, cold stress reduces blood flow and F-18-FDG uptake in subcutaneous WAT, indicating that the physiologic response is to reduce heat loss rather than to generate heat.