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/m²) underwent ¹¹C-meta-hydroxyephedrin (¹¹C-HED) and ¹⁵O-water PET imaging at rest and after exposure to mild cold (16°C) temperature. In addition, ¹⁸F-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 ¹⁸F-FDG tracer uptake. Blood flow and ¹¹C-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:¹⁸F-FDG uptake identified subjects with high and low levels of cold-activated BAT mass (high BAT, 96 ± 37 g; low-BAT, 16 ± 4 g). ¹¹C-HED RI under thermoneutral conditions significantly predicted ¹⁸F-FDG uptake during cold stress (R² = 0.68, P < 0.01). In contrast to the significant increase of ¹¹C-HED RI during cold in BAT (2.42 ± 0.85 vs. 3.43 ± 0.93, P = 0.02), cold exposure decreased the ¹¹C-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 kcal/d). Conclusion: The level of sympathetic innervation, as determined by ¹¹C-HED RI, can predict levels of functional BAT. Overall, blood flow is the best independent predictor of ¹¹C-HED RI and ¹⁸F-FDG uptake across thermoneutral and cold conditions. In contrast to BAT, cold stress reduces blood flow and ¹⁸F-FDG uptake in subcutaneous WAT, indicating that the physiologic response is to reduce heat loss rather than to generate heat.