TY - JOUR T1 - Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.116.180992 SP - jnumed.116.180992 AU - Otto Muzik AU - Thomas J Mangner AU - William R Leonard AU - Ajay Kumar AU - James G Granneman Y1 - 2016/10/01 UR - http://jnm.snmjournals.org/content/early/2016/10/26/jnumed.116.180992.abstract N2 - Objective: Recent work in rodents has demonstrated that basal activity of local sympathetic nervous system is critical for maintaining brown adipocyte phenotypes in classic brown (BAT) and white adipose tissue (WAT). Accordingly, we sought to assess the relationship between sympathetic innervation and cold-induced activation of BAT and WAT, and its relation to local and whole body daily energy expenditure (DEE, kcal/d) in lean young adults. Methods: Twenty adult lean normal subjects (10F/10M, 23.3 + 3.8 years, BMI = 23.7 + 2.5) underwent 11C-meta-hydroxyephedrin (HED) and 15O-water PET imaging at rest and following exposure to mild cold (16oC) temperature. In addition, 18F-fluorodeoxyglucose (FDG) images were obtained during the cold stress condition to assess cold-activated BAT mass. Subjects were divided into two groups (High-BAT, Low-BAT) based on the presence of FDG tracer uptake (SUV > 2) in supraclavicular BAT (-150 < HU < -50). Blood flow and HED retention index (RI, an indirect measure of sympathetic innervation) were calculated from dynamic PET scans at the location of BAT, WAT, muscle and visceral WAT. Whole body DEE during rest and cold stress was measured by indirect calorimetry. Tissue level oxygen consumption (MRO2) in BAT was determined and used to calculate the contribution of cold-activated BAT and WAT to daily DEE. Results: FDG uptake identified subjects with high and low levels of cold-activated BAT mass (High-BAT, 96 + 37g; Low-BAT 16 + 4g). HED RI under thermoneutral conditions significantly predicted FDG uptake during cold stress (R2 = 0.68, p<0.01). The HED RI during cold stress was also highly correlated with FDG uptake (R2 = 0.73, p<0.01). In contrast to the significant increase of HED RI during cold in BAT (3.43+0.93 vs. 2.42+0.85, P = 0.02), cold exposure decreased the 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/100g/min). Overall, blood flow, HED RI and SUV in BAT and WAT were highly correlated (R2~0.8), demonstrating a tight coupling between perfusion, sympathetic innervation and glucose uptake. The contribution of WAT to whole body DEE was ~150 kcal/day at rest (149+52 kcal/day) which decreased to ~100 kcal/day during cold (102+47 kcal/day). Conclusion: The level of sympathetic innervation, as determined by HED RI, can predict levels of functional BAT, as determined by FDG uptake. Overall, blood flow is the best independent predictor of HED RI and FDG uptake across thermoneutral and cold conditions. In contrast to BAT, cold stress reduces blood flow and FDG uptake in subcutaneous WAT, indicating that the physiological response is to reduce heat loss rather than to generate heat. ER -