title: Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults.
abstract: 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) underwent11C-meta-hydroxyephedrin (11C-HED) and15O-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 of18F-FDG tracer uptake. Blood flow and11C-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 predicted18F-FDG uptake during cold stress (R2= 0.68,P< 0.01). In contrast to the significant increase of11C-HED RI during cold in BAT (2.42 ± 0.85 vs. 3.43 ± 0.93,P= 0.02), cold exposure decreased the11C-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 by11C-HED RI, can predict levels of functional BAT. Overall, blood flow is the best independent predictor of11C-HED RI and18F-FDG uptake across thermoneutral and cold conditions. In contrast to BAT, cold stress reduces blood flow and18F-FDG uptake in subcutaneous WAT, indicating that the physiologic response is to reduce heat loss rather than to generate heat.
authors: Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan otto@pet.wayne.edu.|Department of Radiology, Wayne State University School of Medicine, Detroit, Michigan.
authors: Otto
authors: O
authors: Muzik
authors: Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan.
authors: Tom J
authors: TJ
authors: Mangner
authors: Department of Anthropology, Northwestern University, Evanston, Illinois.
authors: William R
authors: WR
authors: Leonard
authors: Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan.
authors: Ajay
authors: A
authors: Kumar
authors: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan; and.|Center for Integrative Metabolic and Endocrine Research and Family Medicine.
authors: James G
authors: JG
authors: Granneman
mesh_terms: D002001:Adipose Tissue, Brown / Q000000981:diagnostic imaging / Q000294:innervation / Q000503:physiopathology*; D052436:Adipose Tissue, White / Q000000981:diagnostic imaging / Q000294:innervation / Q000503:physiopathology*; D000328:Adult; D001833:Body Temperature Regulation; D003080:Cold Temperature; D058639:Cold-Shock Response; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D010101:Oxygen Consumption; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013851:Thinness / Q000503:physiopathology*
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C065363:3-hydroxyephedrine; D004809:Ephedrine
keywords: HED PET imaging; brown fat; subcutaneous fat; sympathetic innervation