ABSTRACT
UNLABELLED: There is rising interest in recruitment of brown adipocytes into white adipose tissue (WAT) as a means to augment energy expenditure for weight reduction. We thus investigated the potential of (18)F-FDG uptake as an imaging biomarker that can monitor the process of WAT browning. METHODS: C57BL/6 mice were treated daily with the ß3 agonist CL316,243 (5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylic acid disodium salt), whereas controls received saline. (18)F-FDG small-animal PET/CT was serially performed at 1 h after CL316,243 injection. After sacrifice, interscapular brown adipose tissue (BAT) and WAT depots were extracted, weighed, and measured for (18)F-FDG uptake. Tissues underwent immunostaining, and UCP1 content was quantified by Western blotting. RESULTS: PET/CT showed low (18)F-FDG uptake in both BAT and inguinal WAT at baseline. BAT uptake was substantially increased by a single stimulation with CL316,243. Uptake in inguinal WAT was only modestly elevated by the first stimulation uptake but gradually increased to BAT level by prolonged stimulation. Ex vivo measurements recapitulated the PET findings, and measured (18)F-FDG uptake in other WAT depots was similar to inguinal WAT. WAT browning by prolonged stimulation was confirmed by a substantial increase in uncoupling protein 1 (UCP1), cytochrome-c oxidase 4 (COX4), and PR domain containing 16 (PRDM16) staining as markers of brown adipocytes. UCP1 content, which served as a measure for extent of browning, was low in baseline inguinal WAT but linearly increased over 10 d of CL316,243 injection. Finally, image-based and ex vivo-measured (18)F-FDG uptake in inguinal WAT correlated well with UCP1 content. CONCLUSION: (18)F-FDG PET/CT has the capacity to monitor brown adipocyte recruitment into WAT depots in vivo and may thus be useful for screening the efficacy of strategies to promote WAT browning.
Subject(s)
Adipocytes, Brown/cytology , Adipose Tissue, White/cytology , Dioxoles/pharmacology , Fluorodeoxyglucose F18 , Multimodal Imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Adipocytes, Brown/diagnostic imaging , Adipocytes, Brown/drug effects , Adipose Tissue, White/diagnostic imaging , Adipose Tissue, White/drug effects , Adrenergic beta-3 Receptor Agonists/pharmacology , Animals , Biological Transport/drug effects , Fluorodeoxyglucose F18/metabolism , Gene Expression Regulation/drug effects , Glucose Transporter Type 4/metabolism , Hexokinase/metabolism , Ion Channels/metabolism , Male , Mice , Mitochondrial Proteins/metabolism , Receptors, Adrenergic, beta-3/metabolism , Uncoupling Protein 1ABSTRACT
INTRODUCTION: Ganglioneuroma is a rare tumor in the posterior mediastinum; fat-containing ganglioneuromas are rarely reported. The present case report documents a brown fat-containing, posterior mediastinal ganglioneuroma, which has not been reported previously. Radiological examination, in particular 18F-2-fluoro-2-deoxyglucose-positron emission tomography, suggested that the tumor had low-grade malignant potential. This led to uncertainty at preoperative diagnosis. CASE PRESENTATION: An asymptomatic 66-year-old Japanese woman with no significant past medical history was referred for the evaluation of a posterior mediastinal mass. Although its size had not changed in the past 5 years, a malignant lipomatous tumor could not be excluded due to the presence of intratumoral fat and increased 18F-2-fluoro-2-deoxyglucose uptake observed by positron emission tomography imaging. A computed tomography-guided core-needle biopsy revealed a mixture of mature adipocytes, spindle-shaped cells, and fibrotic stroma. Definite diagnosis was not possible, and surgical resection was performed. Three years after the surgery, she remains disease-free. CONCLUSIONS: Histological diagnosis of the surgically resected mass confirmed ganglioneuroma with substantial amounts of white and brown adipose tissues in peripheral areas. The existence of both ganglion cells and brown fat tissue intensified the accumulation of 18F-2-fluoro-2-deoxyglucose, resulting in a false-positive result by positron emission tomography. Considering this, ganglioneuroma should not be excluded either clinically or pathologically in fat-containing, posterior mediastinal tumors.
Subject(s)
Adipocytes, Brown/pathology , Adipocytes, White/pathology , Fluorodeoxyglucose F18 , Ganglioneuroma/diagnostic imaging , Mediastinal Neoplasms/diagnostic imaging , Positron-Emission Tomography , Radiopharmaceuticals , Adipocytes, Brown/diagnostic imaging , Adipocytes, White/diagnostic imaging , Aged , Biopsy, Large-Core Needle , False Positive Reactions , Female , Ganglioneuroma/pathology , Humans , Mediastinal Neoplasms/pathologyABSTRACT
UNLABELLED: The role of brown adipose tissue (BAT) in adult metabolism is poorly understood. This study aimed to examine the differential effects of an overnight fast and the postprandial state on BAT activity. METHODS: We included 10 healthy, lean male volunteers. BAT uptake of glucose was visualized using (18)F-FDG PET/CT during mild cold exposure. Each subject underwent PET/CT twice. The first scan was obtained after an overnight fast; the second after a standardized meal. RESULTS: (18)F-FDG uptake in BAT was observed in 6 of 10 volunteers. These subjects were found to have a higher maximal standardized uptake value when fasting (median, 13.1 g/mL; range, 6.1-27.6 g/mL) than when in the postprandial state (median, 6.8 g/mL; range, 2.1-13.4 g/mL) (P = 0.03). CONCLUSION: Cold-stimulated (18)F-FDG uptake by BAT in humans is more pronounced during fasting. The lower maximal standardized uptake value in the postprandial state may be explained by increased insulin-stimulated glucose uptake in muscle.
