title: 18F-FDG PET/CT monitoring of β3 agonist-stimulated brown adipocyte recruitment in white adipose tissue.
abstract: 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 β3 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.
  
  
  CONCLUSIONS
  (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.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Cung Hoa Thien
authors.initials: CH
authors.lastname: Quach
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea khnm.lee@samsung.com.
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology* / Q000000981:diagnostic imaging / Q000187:drug effects; D052436:Adipose Tissue, White / Q000166:cytology* / Q000000981:diagnostic imaging / Q000187:drug effects; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D000071256:Uncoupling Protein 1
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D004149:Dioxoles; D051275:Glucose Transporter Type 4; D007473:Ion Channels; D024101:Mitochondrial Proteins; D022702:Receptors, Adrenergic, beta-3; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D019788:Fluorodeoxyglucose F18; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D006593:Hexokinase
keywords: 18F-FDG; PET; UCP1; beige cell; brown adipose tissue; white adipose tissue