title: Functional imaging of brown fat in mice with 18F-FDG micro-PET/CT.
abstract: Brown adipose tissue (BAT) differs from white adipose tissue (WAT) by its discrete location and a brown-red color due to rich vascularization and high density of mitochondria. BAT plays a major role in energy expenditure and non-shivering thermogenesis in newborn mammals as well as the adults (1). BAT-mediated thermogenesis is highly regulated by the sympathetic nervous system, predominantly via β adrenergic receptor (2, 3). Recent studies have shown that BAT activities in human adults are negatively correlated with body mass index (BMI) and other diabetic parameters (4-6). BAT has thus been proposed as a potential target for anti-obesity/anti-diabetes therapy focusing on modulation of energy balance (6-8). While several cold challenge-based positron emission tomography (PET) methods are established for detecting human BAT (9-13), there is essentially no standardized protocol for imaging and quantification of BAT in small animal models such as mice. Here we describe a robust PET/CT imaging method for functional assessment of BAT in mice. Briefly, adult C57BL/6J mice were cold treated under fasting conditions for a duration of 4 hours before they received one dose of (18)F-Fluorodeoxyglucose (FDG). The mice were remained in the cold for one additional hour post FDG injection, and then scanned with a small animal-dedicated micro-PET/CT system. The acquired PET images were co-registered with the CT images for anatomical references and analyzed for FDG uptake in the interscapular BAT area to present BAT activity. This standardized cold-treatment and imaging protocol has been validated through testing BAT activities during pharmacological interventions, for example, the suppressed BAT activation by the treatment of β-adrenoceptor antagonist propranolol (14, 15), or the enhanced BAT activation by β3 agonist BRL37344 (16). The method described here can be applied to screen for drugs/compounds that modulate BAT activity, or to identify genes/pathways that are involved in BAT development and regulation in various preclinical and basic studies.
authors.affiliation: Department of Translational Imaging, The Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Xukui
authors.initials: X
authors.lastname: Wang
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Minze
authors.forename: Zheng-Zheng
authors.initials: ZZ
authors.lastname: Shi
mesh_terms: D002001:Adipose Tissue, Brown / Q000000981:diagnostic imaging* / Q000187:drug effects; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry*
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18