TY - JOUR T1 - <sup>18</sup>F-FDG Uptake in Adipose Tissue Parallels Molecular Markers of the Brown Adipose Tissue Phenotype <strong/> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1393 LP - 1393 VL - 62 IS - supplement 1 AU - Joseph Frankl AU - Yu An AU - Amber Sherwood AU - Guiyang Hao AU - Feng-Yun Huang AU - Xiankai Sun AU - Philipp Scherer AU - Orhan Oz Y1 - 2021/05/01 UR - http://jnm.snmjournals.org/content/62/supplement_1/1393.abstract N2 - 1393Objectives: The COVID-19 pandemic has again shown the vast public health cost of high obesity prevalence in Western countries. Brown adipose tissue (BAT) is an anti-obesity drug target because of its adipokine production and energy consumption. Ongoing human studies are also assessing its role in response to current anti-obesity treatments like bariatric surgery. Therefore, a non-invasive test of brown adipose tissue presence and function is highly valuable. 18F-fluordeoxyglucose-positron emission tomography (FDG-PET) is often used, although the correlation between FDG uptake and the physiologic status of a given fat pad is incompletely understood. In this study, we compare FDG uptake in murine inguinal adipose tissue, a tissue that is sensitive to “browning”, to tissue-based markers of the brown adipose tissue phenotype following a brown adipose tissue stimulation protocol. Methods: A total of 10 mice (5 treatment/control pairs) were injected with the BAT-activating β3-agonist CL-316,243 (treatment) or normal saline (control) for 7 days prior to FDG-PET. Mice fasted overnight prior to PET-CT. On the day of scanning, they were briefly anesthetized with isoflurane and injected with 3.7 MBq (0.1 mCi) FDG through the lateral tail vein. After a 1-hour uptake period, they were re-anesthetized and maintained under isoflurane anesthesia for the PET/CT. Manufacturer software was used to co-register CT and PET images and perform image analysis. Small circular regions of interest were drawn in the inguinal fat depots immediately superior the hip on anterior-posterior images using a regional lymph node as a guide and mean standardized uptake values (SUV) determined. In a parallel cohort, 10 additional mice (5 treatment/control pairs) underwent the same BAT-stimulation protocol prior to sacrifice for tissue studies. Mitochondrial oxygen consumption rate, a measure of energy expenditure, was assessed in freshly dissected inguinal adipose tissue with an extracellular flux analyzer. To characterize the inducible brown phenotype, the excised tissues were examined by histology, UCP1 and TOMM40 immunohistochemistry, and Ucp1 quantitative polymerase chain reaction. Results: Inguinal WAT demonstrated consistently greater FDG uptake in treated mice than controls (0.20±0.04 vs 0.10±0.05, p=0.01). Basal oxygen consumption rate increased by 7.1±7.8 pmol/min/mg tissue in this fat pad. Interspersed multiloculated adipocytes, indicative of a browning phenotype, were found in histologic sections from CL-316,243-treated animals but not controls. There was increased mitochondrial density and UCP1 content in treated animals relative to controls when assessed by immunohistochemistry. Additionally, there was a 4.8-fold increase (p&lt;0.01) in Ucp1 mRNA content in treated versus control animals. Conclusions: FDG uptake by adipose tissue with an induced browning phenotype parallels energy expenditure, changes in cell morphology, and increased mitochondrial density and UCP1 content. These findings are particularly relevant to research with human subjects as metabolically active fat in humans closely resembles the inducible browning phenotype in mice. It is known that FDG-PET imaging does not identify all adipose depots undergoing “browning.” However, the lower limit of sensitivity of FDG-PET has not been established. This work establishes our model as useful in this regard using gold standard molecular and biochemical assays. Research Support: Grant number RR2024 from the Radiologic Society of North America in part supports this work. ER -