SFEBES2022 Oral Communications Metabolism, Obesity and Diabetes (6 abstracts)
Human brown adipose tissue demonstrates substantial choline uptake for incorporation into phosphatidylcholines
Karla Suchacki 1 , Lynne Ramage 1 , Calum Gray 1,2 , Giovanny Rodrguez Blanco 1 , T’ng Choong Kwok 1 , Luke Boyle 1 , Gillian MacNaught 1,2 , Maria-lena Gregoriades 3 , Sonia Wakelin 4 , Alex von Kriegsheim 1 , Andrew Finch 1,5 , Dilip Patel 2 , Edwin van Beek 1,2 & Roland Stimson 1
1University of Edinburgh, Edinburgh, United Kingdom; 2Edinburgh Imaging Facility, Edinburgh, United Kingdom; 3Department of Radiology, Western General Hospital, Edinburgh, United Kingdom; 4Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom; 5Cancer Research UK Barts Centre, London, United Kingdom
Background: 18F-fluorodeoxyglucose (18FDG) PET is commonly used to quantify brown adipose tissue (BAT) mass/activity in humans but requires cold exposure. Rodent brown (BAds) but not white adipocytes (WAds) exhibit high choline content, thus we hypothesised that human BAT would demonstrate substantial 18F-fluorocholine (18FCH) uptake in vivo during warm and cold conditions.
Methods: (1) Six male volunteers (age 21.4±1.1y, BMI 23.2±0.7kg/m2) with detectable BAT by 18FDG-PET underwent 18FCH-PET/MR scanning during warm (~23°C) and cold (17°C) exposure in a randomised crossover design. (2) 18FCH uptake by supraclavicular (SCVAT) and abdominal white adipose tissue (WAT) depots were quantified in patients with prostate cancer who had undergone 18FCH-PET/CT scanning at room temperature as part of their clinical care. (3) Choline transporter expression levels were measured in human BAds and WAds. (4) Human BAds were incubated with 15N-choline and incorporation into 15N-metabolites was analysed by LC-MS/MS.
Results: (1) Cold exposure increased circulating noradrenaline, non-esterified fatty acids and decreased supraclavicular and sternal skin temperature without changing insulin or glucose levels. There was detectable 18FCH uptake by supraclavicular BAT in all subjects during warm and cold exposure. Cold exposure increased 18FCH-detected BAT volume (by ~100%) and total BAT activity (by ~50%); 18FCH detected substantially lower BAT though than 18FDG during both conditions. (2) 18FCH uptake was ~2.5-fold higher in human SCVAT compared to abdominal subcutaneous WAT in patients scanned at room temperature. (3) In parallel with the in vivo data, mRNA levels of the choline transporter SLC44A2 were higher in BAds than WAds. (4) 15N-Choline tracing revealed that choline was incorporated into multiple phosphatidylcholine species in BAds.
Conclusion: 18FCH can be used to detect human BAT and acute cold exposure increases choline uptake by BAT. Human BAT utilises choline to synthesise phosphatidylcholines that may play an important role in optimal BAT function.
Volume 86
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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