18F-Fluorocholine uptake is greater by human supraclavicular brown than white adipose tissue and inversely associated with body mass index

Abstract Background Brown Adipose Tissue (BAT) is composed of mitochondrial-rich, multilocular adipocytes, which dissipate energy to produce heat. Quantification of BAT mass is most commonly performed by 18 F-fluorodeoxyglucose positron emission tomography (PET), which requires antecedent cold exposure. We hypothesized that 18 F-fluorocholine PET could detect human BAT due to its requirement for considerable phosphatidylcholine synthesis, secondary to brown adipocytes’ high mitochondrial density and multiple lipid droplets. Methods (1) Six healthy men with detectable 18 F-fluorodeoxyglucose uptake by BAT were recruited to a randomised crossover study investigating 18 F-fluorocholine uptake by BAT during warm and cold exposure. (2) 18 F-Fluorocholine uptake by supraclavicular adipose tissue was quantified in 76 patients who had previously undergone 18 F-fluorocholine PET/CT scanning. (3) Choline transporter expression was quantified in human BAT and white adipose tissue (WAT), and in brown and white adipocytes. (4) Lipidomics was performed on human brown adipocytes incubated with 15 N-choline to determine phospholipid synthesis. Results (1) 18 F-Fluorocholine uptake by BAT was substantially greater than by WAT during both warm and cold exposure. (2) 18 F-Fluorocholine uptake by supraclavicular adipose tissue was higher in the colder seasons and inversely associated with body mass index (unlike superficial neck WAT), and positively associated with tissue radiodensity. (3) Expression of the choline transporter SLC44A3 was higher in human supraclavicular BAT than WAT, while SLC44A2 was expressed more highly in human brown than white adipocytes. (4) 15 N-Choline tracing in human brown adipocytes identified incorporation into > 30 phosphatidylcholine species. Conclusions Human supraclavicular BAT demonstrates greater 18 F-fluorocholine uptake than WAT, consistent with increased choline utilisation for phosphatidylcholine synthesis. 18 F-Fluorocholine uptake in supraclavicular adipose tissue at room temperature may be a marker of human BAT.