Human brown adipose tissue demonstrates substantial 18F-fluorocholine uptake at room temperature for phosphatidylcholine synthesis

Abstract

ObjectiveBrown 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 18F-fluorodeoxyglucose positron emission tomography (PET), which requires antecedent cold exposure. We hypothesized that 18F-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. Methods1) Six healthy men with detectable 18F-fluorodeoxyglucose uptake by BAT were recruited to a randomised crossover study investigating 18F-fluorocholine uptake by BAT during warm and cold exposure. 2) 18F-fluorocholine uptake by supraclavicular adipose tissue was quantified in 76 patients who had undergone 18F-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 15N-choline to determine phospholipid synthesis. Results1) 18F-Fluorocholine uptake by BAT was substantially greater than by WAT during both warm and cold exposure. 2) 18F-Fluorocholine uptake by supraclavicular adipose tissue was higher in the colder seasons, inversely associated with body mass index, 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) 15N-choline tracing in human brown adipocytes identified incorporation into >30 phosphatidylcholine species. Conclusions18F-fluorocholine PET may be a novel method to quantify human BAT at room temperature. HighlightsO_LI18F-Fluorocholine (FCH) PET can detect human BAT without the need for cold exposure. C_LIO_LI18F-FCH uptake by supraclavicular AT is inversely associated with body mass index. C_LIO_LIThe choline transporter SLC44A3 is more highly expressed in BAT than WAT. C_LIO_LIHuman brown adipocytes utilise choline for phosphatidylcholine synthesis. C_LI O_FIG O_LINKSMALLFIG WIDTH=168 HEIGHT=200 SRC="FIGDIR/small/671970v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@11e85forg.highwire.dtl.DTLVardef@1aec87forg.highwire.dtl.DTLVardef@1ed3bf3org.highwire.dtl.DTLVardef@1fadbd1_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACT C_FIG