ATP synthase is a promising target for identifying activated and non-activated adipose tissues

Abstract Adipose tissue has gained increasing attention as a therapeutic target to combat human obesity and related metabolic disorders. We propose ATP synthase as a target to identify activated and non-activated adipose tissue. We investigated ATP synthase using the radiotracer 11 CJ147 and confirmed the specificity of the radiotracer by in vitro autoradiography, cell knockdown studies, and in vivo competition binding studies. In addition to the interscapular brown adipose tissue (BAT), 11 CJ147 could visualise several other BAT depots (supraspinal, infrascapular and axillary BAT) via in vivo positron emission tomography imaging after activation with a β 3 -adrenergic receptor agonist, as confirmed by immunohistochemistry and biodistribution studies. Furthermore, 11 CJ147 demonstrated higher sensitivity for BAT and WAT (white adipose tissue) identification compared to the commonly used radiotracer 18 FFDG and the mitochondrial complex I tracer 18 FBCPP-EF. Our study uncovers ATP synthase as a promising target for monitoring adipose tissue and 11 CJ147 could facilitate drug development for metabolic diseases such as obesity.