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

Abstract

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 C]J147 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 C]J147 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 C]J147 demonstrated higher sensitivity for BAT and WAT (white adipose tissue) identification compared to the commonly used radiotracer [ 18 F]FDG and the mitochondrial complex I tracer [ 18 F]BCPP-EF. Our study uncovers ATP synthase as a promising target for monitoring adipose tissue and [ 11 C]J147 could facilitate drug development for metabolic diseases such as obesity.