<p>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 [<sup>11</sup>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), [<sup>11</sup>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<sub>3</sub>-adrenergic receptor agonist, as confirmed by immunohistochemistry and biodistribution studies. Furthermore, [<sup>11</sup>C]J147 demonstrated higher sensitivity for BAT and WAT (white adipose tissue) identification compared to the commonly used radiotracer [<sup>18</sup>F]FDG and the mitochondrial complex I tracer [<sup>18</sup>F]BCPP-EF. Our study uncovers ATP synthase as a promising target for monitoring adipose tissue and [<sup>11</sup>C]J147 could facilitate drug development for metabolic diseases such as obesity.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

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

  • Caitlin V.M.L. Jie,
  • Aro Delparente,
  • Tongtong Wang,
  • Lisa Reichert,
  • Petra Krajnovic,
  • Marc Schläppi,
  • Lukas Reininger,
  • Laura T. L. Brandt,
  • Claudia Keller,
  • Julien Orts,
  • Roland Riek,
  • Stefanie D. Krämer,
  • Markus Stoffel,
  • Christian Wolfrum,
  • Roger Schibli,
  • Linjing Mu

摘要

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 [11C]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), [11C]J147 could visualise several other BAT depots (supraspinal, infrascapular and axillary BAT) via in vivo positron emission tomography imaging after activation with a β3-adrenergic receptor agonist, as confirmed by immunohistochemistry and biodistribution studies. Furthermore, [11C]J147 demonstrated higher sensitivity for BAT and WAT (white adipose tissue) identification compared to the commonly used radiotracer [18F]FDG and the mitochondrial complex I tracer [18F]BCPP-EF. Our study uncovers ATP synthase as a promising target for monitoring adipose tissue and [11C]J147 could facilitate drug development for metabolic diseases such as obesity.