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April 17, 2026Nature Communications0 citationsOpen Access

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

CJCaitlin JieADAro DelparenteTWT Wang

Key Result

[11C]J147 demonstrated significantly higher uptake in activated interscapular brown adipose tissue compared to [18F]FDG (P < 0.0001) and successfully visualized multiple BAT depots in mice.

Key Points

  • The study aims to evaluate ATP synthase as a specific target for differentiating between activated and non-activated adipose tissues.
  • Utilized the radiotracer [11C]J147 to investigate adipose tissue activation.
  • Conducted in vitro autoradiography, cell knockdown, and in vivo competition binding studies for specificity confirmation.
  • Performed positron emission tomography imaging to visualize various BAT depots post-activation.
  • Conducted immunohistochemistry and biodistribution studies to support findings.
  • [11C]J147 successfully visualized multiple BAT depots in vivo.
  • Demonstrated higher sensitivity for identifying BAT and WAT compared to [18F]FDG and [18F]BCPP-EF.
  • Revealed ATP synthase as a promising target for monitoring adipose tissue alterations.

Structured PICO

Does the radiotracer [11C]J147 targeting ATP synthase improve the identification of activated and non-activated adipose tissue compared to [18F]FDG in preclinical models?

P
Population
Preclinical models (in vitro cells and in vivo models) for adipose tissue imaging
I
Intervention
Radiotracer [11C]J147 targeting ATP synthase
C
Comparator
[18F]FDG and [18F]BCPP-EF
O
Outcome
Identification and visualization of activated and non-activated brown and white adipose tissuesurrogate

The radiotracer [11C]J147 targeting ATP synthase shows higher sensitivity for identifying brown and white adipose tissue compared to standard tracers, offering a promising tool for metabolic disease research.

Main Result

p-value: p=<0.0001

Limitations

  • Modest effects in competition binding studies likely due to incomplete receptor occupancy and partial non-specific uptake
  • High abundance of ATP synthase may require higher doses and continuous infusion rather than a single bolus injection
  • Relatively low tracer uptake in white adipose tissues could be attributed to the short duration of activation in the study

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 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.

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Cite This Study

Jie et al. (2026) studied Adipose tissue imaging. [11C]J147 vs. [18F]FDG and [18F]BCPP-EF was evaluated on Tracer uptake in interscapular brown adipose tissue (BAT) (p=<0.0001). [11C]J147 demonstrated significantly higher uptake in activated interscapular brown adipose tissue compared to [18F]FDG (P < 0.0001) and successfully visualized multiple BAT depots in mice.

synapsesocial.com/papers/69e1ce3b5cdc762e9d8574eehttps://doi.org/10.1038/s41467-026-71343-w
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