Noradrenaline transporter availability on [11C]MRB PET predicts weight loss success in highly obese adults
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Although the mechanisms by which the central noradrenaline (NA) system influences appetite and controls energy balance are quite well understood, its relationship to changes in body weight remains largely unknown. The main goal of this study was to further clarify whether the brain NA system is a stable trait or whether it can be altered by dietary intervention.
We aimed to compare central NA transporter (NAT) availability in ten obese, otherwise healthy individuals with a body mass index (BMI) of 42.4 ± 3.7 kg/m2 (age 34 ± 9 years, four women) and ten matched non-obese, healthy controls (BMI 23.9 ± 2.5 kg/m2, age 33 ± 10 years, four women) who underwent PET with the NAT-selective radiotracer (S,S)-[11C]O-methylreboxetine (MRB) before and 6 months after dietary intervention.
MRI-based individual volume-of-interest analyses revealed an increase in binding potential (BPND) in the insula and the hippocampus of obese individuals, which correlated well with changes in BMI (−3.3 ± 5.3%; p = 0.03) following completion of the dietary intervention. Furthermore, voxel-wise regression analyses showed that lower BPND in these regions, but also in the midbrain and the prefrontal cortex, at baseline was associated with higher achieved weight loss (e.g., hippocampal area R2 = 0.80; p < 0.0001). No changes were observed in non-obese controls.
These first longitudinal interventional data on NAT availability in highly obese individuals indicate that the central NA system is modifiable. Our findings suggest that NAT availability before intervention could help predict the amount and success of weight loss in obese individuals and help adjust treatment options individually by allowing prediction of the benefit of a dietary intervention.
KeywordsObesity BMI PET MRI Noradrenaline Noradrenaline transporter
This work was supported by the IFB Adiposity Diseases, Federal Ministry of Education and Research (BMBF), Germany; FKZ 01E01001 (http://www.bmbf.de).
Compliance with ethical standards
Conflicts of interest
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board. The study was approved by the Bundesamt für Strahlenschutz (BfS, Federal Office for Radiation Protection; local EC number 206-10-08032010; EudraCT 2012-000568-32) and was performed in accordance with the ICH Guideline for Good Clinical Practice (GCP) and with the principles of the Declaration of Helsinki. The study was registered with the German Clinical Trials Register (DRKS).
Informed consent was obtained from all individual participants included in the study.
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