Franziska J Vettermann1,2,3, Michael Rullmann4,5, Georg A Becker5, Julia Luthardt5, Franziska Zientek4,5, Marianne Patt5, Philipp M Meyer5, Anke McLeod5, Matthias Brendel6, Matthias Blüher7, Michael Stumvoll4,7, Anja Hilbert4,8, Yu-Shin Ding9, Osama Sabri4,5, Swen Hesse4,5. 1. Integrated Research and Treatment Center (IFB) AdiposityDiseases, University Medical Center, Leipzig, Germany. Franziska.Vettermann@med.uni-muenchen.de. 2. Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany. Franziska.Vettermann@med.uni-muenchen.de. 3. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany. Franziska.Vettermann@med.uni-muenchen.de. 4. Integrated Research and Treatment Center (IFB) AdiposityDiseases, University Medical Center, Leipzig, Germany. 5. Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany. 6. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany. 7. Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany. 8. Department of Medical Psychology and Medical Sociology, Psychiatry and Chemistry New York University School of Medicine Faculty, New York, NY, USA. 9. Departments of Radiology, Psychiatry and Chemistry , New York University School of Medicine Faculty, New York, NY, USA.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Entities:
Keywords:
BMI; MRI; Noradrenaline; Noradrenaline transporter; Obesity; PET
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