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  Inverse relationship between central serotonin and noradrenaline transporter availability in humans with high BMI range - a potential biological mechanism in obesity

Hesse, S., Rullmann, M., Bresch, A., Heinicke, M., Schincke, C., Vettermann, F., et al. (2017). Inverse relationship between central serotonin and noradrenaline transporter availability in humans with high BMI range - a potential biological mechanism in obesity. Journal of Cerebral Blood Flow and Metabolism, 37(Suppl. 1): BPS06-4, 95-95. doi:10.1177/0271678X17695978.

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Hesse, S.1, Author
Rullmann, Michael2, Author              
Bresch, A.1, Author
Heinicke, M.1, Author
Schincke, C.1, Author
Vettermann, F.1, Author
Hankir, M.1, Author
Luthardt, J.1, Author
Becker, G.-A.1, Author
Patt, M.1, Author
Meyer, P.M.1, Author
Fasshauer, M.1, Author
Blueher, M.1, Author
Fenske, W.1, Author
Then Bergh, F.1, Author
Hilbert, A.1, Author
Ding, Y.-S.1, Author
Sabri, O.1, Author
1External Organizations, ou_persistent22              
2Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              


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 Abstract: Objective The brain neurotransmitters serotonin (5-HT) and noradrenaline (NA) are both implicated in the regulation of appetite and energy balance. Disturbances of these systems, i.e. in key areas of feeding control such as the hypothalamus, lead to eating disorders and obesity. The mechanism by which an impaired 5-HT/NA signalling contributes is still unclear. Methods A PET study using either central 5-HT transporter (5-HTT)- or NA transporter (NAT)-selective [11C]DASB/[11C]MRB in 65 lean-to-highly obese individuals (BMI range: 19.1–54.1 kg/m2). 5-HTT/NAT binding potential BPND was obtained as PET outcome measures and correlated with BMI. Results 5-HTT BPND and NAT BPND tend towards an inverse relationship with increasing BMI (e.g., in the midbrain: Fig. 1A; p = 0.13 and p = 0.06, respectively). Such an opponent association is supported by correlative data with neurobehavioral scores (Y-FAS, FEV II), pharmacological stress test results, and follow-up BPND after 6-months diet. Although the participants were free of major depressive disorder (as assessed by structured clinical interview), correlative analyses showed a relationship between midbrain NAT BPND and Beck Depression Inventory (BDI) as an index for sub-threshold depression (r = −0.408; p = 0.07) as well as a correlation between BMI and BDI in both groups (5-HTT: p < 0.01; NAT: p = 0.19; Fig. 1B). Conclusion High 5-HTT and low NAT are associated with high BMI. This indicates a potential mechanism in the pathogenesis of human obesity reflecting high NA tone and low 5-HT levels. Together with certain eating behaviours and other biomarkers (pharmacogenotypes) the hypothesized association may lead to more individualised approaches if confirmed. It also questioned the presumed mechanism of action of the drug sibutramine, which is a combined NAT and 5-HTT inhibitor. Sub-threshold depression is an important modulator but may not explain the findings alone.


Language(s): eng - English
 Dates: 2017-04-01
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1177/0271678X17695978
PMID: 28366133
 Degree: -


Title: 28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET
Place of Event: Berlin
Start-/End Date: 2017-04-01 - 2017-04-01

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Title: Journal of Cerebral Blood Flow and Metabolism
Source Genre: Journal
Publ. Info: New York : Lippincott Williams & Wilkins
Pages: - Volume / Issue: 37 (Suppl. 1) Sequence Number: BPS06-4 Start / End Page: 95 - 95 Identifier: ISSN: 0271-678X
CoNE: https://pure.mpg.de/cone/journals/resource/954925503202