Skip to main content
SpringerLink
Log in

Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [11C] DASB positron emission tomography study

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The role of the central serotonin (5-hydroxytryptamine, 5-HT) system in feeding has been extensively studied in animals with the 5-HT family of transporters (5-HTT) being identified as key molecules in the regulation of satiety and body weight. Aberrant 5-HT transmission has been implicated in the pathogenesis of human obesity by in vivo positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging techniques. However, results obtained thus far from studies of central 5-HTT availability have been inconsistent, which is thought to be brought about mainly by the low number of individuals with a high body mass index (BMI) previously used. The aim of this study was therefore to assess 5-HTT availability in the brains of highly obese otherwise healthy individuals compared with non-obese healthy controls.

Methods

We performed PET using the 5-HTT selective radiotracer [11C] DASB on 30 highly obese (BMI range between 35 and 55 kg/m2) and 15 age- and sex-matched non-obese volunteers (BMI range between 19 and 27 kg/m2) in a cross-sectional study design. The 5-HTT binding potential (BPND) was used as the outcome parameter.

Results

On a group level, there was no significant difference in 5-HTT BPND in various cortical and subcortical regions in individuals with the highest BMI compared with non-obese controls, while statistical models showed minor effects of age, sex, and the degree of depression on 5-HTT BPND.

Conclusion

The overall finding of a lack of significantly altered 5-HTT availability together with its high variance in obese individuals justifies the investigation of individual behavioral responses to external and internal cues which may further define distinct phenotypes and subgroups in human obesity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Leibowitz SF. Hypothalamic neurotransmitters in relation to normal and disturbed eating patterns. Ann N Y Acad Sci. 1987;499:137–43.

    Article  CAS  PubMed  Google Scholar 

  2. Garfield AS, Heisler LK. Pharmacological targeting of the serotonergic system for the treatment of obesity. J Physiol. 2009;587:49–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, et al. Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363:245–56.

    Article  CAS  PubMed  Google Scholar 

  4. Huang XF, Huang X, Han M, Chen F, Storlien L, Lawrence AJ. 5-HT2A/2C receptor and 5-HT transporter densities in mice prone or resistant to chronic high-fat diet-induced obesity: a quantitative autoradiography study. Brain Res. 2004;1018:227–35.

    Article  CAS  PubMed  Google Scholar 

  5. Ratner C, Ettrup A, Bueter M, Haahr ME, Compan V, le Roux CW, et al. Cerebral markers of the serotonergic system in rat models of obesity and after Roux-en-Y gastric bypass. Obesity (Silver Spring). 2012;20:2133–41.

    Article  CAS  Google Scholar 

  6. Haahr ME, Rasmussen PM, Madsen K, Marner L, Ratner C, Gillings N, et al. Obesity is associated with high serotonin 4 receptor availability in the brain reward circuitry. Neuroimage. 2012;61:884–8.

    Article  CAS  PubMed  Google Scholar 

  7. Erritzoe D, Frokjaer VG, Haugbol S, Marner L, Svarer C, Holst K, et al. Brain serotonin 2A receptor binding: relations to body mass index, tobacco and alcohol use. Neuroimage. 2009;46:23–30.

    Article  CAS  PubMed  Google Scholar 

  8. Erritzoe D, Frokjaer VG, Haahr MT, Kalbitzer J, Svarer C, Holst KK, et al. Cerebral serotonin transporter binding is inversely related to body mass index. Neuroimage. 2010;52:284–9.

    Article  CAS  PubMed  Google Scholar 

  9. Hesse S, Villringer A, Schönknecht P, Becker GA, Patt M, Bresch A, et al. Serotonin transporter (SERT) availability, body mass index (BMI) and depression. J Nucl Med. 2009;50 Suppl 2:1294.

    Google Scholar 

  10. Haahr ME, Hansen DL, Fisher PM, Svarer C, Stenbæk DS, Madsen K, et al. Central 5-HT Neurotransmission modulates weight loss following gastric bypass surgery in obese individuals. J Neurosci. 2015;35:5884–9.

    Article  CAS  PubMed  Google Scholar 

  11. Hautzinger M. Das Beck Depressions-Inventar (BDI) in der Klinik. Nervenarzt. 1991;62:689–6.

    CAS  PubMed  Google Scholar 

  12. Hesse S, Stengler K, Regenthal R, Patt M, Becker GA, Franke A, et al. The serotonin transporter availability in untreated early-onset and late-onset patients with obsessive-compulsive disorder. Int J Neuropsychopharmacol. 2011;14:606–17.

    Article  CAS  PubMed  Google Scholar 

  13. Wilson AA, Ginovart N, Schmidt M, Meyer JH, Threlkeld PG, Houle S. Novel radiotracers for imaging the serotonin transporter by positron emission tomography: synthesis, radiosynthesis, and in vitro and ex vivo evaluation of 11C-labeled 2-(phenylthio)araalkylamines. J Med Chem. 2000;43:3103–10.

    Article  CAS  PubMed  Google Scholar 

  14. Ichise M, Liow JS, Lu JQ, Takano A, Model K, Toyama H, et al. Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain. J Cereb Blood Flow Metab. 2003;23:1096–112.

    Article  PubMed  Google Scholar 

  15. Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27:1533–9.

    Article  CAS  PubMed  Google Scholar 

  16. Mai JK, Assheuer J, Paxinos G. Atlas of the human brain. 2nd ed. San Diego: Elsevier Academic; 2004.

    Google Scholar 

  17. Hainer V, Kabrnova K, Aldhoon B, Kunesova M, Wagenknecht M. Serotonin and norepinephrine reuptake inhibition and eating behavior. Ann N Y Acad Sci. 2006;1083:252–69.

    Article  CAS  PubMed  Google Scholar 

  18. Stark JA, Davies KE, Williams SR, Luckman SM. Functional magnetic resonance imaging and c-Fos mapping in rats following an anorectic dose of m-chlorophenylpiperazine. Neuroimage. 2006;31:1228–37.

    Article  PubMed  Google Scholar 

  19. Hesse S, van de Giessen E, Zientek F, Petroff D, Winter K, Dickson JC, et al. Association of central serotonin transporter availability and body mass index in healthy Europeans. Eur Neuropsychopharmacol. 2014;24(8):1240–7.

    Article  CAS  PubMed  Google Scholar 

  20. Koopman KE, Booij J, Fliers E, Serlie MJ, la Fleur SE. Diet-induced changes in the Lean Brain: Hypercaloric high-fat-high-sugar snacking decreases serotonin transporters in the human hypothalamic region. Mol Metab. 2013;2:417–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Li CS, Potenza MN, Lee DE, Planeta B, Gallezot JD, Labaree D, et al. Decreased norepinephrine transporter availability in obesity: positron emission tomography imaging with (S, S)-[11C]O-methylreboxetine. Neuroimage. 2014;86:306–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Uçeyler N, Schütt M, Palm F, Vogel C, Meier M, Schmitt A, et al. Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity. Int J Obes (Lond). 2010;34:701–11.

    Article  Google Scholar 

  23. Homberg JR, la Fleur SE, Cuppen E. Serotonin transporter deficiency increases abdominal fat in female, but not male rats. Obesity (Silver Spring). 2010;18:137–45.

    Article  CAS  Google Scholar 

  24. Gryglewski G, Lanzenberger R, Kranz GS, Cumming P. Meta-analysis of molecular imaging of serotonin transporters in major depression. J Cereb Blood Flow Metab. 2014;34:1096–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Udo T, McKee SA, Grilo CM. Factor structure and clinical utility of the Beck depression inventory in patients with binge eating disorder and obesity. Gen Hosp Psychiatry. 2015;37:120–25.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Zou N, Chetelat G, Baydogan MG, Li J, Fischer FU, Titov D, et al. Metabolic connectivity as index of verbal working memory. J Cereb Blood Flow Metab. 2015;35:1122–6.

    Article  CAS  PubMed  Google Scholar 

  27. Scharmüller W, Übel S, Ebner F, Schienle A. Appetite regulation during food cue exposure: a comparison of normal-weight and obese women. Neurosci Lett. 2012;518:106–10.

    Article  PubMed  Google Scholar 

  28. Drevets WC, Price JL, Furey ML. Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Funct. 2008;213:93–118.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Northoff G, Wiebking C, Feinberg T, Panksepp J. The ‘resting-state hypothesis’ of major depressive disorder-a translational subcortical-cortical framework for a system disorder. Neurosci Biobehav Rev. 2011;35:1929–45.

    Article  PubMed  Google Scholar 

  30. Bearer EL, Zhang X, Janvelyan D, Boulat B, Jacobs RE. Reward circuitry is perturbed in the absence of the serotonin transporter. Neuroimage. 2009;46:1091–104.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We are very grateful to Damian McLeod, School of Biomedical Sciences and Pharmacy, University of Newcastle, Australia, for careful line editing and English proofreading of the first draft of the manuscript.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, University of Leipzig, Liebigstraße 18, 04103, Leipzig, Germany

    Swen Hesse, Michael Rullmann, Julia Luthardt, Georg-Alexander Becker, Anke Bresch, Marianne Patt, Philipp M. Meyer & Osama Sabri

  2. Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig, Germany

    Swen Hesse, Michael Rullmann, Mohammed K. Hankir, Franziska Zientek, Georg Reissig, Mandy Drabe, Mathias Fasshauer, Wiebke K. Fenske, Michael Stumvoll & Osama Sabri

  3. Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Leipzig, Germany

    Michael Rullmann & Katrin Arelin

  4. Centre for Translational Regenerative Medicine, University of Leipzig, Leipzig, Germany

    Karsten Winter

  5. Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany

    Karsten Winter

  6. Division of Clinical Pharmacology, Rudolf Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany

    Ralf Regenthal

  7. Department of Neurology, University of Leipzig, Leipzig, Germany

    Christian Schinke

  8. Day Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany

    Katrin Arelin

  9. Department of Neuroradiology, University of Leipzig, Leipzig, Germany

    Donald Lobsien

  10. Medical Department III, University of Leipzig, Leipzig, Germany

    Mathias Fasshauer, Wiebke K. Fenske, Matthias Blüher & Michael Stumvoll

  11. Collaborative Research Centre 1052 Obesity Mechanisms, University of Leipzig, Leipzig, Germany

    Matthias Blüher

Authors
  1. Swen Hesse
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Rullmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julia Luthardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karsten Winter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammed K. Hankir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Georg-Alexander Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Franziska Zientek
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Georg Reissig
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ralf Regenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mandy Drabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christian Schinke
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Anke Bresch
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Katrin Arelin
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Donald Lobsien
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Marianne Patt
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Philipp M. Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Mathias Fasshauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Wiebke K. Fenske
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Matthias Blüher
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Michael Stumvoll
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Osama Sabri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Swen Hesse.

Ethics declarations

Funding

This study was supported by the German Federal Ministry of Education and Research (FKZ: 01EO1001).

Conflict of interest

The authors report no conflicts of interest relating to the content of this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ICH Guideline for Good Clinical Practice (GCP) and with the 1964 Helsinki declaration and its later amendments. The study was approved by the ethics committee of the Medical Faculty of the University of Leipzig (registered under the number 206-10-08032010) and the German Bundesamt für Strahlenschutz/Federal Office for Radiation Protection (number Z5-22461-2-2011-002), and registered at the European clinical trial database EudraCT 2012-000568-32) and the German Clinical Trials Register (DRKS).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hesse, S., Rullmann, M., Luthardt, J. et al. Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [11C] DASB positron emission tomography study. Eur J Nucl Med Mol Imaging 43, 1096–1104 (2016). https://doi.org/10.1007/s00259-015-3243-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-015-3243-y

Keywords

Search

Navigation