The effect of serum BDNF levels on central serotonin transporter availability in obese versus non-obese adults: A [(11)C]DASB positron emission tomography study.
Serotonin (5-HT) and its neurotrophic support system, specifically brain-derived neurotrophic factor (BDNF), are thought to modulate energy homeostasis and susceptibility to obesity. Moreover, a polymorphism (5-HTTLPR) in the serotonin reuptake transporter (5-HTT) gene impairs its transcription, thereby altering serotonergic tone and potentially contributing to such susceptibility. This study aims to investigate the effect of BDNF, biallelic 5-HTTLPR, and central in-vivo 5-HTT availability in highly obese versus non-obese subjects using positron emission tomography (PET) and 5-HTT selective [(11)C]DASB.



Thirty-eight subjects, 24 obese, otherwise mentally and physically healthy, and 14 non-obese healthy controls were included in this study. Parametric images of binding potential were generated from PET data. Central 5-HTT availability, 5-HTTLPR genotype, and serum BDNF concentrations were analyzed, first in a volume of interest, then in a voxel-wise manner.



Overall, our results showed an absence of a linear correlation between BDNF, in-vivo central 5-HTT availability, and body mass index (BMI). 5-HTTLPR genotyping revealed BDNF and hippocampal 5-HTT availability to be negatively correlated (r = -0.57, p = 0.007) in long allelic homozygotes. However, obese subjects exhibited opposing effects of BDNF levels on 5-HTT availability in the nucleus accumbens (NAcc) relative to our non-obese controls.



Our data did not confirm an overall correlation between serum BDNF, in-vivo central 5-HTT availability, 5-HTTLPR, and BMI. However, there is evidence that serotonergic tone linked to BDNF, specifically in the NAcc, is involved in the pathophysiology of obesity, although this needs further exploration over a wide range of reward-related eating behaviors.
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Philipp
P
Hinderberger
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Michael
M
Rullmann
Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Mandy
M
Drabe
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
Julia
J
Luthardt
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
Georg-Alexander
GA
Becker
Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Matthias
M
Blüher
Division of Clinical Pharmacology, Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany.
Ralf
R
Regenthal
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Osama
O
Sabri
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany. Electronic address: Swen.Hesse@medizin.uni-leipzig.de.
Swen
S
Hesse
D000328:Adult; D000814:Aniline Compounds; D015992:Body Mass Index; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D013440:Sulfides; D055815:Young Adult
C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D019208:Brain-Derived Neurotrophic Factor; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; C579455:BDNF protein, human
Brain-derived neurotrophic factor; Energy homeostasis; Neurotrophin; Obesity; Positron emission tomography; Serotonergic tone; Serotonin; Serotonin transporter; Serotonin-transporter-linked polymorphic region