Philipp Hinderberger1, Michael Rullmann1, Mandy Drabe2, Julia Luthardt3, Georg-Alexander Becker3, Matthias Blüher2, Ralf Regenthal4, Osama Sabri1, Swen Hesse5. 1. Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany. 2. Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany. 3. Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany. 4. Division of Clinical Pharmacology, Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany. 5. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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