Journal
NEUROPHARMACOLOGY
Volume 110, Issue -, Pages 530-536Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2016.04.030
Keywords
Brain-derived neurotrophic factor; Neurotrophin; Serotonin; Serotonin transporter; Serotonin-transporter-linked polymorphic region; Serotonergic tone; Positron emission tomography; Energy homeostasis; Obesity
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Funding
- German Federal Ministry of Education and Research [FKZ: 01EO1001]
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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 [C-11]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 HIT 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. (C) 2016 Elsevier Ltd. All rights reserved.
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