The effect of serum BDNF levels on central serotonin transporter availability in obese versus non-obese adults: A [11C]DASB positron emission tomography study

NEUROPHARMACOLOGY

卷:110

Article

Hinderberger, Philipp^1,2  Rullmann, Michael^1,2  Drabe, Mandy²  Luthardt, Julia¹  Becker, Georg-Alexander¹  Blueher, Matthias²  Regenthal, Ralf³  Sabri, Osama^1,2  Hesse, Swen^1,2 

[1] Univ Leipzig, Dept Nucl Med, Liebigstr 18, D-04103 Leipzig, Germany

[2] Univ Leipzig, Integrated Res & Treatment Ctr IFB Adipos Dis, Leipzig, Germany

[3] Univ Leipzig, Rudolf Boehm Inst Pharmacol & Toxicol, Div Clin Pharmacol, Leipzig, Germany

关键词: Brain-derived neurotrophic factor;    Neurotrophin;    Serotonin;    Serotonin transporter;    Serotonin-transporter-linked polymorphic region;    Serotonergic tone;    Positron emission tomography;    Energy homeostasis;    Obesity;   

DOI  :  10.1016/j.neuropharm.2016.04.030

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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