Abstract
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Objectives: Mutations in the gene encoding BDNF lead to insatiable appetite and severe weight gain. The T allele of rs10767664, a single-nucleotid polymorphism of the BDNF gene, has been linked with obesity; however, the mechanism-of-action is not understood though a close relation with neurotransmitter release, i.e. an interaction with the central catecholemines dopamine and noradrenaline (NA) has to be assumed. The present study is the first to investigate the assocation between in vivo NA transporter availability and a variation of the BDNF rs10767664 gene locus in human obesity.
Methods: TaqMan Assay and PET using [11C]methylreboxetin were performed in 20 mental healthy participants (10 obese, body mass index BMI 43±4 kg/m2, 6♀, age 35±9kg/m2; 10 non-obese, BMI 24±2 kg/m2, 6♀, age 35±9kg/m2). Regional NA transporter binding potential (BPND) was calculated atlas-based on individual MRI coregistration using multi-linear reference tissue model with two parameters (MRTM2) and volume-of-interest (VOI) analysis.
Results: In T allele carriers, significantly lower BPND were found in the hypothalamus and the locus coeruleus compared with the carriers of the more common A-allele gene (0.32±0.09 vs. 0.48±0.18, p=0.04, and 0.14±0.09 vs. 0.41±0.20, p=0.003, respectively). T allele carriers also exhibit higher scores of the FEVII questionnaire indicating higher levels of emotional eating. In addition, negative correlative data showed that FEVII scores predict mean BPND in the locus coeruleus whereas a significant association between T/A allele carriers and BMI could not been detected thus far.
Conclusion: The data suggest that BDNF rs10767664 is associated with the availability of central NA transporter, and hence the activity of NA, in regions relevant for energy homeostasis (i.e. the hypothalamus) and cognitive control of distinct (eating) behaviors, which is the locus coereulus. These findings together support the assumption of a relation between BDNF and feeding in humans; however, it remains to be elucidated how BDNF regulates food intake and which role BDNF plays in the development of human obesity. Research Support: This study was supported by the German Federal Ministry of Education and Research (FKZ: 01EO1001).