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06.09.2016 | Article

Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity

verfasst von: Martin Heni, Stephanie Kullmann, Emma Ahlqvist, Robert Wagner, Fausto Machicao, Harald Staiger, Hans-Ulrich Häring, Peter Almgren, Leif C. Groop, Dana M. Small, Andreas Fritsche, Hubert Preissl

Erschienen in: Diabetologia | Ausgabe 12/2016

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Abstract

Aims/hypothesis

Variations in FTO are the strongest common genetic determinants of adiposity, and may partly act by influencing dopaminergic signalling in the brain leading to altered reward processing that promotes increased food intake. Therefore, we investigated the impact of such an interaction on body composition, and peripheral and brain insulin sensitivity.

Methods

Participants from the Tübingen Family study (n = 2245) and the Malmö Diet and Cancer study (n = 2921) were genotyped for FTO SNP rs8050136 and ANKK1 SNP rs1800497. Insulin sensitivity in the caudate nucleus, an important reward area in the brain, was assessed by fMRI in 45 participants combined with intranasal insulin administration.

Results

We found evidence of an interaction between variations in FTO and an ANKK1 polymorphism that associates with dopamine (D2) receptor density. In cases of reduced D2 receptor availability, as indicated by the ANKK1 polymorphism, FTO variation was associated with increased body fat and waist circumference and reduced peripheral insulin sensitivity. Similarly, altered central insulin sensitivity was observed in the caudate nucleus in individuals with the FTO obesity-risk allele and diminished D2 receptors.

Conclusions/interpretation

The effects of variations in FTO are dependent on dopamine D2 receptor density (determined by the ANKK1 polymorphism). Carriers of both risk alleles might, therefore, be at increased risk of obesity and diabetes.

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Titel: Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity
verfasst von: Martin Heni
Stephanie Kullmann
Emma Ahlqvist
Robert Wagner
Fausto Machicao
Harald Staiger
Hans-Ulrich Häring
Peter Almgren
Leif C. Groop
Dana M. Small
Andreas Fritsche
Hubert Preissl
Publikationsdatum: 06.09.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 12/2016
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-016-4095-0

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Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity

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