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

Heni, Martin; Kullmann, Stephanie; Ahlqvist, Emma LU ; Wagner, Robert; Machicao, Fausto; Staiger, Harald; Häring, Hans Ulrich; Almgren, Peter LU ; Groop, Leif C. LU and Small, Dana M., et al. (2016) In Diabetologia 59(12). p.2622-2631
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... (More)

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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publication status
published
subject
keywords
ANKK1, Body fat, Dopamine, FTO, Insulin sensitivity, TaqIA
in
Diabetologia
volume
59
issue
12
pages
10 pages
publisher
Springer Verlag
external identifiers
  • scopus:84986271712
  • wos:000387596300019
ISSN
0012-186X
DOI
10.1007/s00125-016-4095-0
language
English
LU publication?
yes
id
34bdd91f-6131-46be-936d-3e8cbd2e5b26
date added to LUP
2016-11-17 10:16:06
date last changed
2017-11-12 04:26:13
@article{34bdd91f-6131-46be-936d-3e8cbd2e5b26,
  abstract     = {<p>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.</p>},
  author       = {Heni, Martin and Kullmann, Stephanie and Ahlqvist, Emma and Wagner, Robert and Machicao, Fausto and Staiger, Harald and Häring, Hans Ulrich and Almgren, Peter and Groop, Leif C. and Small, Dana M. and Fritsche, Andreas and Preissl, Hubert},
  issn         = {0012-186X},
  keyword      = {ANKK1,Body fat,Dopamine,FTO,Insulin sensitivity,TaqIA},
  language     = {eng},
  number       = {12},
  pages        = {2622--2631},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity},
  url          = {http://dx.doi.org/10.1007/s00125-016-4095-0},
  volume       = {59},
  year         = {2016},
}