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Interaction between...
Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity
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- Heni, Martin (author)
- University of Tübingen,German Center for Diabetes Research
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- Kullmann, Stephanie (author)
- University of Tübingen,German Center for Diabetes Research
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- Ahlqvist, Emma (author)
- Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Translationell muskelforskning,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Translational Muscle Research
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- Wagner, Robert (author)
- German Center for Diabetes Research,University of Tübingen
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- Machicao, Fausto (author)
- German Center for Diabetes Research,University of Tübingen
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- Staiger, Harald (author)
- University of Tübingen,German Center for Diabetes Research
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- Häring, Hans Ulrich (author)
- German Center for Diabetes Research,University of Tübingen
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- Almgren, Peter (author)
- Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Translationell muskelforskning,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Translational Muscle Research
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- Groop, Leif C. (author)
- Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Translationell muskelforskning,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Translational Muscle Research,University of Helsinki
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- Small, Dana M. (author)
- Yale University,John B Pierce Laboratory
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- Fritsche, Andreas (author)
- University of Tübingen,German Center for Diabetes Research
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- Preissl, Hubert (author)
- Helmholtz Zentrum München
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(creator_code:org_t)
- 2016-09-06
- 2016
- English 10 s.
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:12, s. 2622-2631
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- ANKK1
- Body fat
- Dopamine
- FTO
- Insulin sensitivity
- TaqIA
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Heni, Martin
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Kullmann, Stepha ...
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Ahlqvist, Emma
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Wagner, Robert
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Machicao, Fausto
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Staiger, Harald
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Häring, Hans Ulr ...
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Almgren, Peter
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Groop, Leif C.
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Small, Dana M.
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Fritsche, Andrea ...
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Preissl, Hubert
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetologia
- By the university
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Lund University