The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Leif Groop

Leif Groop

Principal investigator

Leif Groop

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

Author

  • 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

Summary, in English

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.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2016-12

Language

English

Pages

2622-2631

Publication/Series

Diabetologia

Volume

59

Issue

12

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • ANKK1
  • Body fat
  • Dopamine
  • FTO
  • Insulin sensitivity
  • TaqIA

Status

Published

Research group

  • LUDC (Lund University Diabetes Centre)
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 0012-186X