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  • Heni, MartinGerman Center for Diabetes Research,University of Tübingen (author)

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

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-09-06
  • Springer Science and Business Media LLC,2016
  • 10 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:34bdd91f-6131-46be-936d-3e8cbd2e5b26
  • https://lup.lub.lu.se/record/34bdd91f-6131-46be-936d-3e8cbd2e5b26URI
  • https://doi.org/10.1007/s00125-016-4095-0DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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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  • Kullmann, StephanieUniversity of Tübingen,German Center for Diabetes Research (author)
  • Ahlqvist, EmmaLund 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(Swepub:lu)infl-eah (author)
  • Wagner, RobertGerman Center for Diabetes Research,University of Tübingen (author)
  • Machicao, FaustoGerman Center for Diabetes Research,University of Tübingen (author)
  • Staiger, HaraldGerman Center for Diabetes Research,University of Tübingen (author)
  • Häring, Hans UlrichUniversity of Tübingen,German Center for Diabetes Research (author)
  • Almgren, PeterLund 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(Swepub:lu)endo-pal (author)
  • Groop, Leif C.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(Swepub:lu)endo-lgr (author)
  • Small, Dana M.Yale University,John B Pierce Laboratory (author)
  • Fritsche, AndreasUniversity of Tübingen,German Center for Diabetes Research (author)
  • Preissl, HubertHelmholtz Zentrum München (author)
  • German Center for Diabetes ResearchUniversity of Tübingen (creator_code:org_t)

Related titles

  • In:Diabetologia: Springer Science and Business Media LLC59:12, s. 2622-26310012-186X1432-0428

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