Open Access Green as soon as Postprint is submitted to ZB.
Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity.
Diabetologia 59, 1-10 (2016)
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.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Ankk1 ; Body Fat ; Dopamine ; Fto ; Insulin Sensitivity ; Taqia; Deep Brain-stimulation; Nucleus-accumbens; Adult Obesity; Food Reward; Body-fat; Variant; Polymorphisms; Resistance; Association; Circuitry
ISSN (print) / ISBN
0012-186X
e-ISSN
1432-0428
Journal
Diabetologia
Quellenangaben
Volume: 59,
Issue: 12,
Pages: 1-10
Publisher
Springer
Publishing Place
Berlin ; Heidelberg [u.a.]
Non-patent literature
Publications
Reviewing status
Peer reviewed