Sevgi, Meltem, Rigoux, Lionel, Kuehn, Anne B., Mauer, Jan ORCID: 0000-0002-0189-5876, Schilbach, Leonhard ORCID: 0000-0001-5547-8309, Hess, Martin E., Gruendler, Theo O. J., Ullsperger, Markus ORCID: 0000-0003-3970-1982, Stephan, Klaas Enno ORCID: 0000-0002-8594-9092, Bruening, Jens C. and Tittgemeyer, Marc (2015). An Obesity-Predisposing Variant of the FTO Gene Regulates D2R-Dependent Reward Learning. J. Neurosci., 35 (36). S. 12584 - 12593. WASHINGTON: SOC NEUROSCIENCE. ISSN 0270-6474

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Abstract

Variations in the fat mass and obesity-associated (FTO) gene are linked to obesity. However, the underlying neurobiological mechanisms by which these genetic variants influence obesity, behavior, and brain are unknown. Given that Fto regulates D2/3R signaling in mice, we tested in humans whether variants in FTO would interact with a variant in the ANKK1 gene, which alters D2R signaling and is also associated with obesity. In a behavioral and fMRI study, we demonstrate that gene variants of FTO affect dopamine (D2)-dependent midbrain brain responses to reward learning and behavioral responses associated with learning from negative outcome in humans. Furthermore, dynamic causal modeling confirmed that FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic predisposition alters reward processing not only in obesity, but also in other disorders with altered D2R-dependent impulse control, such as addiction.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Sevgi, MeltemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rigoux, LionelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuehn, Anne B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mauer, JanUNSPECIFIEDorcid.org/0000-0002-0189-5876UNSPECIFIED
Schilbach, LeonhardUNSPECIFIEDorcid.org/0000-0001-5547-8309UNSPECIFIED
Hess, Martin E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruendler, Theo O. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ullsperger, MarkusUNSPECIFIEDorcid.org/0000-0003-3970-1982UNSPECIFIED
Stephan, Klaas EnnoUNSPECIFIEDorcid.org/0000-0002-8594-9092UNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tittgemeyer, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-393100
DOI: 10.1523/JNEUROSCI.1589-15.2015
Journal or Publication Title: J. Neurosci.
Volume: 35
Number: 36
Page Range: S. 12584 - 12593
Date: 2015
Publisher: SOC NEUROSCIENCE
Place of Publication: WASHINGTON
ISSN: 0270-6474
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DOPAMINE-RECEPTOR GENE; BODY-MASS INDEX; GENETICALLY-DETERMINED DIFFERENCES; BAYESIAN MODEL SELECTION; PREDICTION ERRORS; FAT MASS; GREATER IMPULSIVITY; HEALTHY-VOLUNTEERS; GABAERGIC NEURONS; MIDBRAIN DOPAMINEMultiple languages
NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39310

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