Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Sevgi, Meltem UNSPECIFIED UNSPECIFIED UNSPECIFIED Rigoux, Lionel UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuehn, Anne B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauer, Jan UNSPECIFIED orcid.org/0000-0002-0189-5876 UNSPECIFIED Schilbach, Leonhard UNSPECIFIED orcid.org/0000-0001-5547-8309 UNSPECIFIED Hess, Martin E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruendler, Theo O. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ullsperger, Markus UNSPECIFIED orcid.org/0000-0003-3970-1982 UNSPECIFIED Stephan, Klaas Enno UNSPECIFIED orcid.org/0000-0002-8594-9092 UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tittgemeyer, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language DOPAMINE-RECEPTOR GENE; BODY-MASS INDEX; GENETICALLY-DETERMINED DIFFERENCES; BAYESIAN MODEL SELECTION; PREDICTION ERRORS; FAT MASS; GREATER IMPULSIVITY; HEALTHY-VOLUNTEERS; GABAERGIC NEURONS; MIDBRAIN DOPAMINE Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39310