An Obesity-Predisposing Variant of the FTO Gene Regulates D2R-Dependent Reward Learning.
J Neurosci
; 35(36): 12584-92, 2015 Sep 09.
Article
en En
| MEDLINE
| ID: mdl-26354923
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. Significance statement Variations in the fat mass and obesity-associated (FTO) gene are associated with obesity. Here we demonstrate that variants of FTO affect dopamine-dependent midbrain brain responses and learning from negative outcomes in humans during a reward learning task. Furthermore, FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic vulnerability in reward processing can increase predisposition to obesity.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Recompensa
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Proteínas
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Receptores de Dopamina D2
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Proteínas Serina-Treonina Quinasas
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Polimorfismo de Nucleótido Simple
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
J Neurosci
Año:
2015
Tipo del documento:
Article
País de afiliación:
Alemania