FTO gene variant modulates the neural correlates of visual food perception

• Published in: NeuroImage (Orlando, Fla.) Vol. 128; pp. 21 - 31
• Main Authors: Kühn, Anne B., Feis, Delia-Lisa, Schilbach, Leonhard, Kracht, Lutz, Hess, Martin E., Mauer, Jan, Brüning, Jens C., Tittgemeyer, Marc
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2016; Elsevier Limited
• Subjects: Addictive behaviors; Adipocytes; Adult; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; Body mass index; Drug abuse; Fasting; Female; Food; FTO gene; Funding; Genetic Predisposition to Disease - genetics; Genotype; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Morphological classification; NMR; Nuclear magnetic resonance; Obesity; Obesity - genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Studies; Support Vector Machine; Temporal Lobe - physiology; Visual food perception; Visual Perception; Obesity; Morphological classification; FTO gene; Visual food perception
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2015.12.049

Variations in the fat mass and obesity associated (FTO) gene are currently the strongest known genetic factor predisposing humans to non-monogenic obesity. Recent experiments have linked these variants to a broad spectrum of behavioural alterations, including food choice and substance abuse. Yet, the underlying neurobiological mechanisms by which these genetic variations influence body weight remain elusive.
Here, we explore the brain structural substrate of the obesity-predisposing rs9939609 T/A variant of the FTO gene in non-obese subjects by means of multivariate classification and use fMRI to investigate genotype-specific differences in neural food-cue reactivity by analysing correlates of a visual food perception task. Our findings demonstrate that MRI-derived measures of morphology along middle and posterior fusiform gyrus (FFG) are highly predictive for FTO at-risk allele carriers, who also show enhanced neural responses elicited by food cues in the same posterior FFG area. In brief, these findings provide first-time evidence for FTO-specific differences in both brain structure and function already in non-obese individuals, thereby contributing to a mechanistic understanding of why FTO is a predisposing factor for obesity.
•fMRI and cMRI data were used to explore the effects of an FTO variant.•Morphological substrate is highly predictive for FTO at-risk allele carriers.•Classification identifies MRI-derived markers along middle and posterior FFG.•Enhanced neural responses are elicited by food cues in the same posterior FFG area.•FTO-specific differences are evident from brain structure and function already in lean subjects.