An obesity‐associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images

Abstract

Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight-loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low- or high-calorie food while brain activity was measured via fMRI. In a whole-brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non-risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.

Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues

“…3A) did not replicate previously reported effects in adults. Moreover, none of these prior studies in adults reported effects in the ventral striatum of the kind that we observed in children, either because these effects were not present (14,16) or the effects were not examined (15). As such, it is difficult to reconcile the current findings in children with those previously reported in adults.…”

“…It is worth noting, however, that even within the cohorts of adults tested previously, there is little consistency in reported effects across studies. Moreover, with one exception (14), none of the prior work links FTO genotypic differences to neural differences in canonical reward regions despite the fact that previous studies have demonstrated a causal role of FTO in regulating dopaminergic transmission (12) and also in modulating mesocorticolimbic circuitry in adults (13). The effects reported here in children in ventral striatum function and structure, as well as the voxel-wise whole-brain exploratory analysis, constrain the FTO genotypic differences to canonical reward neurocircuitry.…”

“…In particular, studies have demonstrated heightened responsivity to food cues in regions associated with reward (e.g., the putamen) in adults at risk for obesity (14), as well as a modulatory role of FTO on the relationship between neural responses to food and circulating acyl-ghrelin (16). Furthermore, one recent study identified both structural and functional differences in the posterior fusiform gyrus associated with genetic risk for obesity (15), and another observed relationships between FTO rs9939609 and activity in the precuneus and cuneus (14). The whole-brain exploratory analysis reported here (Fig.…”

“…Indeed, findings in these adult studies are somewhat mixed, with gene-related effects reported across a number of brain regions not traditionally associated with reward, including the posterior cingulate, cuneus, precuneus, and fusiform gyrus (14,15). Only one study thus far has reported a relationship between FTO rs9939609 and neural responses to food cues in a canonical reward region: the putamen (14). A separate study observed modulatory effects of physiological state (fed versus fasting) and metabolic state (circulating acetyl-ghrelin) on responses to food in reward-related brain regions (16).…”

“…Prior neuroimaging studies examining the influence of variants in this gene on brain structure and function have primarily been reported in adults, and therefore may be missing important genetic associations that manifest early in development and predispose individuals to develop patterns of unhealthy eating. Indeed, findings in these adult studies are somewhat mixed, with gene-related effects reported across a number of brain regions not traditionally associated with reward, including the posterior cingulate, cuneus, precuneus, and fusiform gyrus (14,15). Only one study thus far has reported a relationship between FTO rs9939609 and neural responses to food cues in a canonical reward region: the putamen (14).…”