Association of the fat mass and obesity‐associated gene risk allele, rs9939609A, and reward‐related brain structures

Abstract

Objective: Recently, the fat mass and obesity-associated gene (FTO) has been identified as a genetic risk factor for developing obesity. The underlying mechanisms remain speculative. SNPs within FTO have been associated with brain atrophy in frontal and occipital regions, suggesting that FTO might affect body weight through cerebral pathways. Behavioral studies suggested a relationship between FTO and the reward-related behavioral traits. Therefore the relationship between the FTO risk allele rs9939609A and volumes of reward-related brain structures has been investigated. Methods: Four hundred and ninety-two Dutch individuals (56% males, age: 70-82 years) participating in the PROSPER study underwent a 3D-T1-weighted MRI to assess the volumes of reward-related brain structures (e.g., amygdala, nucleus accumbens) and of gray matter and white matter. Linear regression analysis was performed to test for the association of subcortical and cortical structures with rs9939609A. Results: rs9939609A is associated with lower volumes of the nucleus accumbens (p=0.03) and trended toward lower cortical gray matter volumes (p=0.08). This association is independent of gender, age, and BMI, FDR corrected. Conclusions: The FTO risk allele is associated with lower nucleus accumbens volumes, suggesting that the higher body weight of risk-allele carriers might be due to changes within reward-related brain structures.

Neuroanatomical correlates of food addiction symptoms and body mass index in the general population

“…This finding is in line with other studies (Coveleskie et al, ; Horstmann et al, ; Veit et al, ) and might reflect previously reported differences in reward processing in obesity (García‐García et al, ; Horstmann, Fenske, & Hankir, ). Yet, volumetric differences in nucleus accumbens in relation to eating behavior or obesity seem to be less consistent than functional alterations (de Groot et al, ) and therefore require further investigation. All findings related to BMI remained essentially unaltered after adjusting for YFAS symptom score.…”

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

“…Region of interest analysis was performed by preparing masks of brain areas based on previous MRI studies on FTO (Karra et al ., ; de Groot et al ., ). Bilateral masks of such areas were produced using the Wake Forest University Pickatlas toolbox (Maldjian et al ., ) within spm .…”

On the origin of obesity: identifying the biological, environmental and cultural drivers of genetic risk among human populations

“…perinatal hypoxia and intraventricular haemorrhage ), conservation of adipogenesis during foetal development may improve fitness. Although obesity‐risk alleles in FTO have been associated with decreased brain volume and 6‐year cognitive decline , rare loss‐of‐function mutations have been associated with microcephaly, severe psychomotor delay and functional brain deficits, without apparent effects on body adiposity . In light of this, we cautiously suggest that genes regulating adipogenesis, particularly during the infantile period, may have been selected to ensure proper neurological function throughout the life course.…”