Reassessing relationships between appetite and adiposity in people at risk of obesity: A twin study using fMRI.

Background: Neuroimaging studies suggest that appetitive drive is enhanced in obesity.

Objective: To test if appetitive drive varies in direct proportion to the level of body adiposity after accounting for genetic factors that contribute to both brain response and obesity risk. Subjects/

Methods: Participants were adult monozygotic (n = 54) and dizygotic (n = 30) twins with at least one member of the pair with obesity. Body composition was assessed by dual-energy X-ray absorptiometry. Hormonal and appetite measures were obtained in response to a standardized meal that provided 20% of estimated daily caloric needs and to an ad libitum buffet meal. Pre- and post-meal functional magnetic resonance imaging (fMRI) assessed brain response to visual food cues in a set of a priori appetite-regulating regions. Exploratory voxelwise analyses outside a priori regions were performed with correction for multiple comparisons.

Results: In a group of 84 adults, the majority with obesity (75%), body fat mass was not associated with hormonal responses to a meal (glucose, insulin, glucagon-like peptide-1 and ghrelin, all P>0.40), subjective feelings of hunger (β=-0.01 mm [95% CI -0.35, 0.34] P = 0.97) and fullness (β=0.15 mm [-0.15, 0.44] P = 0.33), or buffet meal intake in relation to estimated daily caloric needs (β=0.28% [-0.05, 0.60] P = 0.10). Body fat mass was also not associated with brain response to high-calorie food cues in appetite-regulating regions (Pre-meal β=-0.12 [-0.32, 0.09] P = 0.26; Post-meal β=0.18 [-0.02, 0.37] P = 0.09; Change by a meal β=0.29 [-0.02, 0.61] P = 0.07). Conversely, lower fat mass was associated with being weight reduced (β=-0.05% [-0.07, -0.03] P<0.001) and greater pre-meal activation to high-calorie food cues in the dorsolateral prefrontal cortex (Z = 3.63 P = 0.017).

Conclusions: In a large study of adult twins, the majority with overweight or obesity, the level of adiposity was not associated with excess appetitive drive as assessed by behavioral, hormonal, or fMRI measures.