Although twin studies imply that biological factors play a prominent role in the development of obesity, few prospective studies have identified biological factors that increase risk for future weight gain. Recent data suggest that obese adults show abnormalities in reward from food intake and anticipated food intake relative to lean adults, but the precise nature of these abnormalities is unclear and it has not been established whether these abnormalities predate obesity onset or are a consequence. Three pilot studies found that obese relative to lean adolescents showed greater activation in the insula and somatosensory regions in response to anticipated intake of chocolate milkshake and intake of milkshake - regions that encode the sensory and hedonic aspects of food. Yet obese relative to lean adolescents showed less activation in the striatum in response to milkshake intake than lean adolescents, which may reflect lower dopamine receptor availability in this region. These relations were more pronounced for adolescents with the A1 allele of the TaqIA DRD2 gene, which is associated with reduced D2 receptor density and compromised dopamine signaling in the striatum. Most importantly, pilot data indicated that these abnormalities increased risk for elevated weight gain over a 1-year follow-up, particularly for those with the A1 allele of TaqIA. Results suggest that individuals who experience greater hedonic reward from food intake and anticipated intake, but who experience less phasic activation of reward circuitry from food intake, may be at risk for unhealthy weight gain.
Aim 1 of the proposed study is to test whether 140 lean adolescents at high-risk for weight gain (by virtue of having two obese parents) show abnormalities in anticipatory and consummatory food reward on fMRI, behavioral, and self-report measures relative to 40 lean low-risk adolescents with lean parents.
Aim 2 is to test whether adolescents who show abnormalities in anticipatory or consummatory food reward are at elevated risk for future weight gain and obesity onset over a 3-year follow-up.
Aim 3 is to examine moderators that amplify the relations of food reward abnormalities to weight gain, including genetic polymorphisms that impact dopamine signaling in reward circuitry, an unhealthy food environment, trait impulsivity, dietary inhibition, dieting, and emotional eating.
Aim 4 is to examine changes in anticipatory and consummatory food reward after obesity onset relative to changes observed in matched controls not showing obesity onset. This study improves upon prior studies by using a large sample, an objective fMRI paradigm to assess anticipatory and consummatory food reward, objective measures of habitual caloric expenditure and intake, and a prospective design.
The proposed project addresses a vital public health problem because obesity results in marked morbidity and mortality. It would be the first study to examine reward abnormalities that may account for the risk conveyed by parental obesity, test whether these abnormalities predate unhealthy weight gain, examine moderators of these relations, and test whether obesity onset influences food reward abnormalities. An improved understanding of the neural substrates that contribute to obesity should inform the development of more effective prevention and treatment interventions for this pernicious medical condition.
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