Effects of Divalproex Sodium on Food Intake, Energy Expenditure, and Posture Allocation

The purpose of the proposed study is to identify the mechanisms responsible for the weight gain associated with Depakote treatment, and to identify methods to prevent and treat weight gain in people taking Depakote. Both sides of the energy balance equation will be measured in a sample of healthy lean and overweight adults. Energy intake will be measured in the Pennington Center's Eating Laboratory, and total daily energy expenditure (TEE) and posture allocation will be measured with the IDEEA™. Questionnaires that assess food cravings and eating attitudes and behaviors will be used to determine if a behavioral phenotype is associated with weight gain in response to Depakote treatment. It is hypothesized that Depakote treatment will result in increased food intake. It is also hypothesized that the time spent engaging in sedentary behavior will increase in response to Depakote treatment. Time spent engaging in, and the energy expended during, physical activity is expected to decrease significantly. Therefore, it is hypothesized that TEE is expected to decrease significantly. The results will be used to identify specific behavioral targets to prevent weight gain during treatment with Depakote. Potential targets include interventions to modify food intake and physical activity. The degree to which each behavior (food intake or physical activity) will be targeted is dependent on the results of this study. For instance, if the majority of the weight gain associated with Depakote treatment is due to changes in food intake, stronger dietary interventions will be suggested. Additionally, changes in endocrine factors (hormones and peptides) will be evaluated during the study to determine if Depakote is associated with an altered endocrine response that affects satiety, food intake, or energy expenditure. If an altered endocrine response is found, these results will be used to identify adjunctive medications or compounds to correct the endocrine response and reduce weight gain. Genomic studies will also be possible, since gene sequencing and gene expression can be analyzed from archived buffy coat samples.