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Despite the common use of exercise as a weight-loss strategy, little is known about its neuronal effects, and how these may be related to cognitive changes that impact food intake. The current study assessed the effects of a 6-month exercise intervention on intrinsic activity in the default mode network (DMN), a functionally connected network of brain regions including posterior cingulate cortex, cuneus/precuneus, medial prefrontal cortex, medial temporal lobe, and inferior parietal cortices, and salience network, which includes the anterior cingulate cortex and insula. Resting-state functional MRI data were acquired in 12 overweight/obese individuals. The intervention was associated with a reduction in DMN activity in the precuneus (P=0.003, family-wise error-corrected), which was associated with greater fat mass loss (P=0.013) as well as reduced perceived hunger (Three Factor Eating Questionnaire, P=0.024) and hunger ratings in response to a meal (P=0.013). No changes were observed in the salience network in response to the exercise intervention. The association between DMN change and both fat mass loss and reduction of hunger ratings suggests that DMN function may be involved in the regulation of food intake behaviors. Given previous reports of DMN overactivity in overweight/obese individuals, the present findings may indicate an exercise-related ‘normalization’ of network function.