Responsiveness to food cues, especially those associated with high-calorie nutrients may be a factor underlying obesity. An increased motivational potency of foods appears to be mediated in part by the hippocampus. To clarify this, we investigated by means of 3-T magnetic resonance imaging (MRI) the activation of the hippocampus and associated brain structures in response to pictures of high-calorie and low-calorie foods in 12 obese and 12 normal-weight adolescents. To investigate the relationship between neuronal activation patterns (e.g., hippocampus) to the caloric content of food images and plasma insulin levels, we performed a multiple regression analysis. Interestingly, a significant positive correlation between fasting plasma levels of insulin, waist circumference, and right hippocampal activation was seen after stimulation with high-caloric food images. BMI values did not correlate significantly with the hippocampal activation. On the other hand, we found a significant negative correlation in response to high-caloric food images and the plasma levels of insulin in the medial right gyrus frontalis superior and in the left thalamus. In summary, our data show that insulin is importantly involved in the central regulation of food intake. The significant positive relationship between hippocampal activation after stimulation with high-caloric food images, plasma insulin levels, and waist circumference suggests a permissive role of insulin signaling pathways in the hippocampal control of eating behavior. Interestingly, only the waist circumference, as a main indicator of abdominal obesity, correlated significantly with the hippocampal activation patterns, and not the BMI.