Reward-related brain activity and behavior are associated with peripheral ghrelin levels in obesity

•Obese subjects exhibited reduced serum fasting levels of ghrelin when compared to non-obese control subjects.•Activation in dorsolateral prefrontal cortices during non-food reward processing was greater in obese subjects.•Significant associations were found between reduced ghrelin levels and slower post-reward choices.•Reward-related hyperactivity in dorsolateral prefrontal cortices correlated with reduced ghrelin levels. While excessive food consumption represents a key factor in the development of obesity, the underlying mechanisms are still unclear. Ghrelin, a gut-brain hormone involved in the regulation of appetite, is impaired in obesity. In addition to its role in eating behavior, this hormone was shown to affect brain regions controlling reward, including the striatum and prefrontal cortex, and there is strong evidence of impaired reward processing in obesity. The present study investigated the possibility that disrupted reward-related brain activity in obesity relates to ghrelin deficiency. Fifteen severely obese subjects (BMI > 35 kg/m2) and fifteen healthy non-obese control subjects (BMI