Obesity-associated melanocortin-4 receptor mutations are associated with changes in the brain response to food cues

Abstract

Context: Mutations in the melanocortin-4 receptor (MC4R) represent the commonest genetic form of obesity and are associated with hyperphagia. Objective: The aim of this study was to investigate whether melanocortin signaling modulates anticipatory food rewardby studying the brain activation response to food cues in individuals with MC4R mutations. Design/Setting/Participants/Main Outcome Measure: We used functional magnetic resonance imaging to measure blood oxygen level-dependent responses to images of highly palatable, appetizing foods, bland foods, and non-food objectsineight obese individualswith MC4Rmutations, 10equally obese controls, and eightlean controls withnormal MC4R genotypes. Based on previous evidence, we performed a region-of-interest analysis centered on the caudate/putamen (dorsal striatum) and ventral striatum. Results: Compared to non-foods, appetizing foods were associated with activation in the dorsal and ventral striatum in lean controls and in MC4R-deficient individuals. Surprisingly, we observed reduced activation of the dorsal and ventral striatum in obese controls relative to MC4R-deficient patients and lean controls. There were no group differences for the contrast of disgusting foods with bland foods or non-foods, suggesting that the effects observed in response to appetizing foods were not related to arousal. Conclusion: We identified differences in the striatal response to food cues between two groups of obese individuals, those with and those without MC4R mutations. These findings are consistent with a role for central melanocortinergic circuits in the neural response to visual food cues.