Obesity-Associated Melanocortin-4 Receptor Mutations Are Associated With Changes in the Brain Response to Food Cues

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 reward by 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 objects in eight obese individuals with MC4R mutations, 10 equally obese controls, and eight lean controls with normal 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.