Obesity-associated melanocortin-4 receptor mutations are associated with changes in the brain response to food cues.
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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.
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1945-7197
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Medical Research Council (MC_UU_12012/1)
Medical Research Council (G0600717)
Medical Research Council (MC_UU_12012/5/B)
Wellcome Trust (099038/Z/12/Z)
Wellcome Trust (100574/Z/12/Z)
Wellcome Trust (095515/Z/11/Z)
Wellcome Trust (098497/Z/12/Z)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_PC_12012)
Medical Research Council (G0600717/1)