Obesity-Associated Melanocortin-4 Receptor Mutations Are Associated With Changes in the Brain Response to Food Cues
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Authors
van der Klaauw, Agatha
von, dem Hagen Elisabeth AH
Lawrence, Andrew D
Calder, Andrew J
Publication Date
2014-07-25Journal Title
Journal of Clinical Endocrinology and Metabolism
ISSN
0021-972X
Publisher
Endocrine Society
Volume
99
Pages
E2101-E2106
Language
en_US
Type
Article
Metadata
Show full item recordCitation
van der Klaauw, A., von, d. H. E. A., Keogh, J., Henning, E., O'Rahilly, S., Lawrence, A. D., Calder, A. J., & et al. (2014). Obesity-Associated Melanocortin-4 Receptor Mutations Are Associated With Changes in the Brain Response to Food Cues. Journal of Clinical Endocrinology and Metabolism, 99 E2101-E2106. https://doi.org/10.1210/jc.2014-1651
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 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 withMC4Rmutations, 10 equally obese controls, and eight lean controls with normalMC4Rgenotypes. 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.
Sponsorship
MEDICAL RESEARCH COUNCIL (G0900554)
MRC (MC_UU_12012/1)
MRC (G0600717B)
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)
Identifiers
External DOI: https://doi.org/10.1210/jc.2014-1651
This record's URL: https://www.repository.cam.ac.uk/handle/1810/245736
Rights
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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