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  Common genetic variation near MC4R has a sex-specific impact on human brain structure and eating behavior

Horstmann, A., Kovacs, P., Kabisch, S., Böttcher, Y., Schlögl, H., Tönjes, A., et al. (2013). Common genetic variation near MC4R has a sex-specific impact on human brain structure and eating behavior. PLoS One, 8(9): e74362. doi:10.1371/journal.pone.0074362.

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Horstmann, Annette1, 2, Autor           
Kovacs, Peter2, 3, Autor
Kabisch, Stefan4, Autor           
Böttcher, Yvonne2, Autor
Schlögl, Haiko4, Autor           
Tönjes, Anke4, Autor
Stumvoll, Michael2, 4, Autor
Pleger, Burkhard1, 2, 5, Autor           
Villringer, Arno1, 2, 5, 6, Autor           
Affiliations:
1Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
2Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Germany, ou_persistent22              
3Interdisciplinary Centre for Clinical Research, University of Leipzig, Germany , ou_persistent22              
4Faculty of Medicine, University of Leipzig, Germany, ou_persistent22              
5Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
6Berlin School of Mind and Brain, Humboldt University Berlin, Germany, ou_persistent22              

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 Zusammenfassung: Obesity is associated with genetic and environmental factors but the underlying mechanisms remain poorly understood. Recent genome-wide association studies (GWAS) identified obesity- and type 2 diabetes-associated genetic variants located within or near genes that modulate brain activity and development. Among the top hits is rs17782313 near MC4R, encoding for the melanocortin-4-receptor, which is expressed in brain regions that regulate eating. Here, we hypothesized rs17782313-associated changes in human brain regions that regulate eating behavior. Therefore, we examined effects of common variants at rs17782313 near MC4R on brain structure and eating behavior. Only in female homozygous carriers of the risk allele we found significant increases of gray matter volume (GMV) in the right amygdala, a region known to influence eating behavior, and the right hippocampus, a structure crucial for memory formation and learning. Further, we found bilateral increases in medial orbitofrontal cortex, a multimodal brain structure encoding the subjective value of reinforcers, and bilateral prefrontal cortex, a higher order regulation area. There was no association between rs17782313 and brain structure in men. Moreover, among female subjects only, we observed a significant increase of ‘disinhibition’, and, more specifically, on ‘emotional eating’ scores of the Three Factor Eating Questionnaire in carriers of the variant rs17782313’s risk allele. These findings suggest that rs17782313’s effect on eating behavior is mediated by central mechanisms and that these effects are sex-specific.

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Sprache(n): eng - English
 Datum: 2013-02-072013-08-022013-09-16
 Publikationsstatus: Online veröffentlicht
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1371/journal.pone.0074362
PMID: 24066140
PMC: PMC3774636
Anderer: eCollection 2013
 Art des Abschluß: -

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Titel: PLoS One
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: San Francisco, CA : Public Library of Science
Seiten: - Band / Heft: 8 (9) Artikelnummer: e74362 Start- / Endseite: - Identifikator: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850