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Journal of Obesity
Volume 2011, Article ID 283153, 4 pages
http://dx.doi.org/10.1155/2011/283153
Research Article

An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in Humans

1Department of Internal Medicine IV, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany
2Eli Lilly and Company, Lilly Deutschland GmbH, 61352 Bad Homburg, Germany
3Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72076 Tübingen, Germany
4Department of Obstetrics and Gynecology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

Received 30 November 2010; Revised 2 March 2011; Accepted 4 April 2011

Academic Editor: Jack A. Yanovski

Copyright © 2011 Otto Tschritter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Activation of melanocortin-4 receptor (MC4R) by insulin sensitive neurons is a central mechanism in body weight regulation, and genetic variants in the MC4R gene (e.g., rs17782313) are associated with obesity. By using magnetoencephalography, we addressed whether rs17782313 affects the cerebrocortical insulin response. We measured the cerebrocortical insulin response by using magnetoencephalography in a hyperinsulinemic euglycemic clamp (versus placebo) in 51 nondiabetic humans (26 f/25 m, age years, BMI  kg/m2). The C-allele of rs17782313 was minor allele (frequency ), and the genotype distribution (TT 30, TC 19, CC 2) was in Hardy-Weinberg-Equilibrium. Insulin-stimulated cerebrocortical theta activity was decreased in the presence of the C-allele (TT  fT; TC/CC  fT; ), and this effect remained significant after adjusting for BMI and peripheral insulin sensitivity ( ). Cerebrocortical theta activity was impaired in carriers of the obesity risk allele. Therefore, cerebral insulin resistance may contribute to the obesity effect of rs17782313.