An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in Humans
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 cerebrocortic...
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Wiley
2011-01-01
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| Series: | Journal of Obesity |
| Online Access: | http://dx.doi.org/10.1155/2011/283153 |
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| author | Otto Tschritter Axel Haupt Hubert Preissl Caroline Ketterer Anita M. Hennige Tina Sartorius Fausto Machicao Andreas Fritsche Hans-Ulrich Häring |
| author_facet | Otto Tschritter Axel Haupt Hubert Preissl Caroline Ketterer Anita M. Hennige Tina Sartorius Fausto Machicao Andreas Fritsche Hans-Ulrich Häring |
| author_sort | Otto Tschritter |
| collection | DOAJ |
| description | 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 35±3 years, BMI 28±1kg/m2). The C-allele of rs17782313 was minor allele (frequency 23%), 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 33±16 fT; TC/CC −27±20 fT; P=.023), and this effect remained significant after adjusting for BMI and peripheral insulin sensitivity (P=.047). Cerebrocortical theta activity was impaired in carriers of the obesity risk allele. Therefore, cerebral insulin resistance may contribute to the obesity effect of rs17782313. |
| format | Article |
| id | doaj-art-635e9e9d8e80417d8ff3464ef2b7ac1d |
| institution | OA Journals |
| issn | 2090-0708 2090-0716 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Obesity |
| spelling | doaj-art-635e9e9d8e80417d8ff3464ef2b7ac1d2025-08-20T02:35:15ZengWileyJournal of Obesity2090-07082090-07162011-01-01201110.1155/2011/283153283153An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in HumansOtto Tschritter0Axel Haupt1Hubert Preissl2Caroline Ketterer3Anita M. Hennige4Tina Sartorius5Fausto Machicao6Andreas Fritsche7Hans-Ulrich Häring8Department of Internal Medicine IV, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, GermanyDepartment of Internal Medicine IV, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, GermanyInstitute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72076 Tübingen, GermanyDepartment of Internal Medicine IV, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, GermanyDepartment of Internal Medicine IV, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, GermanyDepartment of Internal Medicine IV, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, GermanyDepartment of Internal Medicine IV, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, GermanyDepartment of Internal Medicine IV, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, GermanyDepartment of Internal Medicine IV, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, GermanyActivation 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 35±3 years, BMI 28±1kg/m2). The C-allele of rs17782313 was minor allele (frequency 23%), 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 33±16 fT; TC/CC −27±20 fT; P=.023), and this effect remained significant after adjusting for BMI and peripheral insulin sensitivity (P=.047). Cerebrocortical theta activity was impaired in carriers of the obesity risk allele. Therefore, cerebral insulin resistance may contribute to the obesity effect of rs17782313.http://dx.doi.org/10.1155/2011/283153 |
| spellingShingle | Otto Tschritter Axel Haupt Hubert Preissl Caroline Ketterer Anita M. Hennige Tina Sartorius Fausto Machicao Andreas Fritsche Hans-Ulrich Häring An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in Humans Journal of Obesity |
| title | An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in Humans |
| title_full | An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in Humans |
| title_fullStr | An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in Humans |
| title_full_unstemmed | An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in Humans |
| title_short | An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in Humans |
| title_sort | obesity risk snp rs17782313 near the mc4r gene is associated with cerebrocortical insulin resistance in humans |
| url | http://dx.doi.org/10.1155/2011/283153 |
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