Tschritter Otto, Haupt Axel, Preissl Hubert, Ketterer Caroline, Hennige Anita M, Sartorius Tina, Machicao Fausto, Fritsche Andreas, Häring Hans-Ulrich
Department of Internal Medicine IV, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany.
J Obes. 2011;2011:283153. doi: 10.1155/2011/283153. Epub 2011 Jun 3.
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 ± 1 kg/m(2)). 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.
胰岛素敏感神经元对黑皮质素-4受体（MC4R）的激活是体重调节的核心机制，且MC4R基因中的遗传变异（如rs17782313）与肥胖相关。通过使用脑磁图，我们研究了rs17782313是否影响脑皮质胰岛素反应。我们在51名非糖尿病患者（26名女性/25名男性，年龄35±3岁，BMI 28±1kg/m²）中，通过脑磁图在高胰岛素正常血糖钳夹（与安慰剂相比）期间测量脑皮质胰岛素反应。rs17782313的C等位基因为次要等位基因（频率23%），基因型分布（TT 30例，TC 19例，CC 2例）符合哈迪-温伯格平衡。在存在C等位基因的情况下，胰岛素刺激的脑皮质θ波活动降低（TT 33±16fT；TC/CC -27±20fT；P = 0.023），在调整BMI和外周胰岛素敏感性后，这种效应仍然显著（P = 0.047）。肥胖风险等位基因携带者的脑皮质θ波活动受损。因此，脑胰岛素抵抗可能促成了rs17782313对肥胖的影响。
