Santoro Nicola, Perrone Laura, Cirillo Grazia, Raimondo Paolo, Amato Alessandra, Brienza Carmine, Del Giudice Emanuele Miraglia
Department of Pediatrics "F Fede," Seconda Università degli Studi di Napoli, Napoli, Italy.
Am J Clin Nutr. 2007 Apr;85(4):950-3. doi: 10.1093/ajcn/85.4.950.
The central melanocortin system is critical for the long-term regulation of energy homeostasis. Melanocortin-3 receptor (MC3R) knock-out mice, despite being hypophagic, have increased fat mass and higher feed efficiency than do their wild-type littermates.
The aim was to evaluate whether, in childhood obesity, MC3R variants are associated with changes in fatness reduction as a consequence of a weight-reduction program.
Molecular screening of the MC3R coding region in 184 obese children, 77 girls and 107 boys [x (+/-SEM) body mass index (BMI; in kg/m(2)) z score: 3.3 +/- 2.3; age 9.2 +/- 2 y], was performed. BMI was evaluated at baseline and after 6 and 12 mo of the weight loss program.
No new mutations were found. Two previously described polymorphisms, C17A (Thr6Lys) and G241A (Val81Ile), were observed in 20 patients in almost complete linkage disequilibrium. No significant differences in BMI z scores were observed at baseline of the weight-loss program between the genotypes; however, at follow-up, heterozygotes showed a significantly higher BMI z score (P = 0.03). When the patients were divided according to the amount of weight lost, a higher prevalence of heterozygotes was observed among subjects who lowered their BMI z score <1.5 (P = 0.03).
These results suggest a gene-diet interaction between the MC3R C17A and G241A variants and a weight loss program for the ability to lose weight in childhood obesity.
中枢黑皮质素系统对能量平衡的长期调节至关重要。黑素皮质素-3受体（MC3R）基因敲除小鼠尽管摄食量减少，但与野生型同窝小鼠相比，脂肪量增加且饲料效率更高。
评估在儿童肥胖症中，MC3R基因变异是否与减肥计划导致的体脂减少变化相关。
对184名肥胖儿童（77名女孩和107名男孩[x（±标准误）体重指数（BMI；单位：kg/m²）z评分：3.3±2.3；年龄9.2±2岁]）的MC3R编码区进行分子筛查。在减肥计划的基线、6个月和12个月后评估BMI。
未发现新的突变。在20名患者中观察到两个先前描述的多态性，C17A（Thr6Lys）和G241A（Val81Ile），它们几乎完全处于连锁不平衡状态。在减肥计划基线时，各基因型之间的BMI z评分无显著差异；然而，在随访时，杂合子的BMI z评分显著更高（P = 0.03）。当根据体重减轻量对患者进行分组时，在BMI z评分降低<1.5的受试者中观察到杂合子的患病率更高（P = 0.03）。
这些结果表明，在儿童肥胖症中，MC3R基因的C17A和G241A变异与减肥计划之间存在基因-饮食相互作用，影响减肥能力。
