Effect of the melanocortin-3 receptor C17A and G241A variants on weight loss inchildhood obesity

Abstract Background: The central melanocortin system is critical for the long-term regulation of energy homeostasis. Melanocortin-3 receptor (MC3R) knock-out mice, despite are hypophagic, have increased fat mass and higher feed efficiency than wild-type littermates. Objective: To evaluate whether, in childhood obesity, MC3R variants may be associated with changes in fatness reduction consequent to a weight reduction program. Design: Molecular screening of MC3R coding region in one hundred and eighty four obese children, 77 girls and 107 boys ( z-score BMI 3.3  2.3 , mean age 9.2  2 years) was performed. Body mass index (BMI) was evaluated at baseline and after 6 and 12 months of the weight loss program. Results: No new mutations have been found. Two previously described polymorphisms, C17A (Thr6Lys) and G241A (Val81Ile), in almost complete linkage disequilibrium, were observed in 20 patients. No differences between the z-score BMI were observed at baseline of the weight loss program, while, at follow-up, heterozygotes showed a significantly higher z-score BMI (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 z-score BMI less than 1.5 (p=0.03). Conclusions: These results suggest a gene-diet interaction between MC3R C17A and G241A variants and a weight loss program on the ability to lose weight in childhood obesity.