Effect of the melanocortin-3 receptor Thr6Lys and Val81Ile genetic variants on body composition and substrate oxidation in Chilean obese children

摘要

Mice genetically deficient in the melanocortin-3 receptor gene are characterized by normal body weight, increased body fat, mild hypophagia, reduced locomotor activity, and increased respiratory quotient compared with wild-type mice. In humans, the 6Lys–81Ile haplotype of melanocortin-3 receptor (MC3R) gene has been associated with childhood obesity, higher body fat percentage, and reduced fat oxidation compared to non-carriers. The aim of this study was to evaluate the association between MC3R 6Lys–81Ile haplotype with body composition and substrate oxidation in response to moderate exercise in obese children. Eight Chilean obese children (aged 8–12) carriers of MC3R 6Lys–81Ile haplotype were compared with eight age–gender-matched obese non-carriers. Children were identified through a previous cross-sectional study on genetic determinants of childhood obesity (n = 229). Genotypes for MC3R Thr6Lys and Val81Ile were determined by polymerase chain reaction–restriction fragment length polymorphism. Body composition was assessed by the four-compartment model (dual-energy X-ray absorptiometry, total body water by the deuterium dilution technique, and total fat mass by air-displacement plethysmography). Substrate oxidation was assessed by indirect calorimetry in response to moderate exercise (60% VO2 max). Wilcoxon matched-pairs test was used to compare quantitative variables. No significant differences among carriers and non-carriers were found in anthropometrical and body composition measurements. The Carriers of the 6Lys–81Ile haplotype showed higher respiratory quotient (p = 0.06) and a significantly higher glucose oxidation (p = 0.01) compared with non-carriers after standardization for fat-free mass. Our results are consistent with a possible participation of MC3R 6Lys–81Ile variants in glucose oxidation in response to moderate exercise.