Faculty Bibliography

BACKGROUND:Children with rs9939609 FTO variant alleles (homozygous = AA and heterozygous = AT) are predisposed to greater adiposity than are those with 2 wild-type alleles (TT). OBJECTIVE:Because FTO is highly expressed in hypothalamic regions that are important for appetite, FTO genotype may affect energy balance by influencing eating behavior. Loss of control (LOC) eating, a behavior commonly reported by overweight youth, predicts excessive weight gain in children. However, the relation between FTO genotype and LOC eating has not been previously examined. DESIGN/METHODS:Two-hundred eighty-nine youth aged 6-19 y were genotyped for rs9939609, underwent body-composition measurements, and were interviewed to determine the presence or absence of LOC eating. A subset (n = 190) participated in a lunch buffet test meal designed to model an LOC eating episode. Subjects with AA and AT genotypes were grouped together for comparison with wild-type TT subjects. RESULTS:Subjects with at least one A allele (67.7%) had significantly greater body mass indexes, body mass index z scores (P < 0.01), and fat mass (P < 0.05). Of the AA/AT subjects, 34.7% reported LOC compared with 18.2% of the TT subjects (P = 0.002). Although total energy intake at the test meal did not differ significantly by genotype (P = 0.61), AA/AT subjects consumed a greater percentage of energy from fat than did the TT subjects (P < 0.01). CONCLUSIONS:Children and adolescents with 1 or 2 FTO rs9939609 obesity-risk alleles report more frequent LOC eating episodes and select foods higher in fat at a buffet meal. Both LOC eating and more frequent selection of energy-dense, palatable foods may be mechanisms through which variant FTO alleles lead to excess body weight.

BACKGROUND:Homozygosity for 2 protein-altering polymorphisms in the melanocortin-3 receptor gene (MC3R) coding sequence, C17A and G241A, has been reported to be associated with an obesity phenotype in children, yet how these polymorphisms affect energy homeostasis is unknown. Association between adult body weight and +2138InsCAGACC, another variant in the 3' untranslated region of MC3R, has also been described. OBJECTIVE:The objective of this study was to examine associations of C17A + G241A and +2138InsCAGACC MC3R variants with children's energy balance. DESIGN/METHODS:Children aged 6-19 y were genotyped for MC3R C17A, G241A, and +2138InsCAGACC. Subjects underwent studies of energy intake from a 9835-kcal food array (n = 185), resting energy expenditure (REE) by using indirect calorimetry (n = 302), or total daily energy expenditure (TEE) by using doubly labeled water (n = 120). Linear regression was used to examine the associations between MC3R polymorphisms and the measures of energy balance. RESULTS:Body mass index and fat mass were greater in those with double homozygosity for C17A + G241A (P = 0.001). After accounting for covariates (including body composition), the number of minor C17A + G241A alleles was associated with significantly greater energy intake (beta = +0.15, P = 0.02) but not altered REE or TEE. No significant associations were observed between +2138InsCAGACC and measures of either fat mass or energy balance. CONCLUSIONS:C17A + G241A polymorphisms may be associated with pediatric obesity because of greater energy intake rather than because of diminished energy expenditure. +2138InsCAGACC does not appear to be associated with obesity or measures of energy balance in children.