The FTO gene and measured food intake in children

Abstract

Objective: Polymorphisms in the obesity-associated gene, FTO, have been linked with sensitivity to satiety in children, indicating FTO may be influencing one of the regulatory drivers underlying food intake. In this study, we tested the hypothesis that food intake in a standard eating behaviour paradigm in which palatable food is offered under conditions of satiety would be associated with FTO genotype status, after controlling for differences in body mass index (BMI). Methods: Participants were 131 children aged 4-5 years, taking part in a behavioural study of food intake for whom DNA was available for genotyping. The phenotypic indicator of intake was the child's consumption of palatable food presented after having eaten a meal. We also assessed physical activity using parental reports of the child's enjoyment of active games, their level of activity relative to other children and a standard measure of fidgetiness. Associations between polymorphisms of the intronic FTO single nucleotide polymorphism (rs9939609) and behaviour (food intake and activity) were assessed by analysis of variance controlling for sex, age and BMI s.d. scores. Results: The distribution of AA (homogenous for A allele), AT (heterogeneous T and A alleles) and TT (homogenous for T allele) genotypes was 18, 50 and 32%, respectively. As predicted, TT homozygotes ate significantly less than heterozygotes (P ¼ 0.03) or AA homozygotes (P ¼ 0.02). The effect was not diminished by controlling for BMI s.d. scores. There were no significant associations between FTO genotype and any marker of physical activity. Conclusions: We showed that children with two copies of the lower-risk FTO alleles ate less than those with one or two higherrisk alleles. We conclude that the T allele is protective against overeating by promoting responsiveness to internal signals of satiety.

Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans

“…[15][16][17] However, in this study we found an interaction between rs9939609 genotype and the dietary fat and CHO content in DREE. The difference in DREE between LF and HF diet in TT subjects of 75 kcal/24 h may seem small considering baseline values of REE at 1800-1900 kcal/24 h. It is however a difference in DREE of more than 50%.…”

“…Intake of all macronutrients tended to be greater in A-allele carriers but especially so for fat intake. In addition, the few studies that examined the relationship between appetite 14 and dietary intakes 16,31 with FTO, were performed in children or adolescents. In this context, an understanding of the interactions between macronutrient intake or dietary components and the genotype is important to provide a basis for determining the role of dietary intake and habits in the prevalence and pathogenesis of important conditions such as type 2 diabetes and obesity.…”

“…10 In search for the mechanism by which allelic variation in FTO affect adiposity, both central 11 and peripheral 12,13 mechanisms have been examined. Several studies indicate that FTO variants are associated with appetite 14 and energy intake, 15,16 whereas energy expenditure is unaffected. [15][16][17] Although it is possible that the observed associations between FTO single nucleotide polymorphisms (SNP)s and obesity are caused by KIAA1005 located 200 bp upstream of the 5 0 end of FTO, 1 it is a natural assumption that effects of SNPs in FTO on obesity are mediated through the effects of FTO itself.…”

“…Several studies indicate that FTO variants are associated with appetite 14 and energy intake, 15,16 whereas energy expenditure is unaffected. [15][16][17] Although it is possible that the observed associations between FTO single nucleotide polymorphisms (SNP)s and obesity are caused by KIAA1005 located 200 bp upstream of the 5 0 end of FTO, 1 it is a natural assumption that effects of SNPs in FTO on obesity are mediated through the effects of FTO itself. Studies in rodents provide evidence supporting a central role for Fto in the regulation of energy balance.…”

Association between fat intake, physical activity and mortality depending on genetic variation in FTO

“…FTO gene is highly expressed in hypothalamus, a region involved in appetite regulation, and the A-allele has been associated with increased energy intake, especially fat intake, [1][2][3] and altered appetite 4 in children. There is also evidence in adults implicating that the risk allele carriers consume more energy.…”