Article

The FTO gene rs9939609 obesity-risk allele and loss of control over eating

Unit on Growth and Obesity, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 10/2009; 90(6):1483-8. DOI: 10.3945/ajcn.2009.28439
Source: PubMed

ABSTRACT

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).
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.
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.
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).
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.

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    • "Recently, FTO variants have been found to modulate the response to food cues in brain regions involved in appetite regulation and reward processing (Karra, O'Daly et al. 2013) as also supported by the observation that carriers of the two variants of the gene respond differently to food stimuli after the ingestion of a glucose solution (Heni, Kullmann et al. 2014). The most prominent differences between those carriers of the at-risk compared to the lowrisk alleles were elicited in the prefrontal cortex, a region involved in the inhibitory control ofTanofsky-Kraff, Han et al. 2009). To the best of our knowledge, no studies have investigated the link between the FTO alleles and the connectivity in the resting-state brain, although a few studies have compared obese to lean participants. "
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    • "The subjective sense of LOC over eating is a defining feature of binge eating. Furthermore, LOC over eating predicts future weight gain (Sonneville et al., 2013; Tanofsky-Kraff, Yanovski, et al., 2009) and the development of subclinical and clinical levels of binge eating (Hilbert, Hartmann, Czaja, & Schoebi, 2013; Tanofsky-Kraff et al., 2011). LOC is also pathognomonic independently of how much food is eaten during an episode (Tanofsky- Kraff et al., 2011). "
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