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


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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Available from: Joan C Han
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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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    ABSTRACT: Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in thirty male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.
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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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    ABSTRACT: Objective: The subjective feeling of loss of control (LOC) over eating is common among eating-disordered individuals and has predicted weight gain in past research. Restrained eating and negative affect are risk factors for binge eating (which involves LOC), but intense feelings of pleasure derived from palatable foods might also predict the emergence or intensification of LOC eating. The Power of Food Scale (PFS) assesses preoccupation with the pleasure derived from palatable food. Method: The current sample (n = 294) comprised female college freshmen at risk for weight gain. LOC was assessed using an abbreviated version of the Eating Disorders Examination interview. LOC was assessed at baseline and at 6-week and 12- and 24-month follow-ups. Results: Among those exhibiting LOC eating at baseline (and controlling for baseline depression, restrained eating, and body image dissatisfaction), those scoring higher on the PFS at baseline showed a smaller reduction in LOC frequency over time relative to those scoring lower. Using the same covariates, the PFS predicted the first emergence of LOC over 2 years among those showing no LOC at baseline. Conclusions: These results suggest that powerful hedonic attraction to palatable foods may represent a risk factor for the maintenance of LOC in those initially experiencing it and the emergence of LOC eating in those who are not. An enhanced ability to identify individuals at increased risk of developing or maintaining LOC eating could be useful in prevention programs. (PsycINFO Database Record
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    • "Experiences of teasing and bullying have been shown to be higher among obese children and adolescents (Griffiths, Wolke, Page, & Horwood, 2006; Neumark-Sztainer et al., 2002; Young-Hyman et al., 2006). Weight-related teasing may result in unhealthy weightcontrol behaviors such as binge-or loss of control eating, which could cause further weight gain among overweight and obese youth (Tanofsky-Kraff et al., 2006; Tanofsky-Kraff, Yanovski et al., 2009). With regard to neurocognitive function, many manuscripts have documented cross-sectional associations between body weight and neurocognitive dysfunction among children (Cserjesi, Molnar, Luminet, & Lenard, 2007; Kamijo et al., 2012, 2014; Li, Dai, Jackson, & Zhang, 2008; Verdejo-Garcia et al., 2010). "
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