FTO Genotype Is Associated with Body Mass Index after the Age of Seven Years But Not with Energy Intake or Leisure-Time Physical Activity

Hakanen, Maarit; Raitakari, Olli T.; Lehtimäki, Terho; Peltonen, Nina; Pahkala, Katja; Sillanmäki, Lauri; Lagström, Hanna; Viikari, Jorma; Simell, Olli; Rönnemaa, Tapani

doi:10.1210/jc.2008-1199

Cited by 158 publications

(155 citation statements)

References 41 publications

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“…Consistent with this observation is evidence from the ALSPAC study using 3 day dietary records, where children (10-11years) carrying the risk allele for FTO ingested more energy and specifi cally more dietary fat than those not carrying the risk allele (Timpson et al, 2008). These fi ndings contrast with at least three studies which report no associations with energy intake in children (Hakanen et al, 2009;Okuda et al, 2011;Stutzmann et al, 2009) and to the observation in mice that FTO may modulate energy homeostasis through energy expenditure (Fischer et al, 2009;Speakman, 2010). However, several studies, including a large meta-analysis have recently shown that energy expenditure through activity appears to attenuate the genetic susceptibility to overweight and obesity from FTO in children Scott et al, 2010) and adults (Andreasen et al, 2008;Kilpelainen et al, 2011).…”

Section: Fat Mass and Obesity Associated Gene And Eating Behaviourmentioning

confidence: 64%

“…A temporal dip in the effect of FTO rs9939609 on BMI in children is proposed at the mid-pubertal age of around 13-14 years which may be linked to alterations in physiologic and endocrine factors that trigger puberty (Rutters et al, 2011). Current thinking is that there is no FTO association with foetal growth (Frayling et al, 2007;Hakanen et al, 2009). …”

Section: Fat Mass and Obesity Associated Gene -A Role In Common Obesitymentioning

confidence: 99%

“…A small number of studies conducted in children have measured energy intake either directly or indirectly using parental report and show that the FTO locus confers risk of obesity through increasing energy intake (Cecil et al, 2008;Rendo et al, 2009;Timpson et al, 2008;Wardle et al, 2008b), through reduced satiety responsiveness and a preference for energy dense foods (Cecil et al, 2008;Lee et al, 2010;Tanofsky-Kraff et al, 2009;Timpson et al, 2008), but not through energy expenditure (Hakanen et al, 2009), supporting the adult literature (Haupt et al, 2009;Speakman et al, 2008). In a preload paradigm study, food intake from a test meal was signifi cantly increased in young children (4-10 years) carrying the minor (A) allele for FTO rs9939609, independent of body weight, through greater ingestion of energy dense foods, compared with wildtypes (Cecil et al, 2008).…”

Section: Fat Mass and Obesity Associated Gene And Eating Behaviourmentioning

confidence: 99%

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Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Cecil

Dalton

Finlayson

et al. 2012

International Review of Psychiatry

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The prevalence of childhood obesity is increasing in many countries and confers risks for early type 2 diabetes, cardiovascular disease and metabolic syndrome. In the presence of potent ' obesogenic ' environments not all children become obese, indicating the presence of susceptibility and resistance. Taking an energy balance approach, susceptibility could be mediated through a failure of appetite regulation leading to increased energy intake or via diminished energy expenditure. Evidence shows that heritability estimates for BMI and body fat are paralleled by similar coeffi cients for energy intake and preferences for dietary fat. Twin studies implicate weak satiety and enhanced food responsiveness as factors determining an increase in BMI. Single gene mutations, for example in the leptin receptor gene, that lead to extreme obesity appear to operate through appetite regulating mechanisms and the phenotypic response involves overconsumption and a failure to inhibit eating. Investigations of robustly characterized common gene variants of fat mass and obesity associated ( FTO ), peroxisome proliferator-activated receptor ( PPARG ) and melanocortin 4 receptor ( MC4R ) which contribute to variance in BMI also infl uence the variance in appetite factors such as measured energy intake, satiety responsiveness and the intake of palatable energy-dense food. A review of the evidence suggests that susceptibility to childhood obesity involving specifi c allelic variants of certain genes is mediated primarily through food consumption (appetite regulation) rather than through a decrease in activity-related energy expenditure. This conclusion has implications for early detection of susceptibility, and for prevention and management of childhood obesity.

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Section: Fat Mass and Obesity Associated Gene And Eating Behaviourmentioning

confidence: 64%

Section: Fat Mass and Obesity Associated Gene -A Role In Common Obesitymentioning

confidence: 99%

Section: Fat Mass and Obesity Associated Gene And Eating Behaviourmentioning

confidence: 99%

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Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Cecil

Dalton

Finlayson

et al. 2012

International Review of Psychiatry

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“…Inter-population differences in allele frequencies and patterns of linkage disequilibrium may also contribute to heterogeneity of findings. Previous studies have found that the influence of FTO on adiposity phenotypes is apparent from as young as 7 years old 7,32 and that the strength of the association increases into early adolescence. 10 In the GENESIS cohort, we observed association neither between FTO genotype and adiposity, which is in line with previous findings reporting no association of FTO genotype and childhood BMI in 2-5-year-old children, 33 nor between FTO genotype and energy intake (Supplementary Table 4).…”

Section: Discussionmentioning

confidence: 96%

FTO genotype and adiposity in children: physical activity levels influence the effect of the risk genotype in adolescent males

et al. 2010

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Studies of the fat mass and obesity-associated (FTO) gene provide compelling evidence of genetic variation in the general population that influences fat levels and obesity risk. Studies of the interaction between genetic and environmental factors such as physical activity (PA) will promote the understanding of how lifestyle can modulate genetic contributions to obesity. In this study, we investigated the effect of FTO genotype, and interactions with PA or energy intake, in young children and adolescents. In all, 1-5-year-old children from the Growth, Exercise and Nutrition Epidemiological Study in preSchoolers (GENESIS) study (N¼1980) and 11-18-year-old Greek adolescents (N¼949) were measured for adiposity-related phenotypes and genotyped at the FTO singlenucleotide polymorphism (SNP) marker, rs17817449. Adolescents were classified as physically active or inactive based on self-reported levels of PA. In adolescents, FTO genotype influenced weight (P¼0.001) and BMI (P¼0.007). There was also a significant SNP*PA*gender interaction (P¼0.028) on BMI, which reflected the association between FTO genotype and BMI in males (P¼0.016), but not females (P¼0.15), and significant SNP*PA interaction in males (P¼0.007), but not females (P¼0.74). The FTO genotype effect was more pronounced in inactive than active males. Inactive males homozygous for the G allele had a mean BMI 3 kg/m 2 higher than T carriers (P¼0.008). In the GENESIS study, no significant association between FTO genotype and adiposity was found. The present findings highlight PA as an important factor modifying the effect of FTO genotype.

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“…10 In contrast, reduced energy expenditure and physical activity were not associated with FTO genotypes. 7,8,10,11 Nevertheless, physical activity modified the degree of obesity achieved in the context of the risk allele of FTO. 12,13 These pathomechanisms in man differed from mice lacking the Fto gene.…”

Section: Introductionmentioning

confidence: 93%

The growth hormone—IGF-I axis as a mediator for the association between FTO variants and body mass index: results of the Study of Health in Pomerania

Rosskopf

Schwahn²,

Neumann

et al. 2010

Int J Obes

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Context: Risk alleles of the fat mass-and obesity-associated gene (FTO) are related not only to increased body mass index (BMI) values but also to mortality. It was speculated that cellular effects of the FTO gene affect most organs, especially their ability to maintain or regenerate proper function when afflicted by various diseases. FTO is highly expressed in the hypothalamus and also in the pituitary gland. The decrease in growth hormone (GH) secretion is known to cause a decrease in lean body mass in older subjects. Objective: We hypothesized an association of rs9926289 with insulin-like growth factor (IGF)-I. Design and setting: Cross-sectional data from the Study of Health in Pomerania, a population-based study in the northeastern part of Germany, were used. Participants: For the final analyses, 3882 subjects aged 20-79 years were available. Main outcome measures: Continuous IGF-I, low IGF-I according to clinically meaningful age-and gender-specific reference values, and BMI were used as outcome measures. Results: Over all age groups, a statistically significant relationship between FTO and IGF-I was found. In subjects younger than 55 years of age, homozygous carriers of the FTO risk allele exhibited lower serum IGF-I levels adjusted for 5-year age groups, gender and IGF-I binding protein 3 levels (linear regression, coefficient ± s.e. for FTO AA genotype:À8.6 ± 2.8; P ¼ 0.002). Further adjustments for obesity and diabetes did not suspend this association (coefficient:-7.8; P ¼ 0.005). As expected, the FTO AA genotype effect on BMI was reduced from 0.76 to 0.62 kg m À2 by including IGF-I. No relationship between FTO and IGF-I levels was found in subjects aged 55 years or older (À2.7±2.4; P ¼ 0.260 for FTO AA genotype adjusted for age, gender and IGF-I binding protein 3 levels). Conclusion: We propose that the GHFIGF-I axis is a mediator for the relationship between FTO and BMI.

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FTO Genotype Is Associated with Body Mass Index after the Age of Seven Years But Not with Energy Intake or Leisure-Time Physical Activity

Abstract: Our results suggest that the effect of the FTO genotype on BMI becomes evident only after age 7 yr. These results further suggest that the FTO gene is not directly associated with energy intake or physical activity.

Cited by 158 publications

References 41 publications

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

FTO genotype and adiposity in children: physical activity levels influence the effect of the risk genotype in adolescent males

The growth hormone—IGF-I axis as a mediator for the association between FTO variants and body mass index: results of the Study of Health in Pomerania

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