Variation in the FTO Gene Influences Food Intake but not Energy Expenditure

Haupt, Axel; Thamer, Claus; Staiger, Harald; Tschritter, Otto; Kirchhoff, Kerstin; Machicao, Fausto; Häring, Hans Ulrich; Stefan, Norbert; Fritsche, Andreas

doi:10.1055/s-0028-1087176

Cited by 163 publications

(138 citation statements)

References 21 publications

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“…The enhancement in obesity risk linked to a high CHO intake may be partly explained by the fact that CHO are not able to activate the PPARG protein and could worsen the action of the Ala12 substitution on the receptor activity. The impact of this rs9939609 SNP of FTO gene on human body weight is mainly through energy intake; however, some results are contradictory (Berentzen et al 2008;Do et al 2008;Speakman et al 2008, Goossens et al 2009Haupt et al 2009). In our elderly population, no effect of FTO on obesity was found.…”

Section: Discussionmentioning

confidence: 99%

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

et al. 2012

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Genetic factors may interact with lifestyle factors to modify obesity risk. FTO and PPARG2 are relevant obesogenes. Our aim was to explore the effect of Pro12Ala (rs1801282) of PPARG2 and rs9939609 of FTO on obesity risk and to examine their interaction with lifestyle factors in an elderly population. Subjects (n = 978; aged 69 ± 6) were recruited from the SUN (Seguimiento Universidad de Navarra) Project. DNA was obtained from saliva, and lifestyle and dietary data were collected by validated self-reported questionnaires. Genotyping was assessed by RT-PCR plus allele discrimination. Subjects carrying the Ala allele of PPARG2 gene had a significantly increased obesity risk compared to non-carrier (Pro12Pro) subjects (OR, 1.66; 95 % CI, 1.01-2.74; p = 0.045). Greater obesity risk was also found in inactive or high carbohydrate intake subjects with the Ala12 allele of PPARG2 gene. Interestingly, subjects carrying the Ala allele of the PPARG2 gene and with a high CHO ([246 g/ day) intake had an increased obesity risk compared to Pro12Pro subjects (OR, 2.67; 95 % CI, 1.3-5.46; p = 0.007; p for [CHO 9 PPARG2] interaction = 0.046). Moreover, in subjects with a high CHO intake, the co-presence of the Ala allele of PPARG2 gene and one minor A allele (rs9939609) of FTO gene did increase obesity risk (OR, 3.26; 95 % CI,; p = 0.021) when compared to non-carrier (Pro12Pro/TT) subjects. In conclusion, it appears that lifestyle factors may act as effect modifiers for obesity risk linked to Ala12 allele of the PPARG2 gene and the minor A allele of FTO gene in an elderly population.

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Section: Discussionmentioning

confidence: 99%

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

et al. 2012

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“…FTO is abundantly expressed in the hypothalamus, and epidemiological and functional studies suggested to be directly involved in the regulation of energy intake (Cecil et al, 2008;Haupt et al, 2009). Moreover, FTO is expressed in multiple tissues such as white adipose tissue, skeletal muscle and liver, also having direct influences on adipose tissue metabolism (Grunnet et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Influence of physical activity on the association between the FTO variant rs9939609 and adiposity in young adults

Muc

Padez

Manco

2015

American J Hum Biol

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Objectives: To investigate in a population sample of Portuguese young adults the association of the FTO variant rs9939609 with obesity, BMI and body-fat and interaction with physical activity (PA) on obesity-susceptibility.Methods: SNP rs9939609 A/T was genotyped in 550 subjects (231 males and 319 females; 18-36 year-old; mean age 21 year-old) by TaqMan assay. PA was assessed with a validated self-reported questionnaire of IPAQ. Results:We replicated the association of rs9939609-A risk allele with BMI (P=0.04) and fat-mass (P=0.031), and with overweight (including obesity) under a recessive model (P=0.034). Stratified analyses showed i) a significant association with overweight/obesity in inactive individuals (P=0.02) but not in a group reporting sport practicing (P=0.97). Spearman's correlation test suggested that the impact of a successive increase in PA is a decrease in the body-fat percentage (r=-0.16; P=0.0002), which is more accentuated for homozygous AA (r=-0.34; P=0.002), and an increase in BMI (r=0.14; P=0.001), with a statistically significant correlation for homozygous TT (r=0.22; P=0.002). Conclusions:This study reveals interactions between rs9939609 and PA on obesity indices in Portuguese young adults, suggesting a change in the different body components (lean and fat mass) depending on the FTO genotypes.

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“…6 However, no difference in measured energy expenditure according to FTO genotype has been observed in human studies. [7][8][9] As genetic variation in FTO is associated with fat mass, the A-allele may be related to mortality due to the increase in fatness. However, in a Danish study including 1628 individuals (205 deaths), the A-allele was related to increased mortality that was independent of fatness.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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Objective: We wanted to explore if FTO genotype interacts with fat intake, or leisure-time physical activity, on fat mass, lean mass and mortality. Subjects and methods: Among 22 799 individuals (44-74 years) in the population-based Malmö diet and cancer cohort that were genotyped for rs9939609 in FTO and had information on dietary intake (from a modified diet history method) and no history of diabetes, cancer or cardiovascular disease, 2255 deaths (including 1100 cancer and 674 cardiovascular deaths) occurred during 12.0 years of follow-up. Leisure-time physical activity was determined from a list of 17 different physical activities in a questionnaire. Body composition was measured using bioelectric impedance method. Results: FTO genotype associated strongly with both fat mass and lean mass (P trend o1 Â 10 À16 for both) but we found only significant interactions with fat intake, or physical activity, on fat mass (P interaction ¼ 0.01 and 0.004). No significant interaction between FTO genotype and fat intake (P interaction ¼ 0.72), or leisure-time physical activity (P interaction ¼ 0.07), on total mortality were observed. However, we observed a significant interaction between leisure-time physical activity and FTO genotype on cardiovascular mortality (P interaction ¼ 0.03). The highest vs lowest quintile of physical activity was associated with 46% (95% confidence interval, 17-64%) reduced cardiovascular mortality among TT-carriers (P trend ¼ 0.004), and 11% reduced cardiovascular mortality among A-allele carriers (P trend ¼ 0.68). Conclusion: Our results indicate that FTO genotype associates with both fat mass and lean mass, but the level of fat intake and physical activity only modify the association with fat mass. In addition, FTO genotype may modify the association between physical activity and cardiovascular mortality.

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Variation in the FTO Gene Influences Food Intake but not Energy Expenditure

Cited by 163 publications

References 21 publications

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

Influence of physical activity on the association between the FTO variant rs9939609 and adiposity in young adults

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

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