Impact of Variation in the <i>FTO</i> Gene on Whole Body Fat Distribution, Ectopic Fat, and Weight Loss

Haupt, Axel; Thamer, Claus; Machann, Jiirgen; Kirchhoff, Kerstin; Stefan, Norbert; Tschritter, Otto; Machicao, Fausto; Schick, Fritz; Häring, Hans‐Ulrich; Fritsche, Andreas

doi:10.1038/oby.2008.283

Cited by 106 publications

(111 citation statements)

References 24 publications

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“…Our finding of no main effects of FTO rs9939609 on change in anthropometrics and metabolic estimates during intervention is in agreement with the two studies. 21,22 Other studies than the present are suggestive of modifiable effects of FTO variants. 5,33 Unfortunately, it was not possible to examine the interaction between genotype and fat and CHO content in either of the two previous studies of FTO variants and response to weight loss intervention.…”

Section: Discussionsupporting

confidence: 44%

“…32 Two previous studies have examined FTO variants in relation to weight loss interventions. 21,22 Unfortunately, drop out from the interventions was not analysed in either of these reports. Our finding of no main effects of FTO rs9939609 on change in anthropometrics and metabolic estimates during intervention is in agreement with the two studies.…”

Section: Discussionmentioning

confidence: 99%

“…Two studies are published with findings of no association between FTO variants (rs8050136 and rs9939609, respectively) and weight loss. 21,22 Further, it is unknown whether factors, such as macronutrient composition, affect the association between variants in FTO and weight loss. Previously 42 SNPs in 26 candidate genes for obesity (not including FTO) were examined in relation to weight loss in the NUGENOB study (Nutrient-gene interaction in human obesity: implication for dietary guidelines), in which average weight loss was 6.8 kg after 10 weeks.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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Background: The A risk allele of rs9939609 of the fat mass-and obesity-associated gene (FTO) increases body fat mass. Objective: To examine whether FTO rs9939609 affects obese individuals' response to a high-fat, low-carbohydrate (CHO) (HF) or low-fat, high-CHO (LF), hypo-energetic diet and whether the effect of the FTO variant depends on dietary fat and CHO content. Design: In a 10-week, European, multi-centre dietary intervention study 771 obese women and men were randomized to either LF (20-25% of energy (%E) from fat, 60-65%E from CHO) or HF (40-45%E from fat, 40-45%E from CHO), hypo-energetic diet (measured resting metabolic rate multiplied by 1.3-600 kcal day À1 ). Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation as % of REE (FatOx), insulin release (HOMA-b) and a surrogate measure of insulin resistance (HOMA-IR) were measured at baseline and after the intervention. In all, 764 individuals were genotyped for FTO rs9939609. Results: For A-allele carriers the drop-out rate was higher on HF than LF diet (in AT, P ¼ 0.002; in AT/AA combined, P ¼ 0.003). Among those individuals completing the intervention, we found no effect of FTO rs9939609 genotype on Dweight, DFM, DFFM, DWC or DFatOx. However, participants with TT had a smaller reduction in REE on LF than on HF diet (75 kcal/24 h; interaction: P ¼ 0.0055). These individuals also showed the greatest reduction in HOMA-b and HOMA-IR (interaction: P ¼ 0.0083 and P ¼ 0.047). Conclusion:The FTO rs9939609 may interact with the macronutrient composition in weight loss diets in various ways; carriers of the A allele on LF diet appear to have a lower risk for drop out, and TT individuals have a smaller decrease in REE and greater decrease in HOMA-b and HOMA-IR on LF than on HF diet.

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Section: Discussionsupporting

confidence: 44%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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“…articles Genetics variants are associated with overall body fat mass and ectopic fat storage in the liver (15).…”

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confidence: 99%

Novel Obesity Risk Loci Do Not Determine Distribution of Body Fat Depots: A Whole‐body MRI/MRS study

Haupt

Thamer

Heni

et al. 2010

Obesity

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A recent meta‐analysis of genome‐wide association studies has identified six new risk‐loci for common obesity. We studied whether these risk loci influence the distribution of body fat depots. We genotyped 1,469 nondiabetic subjects for the single‐nucleotide polymorphisms (SNPs) TMEM18 rs6548238, KCTD15 rs11084753, GNPDA2 rs10938397, SH2B1 rs7498665, MTCH2 rs10838738, and NEGR1 rs2815752. We assessed BMI, waist circumference, total body fat, and lean body mass (bioimpedance). All subjects underwent an oral glucose tolerance test (OGTT) for estimation of insulin sensitivity. In 332 subjects, we measured total adipose tissue (TAT), visceral adipose tissue (VAT), nonvisceral adipose tissue (NVAT), liver fat content, and intramyocellular lipids (IMCLs) using whole‐body magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). In the dominant inheritance model, the risk alleles of TMEM18 rs6548238 and MTCH2 rs10838738 were nominally associated with higher BMI (P = 0.04, both). The risk allele of TMEM18 rs6548238 was additionally associated with higher waist circumference and total body fat (P ≤ 0.03), the risk allele of NEGR1 rs2815752 with higher waist circumference (P = 0.05) and unexpectedly with lower BMI (P = 0.01). In the MR cohort, we found an association of the risk allele of SH2B1 rs7498665 with higher VAT (P = 0.009) and of GNPDA2 rs10938397 with increased IMCLs (P = 0.03). After Bonferroni correction for multiple comparisons (corrected α‐level: P = 0.0085), none of the SNPs was significantly associated with measures of adiposity or body fat distribution (all P > 0.009, dominant inheritance model). Therefore, our results suggest that these new obesity SNPs, despite their influence on BMI, are neither associated with a metabolically unfavorable nor with a favorable body composition.

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“…We demonstrated that only SNPs in the FTO gene are associated with SFA and BMI, but not with VFA. FTO rs8050136 has been shown to be marginally associated with visceral fat mass measured by magnetic resonance imaging in Germany (P¼0.05) 36 and rs9939609 with intra-abdominal adipose tissue estimated by dual energy X-ray absorptiometry in Danish (P¼4.7Â10 À3 ). 37 SNP rs8050136 has been reported to be marginally associated with VFA measured by CT in African Americans (P¼0.05), but not in Hispanic Americans.…”

Section: Discussionmentioning

confidence: 99%

Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography

Hotta

Kitamoto

et al. 2012

J Hum Genet

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Visceral fat accumulation has an important role in the development of several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that contribute to the development of type 2 diabetes have been identified by genome-wide association studies. To examine the association of type 2 diabetes susceptibility loci and visceral fat accumulation, we genotyped 1279 Japanese subjects (556 men and 723 women), who underwent computed tomography for measurements of visceral fat area (VFA) and subcutaneous fat area (SFA) for the following single-nucleotide polymorphisms (SNPs): NOTCH2 rs10923931, THADA rs7578597, PPARG rs1801282, ADAMTS9 rs4607103, IGF2BP2 rs1470579, VEGFA rs9472138, JAZF1 rs864745, CDKN2A/CDKN2B rs564398 and rs10811661, HHEX rs1111875 and rs5015480, TCF7L2 rs7901695, KCNQ1 rs2237892, KCNJ11 rs5215 and rs5219, EXT2 rs1113132, rs11037909, and rs3740878, MTNR1B rs10830963, DCD rs1153188, TSPAN8/LGR5 rs7961581, and FTO rs8050136 and rs9939609. None of the above SNPs were significantly associated with VFA. The FTO rs8050136 and rs9939609 risk alleles exhibited significant associations with body mass index (BMI; P¼0.00088 and P¼0.0010, respectively) and SFA (P¼0.00013 and P¼0.00017, respectively). No other SNPs were significantly associated with BMI or SFA. Our results suggest that two SNPs in the FTO gene are associated with subcutaneous fat accumulation. The contributions of other SNPs are inconclusive because of a limitation of the sample power.

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Impact of Variation in the FTO Gene on Whole Body Fat Distribution, Ectopic Fat, and Weight Loss

Cited by 106 publications

References 24 publications

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

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

Novel Obesity Risk Loci Do Not Determine Distribution of Body Fat Depots: A Whole‐body MRI/MRS study

Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography

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