The FTO genotype as a useful predictor of body weight maintenance: initial data from a 5-year follow-up study. The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: the Finnish Diabetes Prevention Study. FTO Genotype and 2-Year Change in Body Composition and Fat Distribution in Response to Weight-Loss Diets FTO predicts weight regain in the Look AHEAD Clinical Trial Fat mass- and obesity-associated genotype, dietary intakes and anthropometric measures in European adults: the Food4Me study. Prospective Analysis of the Association of a Common Variant of FTO (rs9939609) with Adiposity in Children: Results of the IDEFICS Study FTO genotype, dietary protein, and change in appetite: the Preventing Overweight Using Novel Dietary Strategies trial. Fat Mass and Obesity-Associated Gene (FTO) Is Linked to Higher Plasma Levels of the Hunger Hormone Ghrelin and Lower Serum Levels of the Satiety Hormone Leptin in Older Adults Changes in Physical Activity Following a Genetic-Based Internet-Delivered Personalized Intervention: Randomized Controlled Trial (Food4Me) Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans Gene-Gene Interplay and Gene-Diet Interactions Involving the MTNR1B rs10830963 Variant with Body Weight Loss A 3-year intervention with a Mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study. Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study. A haplotype of three SNPs in FTO had a strong association with body composition and BMI in Iranian male adolescents FTO polymorphisms moderate the association of food reinforcement with energy intake TCF7L2 genetic variants modulate the effect of dietary fat intake on changes in body composition during a weight-loss intervention.
OBJECTIVE We examined associations between the fat-mass and obesity-associated ( FTO ) gene ( rs9939609 ) and any weight change over a 5-year period following a 14-week lifestyle intervention  among middle-aged Japanese women . MATERIAL S/ METHODS One hundred twenty-eight Japanese women ( BMI > 25 kg/m² ) participated in a 14-week weight loss intervention between 2004 and 2006 . Of the participants , 62 consented to the 5-year follow-up measurement session . Of these women , 47 women who achieved a weight loss of at least 10 % from their baseline values during the 14-week intervention were included in the analysis . Body weight , body fat , abdominal fat assessed by CT scans , and metabolic risk factors ( i.e. , blood pressure , lipids , and glucose ) were measured at baseline , post-intervention , and at the 5-year follow-up . RESULTS During the 5-year non-intervention period , increases in body weight , fat mass , total abdominal fat , and subcutaneous abdominal fat were significantly greater in subjects with the homozygous minor allele ( AA genotype , n=4 ; 8.5 % ) than in those with the homozygous major allele ( TT genotype , n=31 ; 66.0 % ) or heterozygous allele ( TA genotype , n=12 ; 25.5 % ) . In multiple regression analyses , the variation in rs9939609 was a significant and independent predictor ( P<0.001 ) for regaining weight during the 5-year follow-up . CONCLUSIONS Our data suggest that Japanese women with the risk allele ( AA ) of rs9939609 may have more difficulty preventing fat gain from reoccurring after weight loss intervention than women with the other genotypes The common single-nucleotide polymorphism in the FTO ( fat mass and obesity associated ) gene is consistently associated with an increased risk of obesity . However , the knowledge of a potential modifying effect of the FTO gene on changes in body weight achieved by lifestyle intervention is limited . We examined whether the FTO gene variant ( rs9939609 , T/A ) is associated with body weight and BMI and long-term weight changes in the Finnish Diabetes Prevention Study ( DPS ) . Altogether , 522 ( aged 40 - 65 years ; BMI > or=25 kg/m(2 ) ) subjects with impaired glucose tolerance ( IGT ) were r and omized to control and lifestyle intervention groups . SNP rs9939609 was genotyped from 502 subjects . At baseline , those with the AA genotype had  higher BMI  than subjects with other genotypes ( P = 0.006 ) . The association was observed in women ( P = 0.016 ) but not in men . During the 4-year follow-up , the subjects with the AA genotype had consistently the highest BMI ( P = 0.009 ) in the entire study population . The magnitude of weight reduction was greater in the intervention group , but the risk allele did not modify weight change in either of the groups . Our results confirm the association between the common FTO variant and BMI in a cross-sectional setting and during the long-term lifestyle intervention . We did not observe association between FTO variant and the magnitude of weight reduction achieved by long-term lifestyle intervention . Based on the results from the DPS , it is unlikely that the common variant of the FTO gene affects the success of lifestyle modification on weight loss Recent evidence suggests that the fat mass and obesity-associated gene ( FTO ) genotype may interact with dietary intakes in relation to adiposity . We tested the effect of FTO variant on weight loss in response to 2-year diet interventions . FTO rs1558902 was genotyped in 742 obese adults who were r and omly assigned to one of four diets  differing in the proportions of fat , protein , and carbohydrate .  Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography . We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass , whole body total percentage of fat mass , total adipose tissue mass , visceral adipose tissue mass , and superficial adipose tissue mass ( for all interactions , P < 0.05 ) . Carriers of the risk allele had a greater reduction in weight , body composition , and fat distribution in response to a high-protein diet , whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet . Likewise , significant interaction patterns also were observed at 6 months . Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902 Background : Genome-wide association studies have provided new insights into the genetic factors that contribute to the development of obesity . We hypothesized that these genetic markers would also predict magnitude of weight loss and weight regain after initial weight loss . Methods : Established obesity risk alleles available on the Illumina CARe iSelect ( IBC ) chip were characterized in 3899 overweight or obese participants with type 2 diabetes from the Look AHEAD ( Action for Health in Diabetes ) , a r and omized trial to determine the effects of intensive lifestyle intervention ( ILI ) and diabetes support and education ( DSE ) on cardiovascular morbidity and mortality . Primary analyses examined the interaction between 13 obesity risk polymorphisms in eight genes and r and omized treatment arm in predicting weight change at year 1 , and weight regain at year 4 among individuals who lost 3 % or more of their baseline weight by year 1 . Results : No single-nucleotide polymorphisms ( SNPs ) were significantly associated with magnitude of weight loss or interacted with treatment arm at year 1 . However , fat mass and obesity associated gene ( FTO ) rs3751812 predicted weight regain within DSE ( 1.56 kg per risk allele , P=0.005 ) , but not ILI ( P=0.761 ) , result ing in SNP × treatment arm interaction ( P=0.009 ) . In a partial replication of prior research , the obesity risk ( G ) allele at BDNF rs6265 was associated with greater weight regain across treatment arms ( 0.773 kg per risk allele ) , although results were of borderline statistical significance ( P=0.051 ) . Conclusions : Variations in the FTO and BDNF loci may contribute risk of weight regain after weight loss The interplay between the fat mass- and obesity-associated ( FTO ) gene variants and diet has been implicated in the development of obesity . The aim of the present analysis was to investigate associations between FTO genotype , dietary intakes and anthropometrics among European adults . Participants in the Food4Me r and omised controlled trial were genotyped for FTO genotype ( rs9939609 ) and their dietary intakes , and  diet quality scores ( Healthy Eating Index and PREDIMED-based Mediterranean diet score ) were estimated from FFQ . Relationships between FTO genotype , diet and anthropometrics ( weight , waist circumference ( WC ) and BMI ) were evaluated at baseline . European adults with the FTO risk genotype had greater WC ( AA v. TT : + 1·4 cm ; P=0·003 ) and BMI ( + 0·9 kg/m2 ; P=0·001 ) than individuals with no risk alleles . Subjects with the lowest fried food consumption and two copies of the FTO risk variant had on average 1·4 kg/m2 greater BMI ( Ptrend=0·028 ) and 3·1 cm greater WC ( Ptrend=0·045 ) compared with individuals with no copies of the risk allele and with the lowest fried food consumption . However , there was no evidence of interactions between FTO genotype and dietary intakes on BMI and WC , and thus further research is required to confirm or refute these findings Objectives We investigated cross-sectionally and longitudinally the relationship between FTO rs9939609 and  obesity-related characteristics in the European children of the IDEFICS project and the interaction of this variant with a lifestyle intervention . Population and Methods A cohort of 16224 children ( 2–9 years ) was recruited into a population -based survey ( T0 ) from eight European countries . A second survey ( T1 ) reassessed the children two years later . A r and om sample of 4405 children was extracted for genetic studies . 3168 children were re-examined two years later . Half of them underwent a lifestyle intervention program . The FTO rs9939609 was genotyped . Weight , height , waist circumference , triceps and subscapular skinfolds were measured at T0 and T1 . Results At T0 , the risk A allele of rs9939609 was significantly associated with higher values of body mass index ( BMI ) , waist circumference and skinfolds ( age , sex , and country-adjusted p-values : all p<0.001 ) and with a statistically significant increased risk of overweight/obesity . Over the two year follow-up , no interaction between genotype and intervention was observed . The A allele was associated to a significantly higher increase in all the anthropometric variables examined at T0 independently from the study group ( intervention versus control ) ( p-values : all p<0.002 , adjusted for age , sex , country , intervention/control study group , T0 values , and individual time interval between T0 and T1 ) . Over the two-year follow – up , 210 new cases of overweight/obesity occurred . A statistically significant higher incidence of overweight/obesity was associated to the A allele [ ORA = 1.95 , 95 % CI = ( 1.29 ; 2.97 ) ] . Conclusions We confirmed the association between the FTO rs9939609 and  body mass and overweight/obesity risk in European children . The main finding of the study is that the A allele carriers present higher increase of body mass and central adiposity over time and higher risk of developing overweight/obesity during growth , independently from intervention measures BACKGROUND A common obesity-risk variant rs9939609 in the fat mass- and obesity-associated ( FTO ) gene was recently shown to affect appetite , and the gene is sensitive to the regulation of amino acids . OBJECTIVE We examined the interaction between FTO genotype and protein intake on the long-term changes in appetite in a r and omized controlled trial . DESIGN We genotyped FTO rs9939609 in 737 overweight adults in the 2-y Preventing Overweight Using Novel Dietary Strategies  trial and assessed 4 appetite-related traits including cravings , fullness , hunger , and prospect i ve consumption . RESULTS We showed that dietary protein significantly modified genetic effects on changes in food cravings and appetite scores at 6 mo after adjustment for age , sex , ethnicity , baseline body mass index , weight change , and baseline value for respective outcomes ( P-interaction = 0.027 and 0.048 , respectively ) . The A allele was associated with a greater decrease in food cravings and appetite scores in participants with high-protein-diet intake ( P = 0.027 and 0.047 , respectively ) but not in subjects in the low-protein-diet group ( P = 0.384 and 0.078 , respectively ) . The weight regain from 6 to 24 mo attenuated gene-protein interactions . Protein intakes did not modify FTO genotype effects on other appetite measures . CONCLUSION Our data suggest that individuals with the FTO rs9939609 A allele might obtain more benefits in a reduction of food cravings and appetite by choosing a hypocaloric and higher-protein weight-loss diet . This trial was registered at clinical trials.gov as NCT00072995 The mechanisms through which common polymorphisms in the fat mass and obesity-associated gene ( FTO ) drive the development of obesity in humans are poorly understood . Using cross-sectional data from 985 older people ( 50 % females ) who participated at age 70 years in the Prospect i ve Investigation of the Vasculature in Uppsala Seniors ( PIVUS ) , circulating levels of ghrelin and leptin were measured after an overnight fast . In addition , subjects were genotyped for FTO rs17817449 ( AA , n = 345 [ 35 % ] ; AC/CA , n = 481 [ 48.8 % ] ; CC , n = 159 [ 16.1 % ] ) . Linear regression analyses controlling for sex , self-reported physical activity level , fasting plasma glucose , and BMI were used . A positive relationship between the number of FTO C risk alleles and plasma ghrelin levels was found ( P = 0.005 ; relative plasma ghrelin difference between CC and AA carriers = ∼9 % ) . In contrast , serum levels of the satiety-enhancing hormone leptin were inversely linked to the number of FTO C risk alleles ( P = 0.001 ; relative serum leptin difference between CC and AA carriers = ∼11 % ) . These associations were also found when controlling for waist circumference . The present findings suggest that FTO may facilitate weight gain in humans by shifting the endocrine balance from the satiety hormone leptin toward the hunger-promoting hormone ghrelin Background There is evidence that  physical activity ( PA )  can attenuate the influence of the fat mass- and obesity-associated ( FTO ) genotype on the risk to develop obesity . However , whether providing personalized information on FTO genotype leads to changes in PA is unknown . Objective The purpose of this study was to determine if disclosing FTO risk had an impact on change in PA following a 6-month intervention . Methods The single nucleotide polymorphism ( SNP ) rs9939609 in the FTO gene was genotyped in 1279 participants of the Food4Me study , a four-arm , Web-based r and omized controlled trial ( RCT ) in 7 European countries on the effects of personalized advice on nutrition and PA . PA  was measured objective ly using a TracmorD accelerometer and was self-reported using the Baecke question naire at baseline and 6 months . Differences in baseline PA variables between risk ( AA and AT genotypes ) and nonrisk ( TT genotype ) carriers were tested using multiple linear regression . Impact of FTO risk disclosure on PA change at 6 months was assessed among participants with inadequate PA , by including an interaction term in the model : disclosure ( yes/no ) × FTO risk ( yes/no ) . Results At baseline , data on PA were available for 874 and 405 participants with the risk and nonrisk FTO genotypes , respectively . There were no significant differences in objective ly measured or self-reported baseline PA between risk and nonrisk carriers . A total of 807 ( 72.05 % ) of the participants out of 1120 in the personalized groups were encouraged to increase PA at baseline . Knowledge of FTO risk had no impact on PA in either risk or nonrisk carriers after the 6-month intervention . Attrition was higher in nonrisk participants for whom genotype was disclosed ( P=.01 ) compared with their at-risk counterparts . Conclusions No association between baseline PA and FTO risk genotype was observed . There was no added benefit of disclosing FTO risk on changes in PA in this personalized intervention . Further RCT studies are warranted to confirm whether disclosure of nonrisk genetic test results has adverse effects on engagement in behavior change . Trial Registration Clinical Trials.gov NCT01530139 ; http:// clinical trials.gov/show/NCT01530139 ( Archived by WebCite at : http://www.webcitation.org/6XII1QwHz 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 r and omized 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−1 ) . 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-β ) 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=0.002 ; in AT/AA combined , P=0.003 ) . Among those individuals completing the intervention , we found no effect of FTO rs9939609 genotype on Δweight , ΔFM , ΔFFM , ΔWC or ΔFatOx . However , participants with TT had a smaller reduction in REE on LF than on HF diet ( 75 kcal/24 h ; interaction : P=0.0055 ) . These individuals also showed the greatest reduction in HOMA-β and HOMA-IR ( interaction : P=0.0083 and P=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-β and HOMA-IR on LF than on HF diet Background / Aims : Investigation of the genetic makeup may facilitate the implementation of more personalized nutritional interventions . The aims were to examine whether the rs10830963 MTNR1B polymorphism affects weight loss in response to a hypocaloric diet and to find potential gene-gene interplays and gene-diet interactions . Methods : 167 subjects enrolled in a personalized nutritional intervention for weight loss ( 3 - 6 weeks ) were examined for anthropometric measurements , dietary habits and physical activity at baseline and at the first follow-up visit . Three polymorphisms , which have previously been associated with body weight regulation , rs10830963 ( MTNR1B ) , rs9939609 ( FTO ) and rs17782313 ( MC4R ) , were analyzed using the Luminex ® 100/200 ™ System . Results : After adjusting for covariates , females with the rs10830963 CG/GG genotype showed lower weight loss than those with the CC genotype . In the total population , carriers of variant alleles of both FTO and MC4R showed a significant association with MTNR1B and weight loss outcome . Moreover , among women , higher total protein and animal protein intakes were associated with a lower weight loss in G allele carriers of the MTNR1B variant . Conclusions : Our data evidence d that rs10830963 MTNR1B polymorphism could be associated with individual differences in weight loss induced by a hypocaloric diet . This association was influenced by FTO and MC4R loci and modified by baseline protein intake Introduction : The aim of this study was to analyze the effects of the rs9939609 ( T/A ) gene variant in fat mass and obesity-associated gene ( FTO ) on body weight changes after 3 years and its modification by a r and omized nutritional intervention with a Mediterranean-style diet in a population of subjects at high cardiovascular risk . Design : A sub study of PREDIMED , which is a r and omized trial aim ed at assessing the effect of the Mediterranean diet ( MD ) for primary cardiovascular disease prevention . There were three nutritional intervention groups : two of them with a Mediterranean-style diet and the third was a control group advised to follow a conventional low-fat diet . Subjects : A total of 776 high cardiovascular risk subjects aged 55–80 years . Measurements : Anthropometric measurements were recorded at baseline and at 3 years . The participants were genotyped by RT-PCR , followed by allelic discrimination . Results : Homozygous subjects had the highest baseline body weight . The dominant model showed that subjects carrying the A allele had the lowest body weight gain ( B=−0.685 ; P=0.022 ) after 3 years of nutritional intervention compared with nonmutated subjects ( TT genotype ) regardless of the nutritional intervention . Moreover , this effect was statistically significant in carriers of the A allele only among those allocated to the MD groups ( B=−0.830 ; P=0.018 ) , but it was not significant among those allocated to the control group ( P for interaction=0.649 ) . Conclusion : This study confirmed the association between body weight and the FTO rs9939609 polymorphism . Interestingly , our results showed that , although at baseline the A allele was associated with higher body weight , after 3 years of nutritional intervention with a Mediterranean-style-diet , A-allele carriers had lower body weight gain than wild type subjects . No interaction between nutritional intervention and the polymorphism was found OBJECTIVE To examine whether the effect of FTO loci on obesity-related traits could be modified by  physical activity ( PA ) levels in European adults . METHODS Of 1,607 Food4Me participants r and omized , 1,280 were genotyped for FTO ( rs9939609 ) and had available PA data .  PA was measured objective ly using accelerometers ( TracmorD , Philips ) , whereas anthropometric measures [ BMI and waist circumference ( WC ) ] were self-reported via the Internet . RESULTS FTO genotype was associated with a higher body weight [ β : 1.09 kg per risk allele , ( 95 % CI : 0.14 - 2.04 ) , P = 0.024 ] , BMI [ β : 0.54 kg m(-2 ) , ( 0.23 - 0.83 ) , P < 0.0001 ] , and WC [ β : 1.07 cm , ( 0.24 - 1.90 ) , P = 0.011 ] . Moderate-equivalent PA attenuated the effect of FTO on BMI ( P[interaction ] = 0.020 ) . Among inactive individuals , FTO increased BMI by 1.06 kg m(-2 ) per allele ( P = 0.024 ) , whereas the increase in BMI was substantially attenuated among active individuals ( 0.16 kg m(-2 ) , P = 0.388 ) . We observed similar effects for WC ( P[interaction ] = 0.005 ) : the FTO risk allele increased WC by 2.72 cm per allele among inactive individuals but by only 0.49 cm in active individuals .  CONCLUSIONS PA attenuates the effect of FTO genotype on BMI and WC . This may have important public health implication s because genetic susceptibility to obesity in the presence of FTO variants may be reduced by adopting a physically active lifestyle BACKGROUND Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes . OBJECTIVE This study examined single nucleotide polymorphisms ( SNPs ) in presumed nutrient-sensitive c and i date genes for obesity and obesity-related diseases for main and dietary interaction effects on weight , waist circumference , and fat mass regain over 6 mo . DESIGN In total , 742 participants who had lost ≥ 8 % of their initial body weight were r and omly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein . The SNP main and SNP-diet interaction effects were analyzed by using linear regression models , corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile ( Q-Q ) plots . RESULTS After correction for multiple testing , none of the SNPs were significantly associated with weight , waist circumference , or fat mass regain . Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo ( -3.1 cm/allele ; 95 % CI : -4.6 , -1.6 ; P/Bonferroni-corrected P = 0.000039/0.076 ) , independently of diet . Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP , TNF , and KCNJ11 for main effects ; in LPL and TUB for glycemic index interaction effects on waist circumference regain ; in GHRL , CCK , MLXIPL , and LEPR on weight ; in PPARC1A , PCK2 , ALOX5AP , PYY , and ADRB3 on waist circumference ; and in PPARD , FABP1 , PLAUR , and LPIN1 on fat mass regain for dietary protein interaction . CONCLUSION The observed effects of SNP-diet interactions on weight , waist , and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet . This trial was registered at clinical trials.gov as NCT00390637 Background Single-nucleotide polymorphisms ( SNPs ) , which are located in the first intron of the FTO gene , are reported to be associated with body weight and the body mass index ( BMI ) . However , their effects on anthropometric measurements in adolescents are poorly understood . Objective This study aim ed to investigate the association of three adjacent polymorphisms ( rs9930506 , rs9930501 , & rs9932754 ) in the FTO gene with anthropometric indices in Iranian adolescent males . Design The participants comprised a total of 237 adolescent males who were recruited r and omly from two high schools in Tehran , Iran . The DNA sample s were genotyped for the FTO gene polymorphisms by DNA sequencing .  BMI , body fat percentage ( BF% ) , and body muscle percentage ( BM% ) were determined using a vali date d bioelectrical impedance analysis scale . The association of the FTO polymorphisms with weight , height , BMI , BF% , and BM% was investigated . Results A haplotype of rs9930506 , rs9930501 , and rs9932754 ( GGT ) in the first intron of the FTO with complete linkage disequilibrium ( LD ) was found to be significantly associated with higher weight ( OR = 1.32 ) , BMI ( OR = 5.36 ) and BF% ( OR = 1.46 ) , and lower BM% ( OR = 3.59 ) ( all P<0.001 ) . None of the students with GGC genotypes were underweight , while all of the students with AAT genotypes had high muscle mass . Conclusions A haplotype in the first intron of the FTO gene had a strong association with obesity indices in Iranian adolescent males . The FTO gene polymorphisms might have greater effects on anthropometric indices than what was previously imagined . Moreover , we suggested that the FTO gene exerted their effects on anthropometric measurements through haplotypes ( and not single SNPs ) Food reinforcement ( RRVfood ) is related to increased energy intake , cross-sectionally related to obesity , and prospect ively related to weight gain . The fat mass and obesity-associated ( FTO ) gene is related to elevated body mass index and increased energy intake . The primary purpose of the current study was to determine whether any of 68 FTO single nucleotide polymorphisms ( SNPs ) or a FTO risk score moderate the association between  food reinforcement and energy or macronutrient intake . Energy and macronutrient intake  was measured using a laboratory ad libitum snack food consumption task in 237 adults of varying BMI . Controlling for BMI , the relative reinforcing value of reading ( RRVreading ) and proportion of African ancestry , RRVfood predicted 14.2 % of the variance in energy intake , as well as predicted carbohydrate , fat , protein and sugar intake . In individual analyses , six FTO SNPs ( rs12921970 , rs9936768 , rs12446047 , rs7199716 , rs8049933 and rs11076022 , spanning approximately 251kbp ) moderated the relationship between RRVfood and energy intake to predict an additional 4.9 - 7.4 % of variance in energy intake . We created an FTO risk score based on 5 FTO SNPs ( rs9939609 , rs8050136 , rs3751812 , rs1421085 , and rs1121980 ) that are related to BMI in multiple studies . The FTO risk score did not increase variance accounted for beyond individual FTO SNPs . rs12921970 and rs12446047 served as moderators of the relationship between RRVfood and carbohydrate , fat , protein , and sugar intake . This study shows for the first time that the relationship between RRVfood and energy intake is moderated by FTO SNPs . Research is needed to underst and how these processes interact to predict energy and macronutrient intake BACKGROUND TCF7L2 gene variants have been associated with increased risk of  type 2 diabetes and higher adiposity .  Observational studies and short-term trials have suggested that macronutrients may modify these effects . However , to our knowledge , this has yet to be verified in long-term interventions . OBJECTIVE In a long-term intervention setting , we investigated the effects of TCF7L2 polymorphisms rs7903146 and rs12255372 and dietary total fat on changes in body composition and subsequent glycemic control . DESIGN Data were analyzed for 591 participants in the Preventing Overweight Using Novel Dietary Strategies ( Pounds Lost ) trial , which is a 2-y weight-loss r and omized clinical trial of diets that differed in macronutrient proportions . Adjusted means for changes in body composition at 6 and 24 mo were obtained for gene main effects and interactions with a low-fat diet ( 20 % from energy ) compared with a high-fat diet ( 40 % from energy ) . Interactions with protein and carbohydrate intakes were also tested . Predicted changes in glycemic control from changes in adiposity were determined by genotype and diet type . RESULTS Significant interactions were observed for rs12255372 TT ( risk genotype ) and fat intake for changes in BMI , total fat mass , and trunk fat mass ( all P/q < 0.05 ) at 6 mo , with nonsignificant larger decreases for TT carriers on a low-fat diet . No significant associations were observed at 24 mo or for other macronutrients . Changes in body composition for TT carriers predicted reductions in plasma glucose and insulin only on the low-fat diet . CONCLUSIONS Individuals with the TCF7L2 rs12255372 risk genotype may reduce body adiposity by consuming a diet lower in total fat . These reductions may induce better glycemic control for such individuals predisposed to type 2 diabetes . The Pounds Lost trial was registered at clinical trials.gov as NCT00072995
This meta- analysis suggests that individuals carrying the homozygous FTO obesity-predisposing allele may lose more weight through diet/lifestyle interventions than noncarriers .
BACKGROUND Studies have suggested that the fat mass and obesity-associated ( FTO ) genotype is associated with individual variability in weight loss in response to diet/lifestyle interventions , but results are inconsistent .
OBJECTIVE We aim ed to provide a summary of the literature evaluating the relation between the FTO genotype and weight loss in response to diet/lifestyle interventions .