FTO Genotype and 2-Year Change in Body Composition and Fat Distribution in Response to Weight-Loss Diets Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans 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, dietary protein, and change in appetite: the Preventing Overweight Using Novel Dietary Strategies trial. Fat mass- and obesity-associated genotype, dietary intakes and anthropometric measures in European adults: the Food4Me study. Gene-Gene Interplay and Gene-Diet Interactions Involving the MTNR1B rs10830963 Variant with Body Weight Loss The FTO genotype as a useful predictor of body weight maintenance: initial data from a 5-year follow-up study. Evaluation of weight loss and adipocytokines levels after two hypocaloric diets with different macronutrient distribution in obese subjects with rs9939609 gene variant. A 3-year intervention with a Mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes Dietary Energy Density Affects Fat Mass in Early Adolescence and Is Not Modified by FTO Variants Prospective Analysis of the Association of a Common Variant of FTO (rs9939609) with Adiposity in Children: Results of the IDEFICS Study A haplotype of three SNPs in FTO had a strong association with body composition and BMI in Iranian male adolescents FTO predicts weight regain in the Look AHEAD Clinical Trial Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study. Changes in Physical Activity Following a Genetic-Based Internet-Delivered Personalized Intervention: Randomized Controlled Trial (Food4Me) A preliminary candidate genotype-intermediate phenotype study of satiation and gastric motor function in obesity. 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 Television food advertisement exposure and FTO rs9939609 genotype in relation to excess consumption in children Weight-loss diets modify glucose-dependent insulinotropic polypeptide receptor rs2287019 genotype effects on changes in body weight, fasting glucose, and insulin resistance: the Preventing Overweight Using Novel Dietary Strategies trial. CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials1 Association analyses for dopamine receptor gene polymorphisms and weight status in a longitudinal analysis in obese children before and after lifestyle intervention Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial The 2 x 2 factorial design: its application to a randomized trial of aspirin and carotene in U.S. physicians.
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 : 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 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 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 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 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 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 BACKGROUND Common polymorphisms of the fat mass and obesity associated gene ( FTO ) have been linked to obesity in some population s. One of these genetic variants ( rs9939609 ) has been related to an increased risk of obesity . OBJECTIVE Our aim was to evaluate weight loss and adipocytokine levels after two hypocaloric diets with different macronutrient distribution in obese subjects with RS9939609 gene variant . DESIGN 305 obese patients were enrolled in a prospect i ve way . In the basal visit , patients were r and omly allocated during 3 months to low carbohydrates and low fat . RESULTS After treatment with both diets and in both genotypes , weight , fat mass , waist circumference and systolic blood pressures decreased . With the diet type I and in TT genotype , insulin ( -6.6 ± 9.8 IU/L ) and homeostasis model assessment ( -2.9 ± 6.1 units ) decreased . With the diet type II and in both genotypes ( wild and mutant type ) , insulin ( -5.2 ± 6.1 vs. -3.8 ± 6.1 IU/L ; p < 0.05 ) and homeostasis model assessment ( -2.4 ± 4.8 vs. -1.1 ± 3.8 kg ; p < 0.05 ) decreased . In the A allele group , a significant decrease was detected in total cholesterol levels ( -11.5 ± 20.1 mg/dL ) , low density lipoprotein cholesterol levels ( -13.2 ± 20.9 mg/dL ) and c-reactive protein levels ( -1.3 ± 3.8 mg/dL ) secondary to weight loss after treatment with diet II . The decrease of leptin levels was higher in mutant type group than wild type group with low fat diet ( -10.3 ± 36.1 vs. -28.6 ± 53.7 ng/mL ; p < 0.05 ) . CONCLUSION Metabolic improvement secondary to weight loss was better in A carriers with a low fat hypocaloric diet 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 Background Dietary energy density ( DED ) does not have a simple linear relationship to fat mass in children , which suggests that some children are more susceptible than others to the effects of DED . Children with the FTO ( rs9939609 ) variant that increases the risk of obesity may have a higher susceptibility to the effects of DED because their internal appetite control system is compromised . We tested the relationship between DED and fat mass in early adolescence and its interaction with FTO variants . Methods and Findings We carried out a prospect i ve analysis on 2,275 children enrolled in the Avon Longitudinal Study of Parents and Children ( ALSPAC ) .  Diet was assessed at age 10 y using 3-day diet diaries .  DED ( kJ/g ) was calculated excluding drinks . Children were genotyped for the FTO ( rs9939609  ) variant . Fat mass was estimated at age 13 y using the Lunar Prodigy Dual-energy X-ray Absorptiometry scanner . There was no evidence of interaction between DED at age 10 y and the high risk A allele of the FTO gene in relation to fat mass at age 13 y ( β = 0.005 , p = 0.51 ) , suggesting that the FTO gene has no effect on the relation between DED at 10 y and fat mass at 13 y. When DED at 10 y and the A allele of FTO were in the same model they were independently related to fat mass at 13 y. Each A allele of FTO was associated with 0.35±0.13 kg more fat mass at 13 y and each 1 kJ/g DED at 10 y was associated with 0.16±0.06 kg more fat mass at age 13 y , after controlling for misreporting of energy intake , gender , puberty , overweight status at 10 y , maternal education , TV watching , and physical activity . Conclusions This study reveals the multi-factorial origin of obesity and indicates that although FTO may put some children at greater risk of obesity , encouraging a low dietary energy density may be an effective strategy to help all children avoid excessive fat gain 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 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 ) 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 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 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 Stomach motility contributes significantly to fullness sensation while eating and cessation of food intake in humans . Genes controlling adrenergic and serotonergic mechanisms ( ADRA2A , GNB3 , and SLC6A4 ) affect gastric emptying ( GE ) , volume ( GV ) , and satiation . Fat mass and obesity-associated gene ( FTO ) is linked with satiety . Our aim was to examine the association of these c and i date genes with stomach functions that signal postpr and ial fullness : GE , GV , and maximum tolerated volume ( MTV ) . These biomarkers constitute a component of the intermediate phenotype of satiation . A total of 62 overweight or obese participants underwent genotyping of the c and i date genes , and vali date d measurements of GE of solids and liquids by scintigraphy , fasting and postpr and ial change in GV by SPECT ( single photon emission computed tomography ) , and MTV by nutrient drink test . These markers of satiation were compared for 38 genetic variants in ADRA2A , ADR2C , ADRB3 , uncoupling protein (UCP)-2 and -3 , GNB3 , FTO , and SLC6A4 using a recessive model of inheritance . ADRA2A , ADR2C , UCP-3 , GNB3 , and FTO loci were significantly associated with the intermediate phenotype markers of satiation : ADR2C ( Ins-Del322_325 ) with accelerated GE ; GNB3 ( rs1047776 ) with delayed GE ; ADRA2A ( rs491589 and rs553668 ) and GNB3 ( rs2269355 , rs10849527 , and rs3759348 ) with decreased postpr and ial GV ; ADRA2A ( rs3750625 ) and GNB3 ( rs4963517 and rs1129649 ) with increased postpr and ial GV ; UCP-3 ( rs1685356 ) with increased MTV , and FTO ( rs9939609 ) decreased MTV . Genetic susceptibility to postpr and ial satiation can be identified through intermediate phenotype markers . With independent validation , these markers may guide patient selection of weight-loss therapies directed at gastric motor functions 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 / Objective : Exposure to food advertisements may cue overeating among children , especially among those genetically predisposed to respond to food cues . We aim ed to assess how television food advertisements affect eating in the absence of hunger among children in a r and omized trial . We hypothesized that the fat mass and obesity-associated gene ( FTO ) rs9939609 single-nucleotide polymorphism would modify the effect of food advertisements . Subjects/ Methods : In this r and omized experiment , 200 children aged 9–10 years were served a st and ardized lunch and then shown a 34-min television show embedded with either food or toy advertisements . Children were provided with snack food to consume ad libitum while watching the show and we measured caloric intake . Children were genotyped for rs9939609 and analyses were conducted in the overall sample and stratified by genotype . A formal test for interaction of the food advertisement effect on consumption by rs9939609 was conducted . Results : About 172 unrelated participants were included in this analysis . Children consumed on average 453 ( s.d.=185 ) kcals during lunch and 482 ( s.d.=274 ) kcals during the experimental exposure . Children who viewed food advertisements consumed an average of 48 kcals ( 95 % confidence interval : 10 , 85 ; P=0.01 ) more of a recently advertised food than those who viewed toy advertisements . There was a statistically significant interaction between genotype and food advertisement condition ( P for interaction=0.02 ) , where the difference in consumption of a recently advertised food related to food advertisement exposure increased linearly with each additional FTO risk allele , even after controlling for body mass index percentile . Conclusions : Food advertisement exposure was associated with greater caloric consumption of a recently advertised food , and this effect was modified by an FTO genotype . Future research is needed to underst and the neurological mechanism underlying these associations BACKGROUND Glucose-dependent insulinotropic polypeptide [ also known as gastric inhibitory polypeptide ( GIP ) ] and its receptor ( GIPR ) may link overnutrition to obesity , insulin resistance , and type 2 diabetes . A GIPR variant rs2287019 was recently associated with obesity and glucose metabolism . OBJECTIVE We aim ed to examine whether weight-loss diets that vary in fat content may modify the effect of this variant on changes in body weight , fasting glucose , and insulin resistance in the Preventing Overweight Using Novel Dietary Strategies ( POUNDS LOST ) trial . DESIGN We genotyped the GIPR rs2287019 in 737 overweight adults who were r and omly assigned to 1 of 4 weight-loss diets that varied in macronutrient contents for 2 y. We assessed the percentage changes in body weight , fasting glucose , and insulin resistance ( HOMA-IR ) across genotypes by the low-fat and high-fat diets . RESULTS At 6 mo of diet intervention , the T allele of rs2287019 was associated with greater weight loss ( β ± SE : -1.05 ± 0.56 % ; P = 0.06 ) and greater decreases in fasting glucose ( β ± SE : -2.33 ± 0.86 % ; P = 0.006 ) , fasting insulin ( β ± SE : -8.76 ± 4.13 % ; P = 0.03 ) , and HOMA-IR ( β ± SE : -10.52 ± 4.39 % ; P = 0.01 ) in participants who were assigned to low-fat diets , whereas there was no significant genotype effect on changes in these traits in the group assigned to the high-fat diet ( all P > 0.44 ; P-interaction = 0.08 , 0.04 , 0.10 , and 0.07 , respectively ) . After correction for multiple tests ( significant P = 0.008 ) , the genotype effect on changes in fasting glucose remained significant . Sensitivity analysis in white participants showed that the interactions were more evident on changes in insulin and HOMA-IR ( P-interaction < 0.008 ) . CONCLUSION The T allele of GIPR rs2287019 is associated with greater improvement of glucose homeostasis in individuals who choose a low-fat , high-carbohydrate , and high-fiber diet . The POUNDS LOST trial was registered at clinical trials.gov as NCT00072995 Little is known about whether cholesteryl ester transfer protein ( CETP ) genetic variation may modify the effect of weight-loss diets varying in fat content on changes in lipid levels . We analyzed the interaction between the CETP variant rs3764261 and dietary interventions on changes in lipid levels among 732 overweight/obese adults from a 2 year r and omized weight-loss trial [ Preventing Overweight Using Novel Dietary Strategies ( POUNDS LOST ) ] , and replicated the findings in 171 overweight/obese adults from an independent 2 year weight-loss trial [ Dietary Intervention R and omized Controlled Trial ( DIRECT ) ] . In the POUNDS LOST , participants with the CETP rs3764261 CC genotype on the high-fat diet had larger increases in HDL cholesterol ( P = 0.001 ) and decreases in triglycerides ( P = 0.007 ) than those on the low-fat diet at 6 months , while no significant difference between these two diets was observed among participants carrying other genotypes . The gene-diet interactions on changes in HDL-cholesterol and triglycerides were replicated in the DIRECT ( pooled P for interaction ≤ 0.01 ) . Similar results on trajectory of changes in HDL cholesterol and triglycerides over the 2 year intervention were observed in both trials . Our study provides replicable evidence that individuals with the CETP rs3764261 CC genotype might derive greater effects on raising HDL cholesterol and lowering triglycerides by choosing a low-carbohydrate/high-fat weight-loss diet instead of a low-fat diet Background Dopamine receptors are involved in midbrain reward circuit activation . Polymorphisms in two dopamine receptor genes , DRD2 and DRD4 , have been associated with altered perception of food reward and weight gain . The objective of this study was to determine whether the same risk alleles were associated with overweight/obesity and with lower reduction of overweight after a 1-year lifestyle intervention . Methods In a longitudinal study the association of polymorphisms in DRD2 ( rs18000497 , risk allele : T , formerly A1 allele at the TaqI A1 polymorphism ) and DRD4 ( variable number of t and em repeats ( VNTR ) ; 48 bp repeat in exon III ; risk alleles : 7 repeats or longer : 7R+ ) was tested on weight loss success following a 1-year lifestyle childhood obesity intervention ( OBELDICKS ) . An additional exploratory cross-sectional case-control study was performed to compare the same DRD polymorphisms in these overweight/obese children and adolescents versus lean adult controls . Subjects were 423 obese and 28 overweight children participating in lifestyle intervention ( 203 males ) , age median 12.0 ( interquartile range 10.0–13.7 ) years , body mass index - st and ard deviation score ( BMI -SDS ) 2.4 ± 0.5 ; 583 lean adults ( 232 males ) ; age median 25.3 ( interquartile range 22.5–26.8 ) years , BMI 19.1 ± 1.9 kg/m2  . BMI , BMI -SDS and skinfold thickness measures were assessed at baseline and after 1 year ; genotyping was performed for DRD2 risk variant rs1800497 and DRD4 exon III VNTR . Results The DRD2 genotype had a nominal effect on success in the weight loss intervention . The weakest BMI -SDS reduction was in children homozygous for two rs1800497 T-alleles ( n = 11 ) compared to the combined group with zero ( n = 308 ) or one ( n = 132 ) rs1800497 T-allele ( -0.08 ± 0.36 vs. -0.28 ± 0.34 ; p < 0.05 ) . There was no association between the DRD4 VNTR alleles and genotypes and success in the weight loss intervention . No associations of the risk alleles of the DRD2 and DRD4 polymorphisms and obesity were observed in the cross-sectional part of the study . Conclusions We did not find association between polymorphisms in DRD2 and DRD4 genes and weight status . However , obese carriers of two DRD2 rs1800497 T-alleles may be at risk for weak responses to lifestyle interventions aim ed at weight reduction . Trial registration Obesity intervention program “ Obeldicks ” is registered at clinical trials.gov ( NCT00435734 ) Importance Dietary modification remains key to successful weight loss . Yet , no one dietary strategy is consistently superior to others for the general population . Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets . Objective To determine the effect of a healthy low-fat ( HLF ) diet vs a healthy low-carbohydrate ( HLC ) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss . Design , Setting , and Participants The Diet Intervention Examining The Factors Interacting with Treatment Success ( DIETFITS ) r and omized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40 . The trial enrollment was from January 29 , 2013 , through April 14 , 2015 ; the date of final follow-up was May 16 , 2016 . Participants were r and omized to the 12-month HLF or HLC diet . The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion ( INS-30 ; blood concentration of insulin 30 minutes after a glucose challenge ) were associated with weight loss . Interventions Health educators delivered the behavior modification intervention to HLF ( n = 305 ) and HLC ( n = 304 ) participants via 22 diet-specific small group sessions administered over 12 months . The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality . Main Outcomes and Measures Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern , diet and insulin secretion , and diet and weight loss . Results Among 609 participants r and omized ( mean age , 40 [ SD , 7 ] years ; 57 % women ; mean body mass index , 33 [ SD , 3 ] ; 244 [ 40 % ] had a low-fat genotype ; 180 [ 30 % ] had a low-carbohydrate genotype ; mean baseline INS-30 , 93 & mgr;IU/mL ) , 481 ( 79 % ) completed the trial . In the HLF vs HLC diets , respectively , the mean 12-month macronutrient distributions were 48 % vs 30 % for carbohydrates , 29 % vs 45 % for fat , and 21 % vs 23 % for protein . Weight change at 12 months was −5.3 kg for the HLF diet vs −6.0 kg for the HLC diet ( mean between-group difference , 0.7 kg [ 95 % CI , −0.2 to 1.6 kg ] ) . There was no significant diet-genotype pattern interaction ( P = .20 ) or diet-insulin secretion ( INS-30 ) interaction ( P = .47 ) with 12-month weight loss . There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups . Conclusions and Relevance In this 12-month weight loss diet study , there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet , and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss . In the context of these 2 common weight loss diet approaches , neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom . Trial Registration clinical trials.gov Identifier : The 2 x 2 factorial design calls for r and omizing each participant to treatment A or B to address one question and further assignment at r and om within each group to treatment C or D to examine a second issue , permitting the simultaneous test of two different hypotheses . This design can increase the efficiency of large-scale clinical trials . The Physicians ' Health Study , a r and omized trial of  aspirin and beta-carotene among U.S. physicians , illustrates some features and potential problems in the design and analysis of a factorial trial . The most common concern , interaction between treatments , is generally an advantage rather than a limitation of this design . Although such interactions are relatively uncommon , this design provides a means to measure an effect which otherwise might not be apparent . If the interaction is sufficiently severe , however , then loss of power is possible
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 .