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Assessment of the FTO gene polymorphisms (rs1421085, rs17817449 and rs9939609) in exercise-trained men and women: the effects of a 4-week hypocaloric diet.

ABSTRACT: BACKGROUND:Variations in the fat mass and obesity-associated gene (FTO) are associated with obesity; however, it is unclear if changes in energy intake affect the adaptive response to caloric restriction in those with risk variants. The three FTO single nucleotide polymorphisms (SNPs), rs1421085, rs17817449 and rs9939609, are in strong linkage disequilibrium. Thus, the purpose of this investigation was to determine the role of these FTO SNPs vis-à-vis the effects of a 4-week hypocaloric diet on body composition in exercise-trained men and women. Two salivary biomarkers that associate with energy expenditure were also assessed (cortisol and salivary alpha-amylase, sAA). METHODS:Forty-seven exercise-trained men (n =?11) and women (n =?36) (mean ± SD: age 32 ± 9?years; height 169 ± 8?cm, body mass index 24.5 ± 2.9?kg/m2, hours of aerobic training per week 4.9 ± 3.8, hours of weight training per week 3.9 ± 2.4, years of training experience 13.4 ± 7.0) completed a 4-week hypocaloric diet (i.e., decrease total calories by ~?20-25% while maintaining a protein intake of ~?2.0?g/kg/d). Subjects were instructed to maintain the same training regimen and to decrease energy intake via carbohydrate and/or fat restriction during the treatment period. Body composition was assessed via dual-energy X-ray absorptiometry (DXA) (Model: Hologic Horizon W; Hologic Inc., Danbury CT USA). Total body water was determined via a multifrequency bioelectrical impedance (BIA) device (InBody 770). Saliva samples were collected pre and post intervention in order to genotype the participants as well as to determine the concentrations of cortisol and sAA. RESULTS:Of the 47 subjects, 15 were of normal risk for obesity whereas 32 were carriers of the FTO gene risk alleles. Subjects were grouped based on their genotype for the three FTO SNPs (i.e., rs1421085, rs17817449 and rs9939609) due to their strong linkage disequilibrium. We have classified those with the normal obesity risk as "non-risk allele" versus those that carry the "risk allele" (i.e., both heterozygous and homozygous). Both groups experienced a significant decrease in total energy intake (p

SUBMITTER: Antonio J

PROVIDER: S-EPMC6719365 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Assessment of the FTO gene polymorphisms (rs1421085, rs17817449 and rs9939609) in exercise-trained men and women: the effects of a 4-week hypocaloric diet.

Antonio Jose J Knafo Sarah S Kenyon Madaline M Ali Alina A Carson Cassandra C Ellerbroek Anya A Weaver Cailey C Roberts Justin J Peacock Corey A CA Tartar Jaime L JL

Journal of the International Society of Sports Nutrition 20190902 1

<h4>Background</h4>Variations in the fat mass and obesity-associated gene (FTO) are associated with obesity; however, it is unclear if changes in energy intake affect the adaptive response to caloric restriction in those with risk variants. The three FTO single nucleotide polymorphisms (SNPs), rs1421085, rs17817449 and rs9939609, are in strong linkage disequilibrium. Thus, the purpose of this investigation was to determine the role of these FTO SNPs vis-à-vis the effects of a 4-week hypocaloric ...[more]

PMID: 31477138

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Project description:Although the fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet).Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed.Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern.These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition.

Project description:AimThe aim of the study was to investigate pharmacokinetics of terbutaline after oral and inhaled administration in healthy trained male subjects in relation to doping control.MethodsTwelve healthy well-trained young men (27 ±2 years; mean ± SE) underwent two pharmacokinetic trials that compared 10 mg oral terbutaline with 4 mg inhaled dry powder terbutaline. During each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption. Blood (0-4 h) and urine (0-24 h) samples were collected before and after administration of terbutaline. Samples were analyzed for concentrations of terbutaline by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS).ResultsPharmacokinetics differed between the two routes of administration. Serum Cmax and area under the serum concentration-time curve (AUC) were lower after oral administration compared to inhalation (Cmax: 4.2 ± 0.3 vs. 8.5 ± 0.7 ng/ml, P ≤ 0.001; AUC: 422 ± 22 vs. 1308 ± 119 ng/ml × min). Urine concentrations (sum of the free drug and the glucuronide) were lower after oral administration compared to inhalation 2 h (1100 ± 204 vs. 61 ± 10 ng/ml, P ≤ 0.05) and 4 h (734 ± 110 vs. 340 ± 48 ng/ml, P ≤ 0.001) following administration, whereas concentrations were higher for oral administration than inhalation 12 h following administration (190 ± 41 vs. 399 ± 108 ng/ml, P ≤ 0.05). Urine excretion rate was lower after oral administration than inhalation the first 2 h following administration (P ≤ 0.001). Systemic bioavailability ratio between the two routes of administration was 3.8:1 (inhaled: oral; P ≤ 0.001).ConclusionGiven the higher systemic bioavailability of inhaled terbutaline compared to oral, our results indicate that it is difficult to differentiate allowed inhaled use of terbutaline from prohibited oral ingestion based on urine concentrations in doping control analysis. However given the potential performance enhancing effect of high dose terbutaline, it is essential to establish a limit on the WADA doping list.

Dataset Information

Assessment of the FTO gene polymorphisms (rs1421085, rs17817449 and rs9939609) in exercise-trained men and women: the effects of a 4-week hypocaloric diet.

Publications

Assessment of the FTO gene polymorphisms (rs1421085, rs17817449 and rs9939609) in exercise-trained men and women: the effects of a 4-week hypocaloric diet.

Similar Datasets

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