title: FTO genotype is associated with exercise training-induced changes in body composition.
abstract: The fat mass (FM) and obesity-associated (FTO) gene is the first obesity-susceptibility gene identified by genome-wide association scans and confirmed in several follow-up studies. Homozygotes for the risk allele (A/A) have 1.67 times greater risk of obesity than those who do not have the allele. However, it is not known whether regular exercise-induced changes in body composition are influenced by the FTO genotype. The purpose of our study was to test whether the FTO genotype is associated with exercise-induced changes in adiposity. Body composition was derived from underwater weighing before and after a 20-week endurance training program in 481 previously sedentary white subjects of the HERITAGE Family Study. FTO single-nucleotide polymorphism (SNP) rs8050136 was genotyped using Illumina GoldenGate assay. In the sedentary state, the A/A homozygotes were significantly heavier and fatter than the heterozygotes and the C/C homozygotes in men (P = 0.004) but not in women (P = 0.331; gene-by-sex interaction P = 0.0053). The FTO genotype was associated with body fat responses to regular exercise (P < 0.005; adjusted for age, sex, and baseline value of response trait): carriers of the C allele showed three times greater FM and %body fat losses than the A/A homozygotes. The FTO genotype explained 2% of the variance in adiposity changes. Our data suggest that the FTO obesity-susceptibility genotype influences the body fat responses to regular exercise. Resistance to exercise-induced reduction in total adiposity may represent one mechanism by which the FTO A allele promotes overweight and obesity.
authors: Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. rankint@pbrc.edu
authors: Tuomo
authors: T
authors: Rankinen
authors: Treva
authors: T
authors: Rice
authors: Margarita
authors: M
authors: Teran-Garcia
authors: Dabeeru C
authors: DC
authors: Rao
authors: Claude
authors: C
authors: Bouchard
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D050154:Adiposity / Q000235:genetics*; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D015444:Exercise; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009765:Obesity / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D057185:Sedentary Behavior; D013997:Time Factors; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human