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/m

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 < 0.01); non-risk allele: pre kcal 2081 ± 618, post kcal 1703 ± 495; risk allele: pre kcal 1886 ± 515, post kcal 1502 ± 366). Both groups lost a significant amount of body weight (p < 0.01); however, there was no difference between groups for the change (post minus pre) in each group (risk allele change: - 1.0 ± 1.2 kg, non-risk allele change: - 1.2 ± 1.4 kg). Additionally, both groups lost a significant amount of fat mass (p < 0.01) with no differences between groups for the change in fat mass (risk allele change for fat mass: 1.1 ± 0.7 kg, non-risk allele change - 0.9 ± 0.4 kg). There were no significant changes in either group for fat free mass or total body water. The change in salivary alpha-amylase or cortisol was not different between groups.

Conclusions: In the short-term (i.e., 4 weeks), exercise-trained men and women consuming a hypocaloric diet that is relatively high in protein experience similar changes in body composition due exclusively to a decrement in fat mass and independent of FTO allele status. Therefore, weight and fat loss on a hypocaloric diet is, at least in the short-term, unaffected by the FTO gene.